The puzzle of sympatry. Recent evidence supports the notion of sympatric speciation--the rise of new species in the same location--but the reasons for this phenomenon remain elusive

Sympatric speciation—the rise of new species in the absence of geographical barriers—remains a puzzle for evolutionary biologists. Though the evidence for sympatric speciation itself is mounting, an underlying genetic explanation remains elusive.For centuries, the greatest puzzle in biology was how to account for the sheer variety of life. In his 1859 landmark book, On the Origin of Species, Charles Darwin (1809–1882) finally supplied an answer: his grand theory of evolution explained how the process of natural selection, acting on the substrate of genetic mutations, could gradually produce new organisms that are better adapted to their environment. It is easy to see how adaptation to a given environment can differentiate organisms that are geographically separated; different environmental conditions exert different selective pressures on organisms and, over time, the selection of mutations creates different species—a process that is known as allopatric speciation.It is more difficult to explain how new and different species can arise within the same environment. Although Darwin never used the term sympatric speciation for this process, he did describe the formation of new species in the absence of geographical separation. “I can bring a considerable catalogue of facts,” he argued, “showing that within the same area, varieties of the same animal can long remain distinct, from haunting different stations, from breeding at slightly different seasons, or from varieties of the same kind preferring to pair together” (Darwin, 1859).It is more difficult to explain how new and different species can arise within the same environmentIn the 1920s and 1930s, however, allopatric speciation and the role of geographical isolation became the focus of speciation research. Among those leading the charge was Ernst Mayr (1904–2005), a young evolutionary biologist, who would go on to influence generations of biologists with his later work in the field. William Baker, head of palm research at the Royal Botanic Gardens, Kew in Richmond, UK, described Mayr as “one of the key figures to crush sympatric speciation.” Frank Sulloway, a Darwin Scholar at the Institute of Personality and Social Research at the University of California, Berkeley, USA, similarly asserted that Mayr''s scepticism about sympatry was central to his career.The debate about sympatric and allopatric speciation has livened up since Mayr''s death…Since Mayr''s death in 2005, however, several publications have challenged the notion that sympatric speciation is a rare exception to the rule of allopatry. These papers describe examples of both plants and animals that have undergone speciation in the same location, with no apparent geographical barriers to explain their separation. In these instances, a single ancestral population has diverged to the extent that the two new species cannot produce viable offspring, despite the fact that their ranges overlap. The debate about sympatric and allopatric speciation has livened up since Mayr''s death, as Mayr''s influence over the field has waned and as new tools and technologies in molecular biology have become available.Sulloway, who studied with Mayr at Harvard University, in the late 1960s and early 1970s, notes that Mayr''s background in natural history and years of fieldwork in New Guinea and the Solomon Islands contributed to his perception that the bulk of the data supported allopatry. “Ernst''s early career was in many ways built around that argument. It wasn''t the only important idea he had, but he was one of the strong proponents of it. When an intellectual stance exists where most people seem to have gotten it wrong, there is a tendency to sort of lay down the law,” Sulloway said.Sulloway also explained that Mayr “felt that botanists had basically led Darwin astray because there is so much evidence of polyploidy in plants and Darwin turned in large part to the study of botany and geographical distribution in drawing evidence in The Origin.” Indeed, polyploidization is common in plants and can lead to ‘instantaneous'' speciation without geographical barriers.In February 2006, the journal Nature simultaneously published two papers that described sympatric speciation in animals and plants, reopening the debate. Axel Meyer, a zoologist and evolutionary biologist at the University of Konstanz, Germany, demonstrated with his colleagues that sympatric speciation has occurred in cichlid fish in Lake Apoyo, Nicaragua (Barluenga et al, 2006). The researchers claimed that the ancestral fish only seeded the crater lake once; from this, new species have evolved that are distinct and reproductively isolated. Meyer''s paper was broadly supported, even by critics of sympatric speciation, perhaps because Mayr himself endorsed sympatric speciation among the cichlids in his 2001 book What Evolution Is. “[Mayr] told me that in the case of our crater lake cichlids, the onus of showing that it''s not sympatric speciation lies with the people who strongly believe in only allopatric speciation,” Meyer said.…several scientists involved in the debate think that molecular biology could help to eventually resolve the issueThe other paper in Nature—by Vincent Savolainen, a molecular systematist at Imperial College, London, UK, and colleagues—described the sympatric speciation of Howea palms on Lord Howe Island (Fig 1), a minute Pacific island paradise (Savolainen et al, 2006a). Savolainen''s research had originally focused on plant diversity in the gesneriad family—the best known example of which is the African violet—while he was in Brazil for the Geneva Botanical Garden, Switzerland. However, he realized that he would never be able prove the occurrence of sympatry within a continent. “It might happen on a continent,” he explained, “but people will always argue that maybe they were separated and got together after. […] I had to go to an isolated piece of the world and that''s why I started to look at islands.”Open in a separate windowFigure 1Lord Howe Island. Photo: Ian Hutton.He eventually heard about Lord Howe Island, which is situated just off the east coast of Australia, has an area of 56 km² and is known for its abundance of endemic palms (Sidebar A). The palms, Savolainen said, were an ideal focus for sympatric research: “Palms are not the most diverse group of plants in the world, so we could make a phylogeny of all the related species of palms in the Indian Ocean, southeast Asia and so on.”…the next challenges will be to determine which genes are responsible for speciation, and whether sympatric speciation is common

Sidebar A | Research in paradise

Alexander Papadopulos is no Tarzan of the Apes, but he has spent a couple months over the past two years aloft in palm trees hugging rugged mountainsides on Lord Howe Island, a Pacific island paradise and UNESCO World Heritage site.Papadopulos—who is finishing his doctorate at Imperial College London, UK—said the views are breathtaking, but the work is hard and a bit treacherous as he moves from branch to branch. “At times, it can be quite hairy. Often you''re looking over a 600-, 700-metre drop without a huge amount to hold onto,” he said. “There''s such dense vegetation on most of the steep parts of the island. You''re actually climbing between trees. There are times when you''re completely unsupported.”Papadopulos typically spends around 10 hours a day in the field, carrying a backpack and utility belt with a digital camera, a trowel to collect soil samples, a first-aid kit, a field notebook, food and water, specimen bags, tags to label specimens, a GPS device and more. After several days in the field, he spends a day working in a well-equipped field lab and sleeping in the quarters that were built by the Lord Howe governing board to accommodate the scientists who visit the island on various projects. Papadopulos is studying Lord Howe''s flora, which includes more than 200 plant species, about half of which are indigenous.Vincent Savolainen said it takes a lot of planning to get materials to Lord Howe: the two-hour flight from Sydney is on a small plane, with only about a dozen passengers on board and limited space for equipment. Extra gear—from gardening equipment to silica gel and wood for boxes in which to dry wet specimens—arrives via other flights or by boat, to serve the needs of the various scientists on the team, including botanists, evolutionary biologists and ecologists.Savolainen praised the well-stocked researcher station for visiting scientists. It is run by the island board and situated near the palm nursery. It includes one room for the lab and another with bunks. “There is electricity and even email,” he said. Papadoupulos said only in the past year has the internet service been adequate to accommodate video calls back home.Ian Hutton, a Lord Howe-based naturalist and author, who has lived on the island since 1980, said the island authorities set limits on not only the number of residents—350—but also the number of visitors at one time—400—as well as banning cats, to protect birds such as the flightless wood hen. He praised the Imperial/Kew group: “They''re world leaders in their field. And they''re what I call ‘Gentlemen Botanists''. They''re very nice people, they engage the locals here. Sometimes researchers might come here, and they''re just interested in what they''re doing and they don''t want to share what they''re doing. Not so with these people. Savolainen said his research helps the locals: “The genetics that we do on the island are not only useful to understand big questions about evolution, but we also always provide feedback to help in its conservation efforts.”Yet, in Savolainen''s opinion, Mayr''s influential views made it difficult to obtain research funding. “Mayr was a powerful figure and he dismissed sympatric speciation in textbooks. People were not too keen to put money on this,” Savolainen explained. Eventually, the Leverhulme Trust (London, UK) gave Savolainen and Baker £70,000 between 2003–2005 to get the research moving. “It was enough to do the basic genetics and to send a research assistant for six months to the island to do a lot of natural history work,” Savolainen said. Once the initial results had been processed, the project received a further £337,000 from the British Natural Environment Research Council in 2008, and €2.5 million from the European Research Council in 2009.From the data collected on Lord Howe Island, Savolainen and his team constructed a dated phylogenetic tree showing that the two endemic species of the palm Howea (Arecaceae; Fig 2) are sister taxa. From their tree, the researchers were able to establish that the two species—one with a thatch of leaves and one with curly leaves—diverged long after the island was formed 6.9 million years ago. Even where they are found in close proximity, the two species cannot interbreed as they flower at different times.Open in a separate windowFigure 2The two species of Howea palm. (A) Howea fosteriana (Kentia palm). (B) Howea belmoreana. Photos: William Baker, Royal Botanical Gardens, Kew, Richmond, UK.According to the researchers, the palm speciation probably occurred owing to the different soil types in which the plants grow. Baker explained that there are two soil types on Lord Howe—the older volcanic soil and the younger calcareous soils. The Kentia palm grows in both, whereas the curly variety is restricted to the volcanic soil. These soil types are closely intercalated—fingers and lenses of calcareous soils intrude into the volcanic soils in lowland Lord Howe Island. “You can step over a geological boundary and the palms in the forest can change completely, but they remain extremely close to each other,” Baker said. “What''s more, the palms are wind-pollinated, producing vast amounts of pollen that blows all over the place during the flowering season—people even get pollen allergies there because there is so much of the stuff.” According to Savolainen, that the two species have different flowering times is a “way of having isolation so that they don''t reproduce with each other […] this is a mechanism that evolved to allow other species to diverge in situ on a few square kilometres.”According to Baker, the absence of a causative link has not been demonstrated between the different soils and the altered flowering times, “but we have suggested that at the time of speciation, perhaps when calcareous soils first appeared, an environmental effect may have altered the flowering time of palms colonising the new soil, potentially causing non-random mating and kicking off speciation. This is just a hypothesis—we need to do a lot more fieldwork to get to the bottom of this,” he said. What is clear is that this is not allopatric speciation, as “the micro-scale differentiation in geology and soil type cannot create geographical isolation”, said Baker.…although molecular data will add to the debate, it will not settle it aloneThe results of the palm research caused something of a splash in evolutionary biology, although the study was not without its critics. Tod Stuessy, Chair of the Department of Systematic and Evolutionary Botany at the University of Vienna, Austria, has dealt with similar issues of divergence on Chile''s Juan Fernández Islands—also known as the Robinson Crusoe Islands—in the South Pacific. From his research, he points out that on old islands, large ecological areas that once separated species—and caused allopatric speciation—could have since disappeared, diluting the argument for sympatry. “There are a lot of cases [in the Juan Fernández Islands] where you have closely related species occurring in the same place on an island, even in the same valley. We never considered that they had sympatric origins because we were always impressed by how much the island had been modified through time,” Stuessy said. “What [the Lord Howe researchers] really didn''t consider was that Lord Howe Island could have changed a lot over time since the origins of the species in question.” It has also been argued that one of the palm species on Lord Howe Island might have evolved allopatrically on a now-sunken island in the same oceanic region.In their response to a letter from Stuessy, Savolainen and colleagues argued that erosion on the island has been mainly coastal and equal from all sides. “Consequently, Quaternary calcarenite deposits, which created divergent ecological selection pressures conducive to Howea species divergence, have formed evenly around the island; these are so closely intercalated with volcanic rocks that allopatric speciation due to ecogeographic isolation, as Stuessy proposes, is unrealistic” (Savolainen et al, 2006b). Their rebuttal has found support in the field. Evolutionary biologist Loren Rieseberg at the University of British Columbia in Vancouver, Canada, said: “Basically, you have two sister species found on a very small island in the middle of the ocean. It''s hard to see how one could argue anything other than they evolved there. To me, it would be hard to come up with a better case.”Whatever the reality, several scientists involved in the debate think that molecular biology could help to eventually resolve the issue. Savolainen said that the next challenges will be to determine which genes are responsible for speciation, and whether sympatric speciation is common. New sequencing techniques should enable the team to obtain a complete genomic sequence for the palms. Savolainen said that next-generation sequencing is “a total revolution.” By using sequencing, he explained that the team, “want to basically dissect exactly what genes are involved and what has happened […] Is it very special on Lord Howe and for this palm, or is [sympatric speciation] a more general phenomenon? This is a big question now. I think now we''ve found places like Lord Howe and [have] tools like the next-gen sequencing, we can actually get the answer.”Determining whether sympatric speciation occurs in animal species will prove equally challenging, according to Meyer. His own lab, among others, is already looking for ‘speciation genes'', but this remains a tricky challenge. “Genetic models […] argue that two traits (one for ecological specialisation and another for mate choice, based on those ecological differences) need to become tightly linked on one chromosome (so that they don''t get separated, often by segregation or crossing over). The problem is that the genetic basis for most ecologically relevant traits are not known, so it would be very hard to look for them,” Meyer explained. “But, that is about to change […] because of next-generation sequencing and genomics more generally.”Many researchers who knew Mayr personally think he would have enjoyed the challenge to his viewsOthers are more cautious. “In some situations, such as on isolated oceanic islands, or in crater lakes, molecular phylogenetic information can provide strong evidence of sympatric speciation. It also is possible, in theory, to use molecular data to estimate the timing of gene flow, which could help settle the debate,” Rieseberg said. However, he cautioned that although molecular data will add to the debate, it will not settle it alone. “We will still need information from historical biogeography, natural history, phylogeny, and theory, etc. to move things forward.”Many researchers who knew Mayr personally think he would have enjoyed the challenge to his views. “I can only imagine that it would''ve been great fun to engage directly with him [on sympatry on Lord Howe],” Baker said. “It''s a shame that he wasn''t alive to comment on [our paper].” In fact, Mayr was not really as opposed to sympatric speciation as some think. “If one is of the opinion that Mayr opposed all forms of sympatric speciation, well then this looks like a big swing back the other way,” Sulloway commented. “But if one reads Mayr carefully, one sees that he was actually interested in potential exceptions and, as best he could, chronicled which ones he thought were the best candidates.”Mayr''s opinions aside, many biologists today have stronger feelings against sympatric speciation than he did himself in his later years, Meyer added. “I think that Ernst was more open to the idea of sympatric speciation later in his life. He got ‘softer'' on this during the last two of his ten decades of life that I knew him. I was close to him personally and I think that he was much less dogmatic than he is often made out to be […] So, I don''t think that he is spinning in his grave.” Mayr once told Sulloway that he liked to take strong stances, precisely so that other researchers would be motivated to try to prove him wrong. “If they eventually succeeded in doing so, Mayr felt that science was all the better for it.”? Open in a separate windowAlex Papadopulos and Ian Hutton doing fieldwork on a very precarious ridge on top of Mt. Gower. Photo: William Baker, Royal Botanical Gardens, Kew, Richmond, UK.     

The A to T of historical evidence

Geneticists and historians collaborated recently to identify the remains of King Richard III of England, found buried under a car park. Genetics has many more contributions to make to history, but scientists and historians must learn to speak each other''s languages.The remains of King Richard III (1452–1485), who was killed with sword in hand at the Battle of Bosworth Field at the end of the War of the Roses, had lain undiscovered for centuries. Earlier this year, molecular biologists, historians, archaeologists and other experts from the University of Leicester, UK, reported that they had finally found his last resting place. They compared ancient DNA extracted from a scoliotic skeleton discovered under a car park in Leicester—once the site of Greyfriars church, where Richard was rumoured to be buried, but the location of which had been lost to time—with that of a seventeenth generation nephew of King Richard: it was a match. Richard has captured the public imagination for centuries: Tudor-friendly playwright William Shakespeare (1564–1616) portrayed Richard as an evil hunchback who killed his nephews in order to ascend to the throne, whilst in succeeding years others have leapt to his defence and backed an effort to find his remains.The application of genetics to history is revealing much about the ancestry and movements of groups of humans, from the fall of the Roman Empire to ancient ChinaMolecular biologist Turi King, who led the Leicester team that extracted the DNA and tracked down a descendant of Richard''s older sister, said that Richard''s case shows how multi-disciplinary teams can join forces to answer history''s questions. “There is a lot of talk about what meaning does it have,” she said. “It tells us where Richard III was buried; that the story that he was buried in Greyfriars is true. I think there are some people who [will] try and say: “well, it''s going to change our view of him” […] It won''t, for example, tell us about his personality or if he was responsible for the killing of the Princes in the Tower.”The discovery and identification of Richard''s skeleton made headlines around the world, but he is not the main prize when it comes to collaborations between historians and molecular biologists. Although some of the work has focused on high-profile historic figures—such as Louis XVI (1754–1793), the only French king to be executed, and Vlad the Impaler, the Transylvanian royal whose patronymic name inspired Bram Stoker''s Dracula (Fig 1)—many other projects involve population studies. Application of genetics to history is revealing much about the ancestry and movements of groups of humans, from the fall of the Roman Empire to ancient China.Open in a separate windowFigure 1The use of molecular genetics to untangle history. Even when the historical record is robust, molecular biology can contribute to our understanding of important figures and their legacies and provide revealing answers to questions about ancient princes and kings.Medieval historian Michael McCormick of Harvard University, USA, commented that historians have traditionally relied on studying records written on paper, sheepskin and papyrus. However, he and other historians are now teaming up with geneticists to read the historical record written down in the human genome and expand their portfolio of evidence. “What we''re seeing happening now—because of the tremendous impact from the natural sciences and particularly the application of genomics; what some of us are calling genomic archaeology—is that we''re working back from modern genomes to past events reported in our genomes,” McCormick explained. “The boundaries between history and pre-history are beginning to dissolve. It''s a really very, very exciting time.”…in the absence of written records, DNA and archaeological records could help fill in gapsMcCormick partnered with Mark Thomas, an evolutionary geneticist at University College London, UK, to try to unravel the mystery of one million Romano-Celtic men who went missing in Britain after the fall of the Roman Empire. Between the fourth and seventh centuries, Germanic tribes of Angles, Saxons and Jutes began to settle in Britain, replacing the Romano-British culture and forcing some of the original inhabitants to migrate to other areas. “You can''t explain the predominance of the Germanic Y chromosome in England based on the population unless you imagine (a) that they killed all the male Romano-Celts or (b) there was what Mark called ‘sexual apartheid'' and the conquerors mated preferentially with the local women. [The latter] seems to be the best explanation that I can see,” McCormick said of the puzzle.Ian Barnes, a molecular palaeobiologist at Royal Holloway University of London, commented that McCormick studies an unusual period, for which both archaeological and written records exist. “I think archaeologists and historians are used to having conflicting evidence between the documentary record and the archaeological record. If we bring in DNA, the goal is to work out how to pair all the information together into the most coherent story.”Patrick Geary, Professor of Western Medieval History at the Institute for Advanced Study in Princeton, New Jersey, USA, studies the migration period of Europe: a time in the first millennium when Germanic tribes, including the Goths, Vandals, Huns and Longobards, moved across Europe as the Roman Empire was declining. “We do not have detailed written information about these migrations or invasions or whatever one wants to call them. Primarily what we have are accounts written later on, some generations later, from the contemporary record. What we tend to have are things like sermons bemoaning the faith of people because God''s wrath has brought the barbarians on them. Hardly the kind of thing that gives us an idea of exactly what is going on—are these really invasions, are they migrations, are they small military groups entering the Empire? And what are these ‘peoples'': biologically related ethnic groups, or ad hoc confederations?” he said.Geary thinks that in the absence of written records, DNA and archaeological records could help fill in the gaps. He gives the example of jewellery, belt buckles and weapons found in ancient graves in Hungary and Northern and Southern Italy, which suggest migrations rather than invasions: “If you find this kind of jewellery in one area and then you find it in a cemetery in another, does it mean that somebody was selling jewellery in these two areas? Does this mean that people in Italy—possibly because of political change—want to identify themselves, dress themselves in a new style? This is hotly debated,” Geary explained. Material goods can suggest a relationship between people but the confirmation will be found in their DNA. “These are the kinds of questions that nobody has been able to ask because until very recently, DNA analysis simply could not be done and there were so many problems with it that this was just hopeless,” he explained. Geary has already collected some ancient DNA samples and plans to collect more from burial sites north and south of the Alps dating from the sixth century, hoping to sort out kinship relations and genetic profiles of populations.King said that working with ancient DNA is a tricky business. “There are two reasons that mitochondrial DNA (mtDNA) is the DNA we wished to be able to analyse in [King] Richard. In the first instance, we had a female line relative of Richard III and mtDNA is passed through the female line. Fortunately, it''s also the most likely bit of DNA that we''d be able to retrieve from the skeletal remains, as there are so many copies of it in the cell. After death, our DNA degrades, so mtDNA is easier to retrieve simply due to the sheer number of copies in each cell.”Geary contrasted the analysis of modern and ancient DNA. He called modern DNA analysis “[…] almost an industrial thing. You send it off to a lab, you get it back, it''s very mechanical.” Meanwhile, he described ancient DNA work as artisanal, because of degeneration and contamination. “Everything that touched it, every living thing, every microbe, every worm, every archaeologist leaves DNA traces, so it''s a real mess.” He said the success rate for extracting ancient mtDNA from teeth and dense bones is only 35%. The rate for nuclear DNA is only 10%. “Five years ago, the chances would have been zero of getting any, so 10% is a great step forward. And it''s possible we would do even better because this is a field that is rapidly transforming.”But the bottleneck is not only the technical challenge to extract and analyse ancient DNA. Historians and geneticists also need to understand each other better. “That''s why historians have to learn what it is that geneticists do, what this data is, and the geneticists have to understand the kind of questions that [historians are] trying to ask, which are not the old nineteenth century questions about identity, but questions about population, about gender roles, about relationship,” Geary said.DNA analysis can help to resolve historical questions and mysteries about our ancestors, but both historians and geneticists are becoming concerned about potential abuses and frivolous applications of DNA analysis in their fields. Thomas is particularly disturbed by studies based on single historical figures. “Unless it''s a pretty damn advanced analysis, then studying individuals isn''t particularly useful for history unless you want to say something like this person had blue eyes or whatever. Population level studies are best,” he said. He conceded that the genetic analysis of Richard III''s remnants was a sound application but added that this often is not the case with other uses, which he referred to as “genetic astrology.” He was critical of researchers who come to unsubstantiated conclusions based on ancient DNA, and scientific journals that readily publish such papers.…both historians and geneticists are becoming concerned about potential abuses or frivolous applications of DNA analysis in their fieldsThomas said that it is reasonable to analyse a Y chromosome or mtDNA to estimate a certain genetic trait. “But then to look at the distribution of those, note in the tree where those types are found, and informally, interpretively make inferences—“Well this must have come from here and therefore when I find it somewhere else then that means that person must have ancestors from this original place”—[…] that''s deeply flawed. It''s the most widely used method for telling historical stories from genetic data. And yet is easily the one with the least credibility.” Thomas criticized such facile use of genetic data, which misleads the public and the media. “I suppose I can''t blame these [broadcast] guys because it''s their job to make the programme look interesting. If somebody comes along and says ‘well, I can tell you you''re descended from some Viking warlord or some Celtic princess'', then who are they to question.”Similarly, the historians have reservations about making questionable historical claims on the basis of DNA analysis. Geary said the use of mtDNA to identify Richard III was valuable because it answered a specific, factual question. However, he is turned off by other research using DNA to look at individual figures, such as a case involving a princess who was a direct descendant of the woman who posed for Leonardo Da Vinci''s Mona Lisa. “There''s some people running around trying to dig up famous people and prove the obvious. I think that''s kind of silly. There are others that I think are quite appropriate, and while is not my kind of history, I think it is fine,” he said. “The Richard III case was in the tradition of forensics.”…the cases in which historians and archaeologists work with molecular biologists are rare and remain disconnected in general from the mainstream of historical or archaeological researchNicola Di Cosmo, a historian at the Institute for Advanced Study, who is researching the impact of climate change on the thirteenth century Mongol empire, follows closely the advances in DNA and history research, but has not yet applied it to his own work. Nevertheless, he said that genetics could help to understand the period he studies because there are no historical documents, although monumental burials exist. “It is important to get a sense of where these people came from, and that''s where genetics can help,” he said. He is also concerned about geneticists who publish results without involving historians and without examining other records. He cited a genetic study of a so-called ‘Eurasian male'' in a prestige burial of the Asian Hun Xiongnu, a nomadic people who at the end of the third century B.C. formed a tribal league that dominated most of Central Asia for more than 500 years. “The conclusion the geneticists came to was that there was some sort of racial tolerance in this nomadic empire, but we have no way to even assume that they had any concept of race or tolerance.”Di Cosmo commented that the cases in which historians and archaeologists work with molecular biologists are rare and remain disconnected in general from the mainstream of historical or archaeological research. “I believe that historians, especially those working in areas for which written records are non-existent, ought to be taking seriously the evidence churned out by genetic laboratories. On the other hand, geneticists must realize that the effectiveness of their research is limited unless they access reliable historical information and understand how a historical argument may or may not explain the genetic data” [1].Notwithstanding the difficulties in collaboration between two fields, McCormick is excited about historians working with DNA. He said the intersection of history and genomics could create a new scientific discipline in the years ahead. “I don''t know what we''d call it. It would be a sort of fusion science. It certainly has the potential to produce enormous amounts of enormously interesting new evidence about our human past.”     

Natural healing: How does Nature repair itself after an oil spill?

Few environmental disasters are as indicting of humanity as major oil spills. Yet Nature has sometimes shown a remarkable ability to clean up the oil on its own.In late April 2010, the BP-owned semi-submersible oilrig known as Deepwater Horizon exploded just off the coast of Louisiana. Over the following 84 days, the well from which it had been pumping spewed 4.4 million barrels of crude oil into the Gulf of Mexico, according to the latest independent report (Crone & Tolstoy, 2010). In August, the US Government released an even grimmer estimate: according to the federal Flow Rate Technical Group, up to 4.9 million barrels were excreted during the course of the disaster. Whatever the actual figure, images from NASA show that around 184.8 million gallons of oil have darkened the waters just 80 km from the Louisiana coast, where the Mississippi Delta harbours marshlands and an abundance of biodiversity (NASA Jet Propulsion Laboratory, 2010; Fig 1).…the Deepwater incident is not the first time that a massive oil spill has devastated marine and terrestrial ecosystems, nor is it likely to be the lastOpen in a separate windowFigure 1Images of the Deepwater Horizon oil slick in the Gulf of Mexico. These images were recorded by NASA''s Terra spacecraft in May 2010. The image dimensions are 346 × 258 kilometres and North is toward the top. In the upper panel, the oil appears bright turquoise owing to the combination of images that were used from the Multi-angle Imaging SpectroRadiometer (MISR) aboard the craft. The Mississippi Delta, which harbors marshlands and an abundance of biodiversity, is visible in the top left of the image. The white arrow points to a plume of smoke and the red cross-hairs indicate the former location of the drilling rig. The lower two panels are enlargements of the smoke plume, which is probably the result of controlled burning of collected oil on the surface.© NASA/GSFC/LaRC/JPL, MISR TeamThe resulting environmental and economic situation in the Gulf is undoubtedly dreadful—the shrimp-fishing industry has been badly hit, for example. Yet the Deepwater incident is not the first time that a massive oil spill has devastated marine and terrestrial ecosystems, nor is it likely to be the last. In fact, the US National Oceanic and Atmospheric Association (NOAA) deals with approximately 300 oil spills per year and the Deepwater catastrophe—despite its extent and the enormous amount of oil released—might not be as terrible for the environment as was originally feared. Jacqueline Michel, a geochemist who has worked on almost every major oil spill since the 1970s and who is a member of NOAA''s scientific support team for the Gulf spill, commented that “the marshes and grass are showing some of the highest progresses of [oil] degradation because of the wetness.” This rapid degradation is partly due to an increased number of oil-consuming microbes in the water, whose population growth in response to the spill is cleaning things up at a relatively fast pace (Hazen et al, 2010).It therefore seems that, however bad the damage, Nature''s capacity to repair itself might prevent the unmitigated disaster that many feared on first sight of the Deepwater spill. As the late social satirist George Carlin (1937–2008) once put it: “The planet will shake us off like a bad case of fleas, a surface nuisance[.] The planet will be here for a long, long—LONG—time after we''re gone, and it will heal itself, it will cleanse itself, because that''s what it does, it''s a self-correcting system.”Michel believes that there are times when it is best to leave nature alone. In such cases the oil will degrade naturally by processes as simple as exposure to sunlight—which can break it down—or exposure to the air—which evaporates many of its components. “There have been spills where there was no response because we knew we were going to cause more harm,” Michel said. “Although we''re going to remove heavier layers of surface oil [in this case], the decision has been made to leave oil on the beach because we believe it will degrade in a timescale of months […] through natural processing.”To predict the rate of general environmental recovery, Michel said one should examine the area''s fauna, the progress of which can be very variable. Species have different recovery rates and although it takes only weeks or months for tiny organisms such as plankton to bounce back to their normal population density, it can take years for larger species such as the endangered sea turtle to recover.…however bad the damage, Nature''s capacity to repair itself might prevent the unmitigated disaster that many feared on first sight…Kimberly Gray, professor of environmental chemistry and toxicology at Northwestern University (Evanston, IL, USA), is most concerned about the oil damaging the bottom of the food chain. “Small hits at the bottom are amplified as you move up,” she explained. “The most chronic effects will be at the base of the food chain […] we may see lingering effects with the shrimp population, which in time may crash. With Deepwater, it''s sort of like the straw that broke the shrimp''s back.”Wetlands in particular are a crucial component of the natural recovery of ecosystems, as they provide flora that are crucial to the diets of many organisms. They also provide nesting grounds and protective areas where fish and other animals find refuge from predation. “Wetlands and marsh systems are Nature''s kidneys and they''ve been damaged,” Gray said. The problem is exacerbated because the Louisiana wetlands are already stressed in the aftermath of Hurricane Katrina, which devastated the Gulf coast in August 2005, and because of constant human activity and environmental damage. As Gray commented, “Nature has a very powerful capacity to repair itself, but what''s happening in the modern day is assault after assault.”Ron Thom, a marine ecologist at Pacific Northwest National Laboratory—a US government-funded research facility (Richland, WA, USA)—has done important research on coastal ecosystems. He believes that such habitats are able to decontaminate themselves to a limited degree because of evolution. “[Coastal-related ecosystems are] pretty resilient because they''ve been around a long time and know how to survive,” he said.As a result, wetlands can decontaminate themselves of pollutants such as oil, nitrate and phosphate. However, encountering large amounts of pollutants in a short period of time can overwhelm the healing process, or even stop it altogether. “We did some experiments here in the early 90s looking at the ability for salt marshes to break down oil,” Thom said. “When we put too much oil on the surface of the marsh it killed everything.” He explained that the oil also destroyed the sediment–soil column, where plant roots are located. Eventually, the roots disintegrated and the entire soil core fell apart. According to Thom, the Louisiana marshes were weakened by sediment and nutrient starvation, which suggests that the Deepwater spill destroyed below-ground material in some locations. “You can alter a place through a disturbance so drastic that it never recovers to what it used to be because things have changed so much,” he said.“Nature has a very powerful capacity to repair itself, but what''s happening in the modern day is assault after assault”Michael Blum, a coastal marsh ecologist at Tulane University in New Orleans, said that it is hard to determine the long-term effects of the oil because little is known about the relevant ecotoxicology—the effect of toxic agents on ecosystems. He has conducted extensive research on how coastal marsh plants respond to stress: some marshes might be highly susceptible to oil whereas others could have evolved to deal with natural oil seepage to metabolize hydrocarbons. In the former, marshes might perish after drastic exposure to oil leading to major shifts in plant communities. In the latter case, the process of coping with oil could involve the uptake of pollutants in the oil—known as polycyclic aromatic hydrocarbons (PAHs)—and their reintroduction into the environment. “If plants are growing in the polluted sediments and tapping into those contaminated sources, they can pull that material out of the soil and put it back into the water column or back into the leaf tissue that is a food source for other organisms,” Blum explained.In addition to understanding the responses of various flora, scientists also need to know how the presence of oil in an ecosystem affects the fauna. One model that is used to predict the effects of oil on vertebrates is the killifish; a group of minnows that thrive in the waters of Virginia''s Elizabeth River, where they are continuously exposed to PAHs deposited in the water by a creosote factory (Meyer & Di Giulio, 2003). “The killifish have evolved tolerance to the exposure of PAHs over chronic, long-term conditions,” Blum said. “This suggests that something similar may occur elsewhere, including in Gulf Coast marshes exposed to oil.”Although Michel is optimistic about the potential for environmental recovery, she pointed out that no two spills are the same. “There are lot of things we don''t know, we never had a spill that had surface release for so long at this water depth,” she said. Nevertheless, to better predict the long-term effects, scientists have turned to data from similar incidents.In 1989, the petroleum tanker Exxon Valdez struck Bligh Reef off the coast of Prince William Sound in Alaska and poured a minimum of 11 million gallons of oil into the water—enough to fill 125 Olympic-sized swimming pools. Senior scientist at NOAA, Stanley Rice of Juno, Alaska, studies the long-term effects of the spill and the resulting oil-related issues in Prince William Sound. Rice has worked with the spill since day 3 and, 20 years later, he is seeing major progress. “I never want to give the impression that we had this devastating oil spill in 1989 and it''s still devastating,” he said. “We have pockets of a few species where lingering oil hurts their survival, but in terms of looking at the Sound in its entirety […] it''s done a lot of recovery in 20 years.”…little is known about the relevant ecotoxicology—the effect of toxic agents on ecosystemsDespite the progress, Rice is still concerned about one group of otters. The cold temperature of the water in the Sound—rarely above 5 °C—slows the disintegration of the oil and, every so often, the otters come in contact with a lingering pocket. When they are searching for food, for example, the otters often dig into pits containing oil and become contaminated, which damages their ability to maintain body temperature. As a result, they cannot catch as much food and starve because they need to consume the equivalent of 25% of their body weight every day (Rice, 2009).“Common colds or worse, pneumonia, are extremely debilitating to an animal that has to work literally 365 days a year, almost 8 to 12 hours a day,” Rice explained. “If they don''t eat enough to sustain themselves, they die of hyperthermia.” Nevertheless, in just the last two years, Rice has finally seen the otter population rebound.Unlike the otters, one pod of orca whales has not been so lucky. Since it no longer has any reproductive females, the pod will eventually become extinct. However, as it dies out, orca prey such as seals and otters will have a better chance of reproducing. “There are always some winners and losers in these types of events,” Rice said. “Nature is never static.”The only ‘loser'' that Rice is concerned about at the moment is the herring, as many of their populations have remained damaged for the past 20 years. “Herring are critical to the ecosystem,” he said. “[They are] a base diet for many species […] Prince William Sound isn''t fully recovered until the herring recover.”North America is not alone in dealing with oil-spill disasters—Europe has had plenty of experience too. One of the worst spills occurred when the oil tanker Prestige leaked around 20 million gallons of oil into the waters of the Galacian coast in Northern Spain in 2002. This also affected the coastline of France and is considered Spain''s worst ecological disaster.“The impacts of the Prestige were indeed severe in comparison with other spills around the world,” said attorney Xabier Ezeizabarrena, who represented the Fishermen Guilds of Gipuzkoa in a lawsuit relating to the spill. “Some incidents aren''t even reported, but in the European Union the ratio is at least one oil spill every six months.”For disasters involving oil, oceanographic data to monitor and predict the movement of the spill is essentialIn Ezeizabarrena''s estimation, Spanish officials did not respond appropriately to the leak. The government was denounced for towing the shipwreck further out into the Atlantic Ocean—where it eventually sank—rather than to a port. “There was a huge lack of measures and tools from the Spanish government in particular,” Ezeizabarrena said. “[However], there was a huge response from civil society […] to work together [on restoration efforts].”Ionan Marigómez, professor of cellular biology at the University of the Basque Country, Spain, was the principal investigator on a federal coastal-surveillance programme named Orbankosta. He recorded the effects of the oil on the Basque coast and was a member of the Basque government''s technical advisory commission for the response to the Prestige spill. He was also chair of the government''s scientific committee. “Unfortunately, most of us scientists were not prepared to answer questions related to the biological impact of restoration strategies,” Marigómez said. “We lacked data to support our advice since continued monitoring is not conducted in the area […] and most of us had developed our scientific activity with too much focus on each one''s particular area when the problem needed a holistic view.”…the world consumes approximately 31 billion barrels of oil per year; more than 700 times the amount that leaked during the Deepwater spillFor disasters involving oil, oceanographic data to monitor and predict the movement of the spill is essential. Clean-up efforts were initially encouraged in Spain, but data provided by coastal-inspection programmes such as Orbankosta informed the decision to not clean up the Basque shoreline, allowing the remaining oil debris to disintegrate naturally. In fact, the cleaning activity that took place in Galicia only extended the oil pollution to the supralittoral zone—the area of the beach splashed by the high tide, rather than submerged by it—as well as to local soil deposits. On the Basque coast, restoration efforts were limited to regions where people were at risk, such as rocky areas near beaches and marinas.Eight years later, Galicia still suffers from the after-effects of the Prestige disaster. Thick subsurface layers of grey sand are found on beaches, sometimes under sand that seems to be uncontaminated. In Corme-Laxe Bay and Cies Island in Galicia, PAH levels have decreased. Studies have confirmed, however, that organisms exposed to the area''s sediments had accumulated PAHs in their bodies. Marigómez, for example, studied the long-term effects of the spill on mussels. Depending on their location, PAH levels decreased in the sampled mussel tissue between one and two years after the spill. However, later research showed that certain sites suffered later increases in the level of PAHs, due to the remobilization of oil residues (Cajaraville et al, 2006). Indeed, many populations of macroinvertebrate species—which are the keystones of coastal ecosystems—became extinct at the most-affected locations, although neighbouring populations recolonized these areas. The evidence suggests that only time will tell what will happen to the Galicia ecosystem. The same goes for oil-polluted environments around the world.The concern whether nature can recover from oil spills might seem extreme, considering that oil is a natural product derived from the earth. But too much of anything can be harmful and oil would remain locked underground without human efforts to extract it. “As from Paracelsus'' aphorism, the dose makes the poison,” Marigómez said.According to the US Energy Information Administration, the world consumes approximately 31 billion barrels of oil per year; more than 700 times the amount that leaked during the Deepwater spill. Humanity continues, in the words of some US politicians, to “drill, baby, drill!” On 12 October 2010, less than a year after the Gulf Coast disaster, US President Barack Obama declared that he was lifting the ban on deepwater drilling. It appears that George Carlin got it right again when he satirized a famous American anthem: “America, America, man sheds his waste on thee, and hides the pines with billboard signs from sea to oily sea!”     

Will we wake up to biodiversity?: The International Year of Biodiversity has failed to raise awareness or halt decline as economic crises and political interests have sidelined the environment

Looking back on the International Year of Biodiversity, some conservationists hope that it has raised awareness, if nothing else. Even so, many scientists remain pessimistic about our efforts to halt biodiversity decline.The United Nations'' (UN) International Year of Biodiversity in 2010 was supposed to see the adoption of measures that would slow global environmental decline and the continuing loss of endangered species and habitats. Even before, in 2002, most UN members had committed to halting the decline in biodiversity, which is a measure of the health of ecosystems. But the results of these international efforts have been funereal. Moreover, the current global economic crisis, coupled with growing anti-science attitudes in the USA, are adding to the concern of scientists about whether there is the political will to address the loss of biodiversity and whether habitat loss and extinction rates are reaching a point of no return.“There is not a single report received last year that claimed to have stopped or reduced the loss of biodiversity”Ahmed Djoghlaf, Executive Secretary of the Convention on Biological Diversity under the UN Environment Programme based in Montreal, Canada, said that of the 175 national reports submitted as part of the International Year of Biodiversity to his agency last year, none reported any progress. “There is not a single report received last year that claimed to have stopped or reduced the loss of biodiversity,” he said. “These reports confirm that the rate of loss of biodiversity today is unprecedented and the rate is 1,000 higher than the rate of natural extinction on species, and [his agency''s Global Biodiversity Outlook 2010; UN, 2010a] predicts that if business is allowed to continue then major ecosystems, the ocean, the fish, the forests, will reach the tipping point, meaning that there will be irreversible and irreparable damage done to the ecosystems.”The UN campaign traces its roots to the European Union (EU) commitment in 2001 to halt the loss of biodiversity by 2010. The 2010 goal was incorporated into the UN Millennium Development Goals because of the severe impact of biodiversity loss on human well-being. However, the EU last year conceded in a report that it missed its 2010 target, too. The EU''s Biodiversity Action Plan, launched in 2006, shows that Europe''s biodiversity “remains under severe threat from the excessive demands we are making on our environment, such as changes in land use, pollution, invasive species and climate change.” Yet, EU Environment Commissioner Janez Potočnik has seen some positive signs: “We have learned some very important lessons and managed to raise biodiversity to the top of the political agenda. But we need everyone on board and not just in Europe. The threat around the world is even greater than in the EU,” he wrote last year (EC, 2010).Despite the initiative''s poor report card, Djoghlaf was upbeat about the International Year of Biodiversity. “It was a success because it was celebrated everywhere,” he said. “In Switzerland, they conducted a survey before and after the International Year of Biodiversity and they concluded that at the end of the year, 67% of all the Swiss people are now aware of biodiversity. When the year started it was 40%. People are more and more aware. In addition, biodiversity has entered the top of the political agenda.”In October 2010, delegates from 193 countries attended the UN Convention on Biodiversity in Nagoya, Japan, and adopted 20 strategic goals to be achieved by 2020 (UN, 2010b). The so-called Aichi Biodiversity Targets include increased public awareness of the values of biodiversity and the steps that individuals can take to conserve and act sustainably; the halving or halting of the rate of loss of all natural habitats, including forests; and the conservation of 17% of terrestrial and inland water, and 10% of coastal and marine areas through effective and equitable management, resulting in ecologically representative and well-connected systems. By contrast, 13% of land areas and 1% of marine areas were protected in 2010.However, the Convention on Biological Diversity is not enforceable. Anne Larigauderie, Executive Director of DIVERSITAS (Paris, France), which promotes research on biodiversity science, said that it is up to the individual countries to adopt enforceable legislation. “In principle, countries have committed. Now it depends on what individual countries are going to do with the agreement,” she said. “I would say that things are generally going in the right direction and it''s too early to tell whether or not it''s going to have an impact in terms of responding and in terms of the biodiversity itself.”Researchers, however, have been disappointed by The International Year of Biodiversity. Conservation biologist Stuart Butchart, of Birdlife International in Cambridge, UK—a partnership of non-governmental environmental organizations and colleagues from other environmental groups—compiled a list of 31 indicators to measure progress towards the 2010 goal of the International Year of Biodiversity. He and his collaborators reported in Science (Butchart et al, 2010) that these indicators, including species population trends, extinction risks and habitat conditions, showed declines with no significant rate reductions. At the same time, indicators of pressure on biodiversity, such as resource consumption, invasive alien species, nitrogen pollution, over-exploitation and climate change impacts showed increases. “Despite some local successes and increasing responses (including extent and biodiversity coverage of protected areas, sustainable forest management, policy responses to invasive alien species and biodiversity-related aid), the rate of biodiversity loss does not appear to be slowing,” the researchers wrote.​wrote.Open in a separate window© Thomas Kitchin & Victoria Hurst/Wave/CorbisButchart pointed out that even if the International Year of Biodiversity had an impact on raising awareness and reducing biodiversity loss, detecting the change would take time. He said that the International Year of Biodiversity fell short of increasing awareness in parts of government not dealing with the environment, including ministries of transport, tourism, treasury and finance. It also seems probable that the campaign had little impact on the business sector, which affects development projects with a direct impact on biodiversity. “People can''t even seem to get together on global climate change, which is a whole lot more obvious and right there,” Peter Raven, president emeritus of the Missouri Botanical Gardens in St Louis, USA, explained. “Biodiversity always seems to be a sort of mysterious background thing that isn''t quite there.”“People can''t even seem to get together on global climate change, which is a whole lot more obvious and right there…”Illka Hanski, a professor in the Department of Ecology and Evolutionary Biology at the University of Helsinki in Finland, said that studies such as Butchart''s “indicate that nothing really happened in 2010. Biodiversity decline continued and has been declining over the past 10 years.”Other researchers are more positive, although with reservations. Conservation biologist Thomas Eugene Lovejoy III, Heinz Center Biodiversity Chair and former president of the Center in Washington, DC, USA—a non-partisan, non-profit organization dedicated to advancing sound environmental policy—said that economic trends affect biodiversity and that biodiversity efforts might actually be benefiting from the current global economic crisis. For example, the decline in the housing markets in the USA and Europe has reduced the demand on lumber for new construction and has led to a reduction in deforestation. “Generally speaking, when there is an economic downturn, some of the things that are pressuring biodiversity actually abate somewhat. That''s the good news. The bad news is that the ability to marshal resources to do some things proactively gets harder,” he said.Chris Thomas, a conservation biologist at the University of York in the UK, who studies ecosystems and species in the context of climate change, said that economic depressions do slow the rate of damage to the environment. “But it also takes eyes off the ball of environmental issues. It''s not clear whether these downturns, when you look over a period of a decade, make much difference or not.” Hanski agreed: “[B]ecause there is less economic activity, there may be less use of resources and such. But I don''t think this is a way to solve our problems. It won''t lead to any stable situation. It just leads to a situation where economic policies become more and more dependent on measures that try actually just to increase the growth as soon as possible.”…biodiversity efforts might actually be benefiting from the current global economic crisisRaven said that in bad times, major interests such as those involved in raising cattle, growing soybeans and clearing habitat for oil palms have reduced political clout because there is less money available for investment. But he said economic downturns do not slow poor people scrounging for sustenance in natural habitats.To overcome this attitude of neglect, Lovejoy thinks there ought to be a new type of ‘economics'' that demonstrates the benefits of biodiversity and brings the “natural world into the normal calculus.” Researchers are already making progress in this direction. Thomas said that the valuation of nature is one of the most active areas of research. “People have very different opinions as to how much of it can be truly valued. But it is a rapidly developing field,” he said. “Once you''ve decided how much something is worth, then you''ve got to ask what are the financial or other mechanisms by which the true value of this resource can be appreciated.”Hanski said that the main problem is the short-term view of economic forecasts. “Rapid use of natural resources because of short-term calculation may actually lead to a sort of exploitation rather than conservation or preservation.” He added that the emphasis on economic growth in rich societies in North America and Europe is frustrating. “We have become much richer than in 1970 when there actually was talk of zero growth in serious terms. So now we are richer and we are becoming more and more dependent on continued growth, the opposite of what we should be aiming at. It''s a problem with our society and economics clearly, but I can''t be very optimistic about the biodiversity or other environmental issues in this kind of situation.” He added that biodiversity is still taking a backseat to economics: “There is a very long way to go right now with the economic situation in Europe, it''s clear that these sorts of [biodiversity] issues are not the ones which are currently being debated by the heads of states.”The economic downturn, which has led to reduced government and private funding and declines in endowments, has also hurt organizations dedicated to preserving biodiversity. Butchart said that some of the main US conservation organizations, including the Nature Conservancy and the World Wildlife Federation, have experienced staff cuts up to 30%. “Organizations have had to tighten their belts and reign in programmes just to stay afloat, so it''s definitely impacted the degree to which we could work effectively,” he said. “Most of the big international conservation organizations have had to lay off large numbers of staff.”…a new type of ‘economics'' that demonstrates the benefits of biodiversity and brings the “natural world into the normal calculus”Cary Fowler, Executive Director of the Global Crop Diversity Trust in Rome, Italy, a public–private partnership to fund key crop collections for food security, also feels the extra challenges of the global economic crisis. “We invest our money conservatively like a foundation would in order to generate income that can reliably pay the bills in these seed banks year after year. So I''m always nervous and I have the computer on at the moment looking at what''s happening with the sovereign debt crisis here in Europe. It''s not good,” he said. “Governments are not being very generous with contributions to this area. Donors will rarely give a reason [for cutting funding].”The political situation in the USA, the world''s largest economy, is also not boding well for conservation of and research into biodiversity. The political extremism of the Republican Party during the run up to the 2012 presidential election has worried many involved in biodiversity issues. Republican contender Texas Governor Rick Perry has been described as ‘anti-science'' for his denial of man-made climate change, a switch from the position of 2008 Republican candidate John McCain. Perry was also reported to describe evolution as a “theory that''s out there, and it''s got some gaps in it” at a campaign event in New Hampshire earlier in the year.“Most of the big international conservation organizations have had to lay off large numbers of staff”Raven said this attitude is putting the USA at a disadvantage. “It drives us to an anti-intellectualism and a lack of real verification for anything which is really serious in terms of our general level of scientific education and our ability to act intelligently,” he said.Still, Larigauderie said that although the USA has not signed the conventions on biodiversity, she has seen US observers attend the meetings, especially under the Obama administration. “They just can''t speak,” she said. Meanwhile, Lovejoy said that biodiversity could get lost in the “unbelievable polarisation affecting US politics. I have worked out of Washington for 36 years now—I''ve never seen anything like this: an unwillingness to actually listen to the other side.”Raven said it is vital for the USA to commit to preserving biodiversity nationally and internationally. “It''s extremely important because our progress towards sustainability for the future will depend on our ability to handle biodiversity in large part. We''re already using about half of all the total photosynthetic productivity on land worldwide and that in turn means we''re cutting our options back badly. The US is syphoning money by selling debt and of course promoting instability all over the world,” he explained. “It''s clear that there is no solution to it other than a level population, more moderate consumption levels and new technologies altogether.”The EU and the UN have also changed the time horizon for halting the decline in biodiversity. As part of the Nagoya meeting, the UN announced the UN Decade for Biodiversity. The strategic objectives include a supporting framework for the implementation of the Biodiversity Strategic Plan 2011–2020 and the Aichi Biodiversity Targets, as well as guidance to regional and international organizations, and more public awareness of biodiversity issues.But Butchart remains sceptical. “I suspect ‘decades of whatever'' have even less impact than years,” he said. “2008 was the International Year of the Potato. I don''t know how much impact that had on your life and awareness. I think there is greater awareness and greater potential to make significant progress in addressing biodiversity loss now than there was 10 years ago, but the scale of the challenge is still immense.”“…our progress towards sustainability for the future will depend on our ability to handle biodiversity in large part”Hanski has similar doubts. “I believe it''s inevitable that a very large fraction of the species on Earth will go extinct in the next hundred years. I can''t see any change to that.” But he is optimistic that some positive change can be made. “Being pessimistic doesn''t help. The nations still can make a difference.” He said he has observed ecotourism playing a role in saving some species in Madagascar, where he does some of his research.“We''re not going to fundamentally be able to wipe life off the planet,” Thomas said. “We will wipe ourselves off the planet virtually certainly before we wipe life out on Earth. However, from the point of view of humanity as a culture, and in terms of the resources we might be able to get from biodiversity indirectly or directly, if we start losing things then it takes things millions of years to ‘re-evolve'' something that does an equivalent job. From a human perspective, when we wipe lots of things out, they''re effectively permanently lost. Of course it would be fascinating and I would love to be able to come back to the planet in 10 million years and see what it looks like, assuming humans are not here and other stuff will be.”Djoghlaf, by contrast, is more optimistic about our chances: “I believe in the human survival aspect. When humankind realises that the current pattern of production and consumption and the current way that it is dealing with nature is unsustainable, we will wake up.”     

It's life, but just as we know it

A consensus definition of life remains elusiveIn July this year, the Phoenix Lander robot—launched by NASA in 2007 as part of the Phoenix mission to Mars—provided the first irrefutable proof that water exists on the Red Planet. “We''ve seen evidence for this water ice before in observations by the Mars Odyssey orbiter and in disappearing chunks observed by Phoenix […], but this is the first time Martian water has been touched and tasted,” commented lead scientist William Boynton from the University of Arizona, USA (NASA, 2008). The robot''s discovery of water in a scooped-up soil sample increases the probability that there is, or was, life on Mars.Meanwhile, the Darwin project, under development by the European Space Agency (ESA; Paris, France; www.esa.int/science/darwin), envisages a flotilla of four or five free-flying spacecraft to search for the chemical signatures of life in 25 to 50 planetary systems. Yet, in the vastness of space, to paraphrase the British astrophysicist Arthur Eddington (1822–1944), life might be not only stranger than we imagine, but also stranger than we can imagine. The limits of our current definitions of life raise the possibility that we would not be able to recognize an extra-terrestrial organism.Back on Earth, molecular biologists—whether deliberately or not—are empirically tackling the question of what is life. Researchers at the J Craig Venter Institute (Rockville, MD, USA), for example, have synthesized an artificial bacterial genome (Gibson et al, 2008). Others have worked on ‘minimal cells'' with the aim of synthesizing a ‘bioreactor'' that contains the minimum of components necessary to be self-sustaining, reproduce and evolve. Some biologists regard these features as the hallmarks of life (Luisi, 2007). However, to decide who is first in the ‘race to create life'' requires a consensus definition of life itself. “A definition of the precise boundary between complex chemistry and life will be critical in deciding which group has succeeded in what might be regarded by the public as the world''s first theology practical,” commented Jamie Davies, Professor of Experimental Anatomy at the University of Edinburgh, UK.For most biologists, defining life is a fascinating, fundamental, but largely academic question. It is, however, crucial for exobiologists looking for extra-terrestrial life on Mars, Jupiter''s moon Europa, Saturn''s moon Titan and on planets outside our solar system.In their search for life, exobiologists base their working hypothesis on the only example to hand: life on Earth. “At the moment, we can only assume that life elsewhere is based on the same principles as on Earth,” said Malcolm Fridlund, Secretary for the Exo-Planet Roadmap Advisory Team at the ESA''s European Space Research and Technology Centre (Noordwijk, The Netherlands). “We should, however, always remember that the universe is a peculiar place and try to interpret unexpected results in terms of new physics and chemistry.”The ESA''s Darwin mission will, therefore, search for life-related gases such as carbon dioxide, water, methane and ozone in the atmospheres of other planets. On Earth, the emergence of life altered the balance of atmospheric gases: living organisms produced all of the Earth'' oxygen, which now accounts for one-fifth of the atmosphere. “If all life on Earth was extinguished, the oxygen in our atmosphere would disappear in less than 4 million years, which is a very short time as planets go—the Earth is 4.5 billion years old,” Fridlund said. He added that organisms present in the early phases of life on Earth produced methane, which alters atmospheric composition compared with a planet devoid of life.Although the Darwin project will use a pragmatic and specific definition of life, biologists, philosophers and science-fiction authors have devised numerous other definitions—none of which are entirely satisfactory. Some are based on basic physiological characteristics: a living organism must feed, grow, metabolize, respond to stimuli and reproduce. Others invoke metabolic definitions that define a living organism as having a distinct boundary—such as a membrane—which facilitates interaction with the environment and transfers the raw materials needed to maintain its structure (Wharton, 2002). The minimal cell project, for example, defines cellular life as “the capability to display a concert of three main properties: self-maintenance (metabolism), reproduction and evolution. When these three properties are simultaneously present, we will have a full fledged cellular life” (Luisi, 2007). These concepts regard life as an emergent phenomenon arising from the interaction of non-living chemical components.Cryptobiosis—hidden life, also known as anabiosis—and bacterial endospores challenge the physiological and metabolic elements of these definitions (Wharton, 2002). When the environment changes, certain organisms are able to undergo cryptobiosis—a state in which their metabolic activity either ceases reversibly or is barely discernible. Cryptobiosis allows the larvae of the African fly Polypedilum vanderplanki to survive desiccation for up to 17 years and temperatures ranging from −270 °C (liquid helium) to 106 °C (Watanabe et al, 2002). It also allows the cysts of the brine shrimp Artemia to survive desiccation, ultraviolet radiation, extremes of temperature (Wharton, 2002) and even toyshops, which sell the cysts as ‘sea monkeys''. Organisms in a cryptobiotic state show characteristics that vary markedly from what we normally consider to be life, although they are certainly not dead. “[C]ryptobiosis is a unique state of biological organization”, commented James Clegg, from the Bodega Marine Laboratory at the University of California (Davies, CA, USA), in an article in 2001 (Clegg, 2001). Bacterial endospores, which are the “hardiest known form of life on Earth” (Nicholson et al, 2000), are able to withstand almost any environment—perhaps even interplanetary space. Microbiologists isolated endospores of strict thermophiles from cold lake sediments and revived spores from samples some 100,000 years old (Nicholson et al, 2000).…life might be not only stranger than we imagine, but also stranger than we can imagineAnother problem with the definitions of life is that these can expand beyond biology. The minimal cell project, for example, in common with most modern definitions of life, encompass the ability to undergo Darwinian evolution (Wharton, 2002). “To be considered alive, the organism needs to be able to undergo extensive genetic modification through natural selection,” said Professor Paul Freemont from Imperial College London, UK, whose research interests encompass synthetic biology. But the virtual ‘organisms'' in computer simulations such as the Game of Life (www.bitstorm.org/gameoflife) and Tierra (http://life.ou.edu/tierra) also exhibit life-like characteristics, including growth, death and evolution—similar to robots and other artifical systems that attempt to mimic life (Guruprasad & Sekar, 2006). “At the moment, we have some problems differentiating these approaches from something biologists consider [to be] alive,” Fridlund commented.…to decide who is first in the ‘race to create life'' requires a consensus definition of lifeBoth the genetic code and all computer-programming languages are means of communicating large quantities of codified information, which adds another element to a comprehensive definition of life. Guenther Witzany, an Austrian philosopher, has developed a “theory of communicative nature” that, he claims, differentiates biotic and abiotic life. “Life is distinguished from non-living matter by language and communication,” Witzany said. According to his theory, RNA and DNA use a ‘molecular syntax'' to make sense of the genetic code in a manner similar to language. This paragraph, for example, could contain the same words in a random order; it would be meaningless without syntactic and semantic rules. “The RNA/DNA language follows syntactic, semantic and pragmatic rules which are absent in [a] random-like mixture of nucleic acids,” Witzany explained.Yet, successful communication requires both a speaker using the rules and a listener who is aware of and can understand the syntax and semantics. For example, cells, tissues, organs and organisms communicate with each other to coordinate and organize their activities; in other words, they exchange signals that contain meaning. Noradrenaline binding to a β-adrenergic receptor in the bronchi communicates a signal that says ‘dilate''. “If communication processes are deformed, destroyed or otherwise incorrectly mediated, both coordination and organisation of cellular life is damaged or disturbed, which can lead to disease,” Witzany added. “Cellular life also interprets abiotic environmental circumstances—such as the availability of nutrients, temperature and so on—to generate appropriate behaviour.”Nonetheless, even definitions of life that include all the elements mentioned so far might still be incomplete. “One can make a very complex definition that covers life on the Earth, but what if we find life elsewhere and it is different? My opinion, shared by many, is that we don''t have a clue of how life arose on Earth, even if there are some hypotheses,” Fridlund said. “This underlies many of our problems defining life. Since we do not have a good minimum definition of life, it is hard or impossible to find out how life arose without observing the process. Nevertheless, I''m an optimist who believes the universe is understandable with some hard work and I think we will understand these issues one day.”Both synthetic biology and research on organisms that live in extreme conditions allow biologists to explore biological boundaries, which might help them to reach a consensual minimum definition of life, and understand how it arose and evolved. Life is certainly able to flourish in some remarkably hostile environments. Thermus aquaticus, for example, is metabolically optimal in the springs of Yellowstone National Park at temperatures between 75 °C and 80 °C. Another extremophile, Deinococcus radiodurans, has evolved a highly efficient biphasic system to repair radiation-induced DNA breaks (Misra et al, 2006) and, as Fridlund noted, “is remarkably resistant to gamma radiation and even lives in the cooling ponds of nuclear reactors.”In turn, synthetic biology allows for a detailed examination of the elements that define life, including the minimum set of genes required to create a living organism. Researchers at the J Craig Venter Institute, for example, have synthesized a 582,970-base-pair Mycoplasma genitalium genome containing all the genes of the wild-type bacteria, except one that they disrupted to block pathogenicity and allow for selection. ‘Watermarks'' at intergenic sites that tolerate transposon insertions identify the synthetic genome, which would otherwise be indistinguishable from the wild type (Gibson et al, 2008).Yet, as Pier Luigi Luisi from the University of Roma in Italy remarked, even M. genitalium is relatively complex. “The question is whether such complexity is necessary for cellular life, or whether, instead, cellular life could, in principle, also be possible with a much lower number of molecular components”, he said. After all, life probably did not start with cells that already contained thousands of genes (Luisi, 2007).…researchers will continue their attempts to create life in the test tube—it is, after all, one of the greatest scientific challengesTo investigate further the minimum number of genes required for life, researchers are using minimal cell models: synthetic genomes that can be included in liposomes, which themselves show some life-like characteristics. Certain lipid vesicles are able to grow, divide and grow again, and can include polymerase enzymes to synthesize RNA from external substrates as well as functional translation apparatuses, including ribosomes (Deamer, 2005).However, the requirement that an organism be subject to natural selection to be considered alive could prove to be a major hurdle for current attempts to create life. As Freemont commented: “Synthetic biologists could include the components that go into a cell and create an organism [that is] indistinguishable from one that evolved naturally and that can replicate […] We are beginning to get to grips with what makes the cell work. Including an element that undergoes natural selection is proving more intractable.”John Dupré, Professor of Philosophy of Science and Director of the Economic and Social Research Council (ESRC) Centre for Genomics in Society at the University of Exeter, UK, commented that synthetic biologists still approach the construction of a minimal organism with certain preconceptions. “All synthetic biology research assumes certain things about life and what it is, and any claims to have ‘confirmed'' certain intuitions—such as life is not a vital principle—aren''t really adding empirical evidence for those intuitions. Anyone with the opposite intuition may simply refuse to admit that the objects in question are living,” he said. “To the extent that synthetic biology is able to draw a clear line between life and non-life, this is only possible in relation to defining concepts brought to the research. For example, synthetic biologists may be able to determine the number of genes required for minimal function. Nevertheless, ‘what counts as life'' is unaffected by minimal genomics.”Partly because of these preconceptions, Dan Nicholson, a former molecular biologist now working at the ESRC Centre, commented that synthetic biology adds little to the understanding of life already gained from molecular biology and biochemistry. Nevertheless, he said, synthetic biology might allow us to go boldly into the realms of biological possibility where evolution has not gone before.An engineered synthetic organism could, for example, express novel amino acids, proteins, nucleic acids or vesicular forms. A synthetic organism could use pyranosyl-RNA, which produces a stronger and more selective pairing system than the natural existent furanosyl-RNA (Bolli et al, 1997). Furthermore, the synthesis of proteins that do not exist in nature—so-called never-born proteins—could help scientists to understand why evolutionary pressures only selected certain structures.As Luisi remarked, the ratio between the number of theoretically possible proteins containing 100 amino acids and the real number present in nature is close to the ratio between the space of the universe and the space of a single hydrogen atom, or the ratio between all the sand in the Sahara Desert and a single grain. Exploring never-born proteins could, therefore, allow synthetic biologists to determine whether particular physical, structural, catalytic, thermodynamic and other properties maximized the evolutionary fitness of natural proteins, or whether the current protein repertoire is predominately the result of chance (Luisi, 2007).In the final analysis, as with all science, deep understanding is more important than labelling with words.“Synthetic biology also could conceivably help overcome the ‘n = 1 problem''—namely, that we base biological theorising on terrestrial life only,” Nicholson said. “In this way, synthetic biology could contribute to the development of a more general, broader understanding of what life is and how it might be defined.”No matter the uncertainties, researchers will continue their attempts to create life in the test tube—it is, after all, one of the greatest scientific challenges. Whether or not they succeed will depend partly on the definition of life that they use, though in any case, the research should yield numerous insights that are beneficial to biologists generally. “The process of creating a living system from chemical components will undoubtedly offer many rich insights into biology,” Davies concluded. “However, the definition will, I fear, reflect politics more than biology. Any definition will, therefore, be subject to a lot of inter-lab political pressure. Definitions are also important for bioethical legislation and, as a result, reflect larger politics more than biology. In the final analysis, as with all science, deep understanding is more important than labelling with words.”     

Testing time for telomeres

Our knowledge of the importance of telomeres to health and ageing continues to grow. Some scientists are therefore commercializing their research, whereas others believe we need an even deeper understanding before we can interpret the results.After 30 years of research, the analysis of telomere length is emerging as a commercial biomarker for ageing and disease, as well as a tool in the search for new medications. Several companies offer tests for telomere length, and more are due to launch their products shortly. Even so, and despite the commercial enthusiasm, interpreting precisely what an individual''s telomeres mean for their health and longevity remains challenging. As a result, there is some division within the research community between those who are pushing ahead with ventures to offer tests to the public, and those who feel that telomere testing is not yet ready for prime time.Peter Lansdorp, a scientist at the British Columbia Cancer Agency and a professor at the University of British Columbia (Vancouver, Canada), founded his company, Repeat Diagnostics, in response to the number of questions and requests he received from physicians for tests for telomere length. The company became the first to offer commercial telomere testing in 2005 and now mainly serves medical researchers, although it makes its test available to the public through their physicians for C $400. Nevertheless, Lansdorp thinks that testing is of limited use for the public. “Testing [...] outside the context of research studies is in my view premature. Unfortunately I think some scientists are exploiting it,” he said. “At this point, I would discourage people from getting their telomeres tested unless there are symptoms in the family that may point to a telomere problem, or a disease related to a telomere problem. I don''t see why on Earth you would want to do that for normal individuals.”“Testing [...] outside the context of research studies is in my view premature. Unfortunately I think some scientists are exploiting it”Others are more convinced of the general utility of telomere tests, when used in combination with other diagnostic tools. Elizabeth Blackburn, Professor of Biology and Physiology at the University of California (San Francisco, USA), was a co-recipient of the Nobel Prize for Physiology or Medicine in 2009 for her part in the discovery of telomerase, the enzyme that replenishes telomeres (Sidebar A). She stressed that the point of telomere testing is to obtain an overall picture “using a marker that integrates many inputs, and produces a robust statistical association with [...] disease risks. It is not a specific diagnostic.” Telome Health, Inc. (Menlo Park, California, USA)—the company that Blackburn helped found and that she now advises in a scientific capacity—plans to begin selling its own US $200 telomere test later this year. “The science has been emerging at a rapid pace recently [...] for those who are familiar with the wealth of the evidence and the accumulated data, the overwhelming pattern is that there are clear associations with telomere maintenance, including longitudinal patterns, and health measures that have had well-tested clinical relevance,” she explained.

Sidebar A | Telomeres and telomerase

Telomeres are regions of repetitive DNA sequence that prevent the DNA replication process or damage from degrading the ends of chromosomes, essentially acting as buffers and protecting the genes closest to the chromosome ends. Russian biologist Alexei Olovnikov first hypothesized in the early 1970s that chromosomes could not completely replicate their ends, and that such losses could ultimately lead to the end of cell division (Olovnikov, 1973). Some years later, Elizabeth Blackburn, then a postdoctoral fellow in Joseph Gall''s lab at Yale University (New Haven, Connecticut, USA), and her colleagues published work suggesting that telomere shortening was linked with ageing at the cellular level, affected lifespan and could lead to cancer (Blackburn & Gall, 1978; Szostak & Blackburn, 1982). In 1984, Carol Greider, working as a postdoc in Blackburn''s lab at the University of California (Berkeley, USA), discovered telomerase, the enzyme that replenishes telomeres. Blackburn and Greider, together with Jack Szostak, were awarded the 2009 Nobel Prize in Physiology or Medicine for “the discovery of how chromosomes are protected by telomeres and the enzyme telomerase” (http://nobelprize.org/nobel_prizes/medicine/laureates/2009/).María Blasco, Director of the Centro Nacional de Investigaciones Oncológicas (CNIO; Spanish National Cancer Research Centre; Madrid, Spain), is similarly optimistic about the prospect of telomere testing becoming a routine health test. “As an analogy, telomere length testing could be similar to what has occurred with cholesterol tests, which went in [the] early 80s from being an expensive test for which no direct drug treatment was available to being a routine test in general health check-ups,” she said.Carol Greider, Professor and Director of Molecular Biology and Genetics at Johns Hopkins University (Baltimore, Maryland, USA) and co-recipient of the 2009 Nobel Prize with Blackburn, however, does not believe that testing is ready for widespread use, although she agreed that telomere length can reveal a lot about disease and is an important subject for research. “Certainly, right now, I think it''s very premature to be offering this kind of testing to the public. I don''t think that the research has yet told us about the risks, what we can actually say statistically with high confidence, so it''s unclear to me if there is any real value to the general public to testing telomeres,” she said.Blasco is Chief Scientific Advisor to Life Length, a CNIO spin-off company that launched its test last year to a storm of media attention. “For some scientists, there is always a question that needs to be solved or has not been sufficiently evaluated,” she said. “We have lots of information showing that telomere length is important for understanding ageing and certain diseases [...] New technologies have been developed that allow us now to measure telomere length in a large scale using a simple blood sample or a spit sample. The fact that the technology is here and the science is here makes this a good moment to market this testing.”“We have lots of information showing that telomere length is important for understanding ageing and certain diseases [...] the technology is here and the science is here”Apart from discussion of the science, companies that offer telomere testing are also encountering scepticism from ethicists and other scientists about the value of telomere-length testing for normal healthy people.Lansdorp, who is a medical doctor by training, thinks that practitioners are not yet ready to use and interpret the tests. “It''s a new field and there are good clinical papers out there, but the irony is that our work [that] has highlighted the value of these tests for specific clinical conditions [is] now being used [...] to make the point that it''s really important to have your telomeres tested, but the dots are not connected by a straight line,” he said.Jonathan Stein, Director of Science and Research at SpectraCell Laboratories (Houston, Texas, USA)—which offers its US $250 telomere test as an extension of its nutritional product line that is sold to family physicians, chiropractors and naturopaths—said that there has only really been demand for the telomere test from his company among physicians and their spouses, but not for use in the clinic. “Doctors are incredibly curious about [the test] and then when we do follow-ups in general, they tell us it''s interesting and they know it''s valuable, but they''re not entirely sure what it means to people. Where we go from the bench to bedside, there seems to be a real sticking point,” he said, adding that he thinks demand will increase as the public becomes increasingly educated about telomeres and health.Arthur Caplan, Professor of Bioethics and Director of the Center for Bioethics at the University of Pennsylvania (Philadelphia, USA), is not clear that even an educated public will be interested in what the test can tell them. “We don''t have any great reason to think that people will be interested in knowing facts about themselves [...] if they can''t do anything about it. I think most people would say ''I''m not going to spend money on this until you tell me if there''s something I can do to slow this process or expand my life''.” As such, he thinks that companies that are getting in early to ''cash in'' on the novelty of telomere testing are unlikely to see huge success, partly because the science is not yet settled.Calvin Harley, President and Chief Science Officer at Telome Health, disagrees. He thinks that two things will drive demand for telomere testing: the growing number of clinical studies validating the utility of the test, and the growing interest in lifestyle changes and interventions that help to maintain telomeres....two things will drive demand for telomere testing: the growing number of clinical studies [...] and [...] interest in lifestyle changes and interventions that help maintain telomeresBut these are early days. Jerry Shay, Professor of Cell Biology and Neuroscience at the University of Texas Southwestern Medical Center (Dallas, USA) and an adviser to the company Life Length, said that early adopters are likely to be the health conscious and the curious. “Some people will say, ''Well, look, I had my telomeres measured: I''m a 60 year old with 50-year-old telomeres'',” he explained. “It will have ''My telomeres are longer than your telomeres'' type of cocktail talk appeal. That''s fine. I have no problem with that as long as we can follow this sort of population and individuals over decades.”“It will have ''My telomeres are longer than your telomeres'' type of cocktail talk appeal [...] I have no problem with that as long as we can follow this sort of population and individuals...”Shay''s last point is the key—research and data collection. Even those commercializing telomere-length tests agree that our understanding of telomere biology, although extensive, is incomplete and that we have yet to unpick fully the links between telomeres and disease. Stefan Kiechl, a telomere researcher in the Department of Neurology at Innsbruck Medical University (Austria), published an article last year on telomere length and cancer (Willeit et al, 2010). “The appealing thing with telomere length measurements is that they allow the estimation of the biological—in contrast to the chronological—age of an organism. This was previously not possible. Moreover, long telomere length has been linked with a low risk of advanced atherosclerosis, cardiovascular disease and cancer, and, vice versa, short telomere length is associated with a higher risk of these diseases.”But, he said that problems remain to be resolved, such as whether telomere length can only be measured in cells that are readily available, such as leukocytes, and whether telomere length in leukocytes varies substantially from telomere length in other tissues and cells. “Moreover, there is still insufficient knowledge on which lifestyle behaviours and other factors affect telomere length,” he concluded.This might be a bumpy road. When Life Length announced its launch in May, newspapers carried headlines such as ''The £400 test that tells you how long you''ll live'', reporting: “A blood test that can show how fast someone is ageing—and offers the tantalizing possibility of estimating how long they have left to live—is to go on sale to the general public in Britain later this year” (Connor, 2011).The story was catchy, but Life Length officials are determined to explain that, despite the name of the company, its tests do not predict longevity for individuals. Blasco said that the word ''life'' in the name is meant as an analogy between telomeres and life. “A British newspaper chose to use this headline, but the company name has no intention to predict longevity,” she said. Instead, the name refers to extensive research correlating the shortened chromosome tips with the risk for certain diseases and personal habits, such as smoking, obesity, lack of exercise and stress, Blasco explained.Life Length''s test measures the abundance of short telomeres, as they claim that there is genetic evidence that short telomeres are the ones that are relevant to disease. “The preliminary results are exciting: we are observing that the percent of short telomeres with increasing age is more divergent between individuals than average telomere length for the same group of individuals,” Blasco explained. “This is exactly what you would expect from a parameter [abundance of short telomeres] that reflects the effects of environmental factors and lifestyle on people''s telomeres.” She noted that being in a lower quartile of average telomere length and the higher quartile of abundance of short telomeres would indicate that telomeres are shorter than normal for a given age, which has been correlated with a higher risk of developing certain diseases.So, what can be done about an abundance of short telomeres? Lansdorp said that, as a physician, he would be hard pressed to know what to tell patients to do about it. “The best measure of someone''s age and life expectancy is the date on their birth certificate. Telomere length, as a biomarker, shows a clear correlation with age at the population level. For an individual the value of telomere length is very limited,” he said. “I suspect there''s going to be a lot of false alarms based on biological variation as well as measurement errors using these less accurate tests.”“The best measure of someone''s age and life expectancy is the date on their birth certificate. [...] For an individual the value of telomere length is very limited”Harley, however, said that if telomere length were perfectly correlated with age, it would be a useless biomarker, except for in forensic work. “The differences in telomere length between individuals at any given age is where the utility lies [...] people with shorter telomeres are at higher risk for morbidity and mortality. In addition, there is emerging data suggesting that people with shorter telomeres respond differently to certain drugs than people with longer telomeres. This fits into the paradigm of personalized medicine,” he said....if telomere length were perfectly correlated with age, it would be a useless biomarker, except for in forensic workWhile he was at Geron Corporation, Harley was the lead discoverer of telomerase activators purified from the root of Astragalus membranaceus. Harley, Blasco and colleagues have published two peer-reviewed papers on one of those molecules, TA-65—one in humans and the other in mice (de Jesus et al, 2011; Harley et al, 2011). Both showed positive effects on certain health measures, and Blasco''s lab found that mice treated with TA-65 had improved health status compared with those given a placebo. “However, we did not see significant effects on longevity,” Blasco said.In the meantime, researchers are squabbling about the techniques used by the testing companies. Greider maintains that Flow-FISH (fluorescence in situ hybridization), which was developed by Lansdorp, is the gold standard used by clinical researchers and that it is the most reliable technique. Harley argues that the quantitative real-time (qRT)-PCR assay developed by the Blackburn lab is just as reliable, and easier to scale-up for commercial use. Blasco pointed out that, similarly to its rivals, the qFISH used by Life Length offers measurements of average telomere length, but that it is the only company to report the percentage of short telomeres in individual cells. In the end, Lansdorp suggested that the errors inherent in the tests, along with biological variations and cost, should give healthy people pause for thought about being tested.Ultimately, whichever test for telomere length is used and whatever the results can tell us about longevity and health, it is unlikely that manipulating telomere length will unlock the fountain of youth, à la Spanish explorer Juan Ponce de León y Figueroa (1474–1521). Nevertheless, telomere testing could become a key diagnostic tool for getting a few more years out of life, and it could motivate people to follow healthier lifestyles. As Kiechl pointed out, “[t]here is convincing evidence that calculation of an individual''s risk of cardiovascular disease [...] substantially enhances compliance for taking medicines and the willingness to change lifestyle. Knowing one''s biological age may well have similar favourable effects.”     

Wildlife forensics. Genomics has become a powerful tool to inform conservation measures

Genomics has become a powerful tool for conservationists to track individual animals, analyse populations and inform conservation management. But as helpful as these techniques are, they are not a substitute for stricter measures to protect threatened species.You might call him Queequeg. Like Herman Melville''s character in the 1851 novel Moby Dick, Howard Rosenbaum plies the seas in search of whales following old whaling charts. Standing on the deck of a 12 m boat, he brandishes a crossbow with hollow-tipped darts to harpoon the flanks of the whales as they surface to breathe (Fig 1). “We liken it to a mosquito bite. Sometimes there''s a reaction. Sometimes the whales are competing to mate with a female, so they don''t even react to the dart,” explained Rosenbaum, a conservation biologist and geneticist, and Director of the New York City-based Wildlife Conservation Society''s Ocean Giants programme. Rosenbaum and his colleagues use the darts to collect half-gram biopsy samples of whale epidermis and fat—about the size of a human fingernail—to extract DNA as part of international efforts to save the whales.Open in a separate windowFigure 1Howard Rosenbaum with a crossbow to obtain skin samples from whales. © Wildlife Conservation Society.Like Rosenbaum, many conservation biologists and wildlife managers increasingly rely on DNA analysis tools to identify species, determine sex or analyse pedigrees. George Amato, Director of the Sackler Institute for Comparative Genomics at the American Museum of Natural History in New York, NY, USA, said that during his 25-year career, genetic tools have become increasingly important for conservation biology and related fields. Genetic information taken from individual animals to the extent of covering whole populations now plays a valuable part in making decisions about levels of protection for certain species or populations and managing conflicts between humans and conservation goals.[…] many conservation biologists and wildlife managers increasingly rely on DNA analysis tools to identify species, determine sex or analyse pedigreesMoreover, Amato expects the use and importance of genetics to grow even more, given that conservation of biodiversity has become a global issue. “My office overlooks Central Park. And there are conservation issues in Central Park: how do you maintain the diversity of plants and animals? I live in suburban Connecticut, where we want the highest levels of diversity within a suburban environment,” he said. “Then, you take this all the way to Central Africa. There are conservation issues across the entire spectrum of landscapes. With global climate change, techniques in genetics and molecular biology are being used to look at issues and questions across that entire landscape.”Rosenbaum commented, “The genomic revolution has certainly changed the way we think about conservation and the questions we can ask and the things we can do. It can be a forensic analysis.” The data translates “into a conservation value where governments, conservationists, and people who actively protect these species can use this information to better protect these animals in the wild.”“The genomic revolution has certainly changed the way we think about conservation […]”Rosenbaum and colleagues from the Wildlife Conservation Society, the American Museum of Natural History and other organizations used genomics for the largest study so far—based on more than 1,500 DNA samples—about the population dynamics of humpback whales in the Southern hemisphere [1]. The researchers analysed population structure and migration rates; they found the highest gene flow between whales that breed on either side of the African continent and a lower gene flow between whales on opposite sides of the Atlantic, from the Brazilian coast to southern Africa. The group also identified an isolated population of fewer than 200 humpbacks in the northern Indian Ocean off the Arabian Peninsula, which are only distantly related to the humpbacks breeding off the coast of Madagascar and the eastern coast of southern Africa. “This group is a conservation priority,” Rosenbaum noted.He said the US National Oceanographic and Atmospheric Administration is using this information to determine whether whale populations are recovering or endangered and what steps should be taken to protect them. Through wildlife management and protection, humpbacks have rebounded to 60,000 or more individuals from fewer than 5,000 in the 1960s. Rosenbaum''s data will, among other things, help to verify whether the whales should be managed as one large group or divided into subgroups.He has also been looking at DNA collected from dolphins caught in fishing nets off the coast of Argentina. Argentine officials will be using the data to make recommendations about managing these populations. “We''ve been able to demonstrate that it''s not one continuous population in Argentina. There might be multiple populations that merit conservation protection,” Rosenbaum explained.The sea turtle is another popular creature that is high on conservationists'' lists. To get DNA samples from sea turtles, population geneticist and wildlife biologist Nancy FitzSimmons from the University of Canberra in Australia reverts to a simpler method than Rosenbaum''s harpoon. “Ever hear of a turtle rodeo?” she asked. FitzSimmons goes out on a speed boat in the Great Barrier Reef with her colleagues, dives into the water and wrangles a turtle on board so it can be measured, tagged, have its reproductive system examined with a laparoscope and a skin tag removed with a small scissor or scalpel for DNA analysis (Fig 2).Open in a separate windowFigure 2Geneticist Stewart Pittard measuring a sea turtle. © Michael P. Jensen, NOAA.Like Rosenbaum, she uses DNA as a forensic tool to characterize individuals and populations [2]. “That''s been a really important part, to be able to tell people who are doing the management, ‘This population is different from that one, and you need to manage them appropriately,''” FitzSimmons explained. The researchers have characterized the turtle''s feeding grounds around Australia to determine which populations are doing well and which are not. If they see that certain groups are being harmed through predation or being trapped in ‘ghost nets'' abandoned by fishermen, conservation measures can be implemented.FitzSimmons, who started her career studying the genetics of bighorn sheep, has recently been using DNA technology in other areas, including finding purebred crocodiles to reintroduce them into a wetland ecosystem at Cat Tien National Park in Vietnam. “DNA is invaluable. You can''t reintroduce animals that aren''t purebred,” she said, explaining the rationale for looking at purebreds. “It''s been quite important to do genetic studies to make sure you''re getting the right animals to the right places.”Geneticist Hans Geir Eiken, senior researcher at the Norwegian Institute for Agricultural and Environmental Research in Svanvik, Norway, does not wrestle with the animals he is interested in. He uses a non-intrusive method to collect DNA from brown bears (Fig 3). “We collect the hair that is on the vegetation, on the ground. We can manage with only a single hair to get a DNA profile,” he said. “We can even identify mother and cub in the den based on the hairs. We can collect hairs from at least two different individuals and separate them afterwards and identify them as separate entities. Of course we also study how they are related and try to separate the bears into pedigrees, but that''s more research and it''s only occasionally that we do that for [bear] management.”Open in a separate windowFigure 3Bear management in Scandinavia. (A) A brown bear in a forest in Northern Finland © Alexander Kopatz, Norwegian Institute for Agricultural and Environmental Research. (B) Faecal sampling. Monitoring of bears in Norway is performed in a non-invasive way by sampling hair and faecal samples in the field followed by DNA profiling. © Hans Geir Eiken. (C) Brown-bear hair sample obtained by so-called systematic hair trapping. A scent lure is put in the middle of a small area surrounded by barbed wire. To investigate the smell, the bears have to cross the wire and some hair will be caught. © Hans Geir Eiken. (D) A female, 2.5-year-old bear that was shot at Svanvik in the Pasvik Valley in Norway in August 2008. She and her brother had started to eat from garbage cans after they left their mother and the authorities gave permission to shoot them. The male was shot one month later after appearing in a schoolyard. © Hans Geir Eiken.Eiken said the Norwegian government does not invest a lot of money on helicopters or other surveillance methods, and does not want to not bother the animals. “A lot of disturbing things were done to bears. They were trapped. They were radio-collared,” he said. “I think as a researcher we should replace those approaches with non-invasive genetic techniques. We don''t disturb them. We just collect samples from them.”Eiken said that the bears pose a threat to two million sheep that roam freely around Norway. “Bears can kill several tons of them everyday. This is not the case in the other countries where they don''t have free-ranging sheep. That''s why it''s a big economic issue for us in Norway.” Wildlife managers therefore have to balance the fact that brown bears are endangered against the economic interests of sheep owners; about 10% of the brown bears are killed each year because they have caused damage, or as part of a restricted ‘licensed'' hunting programme. Eiken said that within two days of a sheep kill, DNA analysis can determine which species killed the sheep, and, if it is a bear, which individual. “We protect the females with cubs. Without the DNA profiles, it would be easy to kill the females, which also take sheep of course.”Wildlife managers […] have to balance the fact that brown bears are endangered against the economic interests of sheep owners…It is not only wildlife management that interests Eiken; he was part of a group led by Axel Janke at the Biodiversity and Climate Research Centre in Frankfurt am Main, Germany, which completed sequencing of the brown bear genome last year. The genome will be compared with that of the polar bear in the hope of finding genes involved in environmental adaptation. “The reason why [the comparison is] so interesting between the polar bear and the brown bear is that if you look at their evolution, it''s [maybe] less than one million years when they separated. In genetics that''s not a very long time,” Eiken said. “But there are a lot of other issues that we think are even more interesting. Brown bears stay in their caves for 6 months in northern Norway. We think we can identify genes that allow the bear to be in the den for so long without dying from it.”Like bears, wolves have also been clashing with humans for centuries. Hunters exterminated the natural wolf population in the Scandinavian Peninsula in the late nineteenth century as governments protected reindeer farming in northern Scandinavia. After the Swedish government finally banned wolf hunting in the 1960s, three wolves from Finland and Russia immigrated in the 1980s, and the population rose to 250, along with some other wolves that joined the highly inbred population. Sweden now has a database of all individual wolves, their pedigrees and breeding territories to manage the population and resolve conflicts with farmers. “Wolves are very good at causing conflicts with people. If a wolf takes a sheep or cattle, or it is in a recreation area, it represents a potential conflict. If a wolf is identified as a problem, then the local authorities may issue a license to shoot that wolf,” said Staffan Bensch, a molecular ecologist and ornithologist at Lund University in Sweden.Again, it is the application of genomics tools that informs conservation management for the Scandinavian wolf population. Bensch, who is best known for his work on population genetics and genomics of migratory songbirds, was called to apply his knowledge of microsatellite analysis. The investigators collect saliva from the site where a predator has chewed or bitten the prey, and extract mitochondrial DNA to determine whether a wolf, a bear, a fox or a dog has killed the livestock. The genetic information potentially can serve as a death warrant if a wolf is linked with a kill, and to determine compensation for livestock owners.The genetic information potentially can serve as a death warrant if a wolf is linked with a kill…Yet, not all wolves are equal. “If it''s shown to be a genetically valuable wolf, then somehow more damage can be tolerated, such as a wolf taking livestock for instance,” Bensch said. “In the management policy, there is genetic analysis of every wolf that has a question on whether it should be shot or saved. An inbred Scandinavian wolf has no valuable genes so it''s more likely to be shot.” Moreover, Bensch said that DNA analysis showed that in at least half the cases, dogs were the predator. “There are so many more dogs than there are wolves,” he said. “Some farmers are prejudiced that it is the wolf that killed their sheep.”According to Dirk Steinke, lead scientist at Marine Barcode of Life and an evolutionary biologist at the Biodiversity Institute of Ontario at the University of Guelph in Canada, DNA barcoding could also contribute to conservation efforts. The technique—usually based on comparing the sequence of the mitochondrial CO1 gene with a database—could help to address the growing trade in shark fins for wedding feasts in China and among the Chinese diaspora, for example. Shark fins confiscated by Australian authorities from Indonesian ships are often a mess of tissue; barcoding helps them to identify the exact species. “As it turns out, some of them are really in the high-threat categories on the IUCN Red List of Threatened Species, so it was pretty concerning,” Steinke said. “That is something where barcoding turns into a tool where wildlife management can be done—even if they only get fragments of an animal. I am not sure if this can prevent people from hunting those animals, but you can at least give them the feedback on whether they did something illegal or not.”Steinke commented that DNA tools are handy not only for megafauna, but also for the humbler creatures in the sea, “especially when it comes to marine invertebrates. The larval stages are the only ones where they are mobile. If you''re looking at wildlife management from an invertebrate perspective in the sea, then these mobile life stages are very important. Their barcoding might become very handy because for some of those groups it''s the only reliable way of knowing what you''re looking at.” Yet, this does not necessarily translate into better conservation: “Enforcement reactions come much quicker when it''s for the charismatic megafauna,” Steinke conceded.“Enforcement reactions come much quicker when it''s for the charismatic megafauna”Moreover, reliable identification of animal species could even improve human health. For instance, Amato and colleagues from the US Centers for Disease Control and Prevention demonstrated for the first time the presence of zoonotic viruses in non-human primates seized in American airports [3]. They identified retroviruses (simian foamy virus) and/or herpesviruses (cytomegalovirus and lymphocryptovirus), which potentially pose a threat to human health. Amato suggested that surveillance of the wildlife trade by using barcodes would help facilitate prevention of disease. Moreover, DNA barcoding could also show whether the meat itself is from monkeys or other wild animals to distinguish illegally hunted and traded bushmeat—the term used for meat from wild animals in Africa—from legal meats.Amato''s group also applied barcoding to bluefin tuna, commonly used in sushi, which he described as the “bushmeat of the developed world”, as the species is being driven to near extinction through overharvesting. Developing barcodes for tuna could help to distinguish bluefin from yellowfin or other tuna species and could assist measures to protect the bluefin. “It can be used sort of like ‘Wildlife CSI'' (after the popular American TV series),” he said.As helpful as these technologies are […] they are not sufficient to protect severely threatened species…In fact, barcoding for law enforcement is growing. Mitchell Eaton, assistant unit leader at the US Geological Survey New York Cooperative Fish and Wildlife Research Unit in Ithaca, NY, USA, noted that the technique is being used by US government agencies such as the FDA and the US Fish & Wildlife Service, as well as African and South American governments, to monitor the illegal export of pets and bushmeat. It is also used as part of the United Nations'' Convention on Biological Diversity for cataloguing the Earth''s biodiversity, identifying pathogens and monitoring endangered species. He expects that more law enforcement agencies around the world will routinely apply these tools: “This is actually easy technology to use.”In that way, barcoding as well as genetics and its related technologies help to address a major problem in conservation and protection measures: to monitor the size, distribution and migration of populations of animals and to analyse their genetic diversity. It gives biologists and conservations a better picture of what needs extra protective measures, and gives enforcement agencies a new and reliable forensic tool to identify and track illegal hunting and trade of protected species. As helpful as these technologies are, however, they are not sufficient to protect severely threatened species such as the bluefin tuna and are therefore not a substitute for more political action and stricter enforcement.     

Reading the tea leaves of Congress. With a new Republican majority in the House of Representatives, scientific research in the USA might face budget cuts

The increasing influence of the Tea Party in Congress and politics has potential repercussions for public funding of scientific research in the USAIn 2009, Barack Obama became the 44th President of the USA, amid hopes that he would fix the problems created or left unresolved by his predecessor. However, despite his positive mantra, “Yes we can,” the situation was going to get worse: the country was spiralling towards an economic recession, a collapsing residential real-estate market and the loss of millions of jobs. Now, the deficit lingers around US$14 trillion (US Department of the Treasury, 2011). In response to these hardships and the presence of a perceived ‘socialist'' president in office, a new political movement started brewing that would challenge both the Democrats and the Republicans—the two parties that have dominated US politics for generations. Known as the Tea Party, this movement has been gaining national momentum in its denouncement of the status quo of the government, especially in relation to federal spending, including the support of scientific research.The name is a play on the Boston Tea Party, at which more than 100 American colonists dumped 45 tonnes of tea into Boston Harbour (Massachusetts, USA) in 1773 to protest against the British taxation of imported tea. Whereas the 18th century Boston Tea Party formed to protest against a specific tax, the Tea Party of the 21st century protests against taxes and ‘big'' government in general.Many view Tea Party followers as modern muckrakers, but supporters claim their movement is fundamentally about upholding the US Constitution. Tea Party Patriots, a non-partisan organization, considers itself to be the official home of the Tea Party movement. Fuelled by the values of fiscal responsibility, limited government and free markets, Tea Party Patriots believe, these three principles are granted by the Constitution, although not necessarily upheld by the administration.“If you read the Constitution, the limits of government involvement in society [are] pretty well-defined and our government has gone farther and farther beyond the specific limits of the Constitution,” said Mark Meckler, one of the co-founders of Tea Party Patriots. “Our Constitution is not designed as an empowering document, but as a limiting document… [and] was intended to be used as a weapon by the people against the government to keep it in the box.” Tea Partiers tend to be especially critical when it comes to spending tax dollars on bank bailouts and health care, but anything goes when it comes to cutting back on public spending—even science. “We believe everything needs to be on the table since the government is virtually bankrupt,” Meckler said. “We need to cut the waste, cut the abuse [and] get rid of the departments that shouldn''t exist.”Tea Partiers tend to be especially critical when it comes to spending tax dollars on bank bailouts and health care, but anything goes when […]cutting […] public spending—even scienceOn 19 February 2011, the US House of Representatives, which is currently controlled by the Republicans, passed a federal-spending bill for the remainder of the 2011 fiscal year budget. Among other cuts, the bill called for billions of dollars to be slashed from the budgets of federal science agencies. If the bill is signed into law, the National Institutes of Health (NIH) will have $1.6 billion cut from its budget—a 5.2% decrease—and the Department of Energy (DOE) will experience an 18% cut in funding for its Office of Science. Other agencies targeted include the Environmental Protection Agency (EPA), the National Aeronautics and Space Administration (NASA), the National Institute of Standards and Technology (NIST) and the National Science Foundation (NSF; Anon, 2011; Cho, 2011). Although the US Senate, which has a Democratic majority, must consider the bill before any definite amendments to the budget are made, it is likely that there will be some cuts to science funding.Although the House is in favour of science-related cuts, President Obama supports spending more on science education, basic research and clean-energy research. He has also proposed an 11.8% increase in the budget of the DOE, as well as an 8% increase in the NSF budget (Office of Management and Budget, 2011).The House is in favour of science-related cuts, but President Obama is in favour of spending more on science education, basic science and clean-energy researchJoann Roskoski, acting assistant director of the Biology Directorate at the NSF, said her institute is strongly in favour of President Obama''s budget proposal. “President Obama is a very strong supporter of fundamental research and STEM [science, technology, engineering and mathematics] education because he perceives it as investing in the future of the country,” she said. “These are just difficult budgetary times and we''ll just have to wait and see what happens. As they say, the president proposes and Congress disposes.”Karl Scheidt, a professor of chemistry at Northwestern University (Evanston, Illinois, USA), has four grants from federal agencies. “A couple of my grants expire this year, which is happening at the worst, worst possible time,” explained Scheidt, whose grants are funded by the NIH and the NSF. He added that although many politicians either do not understand or believe in the fundamentals of science, they still preach to the masses about what they ‘think'' they know. “I think it''s an absolute travesty that many people don''t understand science and that many of the Republicans who don''t fully understand science perpetuate incorrect assumptions and scientific falsehoods when speaking in public,” he said. “It makes the US less competitive and puts us collectively at a disadvantage relative to other nations if we don''t succeed in scientific education and innovative research in the future.”Although the Tea Party is not technically associated with the Republican Party, all Tea-Party representatives and senators ran as Republican candidates in the last election. While only one-third of seats in the Senate are on the ballot every two years for a six-year term, all House seats are for a two-year term. In the most recent Senatorial election, 50% of Tea Party-backed candidates won; 10 in total. 140 candidates for seats in the House of Representatives were backed by the Tea Party—all of whom were Republicans—but only 40 won. Nevertheless, with around 100 new Republicans in office, a House controlled by a Republican majority and most Congress-based Republicans in agreement with Tea Party ideals, the Tea Party actually has a lot of sway on the voting floor.Of course, as a fundamentally grass-roots movement, their influence is not limited to the halls of power. Since just before the November election last year, Tea Party-backed politicians have received more scrutiny and media exposure, meaning more people have listened to their arguments against spending on science. In fact, Republican politicians associated with the Tea Party have made critical and sometimes erroneous comments about science. Representative Michelle Bachman, for example, claimed that because carbon dioxide is a natural gas, it is not harmful to our atmosphere (Johnson, 2009). Representative Jack Kingston denounced the theory of evolution and stated that he did not come from a monkey (The Huffington Post, 2011). When asked how old he believes the Earth to be, Senator Rand Paul refused to answer (Binckes, 2010). He also introduced a bill to cut the NSF budget by 62%, and targeted the budget of the Center for Disease Control and Prevention.Scheidt believes part of the challenge is that many scientists do not properly articulate the importance of their work to the public, and there is limited representation on behalf of science in Washington. “It''s difficult sometimes to advocate for and explain the critical importance of basic research and for the most part, Congress may not always appreciate the basic fundamental mission of organizations like the NIH,” Scheidt said. “Arlen Specter was one of the few people who could form coalitions with his colleagues on both sides of the aisle and communicate why scientific research is critical. Why discovering new ways to perform transplants and creating new medicines are so important to everyone.”…part of the challenge is that many scientists do not properly articulate the importance of their work to the public, and there is limited representation on behalf of science in WashingtonSpecter, a former senator, was Republican until 2009 when he decided to switch political parties. During the last Democratic primary, he lost the Pennsylvania Senate nomination after serving in Congress for more than four decades. The Democratic nominee, Joe Sestak, eventually lost the coveted seat to Pat Toomey, a Tea Party Republican who sponsored an amendment denying NIH funding for some grants while he was a House member. Toomey is also against funding climate science and clean-energy research with federal dollars.Specter was considered a strong supporter of biomedical research, especially cancer research. He was the catalyst that pushed through a great deal of pro-science legislation, such as adding approximately $10 billion to NIH funding as part of the stimulus package in 2009, and doubling NIH funding in the 1990s. As scientific research was so important to him, he served on the US Senate Committee on Appropriations Subcommittee on Labor, Health and Human Services, Education, and Related Agencies and on the Senate Committee on Environment and Public Works. Specter was a popular political champion of science not only because of all he had accomplished, but also because so few scientists are elected to office.Among those Democrats who lost their seats to Tea Party Republicans was Congressman Bill Foster. Foster, who once worked for the Fermi National Accelerator Laboratory (Fermilab)—which is funded by the DOE—represented Batavia, Ilinois, which is also where Fermilab has its headquarters. “The new representative in the district where Fermilab resides is Randy Hultgren, a Republican, who has been very supportive of the laboratory since he''s been elected,” said Cindy Conger, Chief Financial Officer at Fermilab. “He''s very interested in us and very interested […] in us having adequate funding.”However, Fermilab is suffering financially. “We will […] have some level of layoffs,” Conger said. “Inadequate federal funding could result in more layoffs or not being able to run our machines for part of the year. These are the things we are contemplating doing in the event of a significant budget cut. Nothing is off the table [but] we will do everything we can to run the [Tevatron] accelerator.”But Fermilab''s desperate appeal for $35 million per year for the next three fiscal years was denied by the Obama administration and not included in the 2012 White House budget request. As a result, the most powerful proton–antiproton accelerator in the USA, the Tevatron, is shutting down indefinitely near the end of this year.Another pro-science Republican is former Congressman John Porter, who studied at the Massachusetts Institute of Technology. He encouraged the federal funding of science while serving as chair of the House Subcommittee on Labor, Health and Human Services, and Education, as well as on the House Committee on Appropriations and Related Agencies. Like Scheidt, Porter said a problem is that not many members of Congress really understand science or what goes into scientific research.“Many members of Congress don''t realize that the money appropriated for the funding of scientific research through NIH, NSF […] is sent out to research institutes in their districts and states where the research is conducted,” said Porter, who retired from Congress in 2001 after serving for more than 20 years. “They simply haven''t been exposed to it and that''s the fault of the science community, which has a great responsibility to educate about the mechanisms on how we fund scientific research.”Today, Porter is vice-chair of the Foundation for the NIH and also chairs Research!America, a non-profit organization which aims to further medical, health and scientific research as higher national priorities. He also noted that industry would not fund scientific research in the way the government does because there would essentially be no profits. Therefore, federal funding remains essential.“Let''s take away the phones, iPads and everything else [those against the federal funding of science] depend on and see what''s left,” Porter said. “The US is the world leader in science, technology and research and the way we got there and the way we have created the technology that makes life easier […] is a result of making investments in that area.”For now, Scheidt said the best approach is to educate as many people as possible to understand that scientific research is a necessity, not a luxury. “We unfortunately have a very uneducated population in regard to science and it''s not 100% their fault,” he said. “However, if people took a real interest in science and paid as much attention to stem-cell or drug-discovery research as they did to the Grammy Awards or People magazine I think they would appreciate what''s going on in the science world.”…the best approach is to educate as many people as possible to understand that scientific research is a necessity, not a luxuryInstead, the USA is lagging behind its competitors when it comes to STEM education. According to the 2009 Program for International Student Assessment (PISA), the USA is ranked 17th on science and 25th on maths out of 34 countries (US Department of Education, 2010). “We''re in a cluster now, we''re no longer the leading country,” said D. Martin Watterson, a molecular biologist who sits on NIH peer-review committees to evaluate grant proposals. The reason, according to Watterson, is that the first things to be cut after a budget decrease are training grants for continuing education efforts. Moreover, the USA already lacks highly trained workers in the field of science. “In some disciplines, employers now look to other places in Europe and Asia to find those trained personnel,” Watterson said.Ultimately, most people at least want a final budget to be passed so that there is sufficient time to plan ahead. However, Georgetown University political science professor Clyde Wilcox thinks that a compromise is not so simple. “The problem is that it''s a three-way poker game. People are going to sit down and they''re going to be bargaining, negotiating and bluffing each other,” he said. “The House Republicans just want to cut the programs that they don''t like, so they''re not cutting any Republican programs for the most part.”As a result, institutions such as the EPA find themselves being targeted by the Republicans. Although there is not a filibuster-proof majority of Democrats in the Senate, they still are a majority and will try to preserve science funding. Wilcox said that it is not necessarily a good thing to continue negotiating if nothing gets done and the country is dependent on continuing resolutions.Although there is not a filibuster-proof majority of Democrats in the Senate, they still are a majority and will try to preserve science funding“What the real problem is, when push comes to shove, someone has to blink,” he said. “I don''t think there will be deep cuts in science for a number of reasons, one is science is consistent with the Democratic ideology of education and the Republican ideology of investment. And then, we don''t really spend that much on science anyway so you couldn''t come remotely close to balancing the budget even if you eliminated everything.”Although during his time in Congress representatives of both parties were not as polarized as they are today, Porter believes the reason they are now is because of the political climate. “The president has made [science] a very important issue on his agenda and unfortunately, there are many Republicans today that say if he''s for it, I''m against it,” Porter said. In fact, several government officials ignored repeated requests or declined to comment for this article.“It''s time for everybody from both parties to stand up for the country, put the party aside and find solutions to our problems,” Porter commented. “The American people didn''t just elect us to yell at each other, they elected us to do a job. You have to choose priorities and to me the most important priority is to have our children lead better lives, to have all human beings live longer, healthier, happier lives and to have our economy grow and prosper and our standard of living maintained—the only way to do that is to invest where we lead the world and that''s in science.”     

Tackling animal diseases to protect human health

Veterinary research is gaining in importance not only because of the economic impact of animal diseases, but also because animals are a fertile reservoir of zoonoses; pathogens that could jump the species barrier and infect humans.In 1761, King Louis XV of France proposed that a veterinary school should be founded in Lyon. He had been troubled by the ongoing scourge of cattle disease and inspired by the Italian physician Giovanni Maria Lancisi, who recommended that medical education should include a specialization in animal health. The year 2011 marked the 250th anniversary of that event and was declared ‘World Veterinary Year'' (Vet2011) to celebrate the birth of the veterinary profession and veterinary science. The motto adopted was “Vet for health. Vet for food. Vet for the planet!”, evoking the key role that veterinarians play in protecting both animal and human health, and in enhancing food security. “The emergence of health risks associated with globalization and climate change creates an ever greater need for risk managers at international, regional and national levels. Among these, veterinarians already play and will continue to play a leading role […] for instance performing disease surveillance and providing a first level of alert, so that biological disasters, natural or deliberate and regardless of whether they threaten animals, humans or both, can be stopped at their source in animals,” said Bernard Vallat, Director General of the World Organization for Animal Health (OIE), at the Vet2011 opening ceremony in Versailles, France, on 24 January 2011 (www.oie.int).In the same year, on June 28, delegates from the member countries of the United Nations'' Food and Agriculture Organization (FAO) officially announced the eradication of ‘rinderpest''—a German word for ‘cattle plague''—a highly contagious and deadly virus affecting cattle, buffalo and related species such as African zebu cattle. The mortality rate for rinderpest can reach up to 100% in susceptible herds, and recurring pandemics and outbreaks caused devastating losses to societies dependent on cattle (Fig 1). A severe outbreak of rinderpest in Belgium, in 1920, that originated from imported animals, was the impetus for international cooperation in controlling animal diseases, eventually leading to the establishment of the OIE in 1924.Open in a separate windowFigure 1Animal remains. Dead oxen, some partly buried, thought to have died from rinderpest, circa 1900, South Africa. Photo by Reinhold Thiele/Thiele/Getty Images. Reproduced with permission.After a long series of country-based eradication initiatives that relied on a mixture of quarantine, slaughter and vaccine mass inoculation, the FAO formed the Global Rinderpest Eradication Programme in 1994 to co-ordinate international efforts and to provide technical guidance and financial support, in close co-ordination with the OIE and other institutional partners and donors. The last known case of rinderpest occurred in Kenya in 2001, after which a prolonged phase of surveillance operations started. “This successful eradication shows that actions against animal diseases do not come within concepts of agricultural or merchant good but within the concept of Global Public Good because by alleviating poverty, contributing to public health and food security, and improving market access as well as animal welfare, they benefit all people and generations in the world,” Vallat said in a press release announcing the eradication declaration [1].The year 2011 […]was declared ‘World Veterinary Year'' (Vet2011) to celebrate the birth of the veterinary profession and veterinary science“Rinderpest is the first animal disease to be eradicated by mankind and the second disease in general after smallpox. We must also focus our attention on measures to be taken to ensure that this result is sustainable and benefits future generations. To do this, a post-eradication strategy should be put in place to prevent any recurrence of the disease”, remarked FAO Director-General Jacques Diouf in the press release [1]. “In the final stages of eradication, the virus was entrenched in pastoral areas of the Greater Horn of Africa, a region with weak governance, poor security, and little infrastructure that presented profound challenges to conventional control methods. Although the eradication process was a development activity rather than scientific research, its success owed much to several seminal research efforts in vaccine development and epidemiology and showed what scientific decision-making and management could accomplish with limited resources,” noted Jeffrey Mariner from the Tufts Cummings School of Veterinary Medicine in North Grafton (Massachusetts, USA) and colleagues, in a paper published in Science, which reviewed this remarkable achievement [2]. “The keys to success were the development of a thermostable vaccine and the application of participatory epidemiological techniques that allowed veterinary personnel to interact at a grassroots level with cattle herders to more effectively target control measures”.Potentially dangerous rinderpest virus samples are kept in several laboratories across the world, but not all of those laboratories are considered to work under a regime of sufficient biosecurity. To address this, immediately after rinderpest was stamped out, FAO and OIE member countries agreed to destroy the remaining virus stocks or to safely store them in a limited number of high containment laboratories, banning any research that used the live virus, unless approved by the two organizations. This recommendation came from an external committee composed of seven independent experts, convened by the FAO and OIE, which advised the use of measures similar to those used during the post-eradication period for smallpox; the virus, which might still prove useful for research or vaccine development, should be kept in a limited number of labs—two in the case of smallpox—under the tightest security measures, whilst all other stocks should be destroyed [3]. Monitoring and surveillance for rinderpest virus outbreaks will continue until 2020, and experts are already considering which disease should be the focus of eradication efforts next (Sidebar A).

Sidebar A | Peste des petits ruminants: next in line for eradication?

Now that rinderpest has been stamped out, many experts believe peste des petits ruminants (PPR) is the next disease amenable to global eradication [11]. Also known as ‘goat plague'' or ‘ovine rinderpest'', PPR is a highly contagious viral disease of goats and sheep characterized by fever, painful sores in the mouth, tongue and feet, diarrhoea, pneumonia and death, especially in young animals. It is caused by a virus of the genus Morbillivirus that is related to rinderpest, measles and canine distemper. The disease has spread across Africa between the equator and the Sahara—with outbreaks in Morocco and Tunisia in 2008—through the Arabian Peninsula, the Middle East, south-west Asia, China and the Indian subcontinent, extending its range alarmingly during the past decade. PPR might cause serious production losses in the developing world—with a significant number of people relying on sheep and goats for their sustenance—and poses a major challenge to international livestock trade. “If one is looking to control the disease to the point of eradication, there are three basic questions: should we do it, can we do it and what is the best way to do it?” said Michael Baron, a leading expert in PPR control at the Pirbright Institute, formerly known as the Institute for Animal Health (Pirbright, UK). The question of whether we should eradicate PPR needs no discussion, Baron maintains, as there would be a large benefit to millions of people if the disease were gone. “Can we is a bit harder, but the example of rinderpest assures us that we can, since the viruses in question share the same properties, and all the main tools are in place,” Baron explained. These tools include a safe and reliable vaccine that stops all known PPR strains, together with simple and effective diagnostic tests. Moreover, the virus is spread by close contact only, has a short infectious period and there is no carrier or persistent state, all of which make its eradication possible. Finally, the virus seems to be primarily restricted to livestock, although some research on wildlife is needed to be sure that they cannot act as reservoirs of infection. “How should we is the bit that still needs work. Rinderpest was quite well studied before eradication was proposed—it had been known of for hundreds of years, whereas PPR has only been known about since 1942—and we need to know more about when we should vaccinate, how often, how much surveillance needs to be done, and how to adapt our control programmes to the fact that sheep and/or goats are simply so much more mobile, and people will insist on moving them around illegally,” Baron said. “We could throw a lot of money at the problem, but it might not get solved any faster than if we think about it and plan the campaign, and conduct some smaller scale pilot studies.”Peste des petits ruminants in the field. This photo, by the Indian photographer Somenath Mukhopadhyay, won the ‘Vets in your daily life'' photo contest in 2011, organized by the European Commission and the World Organization for Animal Health (OIE). “I accompanied this village veterinarian on his rounds when I came across this engaging image of him taking the temperature of a goat affected by peste des petits ruminants. On this third visit to the household, the goat was in recovery phase thanks to the medication it had been given. The photo to me is the ultimate portrayal of what a vet means to us,” commented Mukhopadhyay. Credit: CE/OIE. Reproduced with permission.In addition to fighting animal diseases, another front where veterinarians are deployed and where research is more active is the transmission of diseases from animals to humans; in fact, this is an area of growing concern. Some 60% of human epidemics are caused by animal pathogens found in the wild or in domestic animals. Among such ‘zoonoses''—diseases or infections that are naturally transmissible from vertebrate animals to humans—some can be considered as re-emerging diseases. Brucellosis, which is caused primarily by the bacterial pathogens Brucella melitensis and B. abortus, and which affects several farm animals including sheep, goats and cattle, is such a case. Brucellosis is characterized by the constant changing of the disease, with new foci emerging or re-emerging, as humans are infected through contact with diseased animals or by consuming unpasteurized dairy products. Although infections with Brucella are no longer fatal, they still represent a serious public health problem. 500,000 new human cases are reported each year worldwide with significant economic impact from both the loss of labour and the loss of animal production [4]. As such, research into brucellosis is active in several directions, such as the development of vaccines, vaccine delivery strategies, diagnostic testing for brucellosis in animals, mechanisms of intracellular survival of this persistent bacterial colonizer and research into how it circumvents the immune system [5].Various factors influence the re-emergence of zoonoses or the emergence of new pathogens from animal reservoirs. “To support the growing human population, we have an increasing demand for nutritional support, resulting in intensive agricultural practices, sometimes involving enormous numbers of animals, or multiple species farmed within the same region. These practices can facilitate infection to cross species barriers,” wrote Sally Cutler, from the University of East London (London, UK), and colleagues in a review on the topic [6]. The situation is made worse by the ever-increasing transnational transportation of animals and their products, the progressive encroachment of humans into natural habitats with direct exposure to new zoonotic pathogens, and climate changes that might influence the evolution of pathogens and their vectors. These and other elements represent a complex, multifactorial set of changing circumstances that have an impact on the dynamics of zoonoses [6].“Rinderpest is the first animal disease to be eradicated by mankind and the second disease in general after smallpox”Zoonoses with a wildlife reservoir are increasingly recognized as a significant problem. “I think that this is a vitally important topic, as repeated studies have demonstrated that wildlife, collectively, are the major source of new and emerging diseases—and have been so for many years,” commented James Wood from the University of Cambridge in the UK. “Some of the most important human diseases have arisen from animals, including measles, which is derived from the recently eradicated rinderpest virus of cattle, whooping cough, which is derived from a common animal pathogen that causes diseases like kennel cough in domestic dogs, and smallpox, which was most closely related to a similar virus of camels. Examination of the list of the most feared and fatal human pathogens reveals that a significant number have arisen from bats; why this may be the case is the subject of active research in a number of major labs,” Wood explained. Wood and colleagues have proposed a new holistic and interdisciplinary investigation of zoonotic disease emergence and its drivers, by using the spillover of bat pathogens, including Ebola, Marburg, SARS coronavirus, Hendra, Nipah and several rabies and rabies-related viruses as a case study [7].“One of the key missing pieces of knowledge relates to how some of these infections, in particular those other than the immunodeficiency type viruses, transfer from wildlife to humans—and how human livelihood related activities and poverty impact on this risk,” Wood explained. “This is an area of active research for an international consortium named Dynamic Drivers of Disease in Africa [www.driversofdisease.org], considering henipaviruses from bats in Ghana, Rift Valley fever in Kenya, Lassa fever in Sierra Leone and Trypanosomiasis in Zimbabwe and Zambia. Interdisciplinary work in this consortium aims to unpick at least part of that particular puzzle”.Clearly, a better understanding of the complex interactions between ecological, evolutionary, biochemical and sociological mechanisms that enable animal pathogens to cross the species barrier would greatly expand our ability to predict future epidemics of zoonotic infectious diseases. Several approaches have studied the adaptation of pathogens to new hosts—where they have to face a new genetic and immunological environment—and the evolutionary dynamics of this process. These include cross-species infections of heterologous animals, heterologous cell lines and even the expression of single genes from one species in cell lines derived from a second species [8].New threats are looming on the horizon. A research team led by Joanne Devlin at the University of Melbourne, Australia, showed that different vaccine viruses used simultaneously to control laryngotracheitis—an acute respiratory disease occurring in chickens that is caused by a herpesvirus—have recombined to produce new infectious viruses (Fig 2) with significantly increased virulence or replication [9]. “The findings from our research show that we need to consider the risk of recombination when we use live viral vaccines, even for those viruses where the risk of vaccine recombination has traditionally been thought to be very low, such as herpesviruses,” Devlin said. “In Australia, the relevant regulatory body, the Australian Pesticides and Veterinary Medicines Authority (APVMA), is already considering measures to reduce the risk of recombination between different strains of vaccine viruses, including changes to product labels to prevent different strains of the same virus vaccine being used in the same population of animals. This will prevent recombination occurring between the vaccines. It is likely that similar measures will need to be considered elsewhere too.” Notwithstanding the alarming finding that the combined animal vaccines could create new, more dangerous viruses, the risk for human health is low. “Multiple strains of the same live vaccine (with different attenuating changes in their genomes) are required to be present in the one population in order for vaccine–vaccine recombination to occur and for this to generate more virulent viruses,” Devlin explained. “The use of multiple vaccine strains of the same virus in the one population is a feature of veterinary medicine, rather than human medicine.”Open in a separate windowFigure 2Veterinary vaccines might recombine to produce new virus strains. Different vaccine viruses, of European (left) and Australian (right) origin, used simultaneously to control laryngotracheitis infection in chickens, were found to have recombined to produce new infectious viruses [9]. Credit: Australian Science Media Centre. Reproduced with permission.Ultimately, given the increasingly close and frequent contact between humans and animals, both domesticated and wild, veterinarians are important in identifying and combating new potential theats to human health. However, to better understand and eventually defeat diseases at the animal and human interface, an unprecedented level of interdisciplinary collaboration is going to be needed [10].     

Stem-cell battles. Stem-cell research in the USA is facing new legal and political challenges

The US still leads the world in stem-cell research, yet US scientists are facing yet another political and legal battle for federal funding to support research using human embryonic stem cells.Disputes over stem-cell research have been standard operating procedure since James Thompson and John Gearhart created the first human embryonic cell (hESC) lines. Their work triggered an intense and ongoing debate about the morality, legality and politics of using hESCs for biomedical research. “Stem-cell policy has caused craziness all over the world. It is a never-ending, irresolvable battle about the moral status [of embryos],” commented Timothy Caulfield, research director of the Health Law Institute at the University of Alberta in Edmonton, Canada. “We''re getting to an interesting time in history where science is playing a bigger and bigger part in our lives, and it''s becoming more controversial because it''s becoming more powerful. We need to make some interesting choices about how we decide what kind of scientific inquiry can go forward and what can''t go forward.”“Stem-cell policy has caused craziness all over the world…[i]t is a never-ending, irresolvable battle about the moral status [of embryos]”The most contested battleground for stem-cell research has been the USA, since President George W. Bush banned federal funding for research that uses hESCs. His successor, Barack Obama, eventually reversed the ban, but a pending lawsuit and the November congressional elections have once again thrown the field into jeopardy.Three days after the election, the deans of US medical schools, chiefs of US hospitals and heads of leading scientific organizations sent letters to both the House of Representatives and the Senate urging them to pass the Stem Cell Research Advancement Act when they come back into session. The implication was to pass legislation now, while the Democrats were still the majority. Republicans, boosted in the election by the emerging fiscally conservative Tea Party movement, will be the majority in the House from January, changing the political climate. The Republicans also cut into the Democratic majority in the Senate.Policies and laws to regulate stem-cell research vary between countries. Italy, for example, does not allow the destruction of an embryo to generate stem-cell lines, but it does allow research on such cells if they are imported. Nevertheless, the Italian government deliberately excluded funding for projects using hESCs from its 2009 call for proposals for stem-cell research. In the face of legislative vacuums, this October, Science Foundation Ireland and the Health Research Board in Ireland decided to not consider grant applications for projects involving hESC lines. The UK is at the other end of the scale; it has legalized both research with and the generation of stem-cell lines, albeit under the strict regulation by the independent Human Fertility and Embryology Authority. As Caulfield commented, the UK is “ironically viewed as one of the most permissive [on stem-cell policy], but is perceived as one of the most bureaucratic.”Somewhere in the middle is Germany, where scientists are allowed to use several approved cell lines, but any research that leads to the destruction of an embryo is illegal. Josephine Johnston, director of research operations at the Hastings Center in Garrison, NY, USA—a bioethics centre—said: “In Germany you can do research on embryonic stem-cells, but you can''t take the cells out of the embryo. So, they import their cells from outside of Germany and to me, that''s basically outsourcing the bit that you find difficult as a nation. It doesn''t make a lot of sense ethically.”Despite the public debates and lack of federal support, Johnson noted that the USA continues to lead the world in the field. “[Opposition] hasn''t killed stem-cell research in the United States, but it definitely is a headache,” she said. In October, physicians at the Shepherd Center, a spinal cord and brain injury rehabilitation hospital and clinical research centre in Atlanta, GA, USA, began to treat the first patient with hESCs. This is part of a clinical trial to test a stem-cell-based therapy for spinal cord injury, which was developed by the US biotechnology company Geron from surplus embryos from in vitro fertilization.Nevertheless, the debate in the USA, where various branches of government—executive, legislative and legal—weigh in on the legal system, is becoming confusing. “We''re never going to have consensus [on the moral status of fetuses] and any time that stem-cell research becomes tied to that debate, there''s going to be policy uncertainty,” Caulfield said. “That''s what''s happened again in the United States.”Johnson commented that what makes the USA different is the rules about federally funded and non-federally funded research. “It isn''t much discussed within the United States, but it''s a really dramatic difference to an outsider,” she said. She pointed out that, by contrast, in other countries the rules for stem-cell research apply across the board.The election of Barack Obama as US President triggered the latest bout of uncertainty. The science community welcomed him with open arms; after all, he supports doubling the budget of the National Institutes of Health (NIH) over the next ten years and dismantled the policies of his predecessor that barred it from funding projects beyond the 60 extant hESC lines—only 21 of which were viable. Obama also called on Congress to provide legal backing and funding for the research.The executive order had unforeseen consequences for researchers working with embryonic or adult stem cells. Sean Morrison, Director of the University of Michigan''s Centre for Stem Cell Biology (Ann Arbor, MI, USA), said he thought that Obama''s executive order had swung open the door on federal support forever. “Everybody had that impression,” he said.Leonard I. Zon, Director of the Stem Cell Program at Children''s Hospital Boston (MA, USA), was so confident in Obama''s political will that his laboratory stopped its practice of labelling liquid nitrogen containers as P (Presidential) and NP (non-Presidential) to avoid legal hassles. His lab also stopped purchasing and storing separate pipettes and culture dishes funded by the NIH and private sources such as the Howard Hughes Medical Institute (HHMI; Chevy Chase, MD, USA).But some researchers who focused on adult cells felt that the NIH was now biased in favour of embryonic cells. Backed by pro-life and religious groups, two scientists—James Sherley of the Boston Biomedical Research Institute and Theresa Deisher of AVM Biotechnology (Seattle, WA)—questioned the legality of the new NIH rules and filed a lawsuit against the Department of Health and Human Services (HHS) Secretary, Kathleen Sebelius. Deisher had founded her company to “[w]ork to provide safe, effective and affordable alternative vaccines and stem-cell therapies that are not tainted by embryonic or electively aborted fetal materials” (www.avmbiotech.com).…the debate in the USA, where various branches of government—executive, legislative and legal—weigh in on the legal system, is becoming confusingSherley argued in an Australian newspaper in October 2006 that the science behind embryonic stem-cell research is flawed and rejected arguments that the research will make available new cures for terrible diseases (Sherley, 2006). In court, the researchers also argued that they were irreparably disadvantaged in competing for government grants by their work on adult stem cells.Judge Royce C. Lamberth of the District Court of the District of Columbia initially ruled that the plaintiffs had no grounds on which to sue. However, the US District Court of Appeals for the District of Columbia overturned his decision and found that “[b]ecause the Guidelines have intensified the competition for a share in a fixed amount” of NIH funding. With the case back in his court, Lamberth reversed his decision on August 23 this year, granting a preliminary injunction to block the new NIH guidelines on embryonic stem-cell work. This injunction is detailed in the 1995 Dickey-Wicker Amendment, an appropriation bill rider, which prohibits the HHS from funding “research in which a human embryo or embryos are destroyed, discarded or knowingly subjected to risk of injury or death.” By allowing the destruction of embryos, Lamberth argued, the NIH rules violate the law.This triggered another wave of uncertainty as dozens of labs faced a freeze of federal funding. Morrison commented that an abrupt end to funding does not normally occur in biomedical research in the USA. “We normally have years of warning when grants are going to end so we can make a plan about how we can have smooth transitions from one funding source to another,” he said. Morrison—whose team has been researching Hirschsprung disease, a congenital enlargement of the colon—said his lab potentially faced a loss of US$ 250,000 overnight. “I e-mailed the people in my lab and said, ‘We may have just lost this funding and if so, then the project is over''”.Morrison explained that the positions of two people in his lab were affected by the cut, along with a third person whose job was partly funded by the grant. “Even though it''s only somewhere between 10–15% of the funding in my lab, it''s still a lot of money,” he said. “It''s not like we have hundreds of thousands of dollars of discretionary funds lying around in case a problem like that comes up.” Zon noted that his lab, which experienced an increase in the pace of discovery since Obama had signed his order, reverted to its Bush-era practices.On September 27 this year, a federal appeals court for the District of Columbia extended Lamberth''s stay to enable the government to pursue its appeal. The NIH was allowed to distribute US$78 million earmarked for 44 scientists during the appeal. The court said the matter should be expedited, but it could, over the years ahead, make its way to the US Supreme Court.The White House welcomed the decision of the appeals court in favour of the NIH. “President Obama made expansion of stem-cell research and the pursuit of groundbreaking treatments and cures a top priority when he took office. We''re heartened that the court will allow [the] NIH and their grantees to continue moving forward while the appeal is resolved,” said White House press secretary Robert Gibbs. The White House might have been glad of some good news, while it wrestles with the worst economic downturn since the Great Depression and the rise of the Tea Party movement.Even without a formal position on the matter, the Tea Party has had an impact on stem-cell research through its electoral victoriesTimothy Kamp, whose lab at the University of Wisconsin (Madison, WI, USA) researches embryonic stem-cell-derived cardiomyocytes, said that he finds the Tea Party movement confusing. “It''s hard for me to know what a uniform platform is for the Tea Party. I''ve heard a few comments from folks in the Tea Party who have opposed stem-cell research,” he said.However, the position of the Tea Party on the topic of stem-cell research could prove to be of vital importance. The Tea Party took its name from the Boston Tea Party—a famous protest in 1773 in which American colonists protested against the passing of the British Tea Act, for its attempt to extract yet more taxes from the new colony. Protesters dressed up as Native Americans and threw tea into the Boston harbour. Contemporary Tea Party members tend to have a longer list of complaints, but generally want to reduce the size of government and cut taxes. Their increasing popularity in the USA and the success of many Tea Party-backed Republican candidates for the upcoming congressional election could jeopardize Obama''s plans to pass new laws to regulate federal funding for stem-cell research.Even without a formal position on the matter, the Tea Party has had an impact on stem-cell research through its electoral victories. Perhaps their most high-profile candidate was the telegenic Christine O''Donnell, a Republican Senatorial candidate from Delaware. The Susan B. Anthony List, a pro-life women''s group, has described O''Donnell as one of “the brightest new stars” opposing abortion (www.lifenews.com/state5255.html). Although O''Donnell was eventually defeated in the 2 November congressional election, by winning the Republican primary in August, she knocked out nine-term Congressman and former Delaware governor Mike Castle, a moderate Republican known for his willingness to work with Democrats to pass legislation to protect stem-cell research.In the past, Castle and Diane DeGette, a Democratic representative from Colorado, co-sponsored the Stem Cell Research Advancement Act to expand federal funding of embryonic stem-cell research. They aimed to support Obama''s executive order and “ensure a lasting ethical framework overseeing stem cell research at the National Institutes of Health”.Morrison described Castle as “one of the great public servants in this country—no matter what political affiliation you have. For him to lose to somebody with such a chequered background and such shaky positions on things like evolution and other issues is a tragedy for the country.” Another stem-cell research advocate, Pennsylvania Senator Arlen Specter, a Republican-turned-Democrat, was also defeated in the primary. He had introduced legislation in September to codify Obama''s order. Specter, a cancer survivor, said his legislation is aimed at removing the “great uncertainty in the research community”.According to Sarah Binder, a political scientist at George Washington University in Washington, DC, the chances of passing legislation to codify the Obama executive order are decreasing: “As the Republican Party becomes more conservative and as moderates can''t get nominated in that party, it does lead you to wonder whether it''s possible to make anything happen [with the new Congress] in January.”There are a variety of opinions about how the outcome of the November elections will influence stem-cell policies. Binder said that a number of prominent Republicans have strongly promoted stem-cell research, including the Reagan family. “This hasn''t been a purely Democratic initiative,” she said. “The question is whether the Republican party has moved sufficiently to the right to preclude action on stem cells.” Historically there was “massive” Republican support for funding bills in 2006 and 2007 that were ultimately vetoed by Bush, she noted.…the debate about public funding for stem-cell research is only part of the picture, given the role of private business and states“Rightward shifts in the House and Senate do not bode well for legislative efforts to entrench federal support for stem-cell research,” Binder said. “First, if a large number of Republicans continue to oppose such funding, a conservative House majority is unlikely to pursue the issue. Second, Republican campaign commitments to reduce federal spending could hit the NIH and its support for stem-cell research hard.”Binder added that “a lingering unknown” is how the topic will be framed: “If it gets framed as a pro-choice versus pro-life initiative, that''s quite difficult for Congress to overcome in a bipartisan way. If it is framed as a question of medical research and medical breakthroughs and scientific advancement, it won''t fall purely on partisan lines. If members of Congress talk about their personal experiences, such as having a parent affected by Parkinson''s, then you could see even pro-life members voting in favour of a more expansive interpretation of stem-cell funding.”Johnson said that Congress could alter the wording of the Dickey-Wicker Amendment when passing the NIH budget for 2011 to remove the conflict. “You don''t have to get rid of the amendment completely, but you could rephrase it,” she said. She also commented that the public essentially supports embryonic stem-cell research. “The polls and surveys show the American public is morally behind there being some limited form of embryonic stem-cell research funded by federal money. They don''t favour cloning. There is not a huge amount of support for creating embryos from scratch for research. But there seems to be pretty wide support among the general public for the kind of embryonic stem-cell research that the NIH is currently funding.”In the end, however, the debate about public funding for stem-cell research is only part of the picture, given the role of private business and states. Glenn McGee, a professor at the Center for Practical Bioethics in Kansas City, MO, USA, and editor of the American Journal of Bioethics, commented that perhaps too much emphasis is being put on federal funding. He said that funding from states such as California and from industry—which are not restricted—has become a more important force than NIH funding. “We''re a little bit delusional if we think that this is a moment where the country is making a big decision about what''s going to happen with stem cells,” he said. “I think that ship has sailed.”     

Women and telomeres

Last year''s Nobel Prizes for Carol Greider and Elizabeth Blackburn should be encouraging for all female scientists with childrenCarol Greider, a molecular biologist at Johns Hopkins University (Baltimore, MD, USA), recalled that when she received a phone call from the Nobel Foundation early in October last year, she was staring down a large pile of laundry. The caller informed her that she had won the 2009 Nobel Prize in Physiology or Medicine along with Elizabeth Blackburn, her mentor and co-discoverer of the enzyme telomerase, and Jack Szostak. The Prize was not only the ultimate reward for her own achievements, but it also highlighted a research field in biology that, unlike most others, is renowned for attracting a significant number of women.Indeed, the 2009 awards stood out in particular, as five women received Nobel prizes. In addition to the Prize for Greider and Blackburn, Ada E. Yonath received one in chemistry, Elinor Ostrom became the first female Prize-winner in economics, and Herta Müller won for literature (Fig 1).Open in a separate windowFigure 1The 2009 Nobel Laureates assembled for a photo during their visit to the Nobel Foundation on 12 December 2009. Back row, left to right: Nobel Laureates in Chemistry Ada E. Yonath and Venkatraman Ramakrishnan, Nobel Laureates in Physiology or Medicine Jack W. Szostak and Carol W. Greider, Nobel Laureate in Chemistry Thomas A. Steitz, Nobel Laureate in Physiology or Medicine Elizabeth H. Blackburn, and Nobel Laureate in Physics George E. Smith. Front row, left to right: Nobel Laureate in Physics Willard S. Boyle, Nobel Laureate in Economic Sciences Elinor Ostrom, Nobel Laureate in Literature Herta Müller, and Nobel Laureate in Economic Sciences Oliver E. Williamson. © The Nobel Foundation 2009. Photo: Orasis.Greider, the daughter of scientists, has overcome many obstacles during her career. She had dyslexia that placed her in remedial classes; “I thought I was stupid,” she told The New York Times (Dreifus, 2009). Yet, by far the biggest challenge she has tackled is being a woman with children in a man''s world. When she attended a press conference at Johns Hopkins to announce the Prize, she brought her children Gwendolyn and Charles with her (Fig 2). “How many men have won the Nobel in the last few years, and they have kids the same age as mine, and their kids aren''t in the picture? That''s a big difference, right? And that makes a statement,” she said.The Prize […] highlighted a research field in biology that, unlike most others, is renowned for attracting a significant number of womenOpen in a separate windowFigure 2Mother, scientist and Nobel Prize-winner: Carol Greider is greeted by her lab and her children. © Johns Hopkins Medicine 2009. Photo: Keith Weller.Marie Curie (1867–1934), the Polish–French physicist and chemist, was the first woman to win the Prize in 1903 for physics, together with her husband Pierre, and again for chemistry in 1911—the only woman to twice achieve such recognition. Curie''s daughter Irène Joliot-Curie (1897–1956), a French chemist, also won the Prize with her husband Frédéric in 1935. Since Curie''s 1911 prize, 347 Nobel Prizes in Physiology or Medicine and Chemistry (the fields in which biologists are recognized) have been awarded, but only 14—just 4%—have gone to women, with 9 of these awarded since 1979. That is a far cry from women holding up half the sky.Yet, despite the dominance of men in biology and the other natural sciences, telomere research has a reputation as a field dominated by women. Daniela Rhodes, a structural biologist and senior scientist at the MRC Laboratory of Molecular Biology (Cambridge, UK) recalls joining the field in 1993. “When I went to my first meeting, my world changed because I was used to being one of the few female speakers,” she said. “Most of the speakers there were female.” She estimated that 80% of the speakers at meetings at Cold Spring Harbour Laboratory in those early days were women, while the ratio in the audience was more balanced.Since Curie''s 1911 prize, 347 Nobel Prizes in Physiology or Medicine and Chemistry […] have been awarded, but only 14—just 4%—have gone to women…“There''s nothing particularly interesting about telomeres to women,” Rhodes explained. “[The] field covers some people like me who do structural biology, to cell biology, to people interested in cancers […] It could be any other field in biology. I think it''s [a result of] having women start it and [including] other women.” Greider comes to a similar conclusion: “I really see it as a founder effect. It started with Joe Gall [who originally recruited Blackburn to work in his lab].”Gall, a cell biologist, […] welcomed women to his lab at a time when the overall situation for women in science was “reasonably glum”…Gall, a cell biologist, earned a reputation for being gender neutral while working at Yale University in the 1950s and 1960s; he welcomed women to his lab at a time when the overall situation for women in science was “reasonably glum,” as he put it. “It wasn''t that women were not accepted into PhD programs. It''s just that the opportunities for them afterwards were pretty slim,” he explained.“Very early on he was very supportive to a number of women who went on and then had their own labs and […] many of those women [went] out in the world [to] train other women,” Greider commented. “A whole tree that then grows up that in the end there are many more women in that particular field simply because of that historical event.Thomas Cech, who won the Nobel Prize for Chemistry in 1989 and who worked in Gall''s lab with Blackburn, agreed: “In biochemistry and metabolism, we talk about positive feedback loops. This was a positive feedback loop. Joe Gall''s lab at Yale was an environment that was free of bias against women, and it was scientifically supportive.”Gall, now 81 and working at the Carnegie Institution of Washington (Baltimore, MD, USA), is somewhat dismissive about his positive role. “It never occurred to me that I was doing anything unusual. It literally, really did not. And it''s only been in the last 10 or 20 years that anyone made much of it,” he said. “If you look back, […] my laboratory [was] very close to [half] men and [half] women.”During the 1970s and 1980s; “[w]hen I entered graduate school,” Greider recalled, “it was a time when the number of graduate students [who] were women was about 50%. And it wasn''t unusual at all.” What has changed, though, is the number of women choosing to pursue a scientific career further. According to the US National Science Foundation (Arlington, VA, USA), women received 51.8% of doctorates in the life sciences in 2006, compared with 43.8% in 1996, 34.6% in 1986, 20.7% in 1976 and 11.9% in 1966 (www.nsf.gov/statistics).In fact, Gall suspects that biology tends to attract more women than the other sciences. “I think if you look in biology departments that you would find a higher percentage [of women] than you would in physics and chemistry,” he said. “I think […] it''s hard to dissociate societal effects from specific effects, but probably fewer women are inclined to go into chemistry [or] physics. Certainly, there is no lack of women going into biology.” However, the representation of women falls off at each level, from postdoc to assistant professor and tenured professor. Cech estimated that only about 20% of the biology faculty in the USA are women.“[It] is a leaky pipeline,” Greider explained. “People exit the system. Women exit at a much higher proportion than do men. I don''t see it as a [supply] pipeline issue at all, getting the trainees in, because for 25 years there have been a great number of women trainees.“We all thought that with civil rights and affirmative action you''d open the doors and women would come in and everything would just follow. And it turned out that was not true.”Nancy Hopkins, a molecular biologist and long-time advocate on issues affecting women faculty members at the Massachusetts Institute of Technology (Cambridge, MA, USA), said that the situation in the USA has improved because of civil rights laws and affirmative action. “I was hired—almost every woman of my generation was hired—as a result of affirmative action. Without it, there wouldn''t have been any women on the faculty,” she said, but added that: “We all thought that with civil rights and affirmative action you''d open the doors and women would come in and everything would just follow. And it turned out that was not true.”Indeed, in a speech at an academic conference in 2005, Harvard President Lawrence Summers said that innate differences between males and females might be one reason why fewer women than men succeeded in science and mathematics. The economist, who served as Secretary of Treasury under President William Clinton, told The Boston Globe that “[r]esearch in behavioural genetics is showing that things people previously attributed to socialization weren''t [due to socialization after all]” (Bombardieri, 2005).Some attendees of the meeting were angered by Summers''s remarks that women do not have the same ‘innate ability'' as men in some fields. Hopkins said she left the meeting as a protest and in “a state of shock and rage”. “It isn''t a question of political correctness, it''s about making unscientific, unfounded and damaging comments. It''s what discrimination is,” she said, adding that Summers''s views reflect the problems women face in moving up the ladder in academia. “To have the president of Harvard say that the second most important reason for their not being equal was really their intrinsic genetic inferiority is so shocking that no matter how many times I think back to his comments, I''m still shocked. These women were not asking to be considered better or special. They were just asking to have their gender be invisible.”Nonetheless, women are making inroads into academia, despite lingering prejudice and discrimination. One field of biology that counts a relatively high number of successful women among its upper ranks is developmental biology. Christiane Nüsslein-Volhard, for example, is Director of the Max Planck Institute for Developmental Biology in Tübingen, Germany, and won the Nobel Prize for Physiology or Medicine in 1995 for her work on the development of Drosophila embryos. She estimated that about 30% of speakers at conferences in her field are women.…for many women, the recent Nobel Prize for Greider […] and Blackburn […] therefore comes as much needed reassurance that it is possible to combine family life and a career in scienceHowever, she also noted that women have never been the majority in her own lab owing to the social constraints of German society. She explained that in Germany, Switzerland and Austria, family issues pose barriers for many women who want to have children and advance professionally because the pressure for women to not use day care is extremely strong. As such, “[w]omen want to stay home because they want to be an ideal mother, and then at the same time they want to go to work and do an ideal job and somehow this is really very difficult,” she said. “I don''t know a single case where the husband stays at home and takes care of the kids and the household. This doesn''t happen. So women are now in an unequal situation because if they want to do the job, they cannot; they don''t have a chance to find someone to do the work for them. […] The wives need wives.” In response to this situation, Nüsslein-Volhard has established the CNV Foundation to financially support young women scientists with children in Germany, to help pay for assistance with household chores and child care.Rhodes, an Italian native who grew up in Sweden, agreed with Nüsslein-Volhard''s assessment of the situation for many European female scientists with children. “Some European countries are very old-fashioned. If you look at the Protestant countries like Holland, women still do not really go out and have a career. It tends to be the man,” she said. “What I find depressing is [that in] a country like Sweden where I grew up, which is a very liberated country, there has been equality between men and women for a couple of generations, and if you look at the percentage of female professors at the universities, it''s still only 10%.” In fact, studies both from Europe and the USA show that academic science is not a welcoming environment for women with children; less so than for childless women and fathers, who are more likely to succeed in academic research (Ledin et al, 2007; Martinez et al, 2007).For Hopkins, her divorce at the age of 30 made a choice between children or a career unavoidable. Offered a position at MIT, she recalled that she very deliberately chose science. She said that she thought to herself: “Okay, I''m going to take the job, not have children and not even get married again because I couldn''t imagine combining that career with any kind of decent family life.” As such, for many women, the recent Nobel Prize for Greider, who raised two children, and Blackburn (Fig 3), who raised one, therefore comes as much needed reassurance that it is possible to combine family life and a career in science. Hopkins said the appearance of Greider and her children at the press conference sent “the message to young women that they can do it, even though very few women in my generation could do it. The ways in which some women are managing to do it are going to become the role models for the women who follow them.”Open in a separate windowFigure 3Elizabeth Blackburn greets colleagues and the media at a reception held in Genentech Hall at UCSF Mission Bay to celebrate her award of the Nobel Prize in Physiology or Medicine. © University of California, San Francisco 2009. Photo: Susan Merrell.     

Crop shortages

A lack of breeders to apply the knowledge from plant science is jeopardizing public breeding programmes and the training of future plant scientistsIn the midst of an economic downturn, many college and university students in the USA face an uncertain future. There is one crop of graduates, though, who need not worry about unemployment: plant breeders. “Our students start with six-digit salaries once they leave and they have three or four offers. We have people coming to molecular biology and they can''t find jobs. People coming to plant breeding, they have as many jobs as they want,” said Edward Buckler, a geneticist with the US Department of Agriculture''s Agricultural Research Service Institute for Genomic Diversity at Cornell University (Ithaca, NY, USA).The lure of Big Ag depletes universities and research institutes of plant breeders […] and jeopardizes the training of future generations of plant scientists and breedersThe secret behind the success of qualified breeders on the job market is that they can join ‘Big Ag''—big agriculture—that is, major seed companies. Roger Boerma, coordinator of academic research for the Center for Applied Genetic Technologies at the University of Georgia (Athens, GA, USA), said that most of his graduate and postdoctoral students find jobs at companies such as Pioneer, Monsanto and Syngenta, rather than working in the orchards and fields of academic research. According to Todd Wehner, a professor and cucurbit breeder at the Department of Horticultural Science, North Carolina State University (Raleigh, NC, USA), the best-paying jobs—US$100,000 plus good benefits and research conditions—are at seed companies that deal with the main crops (Guner & Wehner, 2003). By contrast, university positions typically start at US$75,000 and tenure track.As a result, Wehner said, public crop breeding in the USA has begun to disappear. “To be clear, there is no shortage of plant breeders,” he said. “There is a shortage of plant breeders in the public sector.” The lure of Big Ag depletes universities and research institutes of plant breeders—who, after all, are the ones who create new plant varieties for agriculture—and jeopardizes the training of future generations of plant scientists and breeders. Moreover, there is an increasing demand for breeders to address the challenge of creating environmentally sustainable ways to grow more food for an increasing human population on Earth.At the same time, basic plant research is making rapid progress. The genomes of most of the main crop plants and many vegetables have been sequenced, which has enabled researchers to better understand the molecular details of how plants fend off pests and pathogens, or withstand drought and flooding. This research has also generated molecular markers—short regions of DNA that are linked to, for example, better resistance to fungi or other pathogens. So-called marker-assisted breeding based on this information is now able to create new plant varieties more effectively than would be possible with the classical strategy of crossing, selection and backcrossing.However, applying the genomic knowledge requires both breeders and plant scientists with a better understanding of each other''s expertise. As David Baulcombe, professor of botany at the University of Cambridge, UK, commented, “I think the important gap is actually in making sure that the fundamental scientists working on genomics understand breeding, and equally that those people doing breeding understand the potential of genomics. This is part of the translational gap. There''s incomplete understanding on both sides.”…applying the genomic knowledge requires both breeders and plant scientists with a better understanding of each other''s expertiseIn the genomic age, plant breeding has an image problem: like other hands-on agricultural work, it is dirty and unglamorous. “A research project in agriculture in the twenty-first century resembles agriculture for farmers in the eighteenth century,” Wehner said. “Harvesting in the fields in the summer might be considered one of the worst jobs, but not to me. I''m harvesting cucumbers just like everybody else. I don''t mind working at 105 degrees, with 95% humidity and insects biting my ankles. I actually like that. I like that better than office work.”For most students, however, genomics is the more appealing option as a cutting-edge and glamorous research field. “The exciting photographs that you always see are people holding up glass test tubes and working in front of big computer screens,” Wehner explained.In addition, Wehner said that federal and state governments have given greater priority and funding to molecular genetics than to plant breeding. “The reason we''ve gone away from plant breeding of course is that faculty can get competitive grants for large amounts of money to do things that are more in the area of molecular genetics,” he explained. “Plant breeders have switched over to molecular genetics because they can get money there and they can''t get money in plant breeding.”“The frontiers of science shifted from agriculture to genetics, especially the genetics of corn, wheat and rice,” agreed Richard Flavell, former Director of the John Innes Centre (Norwich, UK) and now Chief Scientific Officer of Ceres (Thousand Oaks, CA, USA). “As university departments have chased their money, chased the bright students, they have [focused on] programmes that pull in research dollars on the frontiers, and plant breeding has been left behind as something of a Cinderella subject.”In the genomic age, plant breeding has an image problem: like other hands-on agricultural work, it is dirty and unglamorousIn a sense, public plant breeding has become a victim of its own success. Wehner explained that over the past century, the protection of intellectual property has created a profitable market for private corporations to the detriment of public programmes. “It started out where they could protect seed-propagated crops,” he said. “The companies began to hire plant breeders and develop their own varieties. And that started the whole agricultural business, which is now huge.”As a result, Wehner said, the private sector can now outmanoeuvre public breeders at will. “[Seed companies] have huge teams that can go much faster than I can go. They have winter nurseries and big greenhouses and lots of pathologists and molecular geneticists and they have large databases and seed technologists and sales reps and catalogue artists and all those things. They can do much faster cucumber breeding than I can. They can beat me in any area that they choose to focus on.”He said that seed corporations turn only to public breeders when they are looking for rare seeds obtained on expeditions around the world or special knowledge. These crops and the breeders and other scientists who work on them receive far less financial support from government than do the more profitable crops, such as corn and soybean. In effect, these crops are in an analogous position to orphan drugs that receive little attention because the patients who need them represent a small economic market.The dwindling support for public breeding programmes is also a result of larger political developments. Since the 1980s, when British Prime Minister Margaret Thatcher and US President Ronald Regan championed the private sector in all things, government has consistently withdrawn support for public research programmes wherever the private sector can profit. “Plant breeding programmes are expensive. My programme costs about US$500,000 a year to run for my crops, watermelon and cucumber. Universities don''t want to spend that money if they don''t have to, especially if it''s already being done by the private sector,” Wehner said.“Over the last 30 years or so, food supplies and food security have fallen off the agenda of policymakers”…“Over the last 30 years or so, food supplies and food security have fallen off the agenda of policymakers,” Baulcombe explained. “Applied research in academic institutions is disappearing, and so the opportunities for linking the achievements of basic research with applications, at least in the public sector, are disappearing. You''ve got these two areas of the work going in opposite directions.”There''s another problem for plant breeding in the publish-or-perish world of academia. According to Ian Graham, Director of the Centre for Novel Agricultural Products at York University in the UK, potential academics in the plant sciences are turned off by plant breeding as a discipline because it is difficult to publish the research in high-impact journals.Graham, who is funded by the Bill & Melinda Gates Foundation to breed new varieties of Artemisia—the plant that produces the anti-malarial compound artemisinin—said this could change. “Now with the new [genomic] technologies, the whole subject of plant breeding has come back into the limelight. We can start thinking seriously about not just the conventional crops […] but all the marginal crops as well that we can really start employing these technologies on and doing exciting science and linking phenotypes to genes and phenotypes to the underlying biology,” he said. “It takes us back again closer to the science. That will bring more people into plant breeding.”…potential academics in the plant sciences are turned off by plant breeding as a discipline because it is difficult to publish the research in high-impact journalsBuckler, who specializes in functional genomic approaches to dissect complex traits in maize, wheat and Arabidopsis, said that public breeding still moves at a slower pace. “The seed companies are trying to figure out how to move genomics from gene discovery all the way to the breeding side. And it''s moving forward,” he said. “There have been some real intellectual questions that people are trying to overcome as to how fast to integrate genomics. I think it''s starting to occur also with a lot of the public breeders. A lot of it has been that the cost of genotyping, especially for specialty crops, was too high to develop marker systems that would really accelerate breeding.”Things might be about to change on the cost side as well. Buckler said that decreasing costs for sequencing and genotyping will give public breeding a boost. Using today''s genomic tools, researchers and plant breeders could match the achievements of the last century in maize breeding within three years. He said that comparable gains could be made in specialty crops, the forte of public breeding. “Right now, most of the simulations suggest that we can accelerate it about threefold,” Buckler said. “Maybe as our knowledge increases, maybe we can approach a 15-fold rate increase.”Indeed, the increasing knowledge from basic research could well contribute to significant advances in the coming years. “We''ve messed around with genes in a rather blind, sort of non-predictive process,” said Scott Jackson, a plant genomics expert at Purdue University (West Lafayette, IN, USA), who headed the team that decoded the soybean genome (Schmutz et al, 2010). “Having a full genome sequence, having all the genes underlying all the traits in whatever plant organism you''re looking at, makes it less blind. You can determine which genes affect the trait and it has the potential to make it a more predictive process where you can take specific genes in combinations and you can predict what the outcome might be. I think that''s where the real revolution in plant breeding is going to come.”Nevertheless, the main problem that could hold back this revolution is a lack of trained people in academia and the private sector. Ted Crosbie, Head of Plant Breeding at Monsanto (St Louis, MO, USA), commented at the national Plant Breeding Coordinating Committee meeting in 2008 that “[w]e, in the plant breeding industry, face a number of challenges. More plant breeders are reaching retirement age at a time when the need for plant breeders has never been greater […] We need to renew our nation''s capacity for plant breeding.”“…with the new [genomic] technologies, the whole subject of plant breeding has come back into the limelight”Dry bean breeder James Kelly, a professor of crop and soil sciences at Michigan State University (East Lansing, MI, USA), said while there has been a disconnect between public breeders and genomics researchers, new federal grants are designed to increase collaboration.In the meantime, developing countries such as India and China have been filling the gap. “China is putting a huge amount of effort into agriculture. They actually know the importance of food. They have plant breeders all over the place,” Wehner said. “The US is starting to fall behind. And now, agricultural companies are looking around wondering—where are we going to get our plant breeders?”To address the problem, major agriculture companies have begun to fund fellowships to train new plant breeders. Thus far, Buckler said, these efforts have had only a small impact. He noted that 500 new PhDs a year are needed just in maize breeding. “It''s not uncommon for the big companies like Monsanto, Pioneer and Syngenta to spend money on training, on endowing chairs at universities,” Flavell said. “It''s good PR, but they''re serious about the need for breeders.”The US government has also taken some measures to alleviate the problem. Congress decided to establish the US National Institute of Food and Agriculture (Washington, DC, USA) under the auspices of the US Department of Agriculture to make more efficient use of research money, advance the application of plant science and attract new students to plant breeding (see the interview with Roger Beachy in this issue, pp 504–507). Another approach is to use distance education to train breeders, such as technicians who want to advance their careers, in certificate programmes rather than master''s or doctorate programmes.“If [breeding] is not done in universities in the public sector, where is it done?”…“If [breeding] is not done in universities in the public sector, where is it done?” Flavell asked about the future of public breeding. “I can wax lyrical and perhaps be perceived as being over the top, but if we''re going to manage this planet on getting more food out of less land, this has to be almost one of the highest things that has got to be taken care of by government.” Wehner added, “The public in the developed world thinks food magically appears in grocery stores. There is no civilization without agriculture. Without plant breeders to work on improving our crops, civilization is at risk.”     

EU-LIFE revives funding debate: A group of mid-level life science research institutes is reopening the debate on how to fund research at the EU level calling for a stronger emphasis on excellence

EU-LIFE, which represents 10 European life science research institutes, has reopened the debate about how to fund research at the European level by calling for the budget of the European Research Council to be drastically increased.For more than a decade, European scientists have lobbied policy makers in Brussels to increase European Union (EU) funding for research and to spend the money they do provide more efficiently. This debate eventually led to the establishment of the European Research Council (ERC) in 2007, which provides significant grants and does so on the sole criterion of scientific excellence—something for which the scientific community pushed. As such, there seemed to be consensus about how to judge and fund science at the European level, including in the debate about the EU''s Horizon 2020 funding scheme—the EU''s framework for research and innovation—which will spend €80 billion over the next seven years (2014–2020). The conclusion seemed to be that the ERC should continue to support basic research on the basis of excellence, whereas other parts of the programme would focus on large cooperative projects, improving the competitiveness of Europe and meeting societal challenges such as climate change and public health.But a new body called EU-LIFE—set up in May 2013—has reopened the debate about how to fund science and is campaigning for a greater focus on rewarding excellence, even at the expense of funding projects on the grounds of fairness or to correct imbalances between EU member states. EU-LIFE was founded by 10 institutions including the Centre for Genomic Regulation (CRG; Barcelona, Spain), the Institut Curie (Paris, France) and the Max Delbrück Centre (Berlin, Germany), partly to provide a collective voice for mid-sized research institutes in the life sciences that might lack influence on their own (

The recruitment crunch

Despite an increase in the demand for skilled workers, there is a lack of qualified science, engineering and technology graduatesFor the past few years, Germany''s export-oriented economy has undergone impressive growth as the demand for its engineering products has increased globally. However, although this development has driven down national unemployment, it has also resulted in a labour shortage that has German companies urgently looking for skilled workers and engineers: vacancies for engineers rose by nearly 30% in 2006. Last year, the German Ministry of Economy and Technology warned that the lack of workers could result in revenue losses of more than ¤20 billion per year (Bovensiepen, 2007).…rapidly developing nations, notably China and India, have been investing heavily in research and education to advance towards a knowledge-based economyGermany is not the only country faced with this problem. Across the European Union (EU), the lack of highly trained employees, coupled with the ongoing ‘brain drain'' of researchers to the USA, could stifle growth in high-tech industries (EC, 2007). Indeed, the EU estimates that the information sector alone could face a lack of up to 300,000 qualified staff by 2010 (EurActiv, 2007). The USA has been faring better, mainly owing to its ability to attract skilled workers from other nations and its demographic situation, but it has become highly dependent on immigrant labour; foreign students now earn about 30% of science doctorates and more than 50% of engineering doctorates in the USA (NSF, 2006). Moreover, rapidly developing nations, notably China and India, have been investing heavily in research and education to advance towards a knowledge-based economy.The result is an increased global demand and competition for workers in the science, engineering and technology sector. The only long-term solution to this problem—and to ensure growth in high-tech industries—is to increase the number of graduates in these areas and, more generally, to recruit more high-school and college students to science and engineering. However, any sustainable effort must address all stages of education, and tackle the cultural and public perceptions of science.With regard to the latter, engineering and the life sciences—particularly medicine—are faring better than physics or chemistry. Our natural interest in our health ensures that medical research remains popular and well funded, although this is sometimes done to the detriment of fundamental biological research, notably plant science or environmental research.Yet, even the life sciences have been suffering from a recruitment shortfall at the undergraduate level, particularly in the middle and lower ranks of student quality. “Often when people are complaining [about the decline in the standard of science graduates], they are referring to the rump in the middle,” commented Celia Knight, a plant biologist and Director of the undergraduate school at Leeds University in the UK. She argued that, although there are still plenty of outstanding students, factors such as grade inflation and rising student numbers are diluting the quality. “As we expand student numbers, we expect to expand the lower end,” she said. “It is clear there wasn''t a huge population of highly able students out there not going to university in the past.”The Norwegian-led ROSE (the Relevance Of Science Education) study, which measured the attitudes of school children to science in more than 20 countries, confirms this trend and highlights an additional gender gap in science recruitment (Sjøberg & Schreiner, 2007) that also appears at the top quality levels. “The most gifted students are not necessarily taking science—particularly girls,” said Sharmila Banerjee, National Coordinator for the Nuffield Science Bursary scheme in the UK.The quality problem, if the perennial comments of senior scientists are to be believed, is increasingly apparent as biology becomes more analytical and quantitative: the lack of basic mathematical and statistical knowledge among students becomes more obvious. But, as Jonathan Osborne, Professor of Science Education at King''s College, London, UK, insisted, this does not represent the whole story. A lack of knowledge in some fundamental areas might, he argued, be compensated for by the student''s broader grasp of the field. “Today''s youngsters may not, say, be taught about cosines in the same way [that] we were,” he said, “but they have different skills instead that we did not have [...] What people focus on too much is what people cannot do rather than what they can do.”But Osborne was far from suggesting that all is right with science education. He recently co-authored the report Science Education in Europe: Critical Reflections (Osborne & Dillon, 2008), which was published for the Nuffield Foundation (London, UK) in January 2008. In the report, Osborne and co-author Justin Dillon, President of the European Science Education Research Association (ESERA), advocated sweeping changes to the high-school science curricula across Europe. The report reflects the concerns of the Nuffield Foundation that science teaching is losing the battle for hearts and minds by placing too much emphasis on learning by rote. “The main changes needed are to make teachers of science realise that the main achievement of science is the explanatory theories that it offers of the material world and that a miscellany of facts is not the same thing,” Osborne said. “There is a need to provide a science education where the connections to students'' lives are more evident and where there is space to discuss the issues raised by science.”​Open in a separate window© Image Source/CorbisKnight noted that the current science curriculum is also losing touch with the requirements of universities. As she pointed out, universities used to set the A-level exams—the final qualifications of the UK secondary school system taken at age 18—but now have minimal influence over them. This has led, she feels, towards too much medicine and human biology in the syllabus, often at the expense of other fields such as plant biology. Yet, despite its partial omission from the science curriculum, plant biology itself is becoming increasingly relevant to society, particularly in the light of recent global food shortages and the drive towards solar energy conversion by using genetically engineered plants or artificial photosynthesis.Osborne agreed that universities should not regain their old monopoly on setting exams, but emphasized that the current syllabus serves nobody, least of all those who plan to pursue a career in science. This, he pointed out, is why many universities in the UK and elsewhere are now considering setting their own entrance exams. “The reason is that the people who set the A-level exams are failing to write exams which discriminate and test understanding, rather than the ability to regurgitate information or follow algorithmic procedures,” he said. “In its worst incarnation, somebody once described this as ‘bulimic science education''—that is, you are fed a lot of indigestible facts which have no nutritional value and you instantly regurgitate.”To address this trend, Newcastle University in the UK is pursuing an approach that introduces university-style education into the school curriculum and allows some students to bypass the A-level school exams altogether. A school local to the university, Monkseaton High School, initiated the scheme to provide an alternative route to university in the belief that some good students are deterred by traditional exams, which emphasize analytical skills and fact retention. Instead, students at Monkseaton can now take a science module at the Open University (OU; Milton Keynes, UK)—a distance-learning institution that allows degrees to be taken part time and mostly remotely. Newcastle University has agreed to accept undergraduate students from Monkseaton who have taken the OU module.“We do not see this route as an easy route, nor is it a statement that A-levels are not appropriate as preparation for university,” explained Heather Finlayson, Head of the School of Biology at Newcastle University. “The pilot was developed to try to encourage greater participation in science beyond GCSE level [the exams taken at age 16 at the end of compulsory secondary education in the UK]. We believe that the students entering by the OU route will have a broader but less deep knowledge in some subject areas, but their independent study skills, developed while studying the OU modules, will enable them to study effectively and rapidly to make up any lack of specific subject knowledge.”Some educators, however, are sceptical of how much difference systemic changes can make to the overall appeal of science. “We have had so many curriculum innovations, implemented in a top-down manner, that did not bring what was expected,” said Jan Van Driel, a professor at the Leiden University Graduate School of Teaching in the Netherlands. “I would argue that, in general, science should be taught in a way that makes sense—that is comprehensible and relevant—to the specific target group, and this is primarily the responsibility of science teachers. What we need is highly qualified and motivated science teachers, rather than another curriculum reform movement.”…tests are poor predictors of which students will be academic failures, because a significant number of students will become solid achievers despite poor scores on entrance exams…Van Driel was also sceptical of any trend that distances teachers from students, as could happen with a more university-like approach. “In our country, unfortunately, a belief seems to exist that students should work on their own, or in small groups, using computers, or doing practical work. In this context, the role of the teacher has been undervalued,” he said. But, having school students involved in practical work, which could still be administered by universities, would be likely to stimulate their interest, he added. “For talented students in secondary education, in our country, we have had very positive experiences with extra-curricular activities, where students participate in university courses and are given opportunities to engage in research activities.”Van Driel argued that science education should not wait until secondary school when children might have veered towards other subjects or developed negative views of science. “In our country, science teaching at the primary level has been undeservedly ignored. This is mainly due, as in many countries, to teachers not being qualified and motivated to teach science,” he commented. “Recently, we have begun to invest in this issue, on the one hand in projects aimed at stimulating young children to engage in inquiry activities and science projects, and the other hand in projects aiming at professional development of primary teachers. I think that, potentially, this is a very important development when it comes to making science more popular and better understood in our society.”The US Government has also taken up the idea that science teaching needs to be improved. In July 2008, Congress approved the US$40 million Robert Noyce Teacher Scholarship Programme to prepare science and maths teachers for selected schools. “We are also implementing the new Section 10A of the America COMPETES Act, which provides a good stipend to support a mid-career STEM [Science, Technology, Engineering and Maths] professional while they get a Master''s in teaching and then provides a salary supplement,” said Myles Boylan, Lead Program Director for Course, Curriculum and Laboratory Improvement at the US National Science Foundation (NSF; Arlington, VA, USA). “It is expected that as these teachers move into high need schools, the quality of instruction in maths and science will improve and that more high school graduates will go to college and major in STEM.”The USA is also considering offering students alternatives to traditional university exams—similar to the Newcastle University model—as Boylan explained: “I think the traditional exams are pretty good predictors of which students will be high performing and likely to graduate. But I also believe that these tests are poor predictors of which students will be academic failures, because a significant number of students will become solid achievers despite poor scores on entrance exams,” he said, but insisted that this was not tantamount to ‘dumbing down'' the system. “Many students are still quite immature at age 17 when they take these tests and thus can make spectacular gains in learning as they finally ‘grow up'' […] I believe the right approach is to give students multiple chances to succeed.”This chimes with the findings of a 2007 report by the Urban Institute, a US non-profit group in Washington, DC, which collects data and provides advice on science policy and education questions. The report suggests that the USA should no longer compete on the basis of scores in science and maths tests, but instead on creativity within the context of a more broadly based education (Lowell & Salzman, 2007).The main challenge therefore goes beyond improving science education; there is also a serious need to counter the misleading perception that science is in opposition to conservation or sustainable developmentYet, Banerjee suggested that educational reforms alone might not be sufficient to improve recruitment to science. She referred to the ROSE study, which found that a student''s response to the statement “I like school science better than other subjects” was more likely to be negative the more developed their country (Sjøberg & Schreiner, 2007). Banerjee commented that this might just reflect the increased range of choices that students have in these countries, but it could also result from a negative perception of science, as portrayed in the media or by the environmental lobby. The main challenge therefore goes beyond improving science education; there is also a serious need to counter the misleading perception that science is in opposition to conservation or sustainable development.But, there is cause for some optimism in the UK, at least, where the Higher Education Funding Council for England announced in October 2008 that its £350 million six-year programme to increase the number of science students was now working. In the academic year 2007/2008, the number of entries to chemistry courses, a subject that had been in decline, was up by 5.3%; a clear sign that trends can be, and are being, reversed in some countries. Despite this success, however, much more still needs to be done to counter negative cultural perceptions and to attract more women.Moreover, much more needs to be done to ensure that there are sufficient lucrative and attractive jobs for science graduates. The Urban Institute''s 2007 report therefore suggests that leading countries like the USA need to rethink their approach to science education, as they produce large numbers of students with bachelor''s and master''s degrees but fail to keep them interested in these areas. As the study said: “One to two years after graduation, 20 percent of S&E [science and engineering] bachelors are in school but not in S&E studies, while another 45 percent are working but in non-S&E employment (total attrition of 65 percent). One to two years after graduation, 7 percent of S&E master''s graduates are enrolled in school but not in S&E studies, while another 31 percent are working but in non-S&E employment” (Lowell & Salzman, 2007).Indeed, the chance of finding an interesting and well-paid job after graduation seems to be a main factor in solving the problem of recruitment, notwithstanding attitudes or perceptions. The economic boom and the ensuing competition for qualified engineers among German companies in the past few years—although times are now less certain—markedly improved the attractiveness of engineering fields to undergraduates. This year, German universities reported that the number of students enrolling in engineering fields rose by up to 16% for the fall semester (Anon, 2008).     

The health of European medical research. Attempts are under way to update EU regulations, with the aim of harmonizing clinical research across the continent

The 2001 EU Clinical Trials Directive aimed to harmonize the regulation of medical research, but achieved the opposite. Various attempts are underway to update the directive to make it easier to safely conduct medical research in Europe.Medical research, similarly to finance and business, works best with light regulation; however, protecting patients during clinical trials, and afterwards when treatments have been approved, requires regulation. Attempts to square this circle and the challenge of testing sophisticated drugs and therapies have resulted in increasingly strict regulation of clinical research, particularly in Europe''s leading medical research powers Germany, France, the Netherlands and the UK. There is growing concern among these countries with established pharmaceutical industries that clinical trials are increasingly hard to conduct; in fact, the number of applications has declined significantly during the past decade (Cressy, 2010).There is growing concern among these countries with established pharmaceutical industries that clinical trials are increasingly hard to conduct…Meanwhile, the number of applications for clinical trials has increased in the USA, Canada and some southern European countries, notably Italy and Spain, where the regulatory touch has been lighter and combined, in some cases, with financial incentives, according to Paul Stewart, Dean of Medicine at the University of Birmingham in the UK. There is a danger therefore that Europe''s leading research nations could lose their competitive edge in medical research at a time when radical new treatments are on the horizon. “Europe''s weight in clinical research is diminishing,” commented Markus Hartmann, senior consultant at European Consulting & Contracting in Oncology (Saarbrücken, Germany), which provides advice about medical regulatory affairs. The risk of falling behind extends beyond drug-based therapies to surgery and medical devices, Hartmann added. He explained that the European Commission now considers medical devices and drugs as ‘products'' that can be sold in the internal market, and therefore require a common and harmonized regulatory framework.Hartmann, along with other researchers, traces the recent decline in European clinical trial activity back to the European Union (EU)''s Clinical Trials Directive (CTD) 2001/20, which was supposed to provide a common framework for unifying regulation within the EU by 2020. “The Clinical Trials Directive is contributing to this effect, but is not the only factor,” said Hartmann.The root cause of the problem might be growing aversity to risk—which puts more emphasis on patient protection even when this is not necessary—but the EU directive has certainly fuelled this mood. “That initial EU Directive was actually quite a sensible document, but what was crazy was the legal creep that followed,” said Stewart. “What the lawyers did was legislate for the worst possible scenario, instead of seeing the directive as a facilitating document enabling people to go and do research.”The directive actually had the opposite effect from the original intent: it led to even more regulatory fragmentation within the EU. This was first identified in a 2006 report, co-authored by Hartmann, which cited significant divergence in the national implementations of the EU directive (Hartmann & Hartmann-Vareilles, 2006). France was found to have the strictest regime, in which all trials including those involving cosmetics were rigorously supervised.The directive actually had the opposite effect from the original intent: it led to even more regulatory fragmentation within the EUThis divergence still exists. “Basically, the lack of harmonisation has not been resolved, as the Clinical Trials Directive has been transposed into national legislation in the form of laws, ordinances and rules of implementation that still differ in so many procedural and technical aspects,” said Hartmann.Moreover, although the 2001 directive underlined maintaining current levels of patient protection, Hartmann argued that it has done little if anything to improve safety. “Do not forget the TeGenero disaster with compound TGN1412, tested in spring 2006 in a Northern London hospital,” he said. “This was Europe''s largest clinical research catastrophe so far and happened in the UK, after the UK switched from a very liberal trial notification system, where phase I trials with healthy volunteers were even exempted from notification or authorisation, to the provisions laid down by the Clinical Trials Directive.”These problems have now been acknowledged by both national governments and the EU itself, according to Liselotte Højgaard, chair of the Standing Committee of the European Medical Research Councils, and a medical imaging specialist at the University of Copenhagen in Denmark. “We have had very many meetings in Brussels about the issue […] and in the last year the EU has become convinced it is a problem,” she said. As a result the directive is going to be redrafted well before it runs its full 20-year course. “We have been invited to help them draft a new directive,” said Højgaard. “That is a major achievement.”The aim is to learn from previous mistakes and frame the new document to encourage harmonization and a reduction in bureaucracy and paperwork. “We must make it easier to implement in each member state,” commented Højgaard, who added that the approval process also needs to be streamlined so that clinical trial teams do not have to repeat the same steps at different stages of the approvals process. “One of the things we are thinking about here in Denmark is whether we can make a one-stop-shop approvals process so you don''t have to go in and send an application to the medicinal agency, and also to the ethical committee, and also to clinicaltrials.gov,” said Højgaard. She hopes this new structure will be in place by the time Denmark holds the EU presidency in early 2012, and will encourage the rest of Europe to adopt a similar approach.The aim is to learn from previous mistakes and frame the new document to encourage harmonization and a reduction in bureaucracy and paperworkHartmann also acknowledges progress on the harmonization front. He cited the Voluntary Harmonisation Procedure (VHP), which was introduced in early 2009 by a network of national authorities, the Clinical Trials Facilitation Group (CTFG). It was set up precisely to coordinate implementation of the 2001/20 directive across EU member states, with little success at first. Now, the VHP allows applicants to submit protocols for trials to be conducted in many EU countries to the respective authorities, which agree on an assessment. “Then in a subsequent step, the applicant can submit the protocol to the national authorities for authorisation,” said Hartmann. “The VHP pilot aims to prevent divergent outcomes in the trial authorisation process, for example when a protocol approved in one country is blocked in another country.”These developments could eventually lead to a Europe-wide agency dedicated to clinical research regulation, along the same lines as the European Research Council for fundamental research, which Højgaard described as a great success. Such an agency would organize trials across the whole continent through a single streamlined approvals process, thereby covering a population of 500 million people.Attempts to amend the EU 2001 directive have also been welcomed by big funding bodies such as the Wellcome Trust in the UK, a charitable foundation that funds medical and clinical research globally. “We recently issued a response to a public consultation paper from the European Commission, Assessment Of The Functioning Of The “Clinical Trials Directive” 2001/20/EC, in which we highlighted areas where the Directive could be streamlined to reduce bureaucracy, while maintaining an appropriate regulatory framework,” said David Lynn, Head of Strategic Planning and Policy at the Wellcome Trust. “We would like to see a more risk-based approach to regulation of clinical trials, a rationalisation of the multiple layers of bureaucracy and the approvals process.”Bureaucracy notwithstanding, a fundamental problem is finding the right balance between risks associated with different drugs or therapies. The 2001 directive has instead led to a one-size-fits-all approach, according to Stewart. “Part of the work we''ve been doing at the level of the UK Clinical Research Consortium is to look at risk–benefit analysis, so that you have a lower level of regulation on some things and higher on others that are unproven.” If, for example, an existing drug turns out to be effective against a disease for which it was not originally developed, it would not be necessary to conduct thorough safety trials. This was the case with aspirin, initially developed as a pain killer over a century ago, which also protects against both vascular disease and bowel cancer (ATT Collaboration, 2009; Din et al, 2010). During these trials, safety was still an issue as the drug was being used in a different context, but, even so, it was clear that acute side effects were highly unlikely.Bureaucracy notwithstanding, a fundamental problem is finding the right balance between risks associated with different drugs or therapiesWhile medical regulations in Europe err on the side of safety, they do little to regulate and harmonise the reporting of results after trials have occurred. The results from many clinical trials are never published as they fall victim to reporting bias for various reasons, notably because the pharmaceutical companies providing funding have an interest in promoting results favourable to their products and suppressing negative findings. A recent study by the Institute for Quality and Efficiency in Health Care (IQWiG) in Cologne, Germany, confirmed widespread publication bias in the past, which harmed patients through under-reporting of side effects (McGauran et al, 2010).“The most prominent example of harm caused by publication bias is probably the case of Class I anti-arrhythmic drugs,” said Beate Wieseler, deputy head of IQWiG''s Drug Assessment Department. In this 1980 trial, 9 of 49 patients with suspected acute myocardial infarction who were treated with a class I anti-arrhythmic drug (lorcainide) died, compared with only one patient in the placebo group, and yet the investigators ludicrously dismissed this as chance (Cowley et al, 1993). The results of the trial were not published until 1993 and, although the development of lorcainide was discontinued for commercial reasons, the investigators concluded that as a result of this delay in publication, the continuing use of class I drugs had led to several unnecessary deaths.By the same token, ineffective drugs have sometimes gained market approval after over-reporting of their benefits, in some cases ignoring other, more negative, studies. Wieseler and colleagues found that studies reporting positive results for a particular drug were published in higher impact journals and were more likely to be picked up by other publications and the mass media.Many cases of reporting bias, especially involving suppression of negative results, occurred 10 or more years ago. According to Stewart the situation has improved, although he concedes that, almost inevitably, journals will be drawn towards positive results given the increasing competition for readers and advertisers. “Whether publication bias goes on to the same extent now is debatable,” said Stewart, pointing out that clinical trials now have to be registered in Europe and the USA so that the data is public, even if it is not published in a journal.There will inevitably be some risk of bias in research funded by pharmaceutical companies, which, after all, are in the business to make money. It is therefore important to support ‘investigator-driven'' trials that are independent of any company, and it is here that the Wellcome Trust has an important role. “The Wellcome Trust supports the proposal for Investigator Driven Clinical Trials as joint collaborations across Europe,” said Lynn. “We fund academic clinical trials, which are usually independent of drug company interests.”Independent money for academic clinical trials has indeed been more crucial during the past few years, since the EU 2001/20 directive tends to favour research funded by drug companies with the money and resources to overcome the increasingly high bureaucratic hurdles. Lynn commented that universities had not been well served by recent legislation. “Academic institutions are less-well resourced and equipped than commercial sponsors to deal with the bureaucratic burden imposed by the Directive,” he said.In some cases these burdens have caused even young scientists to give up on promising research because they cannot stomach the paperwork involved…In some cases these burdens have caused even young scientists to give up on promising research because they cannot stomach the paperwork involved, according to Højgaard. “For the first time in my life as a boss, I had the experience when I came in to a morning conference and asked one of the young consultants ‘shouldn''t we do a clinical study on this'' and he said ‘no I simply haven''t got the energy for all this paper workload''.” This experience spurred her to lobby for change. Critics such as Højgaard and others therefore hope that the redrafting of the amendment and the ensuing changes in national legislation will liberate European medical research from the regulatory shackles that have held it back.