Genetic Engineering of Algae for Enhanced Biofuel Production

There are currently intensive global research efforts aimed at increasing and modifying the accumulation of lipids, alcohols, hydrocarbons, polysaccharides, and other energy storage compounds in photosynthetic organisms, yeast, and bacteria through genetic engineering. Many improvements have been realized, including increased lipid and carbohydrate production, improved H₂ yields, and the diversion of central metabolic intermediates into fungible biofuels. Photosynthetic microorganisms are attracting considerable interest within these efforts due to their relatively high photosynthetic conversion efficiencies, diverse metabolic capabilities, superior growth rates, and ability to store or secrete energy-rich hydrocarbons. Relative to cyanobacteria, eukaryotic microalgae possess several unique metabolic attributes of relevance to biofuel production, including the accumulation of significant quantities of triacylglycerol; the synthesis of storage starch (amylopectin and amylose), which is similar to that found in higher plants; and the ability to efficiently couple photosynthetic electron transport to H₂ production. Although the application of genetic engineering to improve energy production phenotypes in eukaryotic microalgae is in its infancy, significant advances in the development of genetic manipulation tools have recently been achieved with microalgal model systems and are being used to manipulate central carbon metabolism in these organisms. It is likely that many of these advances can be extended to industrially relevant organisms. This review is focused on potential avenues of genetic engineering that may be undertaken in order to improve microalgae as a biofuel platform for the production of biohydrogen, starch-derived alcohols, diesel fuel surrogates, and/or alkanes.Interest in a variety of renewable biofuels has been rejuvenated due to the instability of petroleum fuel costs, the reality of peak oil in the near future, a reliance on unstable foreign petroleum resources, and the dangers of increasing atmospheric CO₂ levels. Photosynthetic algae, both microalgae and macroalgae (i.e., seaweeds), have been of considerable interest as a possible biofuel resource for decades (165). Several species have biomass production rates that can surpass those of terrestrial plants (41), and many eukaryotic microalgae have the ability to store significant amounts of energy-rich compounds, such as triacylglycerol (TAG) and starch, that can be utilized for the production of several distinct biofuels, including biodiesel and ethanol. It is believed that a large portion of crude oil is of microalgal origin, with diatoms being especially likely candidates, considering their lipid profiles and productivity (153). If ancient algae are responsible for creating substantial crude oil deposits, it is clear that investigation of the potential of living microalgae to produce biofuels should be a priority. Microalgae are especially attractive as a source of fuel from an environmental standpoint because they consume carbon dioxide and can be grown on marginal land, using waste or salt water (41). In addition, it may be possible to leverage the metabolic pathways of microalgae to produce a wide variety of biofuels (Fig. 1). In contrast to corn-based ethanol or soy/palm-based biodiesel, biofuels derived from microalgal feedstocks will not directly compete with the resources necessary for agricultural food production if inorganic constituents can be recycled and saltwater-based cultivation systems are developed.Open in a separate windowFig. 1.Microalgal metabolic pathways that can be leveraged for biofuel production. ER, endoplasmic reticulum.However, several technical barriers need to be overcome before microalgae can be used as an economically viable biofuel feedstock (139). These include developing low-energy methods to harvest microalgal cells, difficulties in consistently producing biomass at a large scale in highly variable outdoor conditions, the presence of invasive species in large-scale ponds, low light penetrance in dense microalgal cultures, the lack of cost-effective bioenergy carrier extraction techniques, and the potentially poor cold flow properties of most microalga-derived biodiesel. To advance the utilization of microalgae in biofuel production, it is important to engineer solutions to optimize the productivity of any microalgal cultivation system and undertake bioprospecting efforts to identify strains with as many desirable biofuel traits as possible. Over 40,000 species of algae have been described, and this is likely only a small fraction of the total number of available species (75). The U.S. Department of Energy''s Aquatic Species Program analyzed approximately 3,000 different microalgae for their potential to produce biofuels, and numerous additional species have subsequently been investigated (165). Although these efforts demonstrated that many species of microalgae have properties that are desirable for biofuel production, most have drawbacks that have prevented the emergence of an economically viable algal biofuel industry. It is postulated that a light-harvesting footprint of at least 20,000 square miles will be required to satisfy most of the current U.S. transportation fuel demand (41). Therefore, even modest improvements in photon conversion efficiencies will dramatically reduce the land area and cost required to produce biofuels. Consequently, continued bioprospecting efforts and the development and engineering of select microalgal strains are required to improve the yields of bioenergy carriers. Current commercial agriculture crops have been cultivated for thousands of years, with desired traits selected over time. It stands to reason that with microalgae, it would be beneficial to use genetic engineering in an attempt to bypass such a lengthy selection process. However, despite the recent advances in biotechnological approaches, the full potential of genetic engineering in some microalgal species, particularly diploid diatoms, can be fully realized only if conventional breeding methods become firmly established, thereby allowing useful traits or mutations to be easily combined (5, 24, 25). Since the topic of microalgal sexual breeding is beyond the scope of this review, we will instead focus on genetic engineering approaches that could be utilized in the industry''s efforts to improve microalgae as a source of biofuels.     

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.     

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!”     

Lipid metabolism and potentials of biofuel and high added-value oil production in red algae

Biomass production is currently explored in microalgae, macroalgae and land plants. Microalgal biofuel development has been performed mostly in green algae. In the Japanese tradition, macrophytic red algae such as Pyropia yezoensis and Gelidium crinale have been utilized as food and industrial materials. Researches on the utilization of unicellular red microalgae such as Cyanidioschyzon merolae and Porphyridium purpureum started only quite recently. Red algae have relatively large plastid genomes harboring more than 200 protein-coding genes that support the biosynthetic capacity of the plastid. Engineering the plastid genome is a unique potential of red microalgae. In addition, large-scale growth facilities of P. purpureum have been developed for industrial production of biofuels. C. merolae has been studied as a model alga for cell and molecular biological analyses with its completely determined genomes and transformation techniques. Its acidic and warm habitat makes it easy to grow this alga axenically in large scales. Its potential as a biofuel producer is recently documented under nitrogen-limited conditions. Metabolic pathways of the accumulation of starch and triacylglycerol and the enzymes involved therein are being elucidated. Engineering these regulatory mechanisms will open a possibility of exploiting the full capability of production of biofuel and high added-value oil. In the present review, we will describe the characteristics and potential of these algae as biotechnological seeds.     

Lipid rafts make for slippery platforms

What''s in a raft? Although cell membranes are certainly not homogeneous mixtures of lipids and proteins, almost all aspects of lipid rafts—how to define them, their size, composition, lifetime, and biological relevance—remain controversial. The answers will shape our views of signaling and of membrane dynamics.In the influential “fluid mosaic” model of Singer and Nicolson, a “mosaic” of integral transmembrane proteins floats about in a “fluid” sea of lipids (Singer and Nicolson, 1972). More recently, researchers have shifted to a view in which membrane lipids are not randomly distributed, but instead show local heterogeneity. One might imagine this as a two-dimensional projection of a lava lamp, with different types of greasy globules in constant motion, endlessly separating and rejoining into distinct but transient domains. These domains are now referred to under the general heading of lipid rafts and domains, a subset of which are the morphologically identifiable “caveolae.”The study of lipid domains has exploded since the debut of the “raft hypothesis” only about fifteen years ago. This torrent of research notwithstanding, there remains heated discussion concerning matters as fundamental as what lipid domains look like—a discussion that peaked but reached little in the way of resolution at a recent conference (Euroconference on Microdomains, Lipid Rafts, and Caveolae; Tomar, Portugal, May 17–22, 2003). Regardless of their actual form, evidence is mounting that lipid rafts are essential participants in signal transduction, membrane and protein sorting, and the pathogenesis of several human diseases.     

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.”     

When life gets physical

Does the spin of an electron allow birds to see the Earth''s magnetic field? Andrea Rinaldi investigates the influence of quantum events in the biological world.The subatomic world is nothing like the world that biologists study. Physicists have struggled for almost a century to understand the wave–particle duality of matter and energy, but many questions remain unanswered. That biological systems ultimately obey the rules of quantum mechanics might be self-evident, but the idea that those rules are the very basis of certain biological functions has needed 80 years of thought, research and development for evidence to begin to emerge (Sidebar A).

Sidebar A | Putting things in their place

Although Erwin Schrödinger (1887–1961) is often credited as the ‘father'' of quantum biology, owing to the publication of his famous 1944 book, What is Life?, the full picture is more complex. While other researchers were already moving towards these concepts in the 1920s, the German theoretical physicist Pascual Jordan (1902–1980) was actually one of the first to attempt to reconcile biological phenomena with the quantum revolution that Jordan himself, working with Max Born and Werner Heisenberg, largely ignited. “Pascual Jordan was one of many scientists at the time who were exploring biophysics in innovative ways. In some cases, his ideas have proven to be speculative or even fantastical. In others, however, his ideas have proven to be really ahead of their time,” explained Richard Beyler, a science historian at Portland State University, USA, who analysed Jordan''s contribution to the rise of quantum biology (Beyler, 1996). “I think this applies to Jordan''s work in quantum biology as well.”Beyler also remarked that some of the well-known figures of molecular biology''s past—Max Delbrück is a notable example—entered into their studies at least in part as a response or rejoinder to Jordan''s work. “Schrödinger''s book can also be read, on some level, as an indirect response to Jordan,” Beyler said.Jordan was certainly a complex personality and his case is rendered more complicated by the fact that he explicitly hitched his already speculative scientific theories to various right-wing political philosophies. “During the Nazi regime, for example, he promoted the notion that quantum biology served as evidence for the naturalness of dictatorship and the prospective death of liberal democracy,” Beyler commented. “After 1945, Jordan became a staunch Cold Warrior and saw in quantum biology a challenge to philosophical and political materialism. Needless to say, not all of his scientific colleagues appreciated these propagandistic endeavors.”Pascual Jordan [pictured above] and the dawn of quantum biology. From 1932, Jordan started to outline the new field''s background in a series of essays that were published in journals such as Naturwissenschaften. An exposition of quantum biology is also encountered in his book Die Physik und das Geheimnis des organischen Lebens, published in 1941. Photo courtesy of Luca Turin.Until very recently, it was not even possible to investigate whether quantum phenomena such as coherence and entanglement could play a significant role in the function of living organisms. As such, researchers were largely limited to computer simulations and theoretical experiments to explain their observations (see A quantum leap in biology, www.emboreports.org). Recently, however, quantum biologists have been making inroads into developing methodology to measure the degree of quantum entanglement in light-harvesting systems. Their breakthrough has turned once ephemeral theories into solid evidence, and has sparked the beginning of an entirely new discipline.How widespread is the direct relevance of quantum effects in nature is hard to say and many scientists suspect that there are only a few cases in which quantum mechanics have a crucial role. However, interest in the field is growing and researchers are looking for more examples of quantum-dependent biological systems. In a way, quantum biology can be viewed as a natural evolution of biophysics, moving from the classical to the quantum, from the atomic to the subatomic. Yet the discipline might prove to be an even more intimate and further-reaching marriage that could provide a deeper understanding of things such as protein energetics and dynamics, and all biological processes where electrons flow.Recently […] quantum biologists have been making inroads into developing methodology to measure the degree of quantum entanglement in light-harvesting systemsAmong the biological systems in which quantum effects are believed to have a crucial role is magnetoreception, although the nature of the receptors and the underlying biophysical mechanisms remain unknown. The possibility that organisms use a ferromagnetic material (magnetite) in some cases has received some confirmation, but support is growing for the explanation lying in a chemical detection mechanism with quantum mechanical properties. This explanation posits a chemical compass based on the light-triggered production of a radical pair—a pair of molecules each with an unpaired electron—the spins of which are entangled. If the products of the radical pair system are spin-dependent, then a magnetic field—like the geomagnetic one—that affects the direction of spin will alter the reaction products. The idea is that these reaction products affect the sensitivity of light sensors in the eye, thus allowing organisms to ‘see'' magnetic fields.The research comes from a team led by Thorsten Ritz at the University of California Irvine, USA, and other groups, who have suggested that the radical pair reaction takes place in the molecule cryptochrome. Cryptochromes are flavoprotein photoreceptors first identified in the model plant Arabidopsis thaliana, in which they play key roles in growth and development. More recently, cryptochromes have been found to have a role in the circadian clock of fruit flies (Ritz et al, 2010) and are known to be present in migratory birds. Intriguingly, magnetic fields have been shown to have an effect on both Arabidopsis seedlings, which respond as though they have been exposed to higher levels of blue light, and Drosophila, in which the period length of the clock is lengthened, mimicking the effect of increased blue light signal intensity on cryptochromes (Ahmad et al, 2007; Yoshii et al, 2009).“The study of quantum effects in biological systems is a rapidly broadening field of research in which intriguing phenomena are yet to be uncovered and understood”Direct evidence that cryptochrome is the avian magnetic compass is currently lacking, but the molecule does have some features that make its candidacy possible. In a recent review (Ritz et al, 2010), Ritz and colleagues discussed the mechanism by which cryptochrome might form radical pairs. They argued that “Cryptochromes are bound to a light-absorbing flavin cofactor (FAD) which can exist in three interconvertable [sic] redox forms: (FAD, FADH^•, FADH⁻),” and that the redox state of FAD is light-dependent. As such, both the oxidation and reduction of the flavin have radical species as intermediates. “Therefore both forward and reverse reactions may involve the formation of radical pairs” (Ritz et al, 2010). Although speculative, the idea is that a magnetic field could alter the spin of the free electrons in the radical pairs resulting in altered photoreceptor responses that could be perceived by the organism. “Given the relatively short time from the first suggestion of cryptochrome as a magnetoreceptor in 2000, the amount of studies from different fields supporting the photo-magnetoreceptor and cryptochrome hypotheses […] is promising,” the authors concluded. “It suggests that we may be only one step away from a true smoking gun revealing the long-sought after molecular nature of receptors underlying the 6^th sense and thus the solution of a great outstanding riddle of sensory biology.”Research into quantum effects in biology took off in 2007 with groundbreaking experiments from Graham Fleming''s group at the University of California, Berkeley, USA. Fleming''s team were able to develop tools that allowed them to excite the photosynthetic apparatus of the green sulphur bacterium Chlorobium tepidum with short laser pulses to demonstrate that wave-like energy transfer takes place through quantum coherence (Engel et al, 2007). Shortly after, Martin Plenio''s group at Ulm University in Germany and Alán Aspuru-Guzik''s team at Harvard University in the USA simultaneously provided evidence that it is a subtle interplay between quantum coherence and environmental noise that optimizes the performance of biological systems such as the photosynthetic machinery, adding further interest to the field (Plenio & Huelga, 2008; Rebentrost et al, 2009). “The recent Quantum Effects in Biological Systems (QuEBS) 2011 meeting in Ulm saw an increasing number of biological systems added to the group of biological processes in which quantum effects are suspected to play a crucial role,” commented Plenio, one of the workshop organizers; he mentioned the examples of avian magnetoreception and the role of phonon-assisted tunnelling to explain the function of the sense of smell (see below). “The study of quantum effects in biological systems is a rapidly broadening field of research in which intriguing phenomena are yet to be uncovered and understood,” he concluded.“The area of quantum effects in biology is very exciting because it is pushing the limits of quantum physics to a new scale,” Yasser Omar from the Technical University of Lisbon, Portugal commented. ”[W]e are finding that quantum coherence plays a significant role in the function of systems that we previously thought would be too large, too hot—working at physiological temperatures—and too complex to depend on quantum effects.”Another growing focus of quantum biologists is the sense of smell and odorant recognition. Mainstream researchers have always favoured a ‘lock-and-key'' mechanism to explain how organisms detect and distinguish different smells. In this case, the identification of odorant molecules relies on their specific shape to activate receptors on the surface of sensory neurons in the nasal epithelium. However, a small group of ‘heretics'' think that the smell of a molecule is actually determined by intramolecular vibrations, rather than by its shape. This, they say, explains why the shape theory has so far failed to explain why different molecules can have similar odours, while similar molecules can have dissimilar odours. It also goes some way to explaining how humans can manage with fewer than 400 smell receptors.…determining whether quantum effects have a role in odorant recognition has involved assessing the physical violations of such a mechanism […] and finding that, given certain biological parameters, there are noneA recent study in Proceedings of the National Academy of Sciences USA has now provided new grist for the mill for ‘vibrationists''. Researchers from the Biomedical Sciences Research Center “Alexander Fleming”, Vari, Greece—where the experiments were performed—and the Massachusetts Institute of Technology (MIT), USA, collaborated to replace hydrogen with deuterium in odorants such as acetophenone and 1-octanol, and asked whether Drosophila flies could distinguish the two isotopes, which are identically shaped but vibrate differently (Franco et al, 2011). Not only were the flies able to discriminate between the isotopic odorants, but when trained to discriminate against the normal or deuterated isotopes of a compound, they could also selectively avoid the corresponding isotope of a different odorant. The findings are inconsistent with a shape-only model for smell, the authors concluded, and suggest that flies can ‘smell molecular vibrations''.“The ability to detect heavy isotopes in a molecule by smell is a good test of shape and vibration theories: shape says it should be impossible, vibration says it should be doable,” explained Luca Turin from MIT, one of the study''s authors. Turin is a major proponent of the vibration theory and suggests that the transduction of molecular vibrations into receptor activation could be mediated by inelastic electron tunnelling (Fig 1; see also The scent of life, www.emboreports.org). “The results so far had been inconclusive and complicated by possible contamination of the test odorants with impurities,” Turin said. “Our work deals with impurities in a novel way, by asking flies whether the presence of deuterium isotope confers a common smell character to odorants, much in the way that the presence of -SH in a molecule makes it smell ‘sulphuraceous'', regardless of impurities. The flies'' answer seems to be ‘yes''.”Open in a separate windowFigure 1Diagram of a vibration-sensing receptor using an inelastic electron tunnelling mechanism. An odorant—here benzaldehyde—is depicted bound to a protein receptor that includes an electron donor site at the top left to which an electron—blue sphere—is bound. The electron can tunnel to an acceptor site at the bottom right while losing energy (vertical arrow) by exciting one or more vibrational modes of the benzaldehyde. When the electron reaches the acceptor, the signal is transduced via a G-protein mechanism, and the olfactory stimulus is triggered. Credit: Luca Turin.One of the study''s Greek co-authors, Efthimios Skoulakis, suggested that flies are better suited than humans at doing this experiment for a couple of reasons. “[The flies] seem to have better acuity than humans and they cannot anticipate the task they will be required to complete (as humans would), thus reducing bias in the outcome,” he said. “Drosophila does not need to detect deuterium per se to survive and be reproductively successful, so it is likely that detection of the vibrational difference between such a compound and its normal counterpart reflects a general property of olfactory systems.”The question of whether quantum mechanics really plays a non-trivial role in biology is still hotly debated by physicists and biologists alikeJennifer Brookes, a physicist at University College London, UK, explained that recent advances in determining whether quantum effects have a role in odorant recognition has involved assessing the physical violations of such a mechanism in the first instance, and finding that, given certain biological parameters, there are none. “The point being that if nature uses something like the quantized vibrations of molecules to ‘measure'' a smell then the idea is not—mathematically, physically and biologically—as eccentric as it at first seems,” she said. Moreover, there is the possibility that quantum mechanics could play a much broader role in biology than simply underpinning the sense of smell. “Odorants are not the only small molecules that interact unpredictably with large proteins; steroid hormones, anaesthetics and neurotransmitters, to name a few, are examples of ligands that interact specifically with special receptors to produce important biological processes,” Brookes wrote in a recent essay (Brookes, 2010).The question of whether quantum mechanics really plays a non-trivial role in biology is still hotly debated by physicists and biologists alike. “[A] non-trivial quantum effect in biology is one that would convince a biologist that they needed to take an advanced quantum mechanics course and learn about Hilbert space and operators etc., so that they could understand the effect,” argued theoretical quantum physicists Howard Wiseman and Jens Eisert in their contribution to the book Quantum Aspects of Life (Wiseman & Eisert, 2008). In their rational challenge to the general enthusiasm for a quantum revolution in biology, Wiseman and Eisert point out that a number of “exotic” and “implausible” quantum effects—including a quantum life principle, quantum computing in the brain, quantum computing in genetics, and quantum consciousness—have been suggested and warn researchers to be cautious of “ideas that are more appealing at first sight than they are realistic” (Wiseman & Eisert, 2008).“One could easily expect many more new exciting ideas and discoveries to emerge from the intersection of two major areas such as quantum physics and biology”Keeping this warning in mind, the view of life from a quantum perspective can still provide a deeper insight into the mechanisms that allow living organisms to thrive without succumbing to the increasing entropy of their environment. But does quantum biology have practical applications? “The investigation of the role of quantum physics in biology is fascinating because it could help explain why evolution has favoured some biological designs, as well as inspire us to develop more efficient artificial devices,” Omar said. The most often quoted examples of such devices are solar collectors that would use efficient energy transport mechanisms inspired by the quantum proficiency of natural light-harvesting systems, and quantum computing. But there is much more ahead. In 2010, the Pentagon''s cutting-edge research branch, DARPA (Defense Advanced Research Projects Agency, USA), launched a solicitation for innovative proposals in the area of quantum effects in a biological environment. “Proposed research should establish beyond any doubt that manifestly quantum effects occur in biology, and demonstrate through simulation proof-of-concept experiments that devices that exploit these effects could be developed into biomimetic sensors,” states the synopsis (DARPA, 2010). This programme will thus look explicitly at photosynthesis, magnetic field sensing and odour detection to lay the foundations for novel sensor technologies for military applications.Clearly a number of civil needs could also be fulfilled by quantum-based biosensors. Take, for example, the much sought-after ‘electronic nose'' that could replace the use of dogs to find drugs or explosives, or could assess food quality and safety. Such a device could even be used to detect cancer, as suggested by a recent publication from a Swedish team of researchers who reported that ovarian carcinomas emit a different array of volatile signals to normal tissue (Horvath et al, 2010). “Our goal is to be able to screen blood samples from apparently healthy women and so detect ovarian cancer at an early stage when it can still be cured,” said the study''s leading author György Horvath in a press release (University of Gothenburg, 2010).Despite its already long incubation time, quantum biology is still in its infancy but with an intriguing adolescence ahead. “A new wave of scientists are finding that quantum physics has the appropriate language and methods to solve many problems in biology, observing phenomena from a different point of view and developing new concepts. The next important steps are experimental verification/falsification,” Brookes said. “One could easily expect many more new exciting ideas and discoveries to emerge from the intersection of two major areas such as quantum physics and biology,” Omar concluded.     

Aiming high,but investing little

The French government has ambitious goals to make France a leading nation for synthetic biology research, but it still needs to put its money where its mouth is and provide the field with dedicated funding and other support.Synthetic biology is one of the most rapidly growing fields in the biological sciences and is attracting an increasing amount of public and private funding. France has also seen a slow but steady development of this field: the establishment of a national network of synthetic biologists in 2005, the first participation of a French team at the International Genetically Engineered Machine competition in 2007, the creation of a Master''s curriculum, an institute dedicated to synthetic and systems biology at the University of Évry-Val-d''Essonne-CNRS-Genopole in 2009–2010, and an increasing number of conferences and debates. However, scientists have driven the field with little dedicated financial support from the government.Yet the French government has a strong self-perception of its strengths and has set ambitious goals for synthetic biology. The public are told about a “new generation of products, industries and markets” that will derive from synthetic biology, and that research in the field will result in “a substantial jump for biotechnology” and an “industrial revolution”[1,2]. Indeed, France wants to compete with the USA, the UK, Germany and the rest of Europe and aims “for a world position of second or third”[1]. However, in contrast with the activities of its competitors, the French government has no specific scheme for funding or otherwise supporting synthetic biology[3]. Although we read that “France disposes of strong competences” and “all the assets needed”[2], one wonders how France will achieve its ambitious goals without dedicated budgets or detailed roadmaps to set up such institutions.In fact, France has been a straggler: whereas the UK and the USA have published several reports on synthetic biology since 2007, and have set up dedicated governing networks and research institutions, the governance of synthetic biology in France has only recently become an official matter. The National Research and Innovation Strategy (SNRI) only defined synthetic biology as a “priority” challenge in 2009 and created a working group in 2010 to assess the field''s developments, potentialities and challenges; the report was published in 2011[1].At the same time, the French Parliamentary Office for the Evaluation of Scientific and Technological Choices (OPECST) began a review of the field “to establish a worldwide state of the art and the position of our country in terms of training, research and technology transfer”. Its 2012 report entitled The Challenges of Synthetic Biology[2] assessed the main ethical, legal, economic and social challenges of the field. It made several recommendations for a “controlled” and “transparent” development of synthetic biology. This is not a surprise given that the development of genetically modified organisms and nuclear power in France has been heavily criticized for lack of transparency, and that the government prefers to avoid similar future controversies. Indeed, the French government seems more cautious today: making efforts to assess potential dangers and public opinion before actually supporting the science itself.Both reports stress the necessity of a “real” and “transparent” dialogue between science and society and call for “serene […] peaceful and constructive” public discussion. The proposed strategy has three aims: to establish an observatory, to create a permanent forum for discussion and to broaden the debate to include citizens[4]. An Observatory for Synthetic Biology was set up in January 2012 to collect information, mobilize actors, follow debates, analyse the various positions and organize a public forum. Let us hope that this observatory—unlike so many other structures—will have a tangible and durable influence on policy-making, public opinion and scientific practice.Many structural and organizational challenges persist, as neither the National Agency for Research nor the National Centre for Scientific Research have defined the field as a funding priority and public–private partnerships are rare in France. Moreover, strict boundaries between academic disciplines impede interdisciplinary work, and synthetic biology is often included in larger research programmes rather than supported as a research field in itself. Although both the SNRI and the OPECST reports make recommendations for future developments—including setting up funding policies and platforms—it is not clear whether these will materialize, or when, where and what size of investments will be made.France has ambitious goals for synthetic biology, but it remains to be seen whether the government is willing to put ‘meat to the bones'' in terms of financial and institutional support. If not, these goals might come to be seen as unrealistic and downgraded or they will be replaced with another vision that sees synthetic biology as something that only needs discussion and deliberation but no further investment. One thing is already certain: the future development of synthetic biology in France is a political issue.     

Genomes, race and health. Racial profiling in medicine might just be a stepping stone towards personalized health care

Considering a patient''s ethnic background can make some diagnoses easier. Yet, ‘racial profiling'' is a highly controversial concept and might soon be replaced by the advent of individualized medicine.In 2005, the US Food and Drug Administration (FDA; Bethesda, MD, USA) approved BiDil—a combination of vasodilators to treat heart failure—and hailed it as the first drug to specifically treat an ethnic group. “Approval of a drug to treat severe heart failure in self-identified black population is a striking example of how a treatment can benefit some patients even if it does not help all patients,” announced Robert Temple, the FDA''s Director of Medical Policy. “The information presented to the FDA clearly showed that blacks suffering from heart failure will now have an additional safe and effective option for treating their condition” (Temple & Stockbridge, 2007). Even the National Medical Association—the African-American version of the American Medical Association—advocated the drug, which was developed by NitroMed, Inc. (Lexington, MA, USA). A new era in medicine based on racial profiling seemed to be in the offing.By January 2008, however, the ‘breakthrough'' had gone bust. NitroMed shut down its promotional campaign for BiDil—a combination of the vasodilators isosorbide dinitrate, which affects arteries and veins, and hydralazine hydrochloride, which predominantly affects arteries. In 2009, it sold its BiDil interests and was itself acquired by another pharmaceutical company.In the meantime, critics had largely discredited the efforts of NitroMed, thereby striking a blow against the drug if not the concept of racial profiling or race-based medicine. Jonathan Kahn, a historian and law professor at Hamline University (St Paul, MN, USA), described the BiDil strategy as “a leap to genetics.” He demonstrated that NitroMed, motivated to extend its US patent scheduled to expire in 2007, purported to discover an advantage for a subpopulation of self-identified black people (Kahn, 2009). He noted that NitroMed conducted a race-specific trial to gain FDA approval, but, as there were no comparisons with other populations, it never had conclusive data to show that BiDil worked in black people differently from anyone else.“If you want to understand heart failure, you look at heart failure, and if you want to understand racial disparities in conditions such as heart failure or hypertension, there is much to look at that has nothing to do with genetics,” Kahn said, adding “that jumping to race as a genetic construct is premature at best and reckless generally in practice.” The USA, he explained, has a century-old tradition of marketing to racial and ethnic groups. “BiDil brought to the fore the notion that you can have ethnic markets not only in things like cigarettes and food, but also in pharmaceuticals,” Kahn commented.“BiDil brought to the fore the notion that you can have ethnic markets not only in things like cigarettes and food, but also in pharmaceuticals”However, despite BiDil''s failure, the search for race-based therapies and diagnostics is not over. “What I have found is an increasing, almost exponential, rise in the use of racial and ethnic categories in biotechnology-related patents,” Kahn said. “A lot of these products are still in the pipeline. They''re still patent applications, they''re not out on the market yet so it''s hard to know how they''ll play out.”The growing knowledge of the human genome is also providing new opportunities to market medical products aimed at specific ethnic groups. The first bumpy steps were taken with screening for genetic risk factors for breast cancers. Myriad Genetics (Salt Lake City, UT, USA) holds broad patents in the USA for breast-cancer screening tests that are based on mutations of the BRCA1 and BRCA2 genes, but it faced challenges in Europe, where critics raised concerns about the high costs of screening.The growing knowledge of the human genome is also providing new opportunities to market medical products aimed at specific ethnic groupsThe European Patent Office initially granted Myriad patents for the BRCA1 and BRCA2-based tests in 2001, after years of debate. But it revoked the patent on BRCA1 in 2005, which was again reversed in 2009. In 2005 Myriad decided to narrow the scope of BRCA2 testing on the basis of ethnicity. The company won a patent to predict breast-cancer risk in Ashkenazi Jewish women on the basis of BRCA2 mutations, which occur in one in 100 of these women. Physicians offering the test are supposed to ask their patients whether they are in this ethnic group, and then pay a fee to Myriad.Kahn said Myriad took this approach to package the test differently in order to protect its financial interests. However, he commented, the idea of ethnic profiling by asking women whether they identify themselves as Ashkenazi Jewish and then paying extra for an ‘ethnic'' medical test did not work in Europe. “It''s ridiculous,” Kahn commented.After the preliminary sequence of the human genome was published a decade ago, experts noted that humans were almost the same genetically, implying that race was irrelevant. In fact, the validity of race as a concept in science—let alone the use of the word—has been hotly debated. “Race, inasmuch as the concept ought to be used at all, is a social concept, not a biological one. And using it as though it were a biological one is as a much an ethical problem as a scientific problem,” commented Samia Hurst, a physician and bioethicist at Geneva University Medical School in Switzerland.​Switzerland.Open in a separate window© Monalyn Gracia/CorbisCiting a popular slogan: “There is no gene for race,” she noted, “there doesn''t seem to be a single cluster of genes that fits with identification within an ethnic group, let alone with disease risks as well. We''re also in an increasingly mixed world where many people—and I count myself among them—just don''t know what to check on the box. If you start counting up your grandparents and end up with four different ethnic groups, what are you going to do? So there are an increasing number of people who just don''t fit into those categories at all.”Still, some dismiss criticism of racial profiling as political correctness that could potentially prevent patients from receiving proper care. Sally Satel, a psychiatrist in Washington, DC, USA, does not shy away from describing herself as a racially profiling physician and argues that it is good medicine. A commentator and resident scholar at the nonpartisan conservative think tank, the American Enterprise Institute (Washington, DC, USA), Satel wrote the book PC, M.D.: How Political Correctness is Corrupting Medicine. “In practicing medicine, I am not color blind. I take note of my patient''s race. So do many of my colleagues,” she wrote in a New York Times article entitled “I am a racially profiling doctor” (Satel, 2002).…some dismiss criticism of racial profiling as political correctness that could potentially prevent patients from receiving proper careSatel noted in an interview that it is an undeniable fact that black people tend to have more renal disease, Native Americans have more diabetes and white people have more cystic fibrosis. She said these differences can help doctors to decide which drugs to prescribe at which dose and could potentially lead researchers to discover new therapies on the basis of race.Satel added that the mention of race and medicine makes many people nervous. “You can dispel that worry by taking pains to specify biological lineage. Simply put, members of a group have more genes in common than members of the population at large. Some day geneticists hope to be able to conduct genomic profiles of each individual, making group identity irrelevant, but until then, race-based therapeutics has its virtues,” she said. “Denying the relationship between race and medicine flies in the face of clinical reality, and pretending that we are all at equal risk for health problems carries its own dangers.”However, Hurst contended that this approach may be good epidemiology, rather than racial profiling. Physicians therefore need to be cautious about using skin colour, genomic data and epidemiological data in decision making. “If African Americans are at a higher risk for hypertension, are you not going to check for hypertension in white people? You need to check in everyone in any case,” she commented.Hurst said European physicians, similarly to their American colleagues, deal with race and racial profiling, albeit in a different way. “The way in which we struggle with it is strongly determined by the history behind what could be called the biases that we have. If you have been a colonial power, if the past is slavery or if the past or present is immigration, it does change some things,” she said. “On the other hand, you always have the difficulty of doing fair and good medicine in a social situation that has a kind of ‘them and us'' structure. Because you''re not supposed to do medicine in a ‘them and us'' structure, you''re supposed to treat everyone according to their medical needs and not according to whether they''re part of ‘your tribe'' or ‘another tribe''.”Indeed, social factors largely determine one''s health, rather than ethnic or genetic factors. August A. White III, an African-American orthopaedic surgeon at Harvard Medical School (Boston, MA, USA) and author of the book Seeing Patients: Unconscious Bias In Health Care, noted that race is linked to disparities in health care in the USA. A similar point can be made in Europe where, for example, Romani people face discrimination in several countries.White said that although genetic research shows that race is not a scientific concept, the way people are labelled in society and how they are treated needs to be taken into account. “It''d be wonderful at some point if we can pop one''s key genetic information into a computer and get a printout of which medications are best of them and which doses are best for them,” he commented. “In the meantime though, I advocate careful operational attempts to treat everyone as human beings and to value everyone''s life, not devalue old people, or devalue women, or devalue different religious faiths, etc.”Notwithstanding the scientific denunciation, a major obstacle for the concept of racial profiling has been the fact that the word ‘race'' itself is politically loaded, as a result of, among other things, the baggage of eugenics and Nazi racism and the legacies of slavery and colonialism. Richard Tutton, a sociologist at Lancaster University in the UK, said that British scientists he interviewed for a Wellcome Trust project a few years ago prefer the term ethnicity to race. “Race is used in a legal sense in relation to inequality, but certainly otherwise, ethnicity is the preferred term, which obviously is different to the US” he said. “I remember having conversations with German academics and obviously in Germany you couldn''t use the R-word.”Jan Helge Solbakk, a physician, theologian and medical ethicist at the University of Oslo in Norway, said the use of the term race in Europe is a non-starter because it makes it impossible for the public and policy-makers to communicate. “I think in Europe it would be politically impossible to launch a project targeting racial differences on the genetic level. The challenge is to find not just a more politically correct concept, but a genetically more accurate concept and to pursue such research questions,” he said. According to Kahn, researchers therefore tend to refer to ethnicity rather than race: “They''re talking about European, Asian and African, but they''re referring to it as ethnicity instead of race because they think somehow that''s more palatable.”Regardless, race-based medicine might just be a stepping stone towards more refined and accurate methods, with the advent of personalized medicine based on genomics, according to Leroy Hood, whose work has helped to develop tools to analyse the human genome. The focus of his company—the Institute for Systems Biology (Seattle, WA, USA)—is to identify genetic variants that can inform and help patients to pioneer individualized health care.“Race as a concept is disappearing with interbreeding,” Hood said. “Race distinction is going to slowly fade away. We can use it now because we have signposts for race, which are colour, fairness, kinkiness of hair, but compared to a conglomeration of things that define a race, those are very few features. The race-defining features are going to be segregating away from one another more and more as the population becomes racially heterogeneous, so I think it''s going to become a moot point.”Hood instead advocates “4P” health care—“Predictive, Personalized, Preventive and Participatory.” “My overall feeling about the race-based correlations is that it is far more important to think about the individual and their individual unique spectra of health and wellness,” he explained. “I think we are not going to deal in the future with racial or ethnic populations, rather medicine of the future is going to be focused entirely on the individual.”Yet, Arthur Caplan, Director of the Center for Bioethics at the University of Pennsylvania (Philadelphia, PA, USA), is skeptical about the prospects for both race-based and personalized medicine. “Race-based medicine will play a minor role over the next few years in health care because race is a minor factor in health,” he said. “It''s not like we have a group of people who keel over dead at 40 who are in the same ethnic group.”Caplan also argued that establishing personalized genomic medicine in a decade is a pipe dream. “The reason I say that is it''s not just the science,” he explained. “You have to redo the whole health-care system to make that possible. You have to find manufacturers who can figure out how to profit from personalized medicine who are both in Europe and the United States. You have to have doctors that know how to prescribe them. It''s a big, big revamping. That''s not going to happen in 10 years.”Hood, however, is more optimistic and plans to advance the concept with pilot projects; he believes that Europe might be the better testing ground. “I think the European systems are much more efficient for pioneering personalized medicine than the United States because the US health-care system is utterly chaotic. We have every combination of every kind of health care and health delivery. We have no common shared vision,” he said. “In the end we may well go to Europe to persuade a country to really undertake this. The possibility of facilitating a revolution in health care is greater in Europe than in the United States.”     

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).     

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.     

Algal biofuels

The world is facing energy crisis and environmental issues due to the depletion of fossil fuels and increasing CO₂ concentration in the atmosphere. Growing microalgae can contribute to practical solutions for these global problems because they can harvest solar energy and capture CO₂ by converting it into biofuel using photosynthesis. Microalgae are robust organisms capable of rapid growth under a variety of conditions including in open ponds or closed photobioreactors. Their reduced biomass compounds can be used as the feedstock for mass production of a variety of biofuels. As another advantage, their ability to accumulate or secrete biofuels can be controlled by changing their growth conditions or metabolic engineering. This review is aimed to highlight different forms of biofuels produced by microalgae and the approaches taken to improve their biofuel productivity. The costs for industrial-scale production of algal biofuels in open ponds or closed photobioreactors are analyzed. Different strategies for photoproduction of hydrogen by the hydrogenase enzyme of green algae are discussed. Algae are also good sources of biodiesel since some species can make large quantities of lipids as their biomass. The lipid contents for some of the best oil-producing strains of algae in optimized growth conditions are reviewed. The potential of microalgae for producing petroleum related chemicals or ready-make fuels such as bioethanol, triterpenic hydrocarbons, isobutyraldehyde, isobutanol, and isoprene from their biomass are also presented.     

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.