Biopedagogy

The world is changing fast and teachers are struggling to familiarize children and young people with the norms and values of society. Biopedagogy—the biology behind pedagogy approaches—might provide some insights and guidance.Humans are the only animals that are subject to cumulative cultural evolution. Biological evolution would be too slow to allow for the invention and continuous improvement of complex artefacts, both material and abstract. One of the mechanisms that makes it possible for humans to pass on social, cultural and technological advances over generations is teaching. Some scholars believe that teaching itself might be an exclusive human trait; others argue that teaching is more prevalent in nature, if it is defined as cooperative behaviour that promotes learning, independent of the mental states and cognitive intentions [1].The science, art and profession of teaching is known as ‘pedagogy'' and its biological basis might well be dubbed ‘biopedagogy''. Pedagogy embeds the learner into a particular culture by exposing the developing mind to cultural values and practices. Human teaching represents two disparate but closely linked activities—education and instruction. To ‘educate'' means to unfold the latent potential of the learner and to cultivate human nature by promoting impulses that conform to a culture and inhibiting those that contradict it. ‘Instruction'' is the provision of knowledge and skills.According to the ethologist Konrad Lorenz, human nature, which is a result of biological evolution, functions as the “inborn schoolmaster” [2] by both allowing and constraining the learning of all the products of cultural evolution. Lorenz received the Nobel Prize for his discovery of ‘imprinting'': the irreversible, life-long fixation of a response to a situation encountered by an organism during development. Imprinting is not specific to humans, but humans have evolved, along with the formation of the central nervous system, more sophisticated mental organs that we call the social brain, the group mind and the darwinian soul. As the physical development of an organism proceeds in stages, so does the mental development. Some of these stages represent critical periods that are particularly sensitive to imprinting. The rapid acquisition of the mother tongue for instance apparently represents such a specific period in human development.According to Lorenz, during and shortly after puberty, humans are prone to a specific kind of imprinting from a culture and its abstract norms and values, driven by a need to become members of a reference group striving for a common ideal [2]. We might call this developmental stage of humans the ‘second (or ideational) imprinting''. This imprinting presupposes a stable society with firmly established norms and values and, in turn, it serves to ensure that stability. The British neuroscientist Sarah-Jayne Blakemore [3] corroborated that the human brain undergoes protracted development and demonstrated that adolescence, in particular, represents a period during which the neuronal basis of the social brain reorganizes. This provides opportunities, but also imposes great responsibility to high-school and university teachers.Jan Amos Comenius, a seventeenth century Moravian educator, already suggested that the mastery of teaching consists in recognizing stages of mental development in which a student is prepared and eager to learn stage-specific knowledge spontaneously. In his view, a teacher is more similar to a gardener, who gives plants care and nutrients to allow them to develop, grow and flourish. Comenius also anticipated the crucial role of positive emotions in pedagogy. His commandment Scola ludus—The School of Play—expresses the fact that teaching and learning can, and should be, associated with pleasure and joy by both teachers and students.Human nature evolved during the Pleistocene about 1.8 million to 10,000 years ago to cope with a hunter–gatherer lifestyle. Yet, modern humans live in and adapt to vastly different environments created by cultural evolution. Apparently, the human genetic outfit is highly versatile and encompasses abstract ‘cultural loci''. Such a cultural locus is an ‘empty slot'' that functions only when it is filled with a meme from the cultural environment; memes would be akin to ‘alleles'' that are specific to a particular cultural locus. This cross-talk of biology and culture makes humans symbolic animals—our social brain allows us to behave altruistically towards ‘symbolic kin'' with whom we share no genetic relationship; and our group mind embraces not only our relatives and friends, but also our tribe or nation and possibly humanity as a whole. Education, and in particular imprinting, essentially determines the extent, quality and scope of this deployment.A developing child has to pass all crucial periods of learning successfully to become a mature human—and humane—being. As Lorenz noted, once a sensitive period has elapsed and the opportunity to learn has been missed, the ability to catch up is considerably reduced or irreversibly lost. We live in a time when cultural values and norms are rapidly changing, often within less than a generation. The ideational imprinting of developing adolescents becomes a problem when the traditional role of family and school is displaced by new social forces such as the internet, Facebook, Twitter and the blogosphere. How to preclude that young people do not develop as persons with stunted social brains, with narrow group minds attuned to fleeting reference groups and with fragmented darwinian souls, and how to promote the development of strong personalities is a challenge for the education of the twenty-first century.     

Motivated research

While Europe is locked in the debate about basic versus applied research, Louis Pasteur solved the problem more than 100 years ago. Antoine Danchin comments on Pasteur''s notion of ‘motivated research'' and how it leads both to new discoveries and to new applications.Three years ago, a senior politician attended his country''s Annual Congress for the Advancement of Science to give the introductory lecture. He asked the attending scientists to make science and research more attractive to young students and the general public, and asked his countrymen to support scientists to address the urgent challenges of global climate change, energy needs and dwindling water resources. It was neither a European nor a US politician, but the Indian Prime Minister Manmohan Singh who made this speech about the relationship between research and its practical applications. This is such an important topic that one might think it deserves appropriate attention in Europe, yet we fail to address it properly. Instead, we just discuss how science should serve society or contribute to the ‘knowledge-based economy'', or how ‘basic'' or ‘fundamental'' research is opposed to ‘applied'' or ‘industrial'' research and how funding for ‘big science'' comes at the expense of ‘little academic'' research.This dichotomy between the research to generate knowledge and the application of that knowledge to benefit humankind seems to be a recent development. In fact, more than 100 years ago Louis Pasteur avoided this debate altogether: one of his major, yet forgotten, contributions to science was the insight that research and its applications are not opposed, but orthogonal to each other (Stokes, 1997). If Niels Bohr ‘invented'' basic academic research—which was nevertheless the basis for many technological inventions and industrial applications—Pasteur developed what we might call ‘motivated'' research.How is research motivated and by what? By definition, scientists are citizens and members of the general public and, like the public, they are motivated by two forces: on the one hand, in Rudyard Kipling''s words, “man''s insatiable curiosity”; on the other hand, a desire for maintaining and improving their well-being. These are not contradictory to one another; curiosity nourishes dreams of a brighter future and leads to discoveries that contribute to well-being.Pasteur understood that it is essential to take account of society''s demands and desires; that science must be motivated by what people want. Still, there are severe misgivings about the nature of research. These stem from the mistaken but popular assumption that the scientists'' main task is to find solutions to current problems or to fulfil our desires. Problems and desires, however, are not enough, because finding solutions also requires creativity and discovery, which, by their very nature, are unpredictable. Often we do not even know what we need or desire and it is only through curiosity and more knowledge that we find new ways to improve our well-being. Motivation by itself is, therefore, not enough to lead to discovery. Motivation simply helps us choose between many different goals and an infinite number of paths to gain novel knowledge. Subsequently, each path, once chosen, must be explored using the scientific method, which is the only way to new discoveries.Motivation helps us to ask relevant questions. For example, why do wine and beer go sour without any apparent reason? Pasteur set out to design experiments that showed that fermentation is caused by microorganisms. A few years later, silkworms were suddenly dying of a terrible disease in the silk factories of southern France. The French government called on Pasteur for help, who eventually found that a parasite had infected silkworm eggs and proposed solutions to eradicate the disease. The original question therefore led to germ theory and bacteriology, helped to develop solutions to infectious diseases, and eventually created the whole field of microbiology.Motivation leads to conceptual and experimental research, which generates discoveries and new technologies. Discoveries, in turn, are the basic resource for the creation of general knowledge and the development of new products, services and other goods that fulfil public demands and generate jobs. The study of the ‘diseases'' of beer and wine also led to the development of fermentation processes that are still in use today. The same motivation that drove Pasteur in the nineteenth century now enables us to tackle current problems, such as pollution, by studying microbial communities that make compost or thrive in garbage dumps. Motivated research therefore reconciles our curiosity with the creation of knowledge and enables us to address pressing needs for humanity.Because it is strongly inspired by—even rooted in—society''s demands and desires, motivated research also raises accompanying ethical, legal, social and safety issues that should be compelling for all research. As mentioned above, scientists are members of the public who share the same concerns and demands as their fellow citizens and therefore participate with a general, public intelligence that, too often, is absent from academic research. This absence of ‘common sense'' or societal expectations generates the misunderstandings concerning research in biology and the development of biotechnology. These misconceptions—whether about the purported risks of genetically modified organisms or the exaggerated expectations for cancer therapies—can create real suffering in society and inefficient allocation of limited resources. It is therefore advisable for researchers to listen more to the public at large in order to find the motivation for their work.     

The A to T of historical evidence

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

To protect and save. A new chapter opens on biodiversity conservation

A more complete catalogue of the Earth''s fauna and flora and a more holistic view of man-made environmental problems could help to slow the rate of biodiversity loss.In the wake of the admission from the United Nations (UN) that, to date, efforts have failed to even slow down the rate of extinction across almost all plant and animal taxa (CBD, 2010), the fight to reverse the human-induced loss of biodiversity is entering a new chapter. The failure to achieve the targets set in 2002 for reducing decline has led to a revised strategy from the Campaign for Biodiversity (CBD). This new approach recognizes that species conservation cannot be treated in isolation from other issues facing humans, including climate change, water scarcity, poverty, agricultural development and global conflict. It also acknowledges that declining biodiversity cannot be tackled properly without a more accurate inventory of the species in existence today. Thus, a large part of the strategy to combat species decline focuses on building an exhaustive catalogue of life.The Global Strategy for Plant Conservation includes such a plan. The intention is to compile an online flora of known plants by 2020, which should enable comprehensive conservation efforts to gather steam. Peter Wyse Jackson, president of the Missouri Botanical Garden in the USA, said that around 25% of the estimated 400,000 plant species in the world, are thought to be threatened. He said that around 850 botanical gardens have, between them, collected around 100,000 species, but only a quarter of these are from the threatened group. “World Flora online will then be an essential baseline to determine the status of individual plant species and threats to them,” Jackson explained. “By 2020 it is proposed that at least 75% of known threatened plants should be conserved both in the wild and in existing collections.”…an online flora of known plants […] should enable comprehensive conservation efforts to gather steamMissouri Botanical Gardens will have an important role in the project and Jackson commented that the first step of the plan has already been achieved: the establishment of an online checklist of flora that is needed to build a comprehensive database of the plant species in the world.Yet, some other plans to halt species decline have drawn criticism. “In my opinion, whilst such international targets are useful to motivate individuals, states and wider society to do conservation, they are not necessarily realistic because they are often ‘pulled out of the hat'' with very little science behind them,” commented Shonil Bhagwat, senior research fellow at the School of Geography and the Environment at Oxford University.The revised CBD plan specifies measures for reversing the decline in biodiversity. One target is to enlarge protected areas for wildlife, within which activities such as logging are prohibited. Ecological corridors could then connect these areas to allow migration and create a network of ‘safe'' places for wildlife.Such a corridor is being created between two parts of the Brazilian Atlantic rainforest—the Pau Brasil National Park and the Monte Pascoal National Park—both of which are already protected. “Well-managed protected areas keep away biodiversity threats, such as deforestation, invasive species, hunting and poaching,” explained Arnd Alexander Rose, marketing manager for Brazil at The Nature Conservancy, a conservation organization that operates on all continents. “We think that the connectivity between the national parks is essential for the long-term permanence of local species, especially fauna,” Rose said.Worldwide, only around 6% of coastlines are within protected areas, but around 12% of the total land area is protected—a figure that is perhaps higher than many would expect, reflecting the large size of many national parks and other designated wildlife zones. Nevertheless, the coverage of different habitats varies greatly: “Only 5% of the world''s temperate needle-leaf forests and woodlands, 4.4% of temperate grasslands and 2.2% of lake systems are protected” (CBD, 2010). The aim of the CBD is to increase the total area of protected land to 17% by 2020, and also to expand the protected coastal zones, as well as extending the area of protected oceans to 10%.Things at sea, however, are different; both in terms of biodiversity and protection. The biggest threat to many marine species is not direct human activity—poaching or habitat encroachment, for example—but the impact of increased ocean acidity due to rising atmospheric carbon dioxide levels. Halting or reversing this increase will therefore contribute to the marine conservation effort and biodiversity in the long term.However, the first task is to establish the extent of marine biodiversity, particularly in terms of invertebrate animals, which are not well catalogued. Ian Poiner is CEO of the Australian Institute of Marine Science and chair of the steering committee for the first Census of Marine Life (Census of Marine Life, 2010), which has revealed the enormity of our remaining uncertainty. “So far 250,000 species [of invertebrates] have been formally described, but at least another 750,000 remain to be discovered, and I think it could be as many as 10 million,” Poiner said. As evidence for this uncertainty he points to the continuing high rate of discovery of new species around coral reefs, where each organism also tends to come with a new parasite. The situation is compounded by the problem of how to define diversity among prokaryotes.“…250,000 species [of invertebrates] have been formally described, but at least another 750,000 remain to be discovered…”Even if the number of non-vertebrate marine species remaining to be discovered turns out to be at the low end of estimates, Poiner points out that the abundance and diversity of life in the oceans will still be far greater than was expected before the census. For fish—a group that has been more extensively analysed than invertebrates—Poiner notes that there are several thousand species yet to be discovered, in addition to the 25,000 or more known species.The levels of diversity are perhaps most surprising for microorganisms. It was expected that these organisms would be present in astronomically large numbers—they are thought to account for 50–90% of the biomass in the oceans, as measured by total amount of carbon—but the high degree of genetic divergence found within even relatively small areas was unexpected. “We found there are about 38,000 kinds of bacteria in a litre of sea water,” Poiner said. “We also found that rarity is common, especially for microbes. If you take two separate litre samples of sea water just 10 or 20 kilometres apart, only a small percentage of the 38,000 bacteria types in each one are of the same kind. The challenge now is to find out why most are so rare.”This mystery is confounded by another result of the census: there is a much greater degree of connectedness than had been expected. Many fish, and even smaller invertebrate species, travel huge distances and navigate with great accuracy, rather like migratory birds. “Pacific white sharks will travel long distances and come back to within 50 metres from where they started,” Poiner said, by way of example.The behaviour of the sharks was discovered by using new tags, measuring just a few centimetres across, that can be attached to the heads of any large creatures to track their location and measure temperature, conductivity—and thereby salinity—and depth. For smaller creatures, such as baby salmon, a different technology is used that involves the attachment of passive acoustic sensors to their bodies. These trigger a signal when the fish swim through arrays of acoustic receivers that are installed in shallower waters at locations throughout the oceans.Although tagging and acoustic monitoring are providing new information about the movements and interactions of many species throughout the oceans, the huge task remains of identifying and cataloguing those species. For this, the quickly maturing technique of DNA barcoding has been useful and provides a relatively inexpensive and convenient way of assessing whether a specimen belongs to a new species or not. The method uses a short DNA sequence in the mitochondrial gene for cytochrome c oxidase subunit 1 (CO1)—around 600 base pairs in most species—which differs little within species but significantly between them (Kress & Erickson, 2008).The Marine Census programme involves several barcoding centres that have determined barcodes for more than 2,000 of the 7,000 known species of holozooplankton, for example (Census of Marine Zooplankton: http://www.cmarz.org). Holozooplankton are small, completely planktonic invertebrates—which spend their lives floating or swimming in open water—and are a particularly sensitive marker of environmental changes such as ocean warming or acidification.DNA barcoding can also be applied to prokaryotes, although it requires alternative sequences owing to the lack of mitochondria. In addition, horizontal gene transfer and uncertainty about how to define prokaryotic species complicate the task of cataloguing them. Nevertheless, by targeting a suitable core subset of a few genes, bacteria and archaea can be identified quite accurately, and barcoding can increase our knowledge and understanding of their behaviour and evolution.Such techniques could be applied to the identification of marine prokaryotic species, but Poiner argues that they need further refinement and will probably need to be combined with analytical methods that help estimate the total diversity, given that it is impossible to identify every single species at present. Indeed, the task of assessing the diversity of even land-based microorganisms is difficult, but such cataloguing is a prerequisite for accurate assessment of their response to environmental change.“There is a general rule that the smaller things are the less we know about them,” commented Stephen Blackmore, Regius Keeper of the Royal Botanical Gardens in Edinburgh, UK, a leading centre for conservation research. “I think it is very difficult or too early to say how biodiversity at the microscopic level is being impacted. Some of the newer approaches using DNA diversity to see, for example, what microorganisms are present in soil, will be important.”In the immediate future, advanced DNA analysis techniques have a more urgent application: the identification of genetic diversity within eukaryotic species. This is important because it determines the ability of populations to cope with rapid change: a species with greater genetic diversity is more likely to have individuals with phenotypes capable of surviving changes in habitat, temperature or nutrient availability. Genetic evidence will help to determine the secret of success for many invasive species of plants and animals, as they have already adapted to human influence.“A major emerging theme is to look at the genetic diversity present in wild plant populations and to try to correlate this with identifying the populations that are best suited for coping with climate change,” Blackmore said. “But it''s a very new field and so far not much is being funded. Meanwhile, the immediate prospect is that plants will continue slipping away more or less un-noticed. Even where the landscape appears green there is generally a steady erosion of plant biodiversity going, on driven by the shrinking of natural habitats, the encroachment of invasive species, climate change and land management practices.”Yet Blackmore is optimistic that knowledge of how to preserve biodiversity is increasing, even for less adaptable species. “We know how to, for example, grow food crops in ways that are more beneficial to biodiversity, but the desire for the cheapest food means that uptake is too limited. We know how to do most of the things needed to protect biodiversity. Unfortunately they are not being done.”There is hope, though, that increased understanding of biodiversity as a single, interconnected problem—rather than a series of unrelated hot spots and particular species—will lead to more coherent strategies for arresting global decline. The fate of flowering plants, for example, is intimately tied to their pollinators and seed dispersers. Most land animals in turn depend directly or indirectly on plants. “Since plants are the base of the food chain in all terrestrial environments, the threats to animals are increasing even more rapidly than those to the plants they depend upon,” Blackmore noted. “It is still the case, however, that most conservation action is framed in terms of charismatic animals—such as tigers, whales, polar bears and pandas—rather than on the continuation of the kinds of place they require to live in.”Due to human nature, this ‘cute'' framing of the problem is perhaps inevitable. However, if it creates a groundswell of public concern leading to voluntary involvement and donation towards biodiversity conservation, then all species might benefit in the end. After all, animals and plants do not respect arbitrary human boundaries, so an ecological corridor and protected habitat created for tigers will also benefit other, less ‘cuddly'' species.     

Funding in the firing line

With large charities such as the Wellcome Trust or the Gates Foundation committed to funding research, is there a risk that politicians could cut public funding for science?Towards the end of 2010, with the British economy reeling from the combined effects of the global recession, the burst bubble of property speculation and a banking crisis, the country came close to cutting its national science and research budget by up to 25%. UK Business Secretary Vince Cable argued, “there is no justification for taxpayers'' money being used to support research which is neither commercially useful nor theoretically outstanding” (BBC, 2010). The outcry from UK scientists was both passionate and reasoned until, in the end, the British budget slashers blinked and the UK government backed down. The Chancellor of the Exchequer, George Osborne, announced in October that the government would freeze science and research funding at £4.6 billion per annum for four years, although even this represents about a 10% cut in real terms, because of inflation.“there is no justification for taxpayers'' money being used to support research which is neither commercially useful nor theoretically outstanding”There has been a collective sigh of relief. Sir John Savill, Chief Executive of the Medical Research Council (UK), said: “The worst projections for cuts to the science budget have not been realised. It''s clear that the government has listened to and acted on the evidence showing investment in science is vital to securing a healthy, sustainable and prosperous future.”Yet Britain is unusual compared with its counterparts elsewhere in the European Union (EU) and the USA, because private charities, such as the Wellcome Trust (London, UK) and Cancer Research UK (London, UK), already have budgets that rival those of their government counterparts. It was this fact, coupled with UK Prime Minister David Cameron''s idea of the ‘big society''—a vision of smaller government, increased government–private partnerships and a bigger role for non-profit organizations, such as single-disease-focused charities—that led the British government to contemplate reducing its contribution to research, relying on the private sector to pick up the slack.Jonathan Grant, president of RAND Europe (London, UK)—a not-for-profit research institute that advises on policy and decision-making—commented: “There was a strong backlash and [the UK Government] pulled back from that position [to cut funding]. But that''s the first time I''ve really ever seen it floated as a political idea; that government doesn''t need to fund cancer research because we''ve got all these not-for-profits funding it.”“…that''s the first time I''ve really ever seen it floated as a political idea; that government doesn''t need to fund cancer research because we''ve got all these not-for-profits funding it”But the UK was not alone in mooting the idea that research budgets might have to suffer under the financial crisis. Some had worried that declining government funding of research would spread across the developed world, although the worst of these fears have not been realized.Peter Gruss, President of the Max Planck Society (Munich, Germany), explained that his organization receives 85% of its more-than €1.5 billion budget from the public purses of the German federal government, German state ministries and the EU, and that not all governments have backed away from their commitment to research. In fact, during the crisis, the German and US governments boosted their funding of research with the goal of helping the economic recovery. In 2009, German Chancellor Angela Merkel''s government, through negotiation with the German state science ministries, approved a windfall of €18 billion in new science funding, to be spread over the next decade. Similarly, US President Barack Obama''s administration boosted spending on research with a temporary stimulus package for science, through the American Recovery and Reinvestment Act.Even so, Harry Greenberg, Senior Associate Dean for Research at Stanford University (California, USA) pointed out that until the US government injected stimulus funding, the budget at the National Institutes of Health (NIH; Bethesda, Maryland, USA) had essentially “been flat as a pancake for five or six years, and that means that it''s actually gone down and it''s having an effect on people being able to sustain their research mission.”Similarly, Gruss said that the research community should remain vigilant. “I think one could phrase it as there is a danger. If you look at Great Britain, there is the Wellcome Trust, a very strong funding organization for life sciences and medical-oriented, health-oriented research. I think it''s in the back of the minds of the politicians that there is a gigantic foundation that supports that [kind of research]. I don''t think one can deny that. There is an atmosphere that people like the Gates family [Bill and Melinda Gates Foundation] invests in health-related issues, particularly in the poorer countries [and that] maybe that is something that suffices.”The money available for research from private foundations and charities is growing in both size and scope. According to Iain Mattaj, Director General of the European Molecular Biology Laboratory (EMBL; Heidelberg, Germany), this growth might not be a bad thing. As he pointed out, private funding often complements government funding, with charities such as the Wellcome Trust going out of their way to leverage government spending without reducing government contributions. “My feeling is that the reason that the UK government is freezing research funding has all to do with economics and nothing to do with the fact that there are potentially private funders,” he said. “Several very large charities in particular are putting a lot of money into health research. The Gates Foundation is the biggest that has just come on the scene, but the Howard Hughes Medical Institute [HHMI; Chevy Chase, Maryland, USA] and the Wellcome Trust are very big, essentially private charities which have their own agendas.”…charities such as the Wellcome Trust [go] out of their way to leverage government spending without reducing government contributions​contributionsOpen in a separate window© CorbisBut, as he explained, these charities actually contribute to the overall health research budget, rather than substituting funds from one area to another. In fact, they often team up to tackle difficult research questions in partnership with each other and with government. Two-thirds of the €140 million annual budget of EMBL comes from the European states that agree to fund it, with additional contributions from private sources such as the Wellcome Trust and public sources such as the NIH.Yet over the years, as priorities have changed, the focus of those partnerships and the willingness to spend money on certain research themes or approaches has shifted, both within governments and in the private sector. Belief in the success of US President Richard Nixon''s famous ‘war on cancer'', for example, has waned over the years, although the fight and the funding continues. “I don''t want to use the word political, because of course the decisions are sometimes political, but actually it was a social priority to fight cancer. It was a social priority to fight AIDS,” Mattaj commented. “For the Wellcome Trust and the Gates Foundation, which are fighting tropical diseases, they see that as a social necessity, rather than a personal interest if you like.”Nevertheless, Mattaj is not surprised that there is an inclination to reduce research spending in the UK and many smaller countries battered by the economic downturn. “Most countries have to reduce public spending, and research is public spending. It may be less badly hit than other aspects of public spending. [As such] it''s much better off than many other aspects of public spending.”A shift away from government funding to private funding, especially from disease-focused charities, worries some that less funding will be available for basic, curiosity-driven research—a move from pure research to ‘cure'' research. Moreover, charities are often just as vulnerable to economic downturns, so relying on them is not a guarantee of funding in harsh economic times. Indeed, greater reliance on private funding would be a return to the era of ‘gentlemen scientists'' and their benefactors (Sidebar A).

Sidebar A | Gentlemen scientists

Greater reliance on private funding would return science to a bygone age of gentlemen scientists relying on the largesse of their wealthy sponsors. In 1831, for example, naturalist Charles Darwin''s (1809–1882) passage on the HMS Beagle was paid for by his father, albeit reluctantly. According to Laura Snyder, an expert on Victorian science and culture at St John''s University (New York, USA), by the time Darwin returned to England in 1836, the funding game had changed and government and private scientific societies had begun to have a bigger role. When Sir John Frederick William Herschel (1791–1871), an English mathematician, astronomer, chemist, experimental photographer and inventor, journeyed to Cape Colony in 1833, the British government offered to give him a free ride aboard an Admiralty ship. “Herschel turned them down because he wanted to be free to do whatever he wanted once he got to South Africa, and he didn''t want to feel beholden to government to do what they wanted him to do,” Snyder explained, drawing from her new book The Philosophical Breakfast Club, which covers the creation of the modern concept of science.Charles Babbage (1791–1871), the mathematician, philosopher, inventor and mechanical engineer who originated the concept of a programmable computer, was a member of the same circle as Herschel and William Whewell (1794–1866), a polymath, geologist, astronomer and theologian, who coined the word ''scientist''. Although he was wealthy, having inherited £100,000 in 1827—valued at about £13.3 million in 2008—Babbage felt that government should help pay for his research that served the public interest.“Babbage was asking the government constantly for money to build his difference engine,” Snyder said. Babbage griped about feeling like a tradesman begging to be paid. “It annoyed him. He felt that the government should just have said, ''We will support the engine, whatever it is that you need, just tell us and we''ll write you a check''. But that''s not what the government was about to do.”Instead, the British government expected Babbage to report on his progress before it loosened its purse strings. Snyder explained, “What the government was doing was a little bit more like grants today, in the sense that you have to justify getting more money and you have to account for spending the money. Babbage just wanted an open pocketbook at his disposal.”In the end the government donated £17,000, and Babbage never completed the machine.Janet Rowley, a geneticist at the University of Chicago, is worried that the change in funding will make it more difficult to obtain money for the kind of research that led to her discovery in the 1970s of the first chromosomal translocations that cause cancer. She calls such work ‘fishing expeditions''. She said that the Leukemia & Lymphoma Society (White Plains, New York, USA), for example—a non-profit funder of research—has modified its emphasis: “They have now said that they are going to put most of their resources into translational work and trying to take ideas that are close to clinical application, but need what are called incubator funds to ramp up from a laboratory to small-scale industrial production to increase the amount of compound or whatever is required to do studies on more patients.”This echoes Vince Cable''s view that taxpayers should not have to spend money on research that is not of direct economic, technological or health benefit to them. But if neither charities nor governments are willing to fund basic research, then who will pay the bill?…if neither charities nor governments are willing to fund basic research, then who will pay the bill?Iain Mattaj believes that the line between pure research and cure research is actually too blurred to make these kinds of funding distinctions. “In my view, it''s very much a continuum. I think many people who do basic research are actually very interested in the applications of their research. That''s just not their expertise,” he said. “I think many people who are at the basic end of research are more than happy to see things that they find out contributing towards things that are useful for society.”Jack Dixon, Vice President and Chief Scientific Officer at HHMI, also thinks that the line is blurry: “This divide between basic research and translational research is somewhat arbitrary, somewhat artificial in nature. I think every scientist I know who makes important, basic discoveries likes to [...] see their efforts translate into things that help humankind. Our focus at the Hughes has always been on basic things, but we love to see them translated into interesting products.” Even so, HHMI spends less than US $1 billion annually on research, which is overshadowed by the $30 billion spent by the NIH and the relatively huge budgets of the Wellcome Trust and Cancer Research UK. “We''re a small player in terms of the total research funding in the US, so I just don''t see the NIH pulling back on supporting research,” Dixon said.By way of example, Brian Druker, Professor of Medicine at the Oregon Health & Science University (Portland, Oregon, USA) and a HHMI scientist, picked up on Rowley''s work with cancer-causing chromosomal translocations and developed the blockbuster anti-cancer drug, imatinib, marketed by Novartis. “Brian Druker is one of our poster boys in terms of the work he''s done and how that is translated into helping people live longer lives that have this disease,” Dixon commented.There is a similar view at Stanford. The distinction between basic and applied is “in the eye of the beholder,” Greenberg said. “Basic discovery is the grist for the mill that leads to translational research and new breakthroughs. It''s always been a little difficult to convey, but at least here at Stanford, that''s number one. Number two, many of our very basic researchers enjoy thinking about the translational or clinical implications of their basic findings and some of them want to be part of doing it. They want some benefit for mankind other than pure knowledge.”“Basic discovery is the grist for the mill that leads to translational research and new breakthroughs”If it had not backed down from the massive cuts to the research budget that were proposed, the intention of the UK Government to cut funding for basic, rather than applied, research might have proven difficult to implement. Identifying which research will be of no value to society is like trying to decide which child will grow up to be Prime Minister. Nevertheless, most would agree that governments have a duty to get value-for-money for the taxpayer, but defining the value of research in purely economic or translational terms is both short-sighted and near impossible. Even so, science is feeling the economic downturn and budgets are tighter than they have been for a long time. As Greenberg concluded, “It''s human nature when everybody is feeling the pinch that you think [yours] is bigger than the next guy''s, but I would be hard pressed to say who is getting pinched, at least in the biomedical agenda, more than who else.”     

The 'National' and the 'Cosmos'. The emergence of synthetic biology in China

How can grass-roots movements evolve into a national research strategy? The bottom-up emergence of synthetic biology in China could give some pointers.Given its potential to aid developments in renewable energy, biosensors, sustainable chemical industries, microbial drug factories and biomedical devices, synthetic biology has enormous implications for economic development. Many countries are therefore implementing strategies to promote progress in this field. Most notably, the USA is considered to be the leader in exploring the industrial potential of synthetic biology (Rodemeyer, 2009). Synthetic biology in Europe has benefited from several cross-border studies, such as the ‘New and Emerging Science and Technology'' programme (NEST, 2005) and the ‘Towards a European Strategy for Synthetic Biology'' project (TESSY; Gaisser et al, 2008). Yet, little is known in the West about Asia''s role in this ‘new industrial revolution'' (Kitney, 2009). In particular, China is investing heavily in scientific research for future developments, and is therefore likely to have an important role in the development of synthetic biology.Initial findings seem to indicate that the emergence of synthetic biology in China has been a bottom-up construction of a new scientific framework…In 2010, as part of a study of the international governance of synthetic biology, the author visited four leading research teams in three Chinese cities (Beijing, Tianjin and Hefei). The main aims of the visits were to understand perspectives in China on synthetic biology, to identify core themes among its scientific community, and to address questions such as ‘how did synthetic biology emerge in China?'', ‘what are the current funding conditions?'', ‘how is synthetic biology generally perceived?'' and ‘how is it regulated?''. Initial findings seem to indicate that the emergence of synthetic biology in China has been a bottom-up construction of a new scientific framework; one that is more dynamic and comprises more options than existing national or international research and development (R&D) strategies. Such findings might contribute to Western knowledge of Chinese R&D, but could also expose European and US policy-makers to alternative forms and patterns of research governance that have emerged from a grass-roots level.…the process of developing a framework is at least as important to research governance as the big question it might eventually addressA dominant narrative among the scientists interviewed is the prospect of a ‘big-question'' strategy to promote synthetic-biology research in China. This framework is at a consultation stage and key questions are still being discussed. Yet, fieldwork indicates that the process of developing a framework is at least as important to research governance as the big question it might eventually address. According to several interviewees, this approach aims to organize dispersed national R&D resources into one grand project that is essential to the technical development of the field, preferably focusing on an industry-related theme that is economically appealling to the Chinese public.Chinese scientists have a pragmatic vision for research; thinking of science in terms of its ‘instrumentality'' has long been regarded as characteristic of modern China (Schneider, 2003). However, for a country in which the scientific community is sometimes described as an “uncoordinated ‘bunch of loose ends''” (Cyranoski, 2001) “with limited synergies between them” (OECD, 2007), the envisaged big-question approach implies profound structural and organizational changes. Structurally, the approach proposes that the foundational (industry-related) research questions branch out into various streams of supporting research and more specific short-term research topics. Within such a framework, a variety of Chinese universities and research institutions can be recruited and coordinated at different levels towards solving the big question.It is important to note that although this big-question strategy is at a consultation stage and supervised by the Ministry of Science and Technology (MOST), the idea itself has emerged in a bottom-up manner. One academic who is involved in the ongoing ministerial consultation recounted that, “It [the big-question approach] was initially conversations among we scientists over the past couple of years. We saw this as an alternative way to keep up with international development and possibly lead to some scientific breakthrough. But we are happy to see that the Ministry is excited and wants to support such an idea as well.” As many technicalities remain to be addressed, there is no clear time-frame yet for when the project will be launched. Yet, this nationwide cooperation among scientists with an emerging commitment from MOST seems to be largely welcomed by researchers. Some interviewees described the excitement it generated among the Chinese scientific community as comparable with the establishment of “a new ‘moon-landing'' project”.Of greater significance than the time-frame is the development process that led to this proposition. On the one hand, the emergence of synthetic biology in China has a cosmopolitan feel: cross-border initiatives such as international student competitions, transnational funding opportunities and social debates in Western countries—for instance, about biosafety—all have an important role. On the other hand, the development of synthetic biology in China has some national particularities. Factors including geographical proximity, language, collegial familiarity and shared interests in economic development have all attracted Chinese scientists to the national strategy, to keep up with their international peers. Thus, to some extent, the development of synthetic biology in China is an advance not only in the material synthesis of the ‘cosmos''—the physical world—but also in the social synthesis of aligning national R&D resources and actors with the global scientific community.To comprehend how Chinese scientists have used national particularities and global research trends as mutually constructive influences, and to identify the implications of this for governance, this essay examines the emergence of synthetic biology in China from three perspectives: its initial activities, the evolution of funding opportunities, and the ongoing debates about research governance.China''s involvement in synthetic biology was largely promoted by the participation of students in the International Genetically Engineered Machine (iGEM) competition, an international contest for undergraduates initiated by the Massachusetts Institute of Technology (MIT) in the USA. Before the iGEM training workshop that was hosted by Tianjin University in the Spring of 2007, there were no research records and only two literature reviews on synthetic biology in Chinese scientific databases (Zhao & Wang, 2007). According to Chunting Zhang of Tianjin University—a leading figure in the promotion of synthetic biology in China—it was during these workshops that Chinese research institutions joined their efforts for the first time (Zhang, 2008). From the outset, the organization of the workshop had a national focus, while it engaged with international networks. Synthetic biologists, including Drew Endy from MIT and Christina Smolke from Stanford University, USA, were invited. Later that year, another training camp designed for iGEM tutors was organized in Tianjin and included delegates from Australia and Japan (Zhang, 2008).Through years of organizing iGEM-related conferences and workshops, Chinese universities have strengthened their presence at this international competition; in 2007, four teams from China participated. During the 2010 competition, 11 teams from nine universities in six provinces/municipalities took part. Meanwhile, recruiting, training and supervising iGEM teams has become an important institutional programme at an increasing number of universities.…training for iGEM has grown beyond winning the student awards and become a key component of exchanges between Chinese researchers and the international communityIt might be easy to interpret the enthusiasm for the iGEM as a passion for winning gold medals, as is conventionally the case with other international scientific competitions. This could be one motive for participating. Yet, training for iGEM has grown beyond winning the student awards and has become a key component of exchanges between Chinese researchers and the international community (Ding, 2010). Many of the Chinese scientists interviewed recounted the way in which their initial involvement in synthetic biology overlapped with their tutoring of iGEM teams. One associate professor at Tianjin University, who wrote the first undergraduate textbook on synthetic biology in China, half-jokingly said, “I mainly learnt [synthetic biology] through tutoring new iGEM teams every year.”Participation in such contests has not only helped to popularize synthetic biology in China, but has also influenced local research culture. One example of this is that the iGEM competition uses standard biological parts (BioBricks), and new BioBricks are submitted to an open registry for future sharing. A corresponding celebration of open-source can also be traced to within the Chinese synthetic-biology community. In contrast to the conventional perception that the Chinese scientific sector consists of a “very large number of ‘innovative islands''” (OECD, 2007; Zhang, 2010), communication between domestic teams is quite active. In addition to the formally organized national training camps and conferences, students themselves organize a nationwide, student-only workshop at which to informally test their ideas.More interestingly, when the author asked one team whether there are any plans to set up a ‘national bank'' for hosting designs from Chinese iGEM teams, in order to benefit domestic teams, both the tutor and team members thought this proposal a bit “strange”. The team leader responded, “But why? There is no need. With BioBricks, we can get any parts we want quite easily. Plus, it directly connects us with all the data produced by iGEM teams around the world, let alone in China. A national bank would just be a small-scale duplicate.”From the beginning, interest in the development of synthetic biology in China has been focused on collective efforts within and across national borders. In contrast to conventional critiques on the Chinese scientific community''s “inclination toward competition and secrecy, rather than openness” (Solo & Pressberg, 2007; OECD, 2007; Zhang, 2010), there seems to be a new outlook emerging from the participation of Chinese universities in the iGEM contest. Of course, that is not to say that the BioBricks model is without problems (Rai & Boyle, 2007), or to exclude inputs from other institutional channels. Yet, continuous grass-roots exchanges, such as the undergraduate-level competition, might be as instrumental as formal protocols in shaping research culture. The indifference of Chinese scientists to a ‘national bank'' seems to suggest that the distinction between the ‘national'' and ‘international'' scientific communities has become blurred, if not insignificant.However, frequent cross-institutional exchanges and the domestic organization of iGEM workshops seem to have nurtured the development of a national synthetic-biology community in China, in which grass-roots scientists are comfortable relying on institutions with a cosmopolitan character—such as the BioBricks Foundation—to facilitate local research. To some extent, one could argue that in the eyes of Chinese scientists, national and international resources are one accessible global pool. This grass-roots interest in incorporating local and global advantages is not limited to student training and education, but also exhibited in evolving funding and regulatory debates.In the development of research funding for synthetic biology, a similar bottom-up consolidation of national and global resources can also be observed. As noted earlier, synthetic-biology research in China is in its infancy. A popular view is that China has the potential to lead this field, as it has strong support from related disciplines. In terms of genome sequencing, DNA synthesis, genetic engineering, systems biology and bioinformatics, China is “almost at the same level as developed countries” (Pan, 2008), but synthetic-biology research has only been carried out “sporadically” (Pan, 2008; Huang, 2009). There are few nationally funded projects and there is no discernible industrial involvement (Yang, 2010). Most existing synthetic-biology research is led by universities or institutions that are affiliated with the Chinese Academy of Science (CAS). As one CAS academic commented, “there are many Chinese scientists who are keen on conducting synthetic-biology research. But no substantial research has been launched nor has long-term investment been committed.”The initial undertaking of academic research on synthetic biology in China has therefore benefited from transnational initiatives. The first synthetic-biology project in China, launched in October 2006, was part of the ‘Programmable Bacteria Catalyzing Research'' (PROBACTYS) project, funded by the Sixth Framework Programme of the European Union (Yang, 2010). A year later, another cross-border collaborative effort led to the establishment of the first synthetic-biology centre in China: the Edinburgh University–Tianjing University Joint Research Centre for Systems Biology and Synthetic Biology (Zhang, 2008).There is also a comparable commitment to national research coordination. A year after China''s first participation in iGEM, the 2008 Xiangshan conference focused on domestic progress. From 2007 to 2009, only five projects in China received national funding, all of which came from the National Natural Science Foundation of China (NSFC). This funding totalled ¥1,330,000 (approximately £133,000; www.nsfc.org), which is low in comparison to the £891,000 funding that was given in the UK for seven Networks in Synthetic Biology in 2007 alone (www.bbsrc.ac.uk).One of the primary challenges in obtaining funding identified by the interviewees is that, as an emerging science, synthetic biology is not yet appreciated by Chinese funding agencies. After the Xiangshan conference, the CAS invited scientists to a series of conferences in late 2009. According to the interviewees, one of the main outcomes was the founding of a ‘China Synthetic Biology Coordination Group''; an informal association of around 30 conference delegates from various research institutions. This group formulated a ‘regulatory suggestion'' that they submitted to MOST, which stated the necessity and implications of supporting synthetic-biology research. In addition, leading scientists such as Chunting Zhang and Huanming Yang—President of the Beijing Genomic Institute (BGI), who co-chaired the Beijing Institutes of Life Science (BILS) conferences—have been active in communicating with government institutions. The initial results of this can be seen in the MOST 2010 Application Guidelines for the National Basic Research Program, in which synthetic biology was included for the first time, among ‘key supporting areas'' (MOST, 2010). Meanwhile, in 2010, NSFC allocated ¥1,500,000 (approximately £150,000) to synthetic-biology research, which is more than the total funding the area had received in the past three years.The search for funding further demonstrates the dynamics between national and transnational resources. Chinese R&D initiatives have to deal with the fact that scientific venture-capital and non-governmental research charities are underdeveloped in China. In contrast to the EU or the USA, government institutions in China, such as the NSFC and MOST, are the main and sometimes only domestic sources of funding. Yet, transnational funding opportunities facilitate the development of synthetic biology by alleviating local structural and financial constraints, and further integrate the Chinese scientific community into international research.This is not a linear ‘going-global'' process; it is important for Chinese scientists to secure and promote national and regional support. In addition, this alignment of national funding schemes with global research progress is similar to the iGEM experience, as it is being initiated through informal bottom-up associations between scientists, rather than by top-down institutional channels.As more institutions have joined iGEM training camps and participated in related conferences, a shared interest among the Chinese scientific community in developing synthetic biology has become visible. In late 2009, at the conference that founded the informal ‘coordination group'', the proposition of integrating national expertise through a big-question approach emerged. According to one professor in Beijing—who was a key participant in the discussion at the time—this proposition of a nationwide synergy was not so much about ‘national pride'' or an aim to develop a ‘Chinese'' synthetic biology, it was about research practicality. She explained, “synthetic biology is at the convergence of many disciplines, computer modelling, nano-technology, bioengineering, genomic research etc. Individual researchers like me can only operate on part of the production chain. But I myself would like to see where my findings would fit in a bigger picture as well. It just makes sense for a country the size of China to set up some collective and coordinated framework so as to seek scientific breakthrough.”From the first participation in the iGEM contest to the later exploration of funding opportunities and collective research plans, scientists have been keen to invite and incorporate domestic and international resources, to keep up with global research. Yet, there are still regulatory challenges to be met.…with little social discontent and no imminent public threat, synthetic biology in China could be carried out in a ‘research-as-usual'' mannerThe reputation of “the ‘wild East'' of biology” (Dennis, 2002) is associated with China'' previous inattention to ethical concerns about the life sciences, especially in embryonic-stem-cell research. Similarly, synthetic biology creates few social concerns in China. Public debate is minimal and most media coverage has been positive. Synthetic biology is depicted as “a core in the fourth wave of scientific development” (Pan, 2008) or “another scientific revolution” (Huang, 2009). Whilst recognizing its possible risks, mainstream media believe that “more people would be attracted to doing good while making a profit than doing evil” (Fang & He, 2010). In addition, biosecurity and biosafety training in China are at an early stage, with few mandatory courses for students (Barr & Zhang, 2010). The four leading synthetic-biology teams I visited regarded the general biosafety regulations that apply to microbiology laboratories as sufficient for synthetic biology. In short, with little social discontent and no imminent public threat, synthetic biology in China could be carried out in a ‘research-as-usual'' manner.Yet, fieldwork suggests that, in contrast to this previous insensitivity to global ethical concerns, the synthetic-biology community in China has taken a more proactive approach to engaging with international debates. It is important to note that there are still no synthetic-biology-specific administrative guidelines or professional codes of conduct in China. However, Chinese stakeholders participate in building a ‘mutual inclusiveness'' between global and domestic discussions.One of the most recent examples of this is a national conference about the ethical and biosafety implications of synthetic biology, which was jointly hosted by the China Association for Science and Technology, the Chinese Society of Biotechnology and the Beijing Institutes of Life Science CAS, in Suzhou in June 2010. The discussion was open to the mainstream media. The debate was not simply a recapitulation of Western worries, such as playing god, potential dual-use or ecological containment. It also focused on the particular concerns of developing countries about how to avoid further widening the developmental gap with advanced countries (Liu, 2010).In addition to general discussions, there are also sustained transnational communications. For example, one of the first three projects funded by the NSFC was a three-year collaboration on biosafety and risk-assessment frameworks between the Institute of Botany at CAS and the Austrian Organization for International Dialogue and Conflict Management (IDC).Chinese scientists are also keen to increase their involvement in the formulation of international regulations. The CAS and the Chinese Academy of Engineering are engaged with their peer institutions in the UK and the USA to “design more robust frameworks for oversight, intellectual property and international cooperation” (Royal Society, 2009). It is too early to tell what influence China will achieve in this field. Yet, the changing image of the country from an unconcerned wild East to a partner in lively discussions signals a new dynamic in the global development of synthetic biology.Student contests, funding programmes, joint research centres and coordination groups are only a few of the means by which scientists can drive synthetic biology forward in ChinaFrom self-organized participation in iGEM to bottom-up funding and governance initiatives, two features are repeatedly exhibited in the emergence of synthetic biology in China: global resources and international perspectives complement national interests; and the national and cosmopolitan research strengths are mostly instigated at the grass-roots level. During the process of introducing, developing and reflecting on synthetic biology, many formal or informal, provisional or long-term alliances have been established from the bottom up. Student contests, funding programmes, joint research centres and coordination groups are only a few of the means by which scientists can drive synthetic biology forward in China.However, the inputs of different social actors has not led to disintegration of the field into an array of individualized pursuits, but has transformed it into collective synergies, or the big-question approach. Underlying the diverse efforts of Chinese scientists is a sense of ‘inclusiveness'', or the idea of bringing together previously detached research expertise. Thus, the big-question strategy cannot be interpreted as just another nationally organized agenda in response to global scientific advancements. Instead, it represents a more intricate development path corresponding to how contemporary research evolves on the ground.In comparison to the increasingly visible grass-roots efforts, the role of the Chinese government seems relatively small at this stageIn comparison to the increasingly visible grass-roots efforts, the role of the Chinese government seems relatively small at this stage. Government input—such as the potential stewardship of the MOST in directing a big-question approach or long-term funding—remain important; the scientists who were interviewed expend a great deal of effort to attract governmental participation. Yet, China'' experience highlights that the key to comprehending regional scientific capacity lies not so much in what the government can do, but rather in what is taking place in laboratories. It is important to remember that Chinese iGEM victories, collaborative synthetic-biology projects and ethical discussions all took place before the government became involved. Thus, to appreciate fully the dynamics of an emerging science, it might be necessary to focus on what is formulated from the bottom up.The experience of China in synthetic biology demonstrates the power of grass-roots, cross-border engagement to promote contemporary researchThe experience of China in synthetic biology demonstrates the power of grass-roots, cross-border engagement to promote contemporary research. More specifically, it is a result of the commitment of Chinese scientists to incorporating national and international resources, actors and social concerns. For practical reasons, the national organization of research, such as through the big-question approach, might still have an important role. However, synthetic biology might be not only a mosaic of national agendas, but also shaped by transnational activities and scientific resources. What Chinese scientists will collectively achieve remains to be seen. Yet, the emergence of synthetic biology in China might be indicative of a new paradigm for how research practices can be introduced, normalized and regulated.     

Not too much and not too little

We tend to think in black and white terms of good versus bad alleles and their meaning for disease. However, in doing so, we ignore the potential importance of heterozygous alleles.The structure and function of any protein is determined by its amino acid sequence. Thus, the substitution of one amino acid for another can alter the activity of a protein or its function. Mutations—or rather, polymorphism, once they become fixed in the population—can be deleterious, such that the altered protein is no longer able to fulfil its role with potentially devastating effects on the cell. Rarely, they can improve protein function and cell performance. In either case, any changes in the amino acid sequence, whether they affect only one amino acid or larger parts of the protein, are encoded by polymorphisms in the nucleotide sequence of that protein''s gene. For any given polymorphism, diploid organisms with two sets of chromosomes can therefore exist in either a heterozygous state or one of two homozygous states. When the polymorphism is rare, most individuals are homozygous for the ‘wild-type'' state, some individuals are heterozygous and a few are homozygous for the rare polymorphic variant. Conversely, if the polymorphism occurs in 50% of the alleles, the heterozygous state is common.At first glance, the deleterious homozygous state seems to be something that organisms try to avoid: close relatives usually do not breed, probably to prevent the homozygous accumulation of deleterious alleles. Thus, human cultural norms, founded in our biology, actively select for heterozygosity as many civilizations and societies regard incest as a social taboo. The fields of animal husbandry and conservation biology are littered with information about the significant positive correlation between genetic diversity, evolutionary advantage and fitness [1]. In sexually reproducing organisms, heterozygosity is generally regarded as ‘better'' in terms of adaptability and evolutionary advantage.Why then do we seldom, if ever, regard allelic heterozygosity as an advantage when it comes to genes linked with health and disease? Perhaps it is because we tend to distinguish between the ‘good'' allele, the ‘bad'' allele and the ‘ugly'' heterozygote—since it is burdened with one ‘bad'' allele. Maybe this attitude is a remnant of the outdated ‘one gene, one disease'' model, or of the early studies on inheritable diseases that focused on monogenic or autosomal-dominant genetic disorders. Even modern genetics almost always assigns ‘risk'' to an allele that is associated with a health condition or disadvantaged phenotype; clearly, then, the one homozygous state must have an advantage—sometimes referred to as wild-type—but the heterozygote is often ignored altogether.Maybe we also shun heterozygosity because it is hard to prove, beyond a few examples, that it might offer advantage. A 2010 paper published in Cell claimed that heterozygosity of the lth4A locus conveys protection against tuberculosis [2]. There is a mechanistic basis for the claim: lth4A encodes leukotriene A4 hydrolase, which is the final catalyst to synthesize leukotriene B4, an efficient pro-inflammatory eicosanoid. However, an extensive case–control study could not confirm the association between heterozygosity and protection against tuberculosis [3]. Therefore, many in the field dismiss the prior claim to protection conferred by the heterozygous state.Yet, we know that most biochemical and physiological processes are highly complex systems that involve multiple, interlinked steps with extensive control and feedback mechanisms. Heterozygosity might be one strategy by which an organism maintains flexibility, as it provides more than one allele to fall back on, should conditions change. We may therefore hypothesize that heterozygosity can be either a risk or an advantage, depending on the penetrance or dominance of the alleles. Indeed, there are a few cases in which heterozygosity confers some advantage. For example, individuals who are homozygous for the CCR5 deletion polymorphism (D32/D32) are protected against HIV1 infection, whereas CCR5/D32 heterozygotes have a slower progression to acquired immunodeficiency syndrome (AIDS). In sickle-cell anaemia, heterozygotes have a protective advantage against malaria, whereas the homozygotes either lack protection or suffer health consequences. Thus, although heterozygosity might not create a general fitness advantage, it is advantageous under certain specific conditions, namely the presence of the malaria parasite.In most aspects of life, there are few absolutes and many shades of grey. The ‘normal'' range of parameters in medicine is a clear example of this: optimal functioning of the relevant physiological processes depends on levels that are ‘just right''. As molecular and genetic research tackles the causes and risk factors of complex diseases, we may perhaps find more examples of how heterozygosity at the genetic level conveys health advantages in humans. As the above example regarding tuberculosis indicates, it is difficult to demonstrate any advantage of the heterozygous state. We simply need to be receptive to such possibilities, and improve and reconcile our understanding of allelic diversity and heterozygosity. Researchers working on human disease could benefit from the insights of evolutionary biologists and breeders, who are more appreciative of the heterozygous state.     

Darwin and Dostoyevsky: twins

The Russian poet Fyodor Dostoyevsky published an insightful treatise on human nature in his novel ‘The Brothers Karamazov'' in 1880. His account of humanity may offer as much insight into human nature for scientists as Darwin''s The Descent of Man.Late in the nineteenth century, Charles Darwin (1809–1882) and Fyodor Dostoyevsky (1821–1881) published accounts of their investigation of humankind. Darwin did so in 1871 in his book The Descent of Man, Dostoyevsky in 1880 in the parable of The Grand Inquisitor in his book The Brothers Karamazov. Last year we celebrated Darwin''s anniversary; for biologists, 2010—the 130th anniversary of Dostoyevsky''s book—might have been the year of Dostoyevsky.Dostoyevsky was familiar with Darwin''s doctrine and he was willing to admit “man''s descent from the ape”. An orthodox Christian, he put this sentiment in religious terms: “It does not really matter what man''s origins are, the Bible does not explain how God moulded him out of clay or carved him out of stone. Yet, he saw a difference between humans and animals: humans have a soul.The philosopher Nikolay Berdyayev noticed: “[Dostoyevsky] concealed nothing, and that''s why he could make astonishing discoveries. In the fate of his heroes he relates his own destiny, in their doubts he reveals his vacillations, in their ambiguity his self-splitting, in their criminal experience the secret crimes of his spirit.”The Grand Inquisitor can be read as Dostoyevsky''s treatise on human nature. In the tale, Jesus Christ revisits Earth during the period of the Inquisition and is arrested by the Church and sentenced to death. The Grand Inquisitor comes to visit Jesus in his prison cell to argue with him about their conceptions of human nature. He explains that humankind needs to be ruled to be happy and that the true freedom Jesus offered doomed humanity to suffering and unhappiness. Dostoyevsky''s superposition of these two points of view on humankind reminds us of the principle of complementarity, by which the physicist Niels Bohr attempted to account for the particle-wave duality of quantum physics.Dostoyevsky conceives of humans as complex, contradictory and inconsistent creatures. Humans perceive personal liberty as a burden and are willing to barter for it, as the Grand Inquisitor explained to Christ, for “miracle, mystery, and authority”. In addition, “the mystery of human being does not only rest in the desire to live, but in the problem: for what should one live at all?” We might say that these faculties make Homo sapiens a religious species. Not in the sense of believing in gods or a god, but in the sense of the Latin word religare, which means to bind, connect or enfold. Humans are mythophilic animals, driven by a need to find a complete explanation for events in terms of intentions and purposes.Research into the neurological bases of imagination, transcendence, metaphorability, art and religion, as well as moral behaviour and judgement (Trimble, 2007) is consistent with Dostoyevsky''s views. It has identified areas of the brain that have been labelled as the ‘god module'' or ‘god spot'' (Alper, 2001). These areas represent a new stratum of evolutionary complexity, an emergence specific to the human species. Their mental translations might be tentatively designated as the Darwinian soul, anchored in the material substrate and neither immortal nor cosmic. As consciousness and volition have become legitimate subjects of neuroscience (Baars, 2003), the Darwinian soul, and with it spirituality, seems to be ripe for scientific inquiry: the quest for meaning, creation and perception of metaphors, the experience of the trinity of Truth, Good and Beauty, the capacity for complex feelings that Immanuel Kant called sublimity, the thrill of humour and play, the power of empathy and the follies of boundless love or hate. Secularization does not erase the superstructure of spirituality: it is reflected, however queer it might seem, in the hypertrophy of the entertainment industry and also, more gloomily, in spiritual conflicts on a global scale.Dostoyevsky''s views on the human soul might be closer to those of Alfred Russel Wallace, who believed that an unknown force directed evolution towards an advanced organization. We can identify this ‘force'' as the second law of thermodynamics (Sharma & Annila, 2007). By moving evolving systems ever farther away from equilibrium, the second law eventually became the Creator of the ‘Neuronal God''.Christ, in the parable of the Grand Inquisitor, might be conceived of as a symbol of the truth outside the human world. Christ was listening to the assertions and questions of his interlocutor, but did not say a single word. His silence is essential to the parable.Similarly, the cosmos, to which humanity has been addressing its questions and predications, remains silent. By science, we increase knowledge only by tiny increments. The ‘god modules'' of our brains, unsatisfied and impatient, have hastily provided the full truth, deposited in the Holy Scripture. There are at least three books claiming to contain the revealed and hence unquestionable truth: the Judaic Torah, Christian Bible and Muslim Qur''an. A dogma of genocentrism in biology might offer an additional Scripture: the sequence of DNA in the genomes.Dostoyevsky''s legacy may suggest an amendment to the UN Charter. We, united humankind, solemnly declare: No truth has ever been revealed to us; we respect and tolerate each other in our independent searching and erring.     

Autosis and autophagic cell death: the dark side of autophagy

It is controversial whether cells truly die via autophagy or whether — in dying cells — autophagy is merely an innocent bystander or a well-intentioned ‘Good Samaritan'' trying to prevent inevitable cellular demise. However, there is increasing evidence that the genetic machinery of autophagy may be essential for cell death in certain settings. We recently identified a novel form of autophagy gene-dependent cell death, termed autosis, which is mediated by the Na⁺,K⁺-ATPase pump and has unique morphological features. High levels of cellular autophagy, as occurs with treatment with autophagy-inducing peptides, starvation, or in vivo during certain types of ischemia, can trigger autosis. These findings provide insights into the mechanisms and strategies for prevention of cell death during extreme stress conditions.     

Aliens at home?

If we ponder how alien life might look like on other planets, we don''t have to go far, Simon Conway Morris argues, since life forms on Earth have already pushed life to the limits.When in 1609 Galileo first saw the moons of Jupiter, he must have been spellbound. I was certainly so enrapt when I saw Europa and her three companions strung like a line of jewels. Galileo may have appreciated the irony that my guide was a Jesuit priest, and the somewhat antiquated telescope we used was but a few yards from the Papal summer residence in Castel Gandolfo. Galileo prized open the door and before long, scientific imagination was fired by the prospect of innumerable inhabited worlds. As the centuries progressed, imagination raced ahead of facts, with the Moon optimistically colonized by Selenites, and Mars transformed by immense canals to supply the parched regions of a planet plunging into desertification. From this dying planet H.G. Wells propelled his aliens to terrorize southern England with immense tripods housing sinister octopoids.Now we might be closer to knowing if Wells was in any sense on the right track. The spectacular success in detecting extrasolar planets has produced a roster in excess of 450, and this technology potentially allows us to detect Earth-like planets. Even if many of the known planets are too large to be habitable and lie, for the most part, beyond the inferred ‘habitable zones'', before long we will get some clues as to how densely our galaxy is inhabited. The consensus points in two directions. First, life is a universal. Second, our biosphere will be of almost no use when it comes to comparisons. Let me draw your attention to a remarkably unappreciated fact: if you want to understand aliens, stay at home.Am I serious? After all it is already clear that extrasolar planetary systems are vastly different to our Solar System. Immense planets orbit their suns every few days, their surfaces far more torrid than that of Venus. Other planets most likely possess giant oceans, hundreds of kilometres deep. The diversity of moons and planets in our Solar System is a reminder of what may await us light years from Earth. Even among our neighbours, a case can be made for possible life in the clouds of Venus and Jupiter, the oceans of Europa and hydrocarbon lakes of Titan, and—with perennial optimism—in the permafrost of Mars. We might assume, therefore, that the range of environments available to life, its ‘habitation box'', is gigantic, and that Earth''s biosphere just nestles in one tiny corner. Oddly enough the evidence is exactly the opposite. Life on Earth has reached the limits of what is possible—anywhere.Temperature? The current limit on Earth is 122 °C. Plunging in the opposite direction the evidence is just as remarkable. At temperatures well below freezing, life carries on cheerfully. Even far beyond the eutectic, in which free water cannot form, organisms remain in a state of suspended animation with rates of damage and repair almost precisely matched. What of extreme desiccation? Evidently life has reached the limits of water activity. Entertainingly some of the hardiest forms are fungi that inhabit the weird alien world of Blue Stilton cheese. So, too, the bright colouration of salt pans is a familiar sight, and these osmotic extremes not only host rich microbial faunas but life that can flourish in the most bitter of brines. What of the extremes of pH—bleach versus battery acid? Once again, alkaliphiles and acidophiles disport themselves in ponds and streams that would have the Health and Safety officers in a state of panic. Pressure, either crushingly high or extremely attenuated? Life, of course, exists in the deepest oceanic trenches, but how much deeper might be viable? The weakest link seems to be the pressure sensitivity of the phospholipid membranes, suggesting that even on planets with titanic oceans life won''t survive much deeper than in the Mariana Trench. The same argument applies to the deep crust: at about 5 km the crushingly high pressures also coincide with the thermal limits imposed by the geothermal gradient. Shall we look to the skies? Clouds carry bacteria, but even at quite modest heights it seems to be accidental freight rather than a nebulous ecosystem.Terrestrial life has conquered nearly all of the ‘habitation box'' and its evolution begs so many questions. Are some forms, such as the hyperthermophiles, survivors from the Earth''s apocalyptic beginnings? Maybe, but most have clearly been reinvented several times. Getting to the limits of life isn''t that difficult, but how do extremophiles not only survive but flourish in these environments? Often the adaptations seem minor, which merely means they are more subtle than we might realize. What of the future? So far as the Earth is concerned it must cope with ever increasing solar luminosity: the last men will long predecease the last microbe. Possibly long before, we will engage in the first great galactic diaspora; but wherever our biologists journey they may find that life ‘out there'' got no further than the blue jewel that is Earth.     

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.”     

A ‘metaphising’ dung beetle

Humans and beetles both have a species-specific Umwelt circumscribed by their sensory equipment. However, Ladislav Kováč argues that humans, unlike beetles, have invented scientific instruments that are able to reach beyond the conceptual borders of our Umwelt.You may have seen the film Microcosmos, produced in 1996 by the French biologists Claude Nuridsany and Marie Perrenou. It does not star humans, but much smaller creatures, mostly insects. The filmmakers'' magnifying camera transposes the viewer into the world of these organisms. For me, Microcosmos is not an ordinary naturalist documentary; it is an exercise in metaphysics.One sequence in the film shows a dung beetle—with the ‘philosophical'' generic name Sisyphus—rolling a ball of horse manure twice its size that becomes stuck on a twig. As the creature struggles to free the dung, it gives the impression that it is both worried and obstinate. As we humans know, the ball represents a most valuable treasure for the beetle: it will lay its eggs into the manure that will later feed its offspring. The behaviour of the beetle is biologically meaningful; it serves its Darwinian fitness.Yet, the dung beetle knows nothing of the function of manure, nor of the horse that dropped the excrement, nor of the human who owned the horse. Sisyphus lives in a world that is circumscribed by its somatic sensors—a species-specific world that the German biologist and philosopher Jakob von Uexküll would have called the dung beetle''s ‘Umwelt''. The horse, too, has its own Umwelt, as does the human. Yet, the world of the horse, just like the world of the man, does not exist for the beetle.If a ‘scholar'' among dung beetles attempted to visualize the world ‘out there'', what would be the dung-beetles'' metaphysics—their image of a part of the world about which they have no data furnished by their sensors? What would be their religions, their truths, or the Truth—revealed, and thus indisputable?Beetles are most successful animals; one animal in every four is a beetle, leading the biologist J.B.S. Haldane to quip that the Creator must have “had an inordinate fondness for beetles”. Are we humans so different from dung beetles? By birth we are similar: inter faeces et urinas nascimur—we are born between faeces and urine—as Aurelius Augustine remarked 1,600 years ago. Humans also have a species-specific Umwelt that has been shaped by biological evolution. A richer one than is the Umwelt of beetles, as we have more sensors than have they. Relative to the body size, we also possess a much larger brain and with it the capacity to make versatile movements with our hands and to finely manipulate with our fingers.This manual dexterity has enabled humans to fabricate artefacts that are, in a sense, extensions and refinements of the human hand. The simplest one, a coarse-chipped stone, represents the evolutionary origins of artefacts. Step-by-step, by a ratchet-like process, artefacts have become ever more complicated: as an example, a Boeing 777 is assembled from more than three million parts. At each step, humans have just added a tiny improvement to the previously achieved state. Over time, the evolution of artefacts has become less dependent on human intention and may soon result in artefacts with the capacity for self-improvement and self-reproduction. In fact, it is by artefacts that humans transcend their biology; artefacts make humans different from beetles. Here is the essence of the difference: humans roll their artefactual balls, no less worried and obstinate than beetles, but, in contrast to the latter, humans often do it even if the action is biologically meaningless, at the expense of their Darwinian fitness. Humans are biologically less rational than are beetles.Artefacts have immensely enriched the human Umwelt. From among them, scientific instruments should be singled out, as they function as novel, extrasomatic sensors of the human species. They have substantially fine-grained human knowledge of the Umwelt. But they are also reaching out—both to a distance and at a rate that is exponentially increasing—behind the boundary of the human Umwelt, behind its conceptual confines that we call Kant''s barriers. Into the world that has long been a subject of human ‘dung-beetle-like'' metaphysics. Nevertheless, our theories about this world could now be substantiated by data coming from the extrasomatic sensors. These instruments, fumbling in the unknown, supply reliable and reproducible data such that their messages must be true. They supersede our arbitrary guesses and fancies, but their truth seems to be out of our conceptual grasp. Conceptually, our mind confines us to our species-specific Umwelt.We continue to share the common fate of our fellow dung beetles: There is undeniably a world outside the confinements of our species-specific Umwelt, but if the world of humans is too complex for the neural ganglia of beetles, the world beyond Kant''s barriers may similarly exceed the capacity of the human brain. The physicist Richard Feynman (1965) stated, perhaps resignedly, “I can safely say that nobody today understands quantum mechanics.” Frank Gannon (2007) likewise commented that biological research, similarly to research in quantum mechanics, might be approaching a state “too complex to comprehend”. New models of the human brain itself may turn out to be “true and effective—and beyond comprehension” (Kováč, 2009).The advances of science notwithstanding, the knowledge of the universe that we have gained on the planet Earth might yet be in its infancy. However, in contrast to the limited capacity of humans, the continuing evolution of artefacts may mean that they face no limits in their explorative potential. They might soon dispense with our conceptual assistance exploring the realms that will remain closed to the human mind forever.     

The tide turns towards microalgae

Current research aims to produce traditional biofuels from algae, but their potential to generate sustainable energy might be even greater and more ‘natural''At the time of writing, oil continues to pour into the Gulf of Mexico. It is one of the worst environmental disasters in human history and a shocking reminder of the costs of our addiction to fossil fuels. However, the alternative sources of sustainable energy, such as wind, waves and sunshine, cannot alone replace fossil fuels in the short or even medium term. As nuclear fusion is bogged down by almost intractable engineering challenges, and nuclear fission produces toxic and radioactive waste, research has focused increasingly on converting solar energy into electricity or fuels through photosynthesis—either through the use of artificial compounds that mimic the process, or bioengineered organisms that do it ‘naturally''.…research has focused increasingly on converting solar energy into electricity or fuels through photosynthesis…In the ‘natural'' camp, microalgae—single-celled algae—have emerged as the most promising candidates, mainly because of their potential for converting solar energy more efficiently and with less negative environmental impact than the alternatives, especially biofuel crops such as corn and soy, for example. Cyanobacteria, which are photosynthesizing prokaryotes, rather than single-celled eukaryotes, also hold promise in this regard. However, as Ben Graziano, technology commercialization manager at the Carbon Trust, an independent non-profit company set up by the UK government to develop low-carbon energy technologies, pointed out: “We may look at cyanobacteria in the future […] but they produce different co-products and we need to look at those when producing a commercial case for biofuel production.”Perhaps surprisingly, the principal foundations of algae biofuel research were laid in the USA during the presidency of George W. Bush, particularly at the US National Renewable Energy Laboratory (NREL; Golden, CO), the largest federal agency dedicated to research on alternative energy. The interest in algae was triggered by the growing conviction that microalgae could greatly reduce the amount of land or water surface needed to produce sustainable energy, according to Mike Seibert, research fellow at NREL. “Corn grain ethanol—a current biofuel—has a solar energy conversion efficiency of about 0.05%, and thus has a huge land footprint,” he explained. “Replacing all the gasoline used in the USA with corn grain ethanol would take a corn field 1,000 miles (1,600 km) a side. Algae on the other hand have [a] theoretical conversion efficiency of 10% and in practice, 2%, and so could replace all US gasoline in an area 110 miles (176 km) a side.”Given this promise, Europe is racing to catch up with the USA. A lobbying group, the European Algae Biomass Association (EABA), has been established with support from the European Commission to promote research and generate funding, thus demonstrating confidence that the commercial production of algae biofuels can be achieved, perhaps within as little as a decade. In the UK, the Carbon Trust has established a programme to achieve commercial-scale production of biofuels from algae by 2020. “I think by then it will have achieved parity with current biofuels, reaching US$1 per litre production costs, about 10 times cheaper than is possible with algae today,” Graziano said.But the large-scale potential of algae biofuels remains unproven and requires more fundamental research, cautioned Pierre-Antoine Vernon, project manager of the European Biodiesel Board (EBB), a non-profit organization in Brussels, Belgium, set up in 1997 by biofuel producers to promote the development and use of biofuel in the European Union (EU). “It should be kept in mind that this is not yet a mature technology, as indicated by the diversity of algae strains, processing techniques and end products, which are typical for a nascent industry sector trying to identify the right technological path to the objective pursued,” he said.The interest in algae was triggered by the growing conviction that microalgae could greatly reduce the amount of land or water surface needed to produce sustainable energy…There are also regulatory and commercial factors that might inhibit large-scale deployment of algae farms for biofuel production. “You should not underestimate the regulatory barriers to the introduction of new technologies,” Vernon said. “The EBB is currently facing strong opposition from the oil and car industries in the context of the technical standardisation for biodiesel and diesel.”Such opposition is rooted partly in the vested interests of the oil industry, but also in a natural desire to raise the bar when it comes to monitoring the safety and environmental suitability of biofuels, which must be seen to be squeaky clean and as carbon neutral as possible. “Biofuels use is under scrutiny wherever they are used, even while they represent a mere 5% of fuels used in the EU,” Vernon said. “By contrast, the remaining 95% of fossil fuels are still free from sustainability reporting, and even massive oil spills with incomparably higher consequences on biodiversity and the environment are not likely to prompt the introduction of sustainability criteria.”There are also regulatory and commercial factors that might inhibit large-scale deployment of algae farms for biofuel productionThis last point is now being put to the test by the BP spillage in the Gulf of Mexico; US President Barack Obama, in his Oval Office speech in June, called for a new focus on alternative sources of energy. Yet even this is a double-edged sword for the biofuel industry, according to Mike Griffin, an expert on the impact of oil spills from Carnegie Mellon University (Pittsburgh, PA, USA). “For the next five years you will see more money in oil spill effects work,” he said. “More money flows after each major spill until the politicians forget. This could mean less money for everything else since, with our economic situation, the pie is shrinking.”Nevertheless, the future of algae biofuel research seems secure, even if the extent of funding depends on larger economic factors. Apart from energy conversion efficiency, algae could score from other by-products that would improve the economics of production. As Vernon noted, the economics of algae is similar to that of current biofuels in the sense that you need to find applications for the main product—the oil used to make biofuels—and the by-products, mainly protein and carbohydrates. “For soybean, which was cultivated to produce soybean meal to feed cattle long before biofuels existed, an application was already there. For algae, the challenge is to find a species whose ‘algae meal'' can be used before considering biofuels production.” Promisingly, it looks as if the “algae meal” too could be used to feed animals (Becker, 2007).In addition to protein and the oils that are used for biofuels, algae also produce carbohydrates, which could be used to produce biogas: methane and carbon dioxide. “You can recycle the CO₂ back into the system, and burn the methane to produce electricity, yielding water and more CO₂, which again would go back into the algae pond,” Graziano explained.Furthermore, the conversion of lipids into biofuels can, as Vernon pointed out, be accomplished by using methods established for biodiesel production from plants. “That is one way to harness the potential of algae, as one possible feedstock for biodiesel production, by making them produce lipids that can in turn be trans-esterified into biodiesel,” he said. “Trans-esterification is a rather simple chemical reaction, for which tried-and-tested production technology emitting little greenhouse gas is available.”There is also the more remote possibility of generating electricity directly from algae. Researchers from Stanford University in the USA and Yonsei University in Seoul, South Korea, inserted gold nanoelectrodes into individual cells, drawing one picoampere (10⁻¹² A) of current from each (Ryu et al, 2010). At this level it would take about a trillion photosynthesizing cells more than an hour to generate the amount of energy stored in a single AA battery. Yet, as the study''s lead author Won Hyoung Ryu from Yonsei University pointed out, electricity could be generated more efficiently by cutting out the intermediate step of producing biofuels, or even by creating hydrogen, for example, as a direct output—the hydrogen would still need to be burned first. “The extraction of photosynthetic electrons requires fewer energy conversion steps compared with hydrogen-based electricity production that requires at least three steps such as solar to hydrogen, hydrogen to heat, and finally heat to electricity,” Ryu said. “Every conversion step involves a certain degree of energy loss.”But, as Ryu conceded, there are fundamental challenges to overcome: “First, we need to find a way to access the thylakoid membranes of millions of cells in parallel to obtain practically meaningful energy. Second, we still use external energy—overvoltage—to extract the photosynthetic electrons.” At present, energy to has to be put in before it can be extracted—an issue that certainly needs to be resolved if microalgae biofuels are ever to be used as constituents of self-charging batteries, for example. Doing so would also involve other challenges such as dealing with dead cells and waste products, which would have to be recycled within the battery.Apart from energy conversion efficiency, algae could score from other by-products that would improve the economics of productionIn the shorter term, microalgae will therefore be used to produce ‘traditional'' biofuels, given the proven advantages of algae over land plants. According to Anastasios Melis, whose laboratory at the University of California, Berkeley, USA, specializes in microalgae, cyanobacteria and plant photosynthesis: “Proven commercial scale productivities of microalgae and cyanobacteria are much better than those of plants because of the ‘carpeting effect'' […] Also, microalgae and cyanobacteria do not invest photosynthate into roots, which is biomass that cannot be harvested or exploited. There may also be secondary reasons for the efficiency advantage, such as the fact that larger plants are often limited by the supply of carbon dioxide, since their stomata tend to close under bright sunlight to protect the tissues against photo damage.”Yet, microalgae also show reduced photosynthetic efficiency under bright sunlight. The reason is that most algal species have adapted to the low light levels below the surface of the ocean by developing large chlorophyll-based antennae for harvesting as much of the limited light available as possible. A lot of energy is then wasted under stronger sunlight because the cell is incapable of converting it all, with the rest mostly dissipated as heat. This wasteful process also mops up the incoming radiation and prevents it reaching cells at greater depths, thus further limiting the scope for the high-cell populations that are necessary to increase energy conversion.Melis and colleagues have tackled this problem by engineering strains with shorter light-harvesting antennae by using DNA insertion mutagenesis in a model species, Chlamydomonas reinhardtii (Melis, 2007). This technique has a long history of use in gene discovery, but the sophistication required to develop algal cells that convert energy more efficiently is new. The fundamental idea is to create random mutations and identify those that generate the desired phenotype, in this case shorter light-harvesting antennae. Melis also inserted an exogenous DNA tag alongside the new base pairs, thus enabling him to locate the genomic DNA flanking the mutation. The gene affected by that mutation can then be identified as one associated with the development of light-harvesting antennae, if these are truncated in the resulting cell.But, as with all mutations, there is a high probability that these will cause other less desirable phenotypic changes in addition to the shortened antennae. Indeed, it has turned out that such phenotypic changes often include reduced photosynthetic efficiency, thus defeating the object of the exercise. In response, Melis developed screening processes to identify those strains with truncated antennae but with fully functioning photosynthesis. This entails visually inspecting candidate colonies, as those with low densities of chlorophyll and therefore short harvesting antennae are yellowish in colour rather than green. The selected strains are then cultured and tested for energy yields during photosynthesis to identify the most efficient energy converters.Melis has already demonstrated that cells with truncated antennae are illuminated much more uniformly in dense cultures and achieve the desired effect of creating a thick carpet of algae that efficiently harvest light. “Accordingly, the truncated light-harvesting chlorophyll antenna size property may find application in the commercial exploitation of microalgae and plants for the generation of biomass, biofuel, chemical feedstock, as well as nutraceutical and pharmaceutical products,” he said.Improving the ability of algae to harvest light is an important step towards improving the efficiency of photosynthesis, especially in the densely populated volumes of water in algae biofuel farms (Fig 1). There is also the hope of going further to bioengineer microalgae to produce biofuels or electricity directly, to cut out the need to convert lipids into biofuels such as biodiesel or hydrogen. This is a harder challenge because it involves engineering a truly fundamental change in the second stage of photosynthesis—the Calvin cycle—to redirect the energy liberated by splitting water away from the normal production of glucose and towards the desired biofuel or electricity.Open in a separate windowFigure 1Schematic drawing of an algae farm for the production of biofuels.Fortunately, evolution has provided a good starting point with the hydrogenase enzyme protecting against damage when the Calvin cycle is unable to mop up all the electrons produced by the light-harvesting process. This can happen just after sunrise when light harvesting kicks in but the Calvin cycle has not yet ‘woken up'' from its night''s rest. Under these circumstances, hydrogenase guides the electrons directly to the protons produced by splitting water to form hydrogen. The enzyme is eventually inhibited by oxygen liberated from the Calvin cycle as it gets going to allow normal photosynthesis to resume for the day.There is also the hope of going further to bioengineer microalgae to produce biofuels or electricity directly…Research has therefore focused on holding back this oxygen feedback mechanism to increase production of hydrogen. The first breakthrough came in 2000 when Melis and Seibert reported that reducing sulphate levels in algal cultures would cut the rate of photosynthesis (Melis et al, 2000). The result was a 90% reduction in oxygen production, sufficient to allow the hydrogenase enzyme to continue diverting electrons towards protons to yield hydrogen for a longer period.Although it was a considerable step forward, it did not solve the problem because the C. reinhardtii cells soon died when deprived of sulphate. Melis, Seibert and others have since worked on various methods to achieve the same effect at a molecular level without depriving the cells of sulphate ions, by diverting electrons away from the Calvin cycle while maintaining overall levels of photosynthesis. This involves getting a number of things right and will probably require tuning several genes at the whole genome level to achieve the desired objectives.The recent announcement by Craig Venter that he has created a synthetic bacterium by transplanting the genome from another species of bacteria (Gibson et al, 2010) has therefore added a new twist to the story. Venter''s technology could enable scientists to make changes to algae at the level of the whole genome, custom-building a suite of enzymatic tools to redirect the energy produced by photosynthesis. Venter''s team took bacteria from the genus Mycoplasma mycoides and re-engineered its genome from digitized sequence information. The resulting genome was then transplanted into bacterial cells of another genus, Mycoplasma capricolum, which then acquired all the phenotypic properties of M. mycoides and was capable of self-replication.Venter''s development might prove a significant step on the road towards algae-derived biofuels, according to Ryu. “I think it is a smart move and look forward to hearing what would come out in the near future,” he said. “Regardless of whether it works or fails, we will always learn something. For our approach, genomic manipulation can help greatly.” A key target, Ryu explained, will be the ferredoxin proteins that act as biological capacitors in photosynthesis by accepting electrons from the chlorophyll antennae and carrying them to the Calvin cycle. “In genetically-modified algae, ferredoxin stops delivering the photosynthetic electrons to the Calvin cycle […] Then we have a better chance of stealing the electrons,” Ryu said.Such exciting prospects stoke further optimism that science could at last provide a significant and sustainable source of energy that could be delivered in a variety of forms that might include transportation fuels, hydrogen, large-scale electricity production and possibly self-charging organic batteries.     

The psycho gene

While the idea of a ‘criminal gene'' is nonsense, there is growing evidence that some psychopathic behaviour might indeed be grounded in genesThe notion that genes play an important role in many diseases has been widely accepted, but many find it much harder to acknowledge a similar link with particular behaviour or even predisposition to crime. Partly for this reason, the study of behavioural genetics remains a controversial topic, with disagreement not just over the science itself, but even more so about the therapeutic, societal and legal implications.Too much might have been made too soon of early findings that made correlations between alleles of certain genes and tendencies to antisocial or criminal behaviour. Indeed, most researchers in the field were appalled by the decision of an Italian appeal court in 2009 to cut the sentence of a convicted murderer by one year on the grounds that he had a version of the MAOA gene, which has been linked to aggression and violence (Feresin, 2009). There is equal dismay over some US courts that went the other way and accepted genetic factors as evidence for the prosecution, leading to higher sentences on the basis that people with particular alleles cannot be cured and will remain a risk to society for longer.“Taking genetic factors into account when sentencing is plain stupid, unless we are talking about something like Down''s syndrome or some other syndrome that drastically reduces intelligence and executive functioning,” insisted Anthony Walsh from the Criminal Justice Department at Boise State University in Idaho, USA. “This is the kind of “genetic determinism” that liberals have worried themselves silly over. They just have to take one or two neuroscience and genetic classes to dispense with their ‘my genes/neurons'' made me do it. Nothing relieves one of the obligation to behave civilized.”Nonetheless, the case against specific alleles has been accumulating, notably for the low-expression variant of MAOA, known as MAOA-L, which has been linked in various studies with increased risk of violent and aggressive behaviour. The gene MAOA encodes monoamine oxidase A, an enzyme that degrades amine neurotransmitters, such as dopamine, noradrenalin and serotonin. A rare genetic disorder caused by an MAOA mutation leads to MAOA deficiency and in turn an excess of monoamine transmitters, causing excessive impulsive behaviour including hypersexuality, sleep disorder and extreme mood swings as well as a tendency to violence, which is known as Brunner syndrome.…the study of behavioural genetics remains a controversial topic, with disagreement not just over the science itself, but even more so about the therapeutic, societal and legal implicationsBut while Brunner''s syndrome is rare, having only been identified in five males of one extended family, the MAOA-L variant is extremely common and occurs in about 40% of the population. Clearly, most of these people are peaceable and have never committed a crime, and yet a study involving researchers from Austria, Italy and the USA—headed by Andreas Meyer-Lindenberg, Director of the Central Institute of Mental Health in Mannheim, Germany—has discovered that at least males with this variant had neurobiological structural factors that would predispose them to violence (Meyer et al, 2006).Using structural MRI scanning, the study identified that people with MAOA-L were more likely to have a smaller limbic system—the hippocampus, amygdala, anterior thalamic nuclei and limbic cortex—which participates in emotion, behaviour and long-term memory. The team then applied functional MRI, which measures changes in blood flow, and discovered that the MAOA-L group also showed hyperresponsiveness of the amygdala during tasks such as copying facial expressions. The amygdala is associated with emotional processing and the MAOA-L group was less able to inhibit strong emotional impulses.But some trigger is still needed to tip MAOA-L people towards violence. An earlier study suggested that this trigger could be persistent maltreatment during childhood (Caspi et al, 2002). At first sight, this suggests that nearly half the human population are predisposed to violence given these triggers, but the situation is not quite that bad—it is merely nearly half of men. Women are protected in two ways: the MAOA gene is linked to the X chromosome so that women with the MAOA-L variety on one chromosome usually have a normal allele on the other; and there is circumstantial evidence that women are also protected by other genes from being disposed to violence.In any case, caution is needed to interpret the findings of Mayer-Lindenberg''s group about the MAOA-L allele, according to Ahmad Hariri, Investigator at the Institute for Genome Sciences & Policy at Duke University (Durham, NC, USA). “This is a significant basic science finding linking genes to brain to behaviour,” he said. “But it is not a significant clinical finding in and of itself. Only in as much as this very, very, very subtle bias in the brain tips the balance toward an aggressive response to provocation is this finding even remotely clinically relevant.” In fact, as Meyer-Lindenberg himself has commented, the MAOA-L allele is just one of several genes—most of which are still not identified—that increase risk of violent or antisocial behaviour.But the whole story takes a rather different turn in the case of psychopathy, which is now widely regarded as a congenital state characterized by lack of empathy or moral compass and defined at least partly by genes, in contrast to other forms of sociopathy or antisocial personality disorder (APD), in which environmental factors make a major contribution (Fontaine & Viding, 2008).“Taking genetic factors into account when sentencing is plain stupid…”“…it is useful to think of psychopathy as mainly the product of genes and sociopathy as more subject to environmental influences”“Psychopathy does seem to be heritable, and appears to have its basis at least in part in “biological” factors linked to basic emotional systems, so that the mature psychopath never develops a complete set of pro-social emotions like empathy, guilt, and the ability to truly care about and for others,” said Richard Wiebe, who specializes in the link between psychology and criminology at Fitchburg State College in Fitchburg, MA, USA. Wiebe added though that the heritability of underlying genetic factors had yet to be conclusively established. “In other words, we know that the dependent variable, that is psychopathy, is heritable, but not enough about its causes to say that they are heritable. Nevertheless it is useful to think of psychopathy as mainly the product of genes and sociopathy as more subject to environmental influences.”Environmental factors do play a part in the behaviour of psychopaths, but in a different way than in other people who develop antisocial tendencies. The condition is more common than was once thought and affects about 0.6% of the population, according to a recent study conducted in the UK (Coid et al, 2009). Obviously, psychopathy does not always lead to crime or extreme violent behaviour; indeed its occurrence in the population used to be significantly underestimated because it was diagnosed only in people who had already shown extreme behaviour when many psychopaths do not.As there is no genetic or clinical test as yet, psychopathy is still diagnosed in terms of behaviour, but taking account of various factors in combination. Robert Hare, who led the UK study and is now at the Department of Psychology of the University of British Columbia in Vancouver, Canada, has designed a test known as the ‘Psychopathy Checklist—Revised'' of about 20 symptoms that he uses to diagnose psychopathy. These include pathological lying, superficial charm, lack of empathy and guilt, proneness to boredom and sexual promiscuity.Although it is not part of the Hare checklist, psychopaths can also be detected by their lack of a “startle reflex”, which means failure of their nervous system to respond to images or events that frighten or shock other people, such as pictures of a decapitated corpse. These tests work just as well for psychopaths who have never indulged in violence and apparently lead normal lives. They can also be used to identify psychopathy in children, who exhibit the same symptoms, in particular pathological lying, lack of empathy, tendency to violence, and lack of startle reflex—in fact, several studies have found evidence of inherited psychopathy in quite young children (Viding et al, 2005).It also appears that psychopathy is more common in men than women. This supports the theory that psychopathy might be an adaptive personality trait that gives men a reproductive advantage through greater tendency and ability to form numerous relationships and so have more children. This is unproven, but it is certainly true that male psychopaths tend to form large numbers of short-term relationships and can have an almost seductive charm.However, the trait would lose its advantage if it became too common in the population. A particular trait tends only to be advantageous in certain environmental conditions as was pointed out in the context of psychopathy by Essi Viding, Co-Director of the Developmental Risk and Resilience Unit at the Department of Psychology at University College London, UK. “I think that the simple game of evolution is to ensure survival of the species under different environmental conditions,” she said. “In some conditions it may be adaptive to be anxious and cooperative, in other conditions it may be good to exploit and be antisocial. This of course is effectively contrasting alleles that have very different effects. Hence, the same allele may serve an individual very well (and in a socially acceptable manner) in one situation, but not in another.”…psychopathy might be an adaptive personality trait that gives men a reproductive advantage through greater tendency and ability to form numerous relationships and so have more childrenThis leads back to the observation that psychopathy seems to be more common in men than women, which could have two possible explanations. First, it might be true at the genetic and neurological level, in particular if some of the relevant genes are linked to the X chromosome. Yet, this is speculative as few genes have been identified that contribute specifically to psychopathy, with most of the evidence for its heritability being statistical. There is the case of the X-linked MAOA gene, but that has only been associated with general antisocial tendencies.…irrespective of where future research leads, genes should not influence sentencing decisions one way or the other because they can never be deemed responsible for behaviourThere is in any case an alternative explanation for the apparent gender difference in psychopathic prevalence. Alice Jones, specialist in childhood and adolescent psychopathy and antisocial behaviour at Goldsmiths College, University of London, UK, suggests that the condition could be much more common among women than studies suggest. It might be that women will, in many cases, fail to register on the Hare Psychopathy Checklist—Revised because the more extreme traits are cushioned by other female factors. “There is some evidence to support this idea,” said Jones, citing work by Randy Salekin at the University of Alabama, in the USA (Salekin et al, 1997) who found that just as many women as men pass the Hare test in terms of their lack of empathy, but not on the more violent and impulsive criteria. “So, while the interpersonal aspects of psychopathy seem to be present and similar in males and females, the behavioural aspects of psychopathy are very much male-heavy,” said Jones.This comes back to the question of treatment and sentencing. Viding argues that irrespective of where future research leads, genes should not influence sentencing decisions one way or the other because they can never be deemed responsible for behaviour. “Any gene alone will be neither necessary, nor sufficient to predispose someone to high levels of psychopathic traits and as such, the responsibility for choosing to offend still resides with an individual,” she said. “Most ‘risk genes'' are common in the population and yet do not cause the majority of the individuals carrying them to offend.”But the situation is different when it comes to treatment—the appropriate therapy will depend on underlying personality tendencies. Psychopaths tend not to respond well to punishment because they cannot associate it with acts they do not consider in any way morally wrong, according to Jones. But they are more likely to respond to reward. “One example of this is currently underway at a school in Buckinghamshire (UK) for primary aged children with Emotional and Behavioural Difficulties,” said Jones. “There have been very encouraging reports from teachers so far. The intervention is largely reward based, and the pupils gain rewards by working toward reaching their behavioural targets each week. Pupils can ‘cash-in'' their rewards daily, or they can save them up for a more substantial reward later in the week.”Whether this will help these children to lead constructive adult lives remains to be seen. It does provide further evidence though that while it might not be possible to cure psychopaths, it may be possible to direct their selfish tendencies away from crime and violence towards more positive and creative activities.     

Microbial rights?

Our ability to disrupt habitats and manipulate living organisms requires a discussion of the ethics of microbiology, even if we argue that microbes themselves have no rights.Synthetic biology and the increasing complexity of molecular biology have brought us to the stage at which we can synthesize new microorganisms. This has generated pressing questions about whether these new organisms have any place in our system of ethics and how we should treat them.The idea that microbes might have some moral claims on us beyond their practical uses or instrumental value is not a new question. Microbiologist Bernard Dixon (1976) presciently asked whether it was ethical to take the smallpox virus to extinction at the height of the attempts of the World Health Organization in the 1970s to eradicate it. There is no unambiguous answer. Today, we might still ask this question, but we might extend it to ask whether the destruction or extinction of a synthetic microbe that was made by humans is also ethically questionable or is such an entity—in that it is designed—more like a machine, which we have no compunction in terminating? Would two lethal pathogens, one of them synthetic and one of them natural, but otherwise identical, command the same moral claims?In a colloquial way, we might ask whether microbes have rights. In previous papers (Cockell, 2004) I have discussed the ‘rights'' of microbes and further explored some issues about the ethics we apply to them (Cockell, 2008). Julian Davies, in a recent opinion article in EMBO reports (Davies, 2010) described my assertion that they should have constitutional rights as ‘ridiculous''. Although I did suggest that environmental law could be changed to recognize the protection of microbial ecosystems—which would imply statutory rights or protection—nowhere have I claimed that microbes should have ‘constitutional'' rights. Nevertheless, this misattribution provides a useful demonstration of the confusion that exists about exactly how we should treat microbes.Few people are in any doubt that microbes should be conserved for their direct uses to humans, for example, in food and drug production, and their indirect uses such as the crucial role they have in the health of ecosystems. Indeed, these motivations can be used to prioritize microbial conservation and protection efforts (Cockell & Jones, 2009). The crucial question is whether microbes have ‘intrinsic value'' beyond their practical uses. If the answer is ‘no'', then we should have no guilt about deliberately driving microbes to extinction for our benefit. However, there are people who feel uneasy with this conclusion, a feeling that calls forth more complex ethical questions.The question is whether microbes have some sort of ‘interests'' that make demands on our treatment of them that go beyond a mere utilitarian calculation. These arguments themselves question what we define as ‘interests'' and whether interests make demands on us. A microbe has no future plans or thought processes; the sorts of interests that are accepted as being of sufficient scope to place demands on our treatment of other human beings, for instance. However, microbes do have biological interests. A halophilic microbe might eventually die if it is dropped into freshwater. Does our knowledge of what is in the biological interests of a microbe mean that we must show it any consideration beyond practical uses? The answer is not obviously negative (Taylor, 1981), but even if we decide that it is, this does not let us off the hook quite yet.There are other intrinsic value arguments that are more obscure, particularly those around the notion of ‘respect''; the idea that we should show empathy towards the trajectory, however deterministic, of other life forms. These unquantifiable and controversial arguments might, nevertheless, partly explain any unease that we have in watching a group of people smash up and destroy some exquisite microbial mats, just because they were bored.Clearly, human instrumental needs do trump microbes at some level. If they did not, we could not use bleach in our houses, an absurd end-point raised in a 1970s science fiction story that explored the futuristic ramifications of full microbial rights, in which household bleaches and deodorants are banned (Patrouch, 1977).However, we should not be so quick to ridicule ideas about microbial ethics and rights. Although it might be true that phages kill a large percentage of the bacterial population of the world every few days, as Julian Davies points out, human society has achieved an unprecedented capacity for destruction and creation. Our ability to poison and disrupt habitats has been unquantified, with respect to the loss of microbial species. Both synthetic biology and bioterrorism raise the spectre of creating new organisms, including pathogens, which we might need to control or deliberately pursue to extinction. Dixon''s dilemma about the smallpox virus, raised more than 30 years ago, has become an urgent point of discussion in the ethics of molecular biology and microbiology.