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

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

Gene patents and capital investment

Will the US Supreme Court''s ruling that genes can no longer be patented in the USA boost venture capital investment into biotech and medical startup companies?Three years ago, Noubar Afeyan, managing partner and CEO of Flagship Ventures, an early-stage venture capital firm in Cambridge, Massachusetts, USA, was working with a biotech start-up company developing techniques for BRCA gene testing for breast cancer risk that avoided the patents held by Myriad Genetics, a molecular diagnostics company in Salt Lake City (Utah, USA) and the only operator in the field. However, despite the promise of the start-up''s techniques, investors were put off by Myriad''s extensive patent portfolio and fiercely defensive tactics: “A lot of investors were simply not willing to take that chance, even though our technology was superior in many ways and patentably different,” Afeyan said. The effort to launch the start-up ultimately failed.…it is also not clear how the Supreme Court''s ruling will affect the […] industry at large, now that one of the most contested patents for a human gene has been ruled invalidAfeyan believes the prospects for such start-ups improved on the morning of 13 June 2013 when the US Supreme Court ruled in an unanimous vote that Myriad''s fundamental patents on the BRCA1 and BRCA2 genes themselves are invalid, opening up the field to new competitors. The court''s ruling, however, validated Myriad''s patents for BRCA cDNA and methods-of-use.The court''s decision comes at a time when venture capital investment into the life sciences is projected to decline in the years ahead. Some believe that the court''s decision sets a precedent and could provide a boost for products, diagnostics and other tests under development that would have been legally difficult in the light of existing patents on human and other DNA sequences.The US Patent Office issued the original patents for the BRCA 1 and BRCA2 genes in 1997 and 1998 for the US National Institute of Environmental Health Services, the University of Utah and Myriad Genetics. One year earlier, Myriad had launched its first diagnostic test for breast cancer risk based on the two genes and has since aggressively defended it against both private and public competitors in court. Many universities and hospitals were originally offering the test for a lower cost, but Myriad forced them to stop and eventually monopolized BRCA-based diagnostics for breast cancer risk in the USA and several other countries.“Myriad did not create anything,” Justice Clarence Thomas wrote in the Supreme Court''s decision. “To be sure, it found an important and useful gene, but separating that gene from its surrounding genetic material is not an act of invention.” Even so, the court did uphold Myriad''s patents on the methodology of its test. Ron Rogers, a spokesman for the biotech firm, said the Supreme Court had “affirmed the patent eligibility of synthetic DNA and underscored the importance and applicability of method-of-use patents for gene-based diagnostic tests. Before the Supreme Court case we had 24 patents and 520 claims. After the Supreme Court decision, we still have 24 patents. […] [T]he number of our patent claims was reduced to 515. In the Supreme Court case itself, only nine of our 520 patent claims were at issue. Of the nine, the Supreme Court ruled that five were not patent-eligible and they ruled that four were patent-eligible. We still have strong intellectual property protection surrounding our BRCA test and the Supreme Court''s decision doesn''t change that.”Within hours of the ruling, capitalism kicked into high gear. Two companies, Ambry Genetics in Alieso Viejo, California, and Gene by Gene Ltd in Houston, Texas, USA, announced that they were launching tests for the BRCA1 and BRCA2 genes for less than the US$3,100 Myriad has been charging privately insured patients and US$2,795 for patients covered by Medicare—the government health plan for the elderly and disabled. Several other companies and universities also announced they would be offering BRCA testing.Entrepreneur Bennett Greenspan, a managing partner of Gene by Gene, explained that his company had been poised to offer BRCA testing if the Supreme Court ruled against Myriad. He said, “We had written a press release with our PR firm a month before the release of the Supreme Court with the intention that if the Supreme Court overruled the patent or invalidated the patent that we would launch right away and if they didn''t, we would just tear up the press release.” His company had previously offered BRCA gene testing in Israel based on guidelines from the European Union.Myriad Genetics has not given up defending its patents, however. On 9 and 10 July 2013, it slapped Ambry and Gene by Gene with lawsuits in the US District Court in Salt Lake City for allegedly infringing on patents covering synthetic DNA and methods-of-use related to the BRCA1 and BRCA2 genes. Rogers commented that the testing processes used by the firms “infringes 10 patents covering synthetic primers, probes and arrays, as well as methods of testing, related to the BRCA1 and BRCA2 genes.”On 6 August 2013, Ambry countersued Myriad, arguing that the company “continues a practice of using overreaching practices to wrongfully monopolize the diagnostic testing of humans'' BRCA1 and BRCA2 genes in the United States and to attempt to injure any competitor […] Due to Myriad''s anticompetitive conduct, customers must pay significantly higher prices for Myriad''s products in the relevant market, often nearly twice as high as the price of Ambry''s products and those of other competitors” [1].Just as the courts will have to clarify whether the competitors in this case infringe on Myriad''s patents, it is also not clear how the Supreme Court''s ruling will affect the biotech and diagnostics industry at large, now that one of the most contested patents for a human gene has been ruled invalid. In recent years, venture capital investment into the life sciences has been in decline. The National Venture Capital Association and the Medical Innovation & Competitiveness Coalition reported from a survey that, “An estimated funding loss of half a billion dollars over the next three years will cost America jobs at a time when we desperately need employment growth” [2]. The survey of 156 venture capital firms found that 39% of respondents said they had reduced investment in the life sciences during the previous three years, and the same proportion intended to do so in the next three years. “[US Food and Drug Administration] FDA regulatory challenges were identified as having the highest impact on these investment decisions,” the report states, adding that many investors intended to shift their focus from the US towards Europe and the Asia/Pacific region.Another report from the same groups explains how public policy involving the FDA and other players in “the medical innovation ecosystem”—including the US patent system, public agencies, tax policy, securities regulation, immigration laws and private groups such as insurers—affect the decisions of investors to commit to funding medical innovation [3].Some investors think that the court decision about the patentability of human DNA will increase confidence and help to attract investors back to the life sciencesSome investors think that the court decision about the patentability of human DNA will increase confidence and help to attract investors back to the life sciences. “The clarity is helpful because for the longest time people didn''t do things because of ambiguity about whether those patents would be enforceable,” Afeyan said. “It''s one thing to not do something because of a patent, it''s another to not do something because you know that they have patents but you''re not sure what it''s going to stop you from doing because it hasn''t been really fully fleshed out. Now I think it is reasonably well fleshed out and I think you will see more innovation in the space.”Others also appreciate the clarification from the Supreme Court about what is a patentable invention in regard to human genes and DNA. “The Myriad decision was a very solid reading of the underlying purpose of our patent law, which is to reward novel invention,” commented Patrick Chung, a partner with New Enterprise Associates, a venture capital firm in Menlo Park, California, which invested in 23andMe, a personal genomics company based in Mountain View (California, USA), and who serves on the 23andMe board.But not everyone agrees that the Supreme Court''s decision has provided clarity. “You could spin it and say that it was beneficial to create some certainty, but at the end of the day, what the Court did was reduce the scope of what you''re allowed to get patent claims on,” said Michael Schuster, a patent lawyer and Intellectual Property Partner and Co-Chair of the Life Sciences Group at Fenwick & West LLP in San Francisco, California, USA. “It''s going to be a continuing dance between companies, smart patent lawyers, and the courts to try to minimize the impact of this decision.”Kevin Noonan, a molecular biologist and patent lawyer with McDonnell Boehnen Hulbert & Berghoff LLP in Chicago, Illinois, USA, commented that he does not expect the Supreme Court decision will have much of an impact on venture investments or anything else. “This case comes at a time fortunately when biotechnology is mature enough so that the more pernicious effects of the decision are not going to be quite as harmful as they would if this had happened ten, 15 or 20 years ago,” he said. “We''re now in the ‘post-genomic'' era; since the late ‘90s and turn of the century, the genomic and genetic data from the Human Genome Project have been on publicly available databases. As a consequence, if a company didn''t apply for a patent before the gene was disclosed publicly, it certainly is not able to apply for a patent now. The days of obtaining these sequences and trying to patent them are behind us.”Noonan also noted that the Myriad Genetics patents were due to expire in 2014–2015 anyway. “Patents are meaningless if you can''t enforce them. And when they expire, you can no longer enforce them. So it really isn''t an impediment to genetic testing now,” he explained. “What the case illustrates is a disconnect between scientists and lawyers. That''s an old battle.”George Church, professor of genetics at Harvard Medical School (Boston, Massachusetts, USA) and Director of the Personal Genome Project, maintains that the Supreme Court decision will have minimal influence on the involvement of venture capitalists in biotech. “I think it''s a non-issue. It''s basically addressing something that was already dead. That particular method of patenting or trying to patent components of nature without modification was never really a viable strategy and in a particular case of genes, most of the patents in the realm of bio-technology have added value to genes and that''s what they depend on to protect their patent portfolio—not the concept of the gene itself,” he said. “I don''t know of any investor who is freaked out by this at all. Presumably there are some, because the stock oscillates. But you can get stock to oscillate with all kinds of nonsense. But I think the sober, long-term investors who create companies that keep innovating are not impacted.”Church suggests that the biggest concern for Myriad now is whole-gene sequencing, rather than the Supreme Court''s decision. “Myriad should be worrying about the new technology, and I''m sure they''ve already considered this. The new technology allows you to sequence hundreds of genes or the whole genome for basically the price they''ve been charging all along for two genes. And from what I understand, they are expanding their collection to many genes, taking advantage of next generation sequencing as other companies have already,” he said.Whatever its consequences in the US, the Supreme Court''s decision will have little impact on other parts of the world, notably Europe, where Myriad also holds patents on the BRCA genes in several countries. Gert Matthijs, Head of the Laboratory for Molecular Diagnostics at the Centre for Human Genetics in Leuven, Belgium, says that even though the US Supreme Court has invalidated the principle of patenting genes in America, the concept remains in Europe and is supported by the European Parliament and the European Patent Convention. “Legally, nothing has changed in Europe,” he commented. “But there is some authority from the US Supreme Court even if it''s not legal authority in Europe. Much of what has been used as arguments in the Supreme Court discussions has been written down by the genetics community in Europe back in 2008 in the recommendations on behalf of the European Society for Human Genetics. The Supreme Court decision is something that most of us in Europe would agree upon only because people have been pushing towards protecting the biotech industry that the pendulum was so way out in Europe.”Benjamin Jackson, Senior Director of legal affairs at Myriad Genetics, commented that Myriad holds several patents in Europe that are not likely to be affected by the Supreme Court''s ruling. “The patent situation both generally and for Myriad is a lot clearer in Europe. The European Union Biotech Directive very clearly says that isolated DNA is patentable even if it shares the same sequence as natural DNA,” he said. “Right now, it''s pretty uncontroversial, or at least it''s well settled law basically in Europe that isolated DNA is patentable.” However, while the Directive states that “biological material which is isolated from its natural environment or produced by means of a technical process” might be patentable “even if it previously occurred in nature”, the European Patent Office (EPO) in Munich, Germany, requires that the subject matter is an inventive step and not just an obvious development of existing technology and that the industrial application and usefulness must be disclosed in the application.Myriad has opened a headquarters in Zurich and a lab in Munich during the past year, hoping to make inroads in Europe. In some EU countries, Myriad offers its BRCA test as part of cancer diagnosis. In other countries, BRCA testing is conducted at a fraction of what Myriad charges in the USA, either because institutions ignore the patents that are not enforced in their jurisdictions, or because these countries, such as Belgium, were not included in the patent granted by the European Patent Office. Moreover, in various countries BRCA testing is only available through the healthcare system and only as part of a more extensive diagnosis of cancer risk. In addition, as Matthijs commented, “[t]he healthcare system in Europe is very heterogeneous and that''s also of course a big impediment for a big laboratory to try and conquer Europe because you have to go through different reimbursement policies in different countries and that''s not easy.”Ultimately, it seems the Supreme Court''s decision might turn out to have little impact on biotech firms in either the USA or Europe. Technological advances, in particular new sequencing technologies, might render the issue of patenting individual genes increasingly irrelevant.     

Women and telomeres

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

A cost-effectiveness analysis of "test" versus "treat" patients hospitalized with suspected influenza in Hong Kong

Background

Seasonal and 2009 H1N1 influenza viruses may cause severe diseases and result in excess hospitalization and mortality in the older and younger adults, respectively. Early antiviral treatment may improve clinical outcomes. We examined potential outcomes and costs of test-guided versus empirical treatment in patients hospitalized for suspected influenza in Hong Kong.

Methods

We designed a decision tree to simulate potential outcomes of four management strategies in adults hospitalized for severe respiratory infection suspected of influenza: “immunofluorescence-assay” (IFA) or “polymerase-chain-reaction” (PCR)-guided oseltamivir treatment, “empirical treatment plus PCR” and “empirical treatment alone”. Model inputs were derived from literature. The average prevalence (11%) of influenza in 2010–2011 (58% being 2009 H1N1) among cases of respiratory infections was used in the base-case analysis. Primary outcome simulated was cost per quality-adjusted life-year (QALY) expected (ICER) from the Hong Kong healthcare providers'' perspective.

Results

In base-case analysis, “empirical treatment alone” was shown to be the most cost-effective strategy and dominated the other three options. Sensitivity analyses showed that “PCR-guided treatment” would dominate “empirical treatment alone” when the daily cost of oseltamivir exceeded USD18, or when influenza prevalence was <2.5% and the predominant circulating viruses were not 2009 H1N1. Using USD50,000 as the threshold of willingness-to-pay, “empirical treatment alone” and “PCR-guided treatment” were cost-effective 97% and 3% of time, respectively, in 10,000 Monte-Carlo simulations.

Conclusions

During influenza epidemics, empirical antiviral treatment appears to be a cost-effective strategy in managing patients hospitalized with severe respiratory infection suspected of influenza, from the perspective of healthcare providers in Hong Kong.     

Let's make Golgi

Does the Golgi self-organize or does it form around an instructive template? Evidence on both sides is piling up, but a definitive conclusion is proving elusive.In the battle to define the Golgi, discussions easily spiral into what can appear like nitpicking. In a contentious poster session, an entire worldview rests on whether you think a particular mutant is arrested with vesicles that are close to but distinct from the ER or almost budded from but still attached to the ER.Sometimes obscured by these details are the larger issues. This debate “gets to the fundamental issue of how you think of the Golgi,” says Ben Glick of the University of Chicago (Chicago, IL). “The dogma has been that you need a template to build an organelle. But in the secretory system it''s possible in principle that you could get de novo organization of structure. That''s the issue that stirs people emotionally and intellectually.”Then there are the collateral issues. There is an ongoing controversy about the nature of forward transport through the Golgi—it may occur via forward movement of small vesicles, or by gradual maturation of one cisterna to form the next. The cisternal maturation model “argues for a Golgi that can be made and consumed,” says Graham Warren (Yale University, New Haven, CT)—a situation that is more difficult to reconcile with Warren''s template-determined universe.Even more confusing is the situation in mitosis. Accounts vary wildly on how much of the Golgi disappears into the ER during mitosis. The answer would determine to what extent the cell has to rebuild the Golgi after mitosis, and what method it might use to do so.Several laboratories have made major contributions to address these issues. But none define them so clearly as those of Warren and Jennifer Lippincott-Schwartz (National Institutes of Health, Bethesda, MD). At almost every turn, on almost every issue, it seems that Warren and Lippincott-Schwartz reach opposite conclusions, sometimes based on similar or identical data.And yet, at least in public, there is a remarkable lack of rancor. “These are not easy experiments for us to do,” says Warren. “It''s all cutting-edge research and we are pushing the technology to the limit. Part of that is that you push your own interpretation.” For her part, Lippincott-Schwartz approaches a lengthy poster-session debate with Warren with something approaching glee. This is not triumphal glee, however. Rather, Lippincott-Schwartz seems to relish the opportunity to exchange ideas, and on this point Warren agrees. “Complacency is the worst thing to have in a field,” he says. The debate “has made all of us think a lot harder.”     

Knowing Right From Wrong In Mental Arithmetic Judgments: Calibration Of Confidence Predicts The Development Of Accuracy

Does knowing when mental arithmetic judgments are right—and when they are wrong—lead to more accurate judgments over time? We hypothesize that the successful detection of errors (and avoidance of false alarms) may contribute to the development of mental arithmetic performance. Insight into error detection abilities can be gained by examining the “calibration” of mental arithmetic judgments—that is, the alignment between confidence in judgments and the accuracy of those judgments. Calibration may be viewed as a measure of metacognitive monitoring ability. We conducted a developmental longitudinal investigation of the relationship between the calibration of children''s mental arithmetic judgments and their performance on a mental arithmetic task. Annually between Grades 5 and 8, children completed a problem verification task in which they rapidly judged the accuracy of arithmetic expressions (e.g., 25+50 = 75) and rated their confidence in each judgment. Results showed that calibration was strongly related to concurrent mental arithmetic performance, that calibration continued to develop even as mental arithmetic accuracy approached ceiling, that poor calibration distinguished children with mathematics learning disability from both low and typically achieving children, and that better calibration in Grade 5 predicted larger gains in mental arithmetic accuracy between Grades 5 and 8. We propose that good calibration supports the implementation of cognitive control, leading to long-term improvement in mental arithmetic accuracy. Because mental arithmetic “fluency” is critical for higher-level mathematics competence, calibration of confidence in mental arithmetic judgments may represent a novel and important developmental predictor of future mathematics performance.     

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.”     

Effect of Formant Frequency Spacing on Perceived Gender in Pre-Pubertal Children's Voices

Background

It is usually possible to identify the sex of a pre-pubertal child from their voice, despite the absence of sex differences in fundamental frequency at these ages. While it has been suggested that the overall spacing between formants (formant frequency spacing - ΔF) is a key component of the expression and perception of sex in children''s voices, the effect of its continuous variation on sex and gender attribution has not yet been investigated.

Methodology/Principal findings

In the present study we manipulated voice ΔF of eight year olds (two boys and two girls) along continua covering the observed variation of this parameter in pre-pubertal voices, and assessed the effect of this variation on adult ratings of speakers'' sex and gender in two separate experiments. In the first experiment (sex identification) adults were asked to categorise the voice as either male or female. The resulting identification function exhibited a gradual slope from male to female voice categories. In the second experiment (gender rating), adults rated the voices on a continuum from “masculine boy” to “feminine girl”, gradually decreasing their masculinity ratings as ΔF increased.

Conclusions/Significance

These results indicate that the role of ΔF in voice gender perception, which has been reported in adult voices, extends to pre-pubertal children''s voices: variation in ΔF not only affects the perceived sex, but also the perceived masculinity or femininity of the speaker. We discuss the implications of these observations for the expression and perception of gender in children''s voices given the absence of anatomical dimorphism in overall vocal tract length before puberty.     

B for bureaucracy

Despite the scientific community''s overwhelming support for the European Research Council, many grant recipients are irked about red tapeThere is one thing that most European researchers agree on: B stands for Brussels and bureaucracy. Research funding from the European Commission (EC), which distributes EU money, is accompanied by strict accountability and auditing rules in order to ensure that European taxpayers'' money is not wasted. All disbursements are treated the same, whether subsidies to farmers or grants to university researchers. However, the creation of the European Research Council (ERC) in 2007 as a new EU funding agency for basic research created high hopes among scientists for a reduced bureaucratic burden.… many researchers who have received ERC funding have been angered with accounting rules inherited from the EC''s Framework Programmes…ERC has, indeed, been a breath of fresh air to European-level research funding as it distributes substantial grants based only on the excellence of the proposal and has been overwhelmingly supported by the scientific community. Nevertheless, many researchers who have received ERC funding have been angered with accounting rules inherited from the EC''s Framework Programmes, and which seem impossible to change. In particular, a requirement to fill out time sheets to demonstrate that scientists spend an appropriate amount of time working on the project for which they received their ERC grant has triggered protests over the paperwork (Jacobs, 2009).Luis Serrano, Coordinator of the Systems Biology Programme at the Centre for Genomic Regulation in Barcelona, Spain, and recipient of a €2 million ERC Advanced Investigator Grant for five years, said the requirement of keeping time sheets is at best a waste of time and worst an insult to the high-level researchers. “Time sheets do not make much sense, to be honest. If you want to cheat, you can always cheat,” he said. He said other grants he receives from the Spanish government and the Human Frontier Science Programme do not require time sheets.Complaints by academic researchers about the creeping bureaucratization of research are not confined to the old continent (see Opinion by Paul van Helden, page 648). As most research, as well as universities and research institutes, is now funded by public agencies using taxpayers'' money, governments and regulators feel to be under pressure to make sure that the funds are not wasted or misappropriated. Yet, the USA and the EU have taken different approaches to making sure that scientists use public money correctly. In the USA, misappropriation of public money is considered a criminal offence that can be penalized by a ban on receiving public funds, fines and even jail time; in fact, a few scientists in the USA have gone to prison.By contrast, the EU puts the onus on controlling how public money is spent upfront. Research funding under the EU''s Framework Programmes requires clearly spelt out deliverables and milestones, and requires researchers to adhere to strict accountability and auditing rules. Not surprisingly, this comes with an administrative burden that has raised the ire of many scientists who feel that their time is better spent doing research. Serrano said in a major research centre such as the CRG, the administration could minimize the paper burden. “My administration prepares them for me and I go one, two, three, four, five and I do all of them. You can even have a machine sign for you,” he commented. “But I can imagine researchers who don''t have the administrative help, this can take up a significant amount of time.” For ERC grants, which by definition are for ‘blue-skies'' research and thus do not have milestones or deliverables, such paperwork is clearly not needed.Complaints by academic researchers about the creeping bureaucratization of research are not confined to the old continentNot everyone is as critical as Serrano though. Vincent Savolainen at the Division of Biology at Imperial College London, UK, and recipient of a €2.5 million, five-year ERC Advanced Investigator Grant, said, “Everything from the European Commission always comes with time sheets, and ERC is part of the European Commission.” Still, he felt it was very confusing to track time spent on individual grants for Principal Investigators such as him. “It is a little bit ridiculous but I guess there are places where people may abuse the system. So I can also see the side of the European Commission,” he said. “It''s not too bad. I can live with doing time sheets every month,” he added. “Still, it would be better if they got rid of it.”Juleen Zierath, an integrative physiologist in the Department of Molecular Medicine at Karolinska Institutet (Stockholm, Sweden), who received a €2.5 million, five-year ERC grant, takes the time sheets in her stride. “If I worked in a company, I would have to fill out a time sheet,” she said. “I''m delighted to have the funding. It''s a real merit. It''s a real honour. It really helps my work. If I have to fill out a time sheet for the privilege of having that amount of funding for five years, it''s not a big issue.”Zierath, a native of Milwaukee (WI, USA) who came to Karolinska for graduate work in 1989, said the ERC''s requirements are certainly “bureaucracy light” compared with the accounting and reporting requirements for more traditional EU funding instruments, such as the ‘Integrated Projects''. “ERC allows you to focus more on the science,” she said. “I don''t take time sheets as a signal that the European Union doesn''t count on us to be doing our work on the project. They have to be able to account for where they''re spending the money somehow and I think it''s okay. I can understand where some people would be really upset about that.”…governments and regulators feel to be under pressure to make sure that the funds are not wasted or misappropriated…The complaints about time sheets and other bureaucratic red tape have caught the attention of high-level scientists and research managers throughout Europe. In March 2009, the EC appointed an outside panel, headed by Vaira Vike-Freiberga, former President of Latvia, to review the ERC''s structures and mechanisms. The panel reported in July last year that the objective of building a world-class institution is not properly served by “undue cumbersome regulations, checks and controls.” Although fraud and mismanagement should be prevented, excessively bureaucratic procedures detract from the mission, and might be counter-productive.Helga Nowotny, President of the ERC, said the agency has to operate within the rules of the EC''s Framework Programme 7, which includes the ERC. She explained that if researchers hold several grants, the EC wants recipients to account for their time. “The Commission and the Rules of Participation of course argue that many of these researchers have more than one grant or they may have other contracts. In order to be accountable, the researchers must tell us how much time they spend on the project. But instead of simply asking if they spent a percentage of time on it, the Commission auditors insist on time sheets. I realize that filling them out has a high symbolic value for a researcher. So, why not leave it to the administration of the host institution?”Particle physicist Ian Halliday, President of the European Science Foundation and a major supporter of the ERC, said that financial irregularities that affected the EU over many years prompted the Commission to tighten its monitoring of cash outlays. “There have been endless scandals over the agricultural subsidies. Wine leaks. Nonexistent olive trees. You name it,” he said. “The Commission''s financial system is designed to cope with that kind of pressure as opposed to trusting the University of Cambridge, for example, which has been there for 800 years or so and has a well-earned reputation by now. That kind of system is applied in every corner of the European Commission. And that is basically what is causing the trouble. But these rules are not appropriate for research.”…financial irregularities that affected the EU over many years prompted the Commission to tighten its monitoring of cash outlaysNowotny is sympathetic and sensitive to the researchers'' complaints, saying that requiring time sheets for researchers sends a message of distrust. “It feels like you''re not trusted. It has this sort of pedantic touch to it,” she said. “If you''ve been recognized for doing this kind of top research, researchers feel, ‘Why bother [with time sheets]?''” But the bureaucratic alternative would not work for the ERC either. This would mean spelling out ‘deliverables'' in advance, which is clearly not possible with frontier research.Moreover, as Halliday pointed out, there is inevitably an element of fiction with time sheets in a research environment. In his area of research, for example, he considers it reasonable to track the hours of a technician fabricating parts of a telescope. But he noted that there is a different dynamic for researchers: “Scientists end up doing their science sitting in their bath at midnight. And you mull over problems and so forth. How do you put that on a time sheet?” Halliday added that one of the original arguments in establishing the ERC was to put it at an arm''s length from the Commission and in particular from financial regulations. But to require scientists to specify what proportion of their neurons are dedicated to a particular project at any hour of the day or night is nonsensical. Nowotny agreed. “The time sheet says I''ve been working on this from 11 in the morning until 6 in the evening or until midnight or whatever. This is not the way frontier research works,” she said.Halliday, who served for seven years as chief executive of the Particle Physics and Astronomy Research Council (Swindon, UK), commented that all governments require accountability. In Great Britain, for instance, much more general accountability rules are applied to grantees, thereby offering a measure of trust. “We were given a lot of latitude. Don''t get me wrong that we allowed fraud, but the system was fit for the purpose of science. If a professor says he''s spending half his time on a certain bit of medical research, let''s say, the government will expect half his salary to show up in the grants he gets from the funding agencies. We believe that if the University of Cambridge says that this guy is spending half his time on this research, then that''s probably right and nobody would get excited if it was 55% or 45%. People would get excited if it was 5%. There are checks and balances at that kind of level, but it''s not at a level of time sheets. It will be checked whether the project has done roughly what it said.”Other funding agencies also take a less bureaucratic approach. Candace Hassall, head of Basic Careers at the Wellcome Trust (London, UK), which funds research to improve human and animal health, said Wellcome''s translation awards have milestones that researchers are expected to meet. But “time sheets are something that the Wellcome Trust hasn''t considered at all. I would be astonished if we would ever consider them. We like to work closely with our researchers, but we don''t require that level of reporting detail,” she said. “We think that such detailed, day-by-day monitoring is actually potentially counterproductive overall. It drives people to be afraid to take risks when risks should be taken.”…to require scientists to specify what proportion of their neurons are dedicated to a particular project at any hour of the day or night is nonsensicalOn the other side of the Atlantic, Jack Dixon, vice president and chief scientific officer at the Howard Hughes Medical Institution (Chevy Chase, MD, USA), who directs Hughes'' investigator programme, said he''d never heard of researchers being asked to keep time sheets: “Researchers filling out time sheets is just something that''s never crossed our minds at the Hughes. I find it sort of goofy if you want to know the truth.”In fact, a system based on trust still works better in the academic worldInstead, Hughes trusts researchers to spend the money according to their needs. “We trust them,” Dixon said. “What we ask each of our scientists to do is devote 75% of their time to research and then we give them 25% of their time which they can use to teach, serve on committees. They can do consulting. They can do a variety of things. Researchers are free to explore.”There is already growing support for eliminating the time sheets and other bureaucratic requirements that come with an ERC grant, and which are obviously just a hangover from the old system. Indeed, there have been complaints, such as reviewers of grant applications having to fax in copies of their passports or identity cards, before being allowed sight of the proposals, said Nowotny. The review panel called on the EC to adapt its rules “based on trust and not suspicion and mistrust” so that the ERC can attain the “full realization of the dream shared by so many Europeans in the academic and policy world as well as in political milieus.”In fact, a system based on trust still works better in the academic world. Hassall commented that lump-sum payments encourage the necessary trust and give researchers a sense of freedom, which is already the principle behind ERC funding. “We think that you have to trust the researcher. Their careers are on the line,” she said. Nowotny hopes ERC will be allowed to take a similar approach to that of the Wellcome Trust, with its grants treated more like “a kind of prize money” than as a contract for services.She sees an opportunity to relax the bureaucratic burden with a scheduled revision of the Rules of Participation but issues a word of caution given that, when it comes to EU money, other players are involved. “We don''t know whether we will succeed in this because it''s up to the finance ministers, not even the research ministers,” she explained. “It''s the finance ministers who decide the rules of participation. If finance ministers agree then the time sheets would be gone.”     

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.”     

The basis of morality

Psychologists, anthropologists and biologists are uncovering the bigger picture behind the development of empathy and altruismMany philosophers and anthropologists might argue that among the attributes that make humans unique, it is our ability to reason morally that sets us apart from all other animals—perhaps in addition to our capacity for spirituality. From Ancient Greece and the Roman Republic, to sixth century China and the European Enlightenment; philosophers throughout the ages have pondered why humans can feel empathy or behave altruistically—and, indeed, why they even contemplate it. Only later, in the twentieth century, did the biological sciences join the quest for understanding by seeking genetic, neurological and evolutionary explanations of self-awareness and morality.The answer has so far been elusive, as biologists have neither been able to find the ‘moral'' gene—if such a thing exists—nor to identify a specific cluster of neurons or region of the brain that takes care of ethical decision making. Yet, some parts of the picture are emerging and they reveal a relationship between the complex emotional processes that enable empathy and altruism and the advanced cognitive abilities, such as mirror self-recognition (MSR), that emerged with the evolution of the more complex structural and functional components of the brain. In addition, these studies show that many more animal species than we had appreciated, including birds, display more or less primitive versions of these traits.These findings have led to a proliferation of research into ‘human-like'' social behaviour in animals. “Empathy research is really taking off, not only on adult humans in neuroscience or on children, but also animals,” commented Dutch primatologist Frans de Waal, now at Emory University in Atlanta, GA, USA, who analyses the behaviour of chimpanzees to gain insight into their emotional and cognitive abilities. “We have collected thousands of observations of so-called consolation behaviour in chimpanzees. As soon as one among them is distressed, for example losing a fight, falling from a tree, or encountering a snake, others will come over to provide reassurance. They embrace the distressed chimp or try to calm him or her with a kiss and grooming. This behaviour is typical of chimps and other apes, and is used in research on children as the main behavioural marker of ‘sympathetic concern'',” he explained.Clues about the cognitive functions and neurological features underlying ‘sympathetic concern'' can be elucidated by correlating the results from studies of children with those of higher animals that appear capable of feeling empathy and possibly altruism. “In children, MSR emerges between 18–24 months of age and its onset is concurrent with the emergence of empathic behaviour and other indices of the theory of mind,” commented Diana Reiss, a specialist in the evolution of intelligence at Hunter College of the City University of New York, USA. Reiss also pointed out that all species that exhibit MSR have large, complex brains relative to their body weight, with evidence of a developmental link between MSR and empathy, as in human children.Researchers are now working to identify the neurological basis for this link, why it evolved and how it develops with the growing individual. MSR, widely regarded as an important requirement for empathic or altruistic behaviour, has now been identified in several species beyond the great apes and humans. Although MSR is not itself interesting from the perspective of cognitive evolution—it confers no direct selective advantage—as de Waal pointed out, the importance of the mirror test resides in what it tells us about the ability of animals to analyse their relationship with their environment, especially with respect to their social partners. “The mirror test is interesting not because it shows that an animal has the capacity for self-recognition but because of the cognitive abilities that are associated with MSR,” he explained.…biologists have neither been able to find the ‘moral'' gene—if such a thing exists—nor to identify a specific cluster of neurons or region of the brain that takes care of ethical decision makingGordon Gallup originally demonstrated MSR in animals in 1970 (Gallup, 1970). He developed a test in which a visible coloured mark is made on a part of the animal''s body that it cannot see without using a mirror. The test determines whether the animal can use the reflection to locate the mark and then touch or rub it, thus revealing that it can tell the reflection is of itself and not of another individual. Since Gallup''s early experiments, MSR has been seen in a number of animals, most notably dolphins (Reiss & Marino, 2001), the Asian elephant (Plotnik et al, 2006) and, a first for birds, the magpie (Prior et al, 2008).Although MSR has now been demonstrated in several species, it is clearly confined to a small group with highly evolved social interactions. Most species in this group are also set apart from the rest of the animal kingdom because they have spindle neurons, which are believed to be a vital component of large brains capable of empathic social behaviour. These neurons tend to be larger and have a streamlined bipolar structure that is well-adapted for the rapid and coordinated transmission of signals. Also known as von Economo neurons (VEN), they occur in areas of the cortex that process a large number of input signals from other brain regions, in particular the fronto-insular cortex and anterior cingulate cortex. Functionally, the VEN architecture seems to be optimized for the parallel receipt and processing of a large amount of diverse information.“Recent research has reported that spindle neurons are found to occur only in the brains of a few species—humans, the great apes, whales, dolphins and elephants—leading to the speculation that they are a possible obligatory neuronal adaptation in very large brains, permitting fast information processing and transfer along highly specific projections and that evolved in relation to emerging social behaviours,” commented Reiss, who was the first to demonstrate MSR in dolphins along with her colleague Lori Marino, also at Emory University. “It has been further suggested that these specialized brain cells may be involved in processing emotions and underlie empathic behaviour.”Although MSR has now been demonstrated in several species, it is clearly confined to a small group with highly evolved social interactionsFurthermore, the absence of spindle neurons in all other primates suggests that these evolved independently among the great apes and other species that are capable of MSR. This finding leads to the question of whether the brains of higher social animals that have spindle neurons have further common structural or functional features that also evolved in parallel. A recent study suggests that this has happened, at least in the case of elephants and humans, both of which have similar extensive regions of neocortex, which is the neurological structure responsible for sensory perception, motor commands and higher level thought processes (Goodman et al, 2009). The study examined several mammalian species to record the number of nucleotide substitutions in genes that have a crucial role in the brain; the results showed that the most substitutions occur in humans and elephants. This suggests that elephant and human brains have both encountered strong selection for this particular group of genes, which the other animals included in the study clearly had not.However, any suggestion that specific neurological structures are essential, at least for MSR, has been challenged by the discovery of MSR in magpies, which do not even have a neocortex. Although the detailed structures are different, the forebrains of magpies, along with some other members of the crow family, are large and have high neuron densities that are more comparable with humans than other bird species. Although spindle neurons have not yet been observed in magpies, their existence in birds has not been ruled out. In any case, it might be that magpies evolved more complex brain functions without the help of spindle neurons to speed up communication.Nonetheless, there seems to be a clear correlation between the emergence of MSR and empathic behaviour. Magpies, for example, have been subject to extensive research precisely because their ecological conditions have driven the evolution of social intelligence (Prior et al, 2008). They steal and store food, but they also form stable partnerships based to some extent on trust, which requires discrimination between other individuals and judgments about their intentions.…the enhanced cognitive and social interactive abilities of dolphins and great apes have allowed these species to develop rudimentary levels of morality and altruismIn the case of dolphins, the selective pressures they face are associated with their social groups—known as pods—which are able to cooperate with neighbouring groups in times of danger or when there is an opportunity to hunt for food on a larger scale. Dolphins are carnivores and have developed highly skilled cooperative techniques for hunting prey, similar to a pack of wolves hunting, but in three dimensions. Dolphins also devote a large amount of time to training their offspring to hunt and survive, and they are the only non-human mammals that exhibit strong evidence of vocal mimicry and physical imitation (Reiss et al, 1997).Although they live in superficially different ecosystems, dolphins and the great apes have been subject to fundamentally similar selective pressures, according to Marino, who co-authored the seminal study of vocal mimicry in dolphins. “Despite the seemingly disparate environmental pressures that would shape cetacean—the mammalian group including dolphins, whales and porpoises—and primate cognitive evolution, these drivers were actually extremely similar,” she said. “Both evolved complex levels of social interaction, and, in that respect, dolphins and primates evolved in, conceptually, very similar environments.”According to Marino, dolphin brain enlargement occurred only when they began to develop the use of echolocation to coordinate hunting and other activities. But other animals have developed echolocation without enlarging their brains. In the case of cetaceans and especially dolphins, Marino believes the key evolutionary driver was the incorporation of this technique into a complex system of social interaction. She argues that the enhanced cognitive and social interactive abilities of dolphins and great apes have allowed these species to develop rudimentary levels of morality and altruism.“Ongoing findings from studies of both primate and cetacean behaviour provide support for the conclusion that social complexity involves the evolution of morality,” Marino explained. “This is true in a number of ways. From an ultimate evolutionarily point of view, complex group living requires ways to regulate interactions among individuals in order to keep the group intact. Frans de Waal has provided abundant evidence for this argument in primates and I would contend the same is true of cetaceans. On a proximate level, much of the morality we see in primate and cetacean groups is underwritten by empathy, which is enabled by the kind of awareness of self and other that dolphins and primates—particularly great apes and humans—demonstrate.”Such behaviour might have evolved partly because altruism enhanced individual survival chances—providing that the cost was not too great. But, according to Antonio Damasio, Director of the Brain and Creativity Institute at the University of Southern California in Los Angeles, CA, USA, the key driver might have been that altruism enabled individuals to make ‘wiser'' decisions. Humans might be unique in the degree to which we apply ethics and morality to rational decision-making, but the presence of empathy in animals provides important clues about the neurological underpinnings of these abilities. In particular, research with animals might help to settle the long-standing argument about whether morality and altruism can be regarded as independent of the brain''s hardware, or whether morality is hard-wired into the brain and is a product of our neurological evolution.…humans commonly appear to balance rational and emotional factors when making judgements, creating the impression that there are distinct neural systems competing with each otherSome studies seem to suggest that the latter is true. For example, an experiment at the University of Zurich, Switzerland, in which subjects were asked to divide up a sum of money on a supposedly fair basis, found that the disruption of cognition altered the moral behaviour of the participants. In the so-called Ultimatum Game, one of the two participants—who does not know how much money is available—is required to make an offer to the other, who does know the size of the pot. If the second player does not accept, neither player receives anything, so in a sense it can be seen as a test of indignation versus greed. If the pot is big, the second player might decide to swallow his or her pride and accept it. The first player, however, might decide to make a generous offer in order to be sure it would be accepted. During the game, the Swiss researchers applied low-frequency transcranial magnetic stimulation to disrupt either the right or left dorsolateral prefrontal cortex of their test subjects. Disruption of the right side made them more susceptible to ‘immoral'' decisions as they were more willing to make offers that they judged to be unfair to their partners. Yet, they retained their ability to determine fairness. The researchers concluded that the right side of the prefrontal cortex has an implicit role in determining how to apply moral or ethical standards to information made available by cognitive processes (Sanfey et al, 2003).This suggests that morality is hard-wired and does not exist independently of the brain''s complex biochemistry, at least according to Damasio. “Emotions and feelings, as we know them, are related to our ‘wet'' biology, to our flesh,” he said. “Formally you can construct them in robotic artefacts but there is no reason to believe [that] they would be the same.”In this regard, Michael Koenigs, from the Department of Psychiatry at the University of Wisconsin–Madison, USA, pointed out that humans commonly appear to balance rational and emotional factors when making judgements, creating the impression that there are distinct neural systems competing with each other. “From a psychological standpoint, in the midst of a sticky moral dilemma it can certainly feel like your mind is being pulled in two different directions,” he said. “And in terms of the brain, it is very clear that certain areas are more concerned with emotion and affect, while other areas are more associated with ‘cold'' cognitive processes. Both systems play a role in determining morality, but at the neural level the relationship between the systems is more of an integration than a competition.”Until recently there was very little direct observation of these neurological processes at work. However, recent research based on functional magnetic resonance imaging has revealed that ‘true'' and ‘false'' statements activate different regions of the prefrontal cortex. The researchers found that people tend to use separate processes to resolve the distinctions between true and false statements, unless the answer is blindingly obvious (Marques et al, 2009). They concluded that people accept statements as true initially and confirm this merely by a call to memory. However, if the initial check suggests that the statement might be false, further reasoning is required to confirm the rejection. “The idea supported by this paper and others is that when the statement to verify is true—and by default we assume [that] it is—the task is to find if we have or recognize that information in our memory,” explained Frederico Marques, one of the authors of the study from the University of Lisbon, Portugal. “When we do not find that information, or if we have doubts, we further process the information, more like problem solving.”Animals that are capable of MSR also possess primitive abilities to assess truth or falsehood. Magpies, for example, have to decide whether a particular individual can be trusted to not steal food. Of course, more research is needed to provide further insight into the neurological processes involved in such assessments and to illuminate the evolutionary history of such a skill. What is established, however, is that the roots of complex social behaviour and the capacity for abstract thought—as well as ethical judgment, perhaps—can be found predominantly in the more advanced warm-blooded and social vertebrates. The capacity for morality is perhaps not, after all, uniquely human.     

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

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

Sidebar A | Research in paradise

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

Needles in a haystack. Genomic tools have become powerful tools for conservation biologists to monitor the spread of invasive species

Early detection and monitoring are key to controlling invasive species. Genomics and new sequencing technologies are now providing powerful new tools to track and combat relentless pestsIn the late 1960s, an Air France pilot and his family took a holiday in swampy Louisiana in the southeastern USA and were intrigued by the giant bullfrogs, Rana catesbeiana. The family introduced a dozen of the animals to a pond in the Bordeaux region of southwestern France, inadvertently starting a major invasion that affected thousands of lakes and creeks with devastating effects on the native fauna. “They eat everything and if you go to a pond where there are bullfrogs, there are no other amphibians [...] because bullfrogs prey on other animals or because they are spreading a disease—chytridiomycosis—that is absent from some European areas,” said conservation biologist Francesco Ficetola of the Department of Environmental Sciences at the University of Milano–Bicocca in Italy. “There was nothing like them in Europe,” he added.As part of his postdoctoral research, Ficetola studied the frog invasion in Europe at the Université de Savoie and the University of Grenoble in France. To monitor their distribution, he pioneered the use of environmental DNA (eDNA) to detect R. catesbeiana without observing the animals themselves. He and his colleagues took water samples, extracted eDNA and used primers monomorphic to nearly 400 bullfrog samples to demonstrate their presence in wetlands, even in low densities.“The significance was that we were able to detect the presence of the species without seeing or hearing the species,” Ficetola said. The eDNA technique has further potential: “As the environment can retain the molecular imprint of inhabiting species, our approach allows the reliable detection of secretive organisms in wetlands without direct observation. Combined with massive sequencing and the development of DNA barcodes that enable species identification, this approach opens new perspectives for the assessment of current biodiversity from environmental samples” (Ficetola et al, 2008)....molecular and genomic tools to identify, monitor and control invasive species have become increasingly sophisticated during the past five years...According to David Lodge, a biologist at the University of Notre Dame (South Bend, IN, USA), molecular and genomic tools to identify, monitor and control invasive species have become increasingly sophisticated during the past five years and are especially valuable in aquatic environments. “Hair traps and scat sampling have been used for mammals for a long time. You don''t have to catch the lynx, for example. You just put a piece of wire or tape on a trail and you get a little bit of hair and then you do genetic analysis to figure out which species it is. With enough sampling and genetic sequencing, you could even estimate the number of individuals in a population,” Lodge explained. Technological advances now make it possible to apply this technique to aquatic ecosystems to track everything from whales down to the smallest organisms.Most invasive species eventually find their ecological niche among the natives, but some can turn into pests, particularly if the new environment does not pose any threats for them such as predators or diseases. The American bullfrog in Europe, the cane toad, Bufo marinus, in Australia, or the zebra mussel, Dreissena polymorpha, in the Great Lakes have all wreaked havoc on the environment and have had an impact on commercial interests. In addition to standard control measures—such as killing animals or halting their further migration with barriers—scientists have also explored biological methods of tracking and controlling invasive species, but it is only in the past few years that these have become efficient enough to find the proverbial needle in a haystack.In the USA, these genomic tools are being applied to track Asian carp species in the Mississippi, its tributary Illinois River and the Great LakesIn the USA, these genomic tools are being applied to track Asian carp species in the Mississippi, its tributary Illinois river and the Great Lakes. The large, jumping carp have negative effects on the native fish and are even able to knock down boaters (http://www.youtube.com/watch?v=yS7zkTnQVaM). Christopher Dionigi, assistant director for National Policy and Programs of the US National Invasive Species Council (Washington, DC, USA), a cooperative of federal agencies created in 1999, said, “They''re large, they do jump out of the water, they can achieve very high densities in specific areas, and [have] impacted a lot of native fisheries, and also game fish.” The silver and bighead carp are harvesting phytoplankton and zooplankton, which are dietary mainstays for many other species. Lodge described the carp as “aquatic cows” that outgrow their predators and compete with other species for food....Lodge and his colleagues are using eDNA to tackle a raging political issue in the American Midwest: whether Asian carp are invading Lake Michigan around Chicago...Inspired by Ficetola''s eDNA work and his own research to develop detection tools for species in the ballast water of ships, Lodge and his colleagues are using eDNA to tackle a raging political issue in the American Midwest: whether Asian carp are invading Lake Michigan around Chicago—and potentially the rest of the Great Lakes—from the Mississippi River.Neighbouring states, led by Michigan, have taken the US Army Corps of Engineers and the Chicago Metropolitan Water Reclamation District to court to get Chicago to close locks on the Chicago Sanitary and Ship Canal, which was built to divert Chicago''s sewage away from Lake Michigan into the Mississippi instead. The main dispute is whether the canal allows the Asian carp to invade Lake Michigan.Since 2009, Lodge''s group has been conducting a risk assessment for the Army Corps to determine whether carp and other invasive species are able to move through the canal into the Great Lakes. The team collected more than 1,000 surface water samples, extracted DNA and used markers specific for Hypophthalmichthys nobilis and H. molitrix (Jerde et al, 2011). Subsequently, commercial fishermen caught an adult bighead carp within 13 km of Lake Michigan, only 4 km upstream from the nearest positive eDNA detection.“There has been a lot of hand-wringing about where the carp are. We wanted to see if we could detect the presence of Asian carp without even seeing them,” Lodge explained. “The most important thing we found (using eDNA) was DNA of both species in many places on the lake side of the electric barriers that the Army Corps of Engineers maintains in the canal [to keep the carp out of the lake]”....eDNA can help in early detection of invasive species, which is key to effective management on the basis of ''early detection, rapid response''He added that eDNA can help in early detection of invasive species, which is key to effective management on the basis of ''early detection, rapid response''. “Because eDNA evidence indicates that at least silver carp have entered Lake Michigan, surveillance is warranted within Great Lakes rivers that may be colonized and could support successful spawning,” Lodge said. “The eDNA method appears well-suited to rapid surveys across the large spatial scale that will be required in the Great Lakes.” He added that it might be possible to poison the carp when they aggregate to spawn.Nathan Bott, a molecular-diagnostic researcher at the South Australian Research and Development Institute (SARDI; Henley Beach, SA, Australia), is adapting a technique to extract DNA from soil to detect invasive species in the ballasts of ships. This approach involves identifying DNA from pests, some of which have the potential to destroy farmed or fished mussel, scallop and abalone. Bott has been working on assays for the Asian bag mussel, Musculista senhousia, northern Pacific sea star, Asterias amurensis, and European fan worm, Sabella spallanzanii.He said SARDI is in the process of purchasing a 454 sequencer to verify positive samples. “The idea is if we are getting positives in the ports, and particularly if the species in question is considered a significant threat, the authorities would want to conduct further surveys.” Bott explained that quantitative PCR can screen thousands of samples per day, and the 454 sequencer would be used to confirm the positives to deliver a rapid result. “If we can carry out a quick and relatively inexpensive experiment on the eDNA result with quantitative PCR using our 454, then we can save everyone a lot of time and money, and rather than concentrating on confirming the presence of the pest, a control strategy can be instigated.”Once an invasive species is identified, what can de done to remove it? The French took to shooting and trapping American bullfrogs, removing eggs and tadpoles and draining wetlands. The Americans built electrical fences to try to stop the Asian carp from entering the Great Lakes. The state of Illinois has even supported a fishing operation to catch Asian carp, shipping the fillets to China—a scheme that could potentially lead to perverse incentives to introduce more fish....biologists are refining an old concept for species control that disrupts the ratio of sexes in order to control or even kill off invasive speciesMeanwhile, biologists are refining an old concept for species control that disrupts the ratio of sexes in order to control or even kill off invasive species. The basic idea—creating sterile males, mainly by using irradiation, and releasing them by the millions—is not new. Sterile males compete with wild males for the females but do not produce offspring. Repeated introductions of these populations can control or even wipe out whole populations. Since its first application in the 1950s, there have been several success stories, including eradication of the screw-worm fly (Cochliomyia hominivorax) in North America and control of several species of fruit flies.In recent years, the concept has been improved by using molecular and genetic approaches. Ron Thresher, a marine ecologist who researches invasive species for the Australian Commonwealth Scientific and Industrial Research Organization in Hobart, Tasmania, Australia, said that common carp—bottom-feeders that foul water and dig up plants—were causing problems Down Under. However, he said that stakeholders, such as public and commercial fishing interests, resist biological controls—introducing predators, parasites or genetically modified viruses to make carp sterile—because these could have unintended consequences.As a result, his group has begun exploring another approach, while gently steering away from the transgenic controversies. “We''ve been careful to make it clear to people that we''re using genetic-modification technology but it''s not transgenic,” he said. “What we''re doing is taking a carp''s native genes and basically rearranging them a little bit. So it''s using wholly native fish genes at this point. This makes a large difference in terms of public acceptability.”Thresher said his group has been developing techniques that control gene activity with the goal of causing sterility in females or causing females to change sex. The approach has been proven in lab studies in zebra fish and is now being applied to carp. He estimates that it would take 50 years to eliminate the carp with this approach. “It''s generation and time dependent,” he said.Like Thresher, John Teem, a molecular biologist at the Florida Department of Agriculture and Consumer Services (Tallahassee, FL, USA), is tinkering with fish genetics and hormones to develop a Trojan fish with two Y chromosomes that would cause a population to collapse over time.Normally, a female has two X chromosomes and males have an X and a Y chromosome; it is the Y chromosome that determines ''maleness''. Teem said his strategy would create female fish with two Y chromosomes. This fish, when introduced into a target invasive population, will begin to mate with normal males (XY) producing only male progeny. Half of those males will be YY males that will themselves mate and produce only male progeny.“We''re trying to change the sex ratio of the population so that there are more males and fewer females at each generation. By flooding the system with Y chromosomes, more and more male fish are produced,” Teem explained. “Ultimately, the population collapses when there are no more females.” For a fish with a one-year mating cycle, he estimated that it would take 70 years to eradicate a population.Production of YY females involves selective breeding of fish that have been sex-reversed by hormone treatment as juveniles. The process uses techniques that are commonly employed in the aquaculture industry and does not rely on recombinant DNA technology. Teem said the approach could work on carp or other fish with an XY-chromosome sex determination, but he has been focusing on tilapia, which was introduced to control invasive aquatic plants in Florida but has now become a pest. “They''re very aggressive when they''re defending their nest,” he said. “They will attack other fish. If the native fish need that same territory to reproduce, tilapia can exclude them from that resource and negatively impact their reproduction.”...the idea of a tricorder has been around for decades and would be a useful tool to identify and monitor invasive species as well as any other plants and animalsUltimately, however, early detection and thorough monitoring is the best defence against invasions. Daniel Janzen, an evolutionary biologist from the University of Pennsylvania (Philadelphia, PA, USA), is working on a gadget that could enable the development of a dense surveillance system for invasive pests, using an army of volunteers. His tool resembles a species-level ''tricorder'', similar to that from the sci-fi franchise Star Trek, in which a character would use the portable device to detect life-forms and resources on an alien planet. Janzen said the idea of a tricorder has been around for decades and would be a useful tool to identify and monitor invasive species as well as any other plants and animals.Since 1978, Janzen has been studying moth and butterfly caterpillars in the northwestern corner of Costa Rica. By 2003, he had built a database of 3,000 species out of an estimated 12,500 in this region. That year, he connected with geneticist Paul Hebert, a researcher from the University of Guelph in Canada and inventor of the ''DNA-barcoding'' technique that uses short snippets of mitochondrial DNA to identify species. Their goal is to develop a hand-held personal reader the size and cost of a pocket comb. Janzen and Herbert envision that their ''barcorders'' would be used by farmers, game wardens, school children or anyone else.“I can''t think of any better way for anybody, everybody out there to be telling you whether invasive species are here, there and otherwise, than to have this device in their back pocket,” Janzen said. “How many farmers and other outdoors people are there in North America? If every one of them had a barcorder and every time he saw a weird weed growing in his wheat fields, he just pulled a little chip off a leaf and stuck it in his barcorder that would tell the USDA or some other central agency, ''Ah! This plant grows there.''”Bott, in South Australia, agreed that such devices would be a great help to monitor the spread of invasive species. “We can''t be everywhere at once sampling all these different areas. But having the ability to actually go down and test them on site would, in the future, really increase the throughput of our testing and make it a lot easier and possibly less expensive to test a wide range of species. It''s not a fantasy. It''s achievable.”     

Twin Town in South Brazil: A Nazi's Experiment or a Genetic Founder Effect?

Cândido Godói (CG) is a small municipality in South Brazil with approximately 6,000 inhabitants. It is known as the “Twins'' Town” due to its high rate of twin births. Recently it was claimed that such high frequency of twinning would be connected to experiments performed by the German Nazi doctor Joseph Mengele. It is known, however, that this town was founded by a small number of families and therefore a genetic founder effect may represent an alternatively explanation for the high twinning prevalence in CG. In this study, we tested specific predictions of the “Nazi''s experiment” and of the “founder effect” hypotheses. We surveyed a total of 6,262 baptism records from 1959–2008 in CG catholic churches, and identified 91 twin pairs and one triplet. Contrary to the “Nazi''s experiment hypothesis”, there is no spurt in twinning between the years (1964–1968) when Mengele allegedly was in CG (P = 0.482). Moreover, there is no temporal trend for a declining rate of twinning since the 1960s (P = 0.351), and no difference in twinning among CG districts considering two different periods: 1927–1958 and 1959–2008 (P = 0.638). On the other hand, the “founder effect hypothesis” is supported by an isonymy analysis that shows that women who gave birth to twins have a higher inbreeding coefficient when compared to women who never had twins (0.0148, 0.0081, respectively, P = 0.019). In summary, our results show no evidence for the “Nazi''s experiment hypothesis” and strongly suggest that the “founder effect hypothesis” is a much more likely alternative for explaining the high prevalence of twinning in CG. If this hypothesis is correct, then this community represents a valuable population where genetic factors linked to twinning may be identified.     

Molecular fossils probe life's origins

Molecular fossils allow evolutionary biologists to look deep into the history of life on the Earth, far beyond the fossil record and possibly to the first living organisms.The fossil record—surviving mineral components or imprints of multicellular life—has provided valuable insights into how animals and plants evolved over millennia, but offers limited scope for discerning the origins of life itself or the separation of organisms into the three domains of eukaryotes, prokaryotes and archaea. The development of new technologies, however, is enabling scientists to analyse molecular fossils, such as the remnants of ancient nucleic acids, sugars, proteins, carbohydrates and lipids, to study the evolution of key metabolic pathways. This knowledge should enable researchers to peer back through time as far as the great oxidation event (GOE) that enabled the emergence of eukaryotic life. In addition to the analysis of the organic molecules themselves, the study of modern genomes to look for ancestral clues might yield knowledge about the protein structures present in the earliest forms of life.The GOE is thought to have occurred when cyanobacteria released free oxygen into the atmosphere through oxidative photosynthesis. While there is reasonable consensus that this occurred around 2.4 billion years ago, there is still uncertainty over how long it took until sufficient free oxygen accumulated to enable oxidative metabolism and, eventually, the emergence of new life forms. Initially, minerals, including iron, which would have been present in metallic form and plentiful, are thought to have taken up the oxygen produced by cyanobacteria. Atmospheric oxidation would not have started until the Earth''s surface minerals had become saturated, but the estimated time to that point ranges from 100 million years to 1 billion years. Because cyanobacteria are widely believed to be one of the first lifeforms because of their ability to thrive in anoxic conditions, resolution of this question could move scientists closer to establishing the origins of life.…molecular fossils provide information about the organisms they are derived from and the biosynthetic pathways in operation at the time of their formationUnlike physical fossils, molecular fossils do not contain material derived directly from the original organism itself, but rather are biomarkers that represent some of its specific chemical composition and provide a ‘signature''. Molecular fossils are embedded in rock or sediment and are altered over time by chemical and physical processes. As such, they can only be dated indirectly by analysis of the surrounding rock or sediment. Although direct dating methods are now considered fairly reliable, indirect methods are controversial because they rely on various assumptions, notably that the sample has not been contaminated and has remained fixed relative to its surroundings. “It is assumed the molecules of the microbes present in these rocks are of similar age,” said Stefan Schouten, an organic geochemist at the Royal Netherlands Institute for Sea Research, Texel, Netherlands. “Generally this assumption is correct, though in recent sediments offsets of up to 5,000 years have been noted.”The molecules are commonly separated from one another by using gas or high-pressure liquid chromatography and identified by mass spectrometry. The surrounding material is dated, usually by using well-established radiometric methods, often combined with stratigraphy: the analysis of rock or sediment formation through the accumulation of successive layers, which assumes that a lower layer must be older than the one above it.Despite the challenges, molecular fossils provide information about the organisms they are derived from and the biosynthetic pathways in operation at the time of their formation. Some of the key biomarkers in old deposits include sesquiterpenes, which indicate that a fossil came from a plant or insect; biphytanes, which point to archaea; hopanes, which suggest bacteria; 2-methylhopanes, which are specifically associated with cyanobacteria; and steranes, which point to eukaryotes. Hopanes, for instance, are derived from hopanoids, which give strength and rigidity to the plasma membranes of bacteria. Sterols fulfil a similar role in eukaryotes and form steranes under the action of sedimentary processes.The most extensive use of molecular fossils to date has been to search for biomarkers […] of the [great oxidation event] and the associated emergence of eukaryotic lifeThe most extensive use of molecular fossils to date has been to search for biomarkers that provide evidence of the GOE and the associated emergence of eukaryotic life. Notable advances have been made, but have raised major controversy over the duration of the GOE. In 1999, Jochen Brocks and colleagues at the University of Sydney, Australia, reported evidence that eukaryotes were present up to 2.7 billion years ago, which is 1 billion years earlier than had previously been believed [1]. In a paper published in Science, the researchers argued that the presence of abundant 2α-methylhopanes, which are characteristic of cyanobacteria, indicated that oxygenic photosynthesis evolved well before the atmosphere became oxidizing. They also wrote that, “the presence of steranes, particularly cholestane and its 28- to 30-carbon analogues, provides persuasive evidence for the existence of eukaryotes 500 million to 1 billion years before the extant fossil record indicates that the lineage arose.”The paper was heralded as a breakthrough and highly cited during the following decade. Brocks, however, discovered that some of the sediment samples that his team had used had been contaminated. In 2008, he coauthored a paper with different colleagues that essentially overturned the findings of the 1999 paper [2]. “The most important point is whether these biomarkers in 2.7 [billion year] old rocks are indeed that old,” Brocks said. “After many years of scientific dispute about them, others embraced the earlier findings and published follow up papers apparently vindicating the original 1999 results, but the community has come to the consensus that these hydrocarbons have entered the Archaean rocks at a later point in time” [3].Simon George, leader of the organic geochemistry group in the Department of Earth and Planetary Sciences at Macquarie University in Sydney, Australia, argues that although the discovery of contamination was a setback for Brocks and others, it does not disprove the validity of all other findings based on samples of an apparently similar age. “Jochen Brocks''s […] inference is that everybody''s work is based on contamination. He''s certainly proven that some of the samples he worked on were affected by contamination, but it''s a bit of a leap to say everyone else''s is,” George explained. He argued that findings of steranes in ancient samples have been repeated in different geographical locations and by a variety of people at several leading institutions. “I''d be surprised if everyone was seeing contamination,” he said.Gordon Love, an organic geochemist at the University of California Riverside, CA, USA, is more cautious. He commented that findings based on archaean rocks are often unreliable because the levels of biomarkers are very low, which makes it harder to sift out contaminants. “The pursuit of Archean lipid biomarkers has always been viewed as a very extreme application of molecular organic geochemistry requiring the most sophisticated and sensitive instrumentation to detect any signals at all,” he said. “We are talking about trace quantities of biomarkers that wouldn''t normally adversely affect ancient biomarker studies or even show up in routine analyses since the absolute yields of these compounds are so low, but which become significant when dealing with highly overmature Archean organic matter [original matter that has been transformed by thermal and chemical processes into oil and gas].” Nevertheless, Love noted that the conclusion that eukaryotes evolved over 2.5 billion years ago might still be correct. “We cannot say that the absence of steranes shows that eukaryotes had not evolved. The most appropriate conclusion, in my strong opinion, is that that organic matter found in Archean rocks has been so thermally transformed that we have no way of knowing whether eukaryotic biomarkers were ever present as original lipid constituents.”Answers might ultimately come from another promising line of research into archaean evolution that relies on the analysis of molecular fossils obtained from ‘fluid inclusions'' within sediment rocks. These are small microscopic bubbles of liquid and gas—typically 0.1–1.0 mm in diameter—trapped within crystals. Because they have been trapped since their formation, they are almost guaranteed to be free from contamination. The problem so far is that they have had to be analysed in bulk to provide enough fluid for separation and mass spectrometry. This requirement makes the work less reliable the further back you go because there is not enough fluid in single samples to date accurately anything that is older than 2.4 billion years.George and colleagues are now applying the well-known technique of ‘time-of-flight'' mass spectrometry to analyse individual fluid inclusions without having to extract them. This technique was developed more than 60 years ago and has long been used in inorganic chemistry. It works by directing ion beams at a sample to identify molecules by their mass-to-charge ratio. “You use beams of ions to drill down into rock and then when you get to the required depth you put the analysis beam on,” George explained. The principle is that the velocity of an ion depends on its mass-to-charge ratio, which can be calculated by measuring the time that it takes for the particle to reach a detector, thus identifying the particle. “It''s a way of assessing very small samples,” George said; adding that a lot more work on instrument development and the interpretation of results will be needed before we can say which biomarkers are present in fluid inclusion zones. “We think there are steranes in there, but it is hard for us to prove it,” George said. “We can definitely see hydrocarbons in there and be sure it is really old material, but because we can''t do gas chromatography separation on these we can''t be sure […] If we are able to prove fluid inclusions are holding this larger chemical record of life, it becomes a very important tool for understanding life''s origins, because we can go back as far as 3.2 billion years.”Love said that analysis of oil-bearing fluid inclusions, as practised by Simon George''s group, is a promising approach because the effects of extreme thermal maturity on organic molecules are often not as acute for migrated petroleum fluids trapped in sandstones under high pressure as they are for rock bitumens found in the parent rocks. But he cautioned that the migration of these fluid inclusions away from the parent rock where they originated introduces some uncertainty over dating. “There will always be some degree of ambiguity concerning the age and stratigraphic position of the parent source rock that actually generated the oil trapped in the inclusion,” Love explained. “At the same time, I look forward to seeing what they will generate from new, cleanly drilled Archean cores using the fluid inclusion approach.”Schouten likewise anticipates the results of this research and suggested that such work could finally settle the question of whether eukaryotes diverged from archaea and prokaryotes during the archaen period. “It is the work of Simon George on fluid inclusions which makes me think that we cannot fully dismiss that possibility yet,” he said.Modern genomes and proteins are also fossils in their own way, littered with evidence of genes that were useful to ancestral organisms but that have been abandoned or adapted in today''s species. The comparative analysis of genomes and surface proteins, for example, could help scientists understand how viruses evolved before the three domains of life split. Viruses are believed to have been around at the time, having coevolved with early life, but their presence is impossible to establish directly because they do not even leave molecular fossils. As such, viral evolution can only be studied through observation of their comparative structures and genetic sequences across life''s three domains. Only recently have virologists been able to look at viral origins and correlate them with the emergence of prokaryotes, eukaryotes and archaea.Sarah Butcher, from the Institute of Biotechnology at the University of Helsinki, Finland, led an international team that made a significant breakthrough in March 2013, based on an archaeal virus found in a salt pan [4]. “The major insight in the paper was to show that the molecular architecture of an archaeal virus is conserved both with the most common bacterial viruses and a wide range of eukaryotic viruses in the herpes family,” Butcher said. The study combined genomic analysis with electron microscopy and computerized image reconstruction to determine that the major coat protein of the isolated archaeal Haloarcula sinaiiensis tailed virus 1 (HSTV-1) has an almost identical structure to that of the bacterial virus Hong Kong 97 (HK97), which is one of the so called head-tailed dsDNA bacteriophages. This similarity had been predicted, but the study provided the first physical proof, backed up by equally compelling genomic evidence, according to Butcher. The analysis revealed that hallmark proteins found in dsDNA bacteriophages, such as terminases and portals, are present in the HSTV-1 genome. Furthermore, the genomes themselves had common structural features.Modern genomes and proteins are also fossils in their own way, littered with evidence of genes that were useful to ancestral organisms…Earlier work had already identified the same fold in herpes viruses, which infect a wide variety of animals, including humans [5]. As Butcher pointed out, the same lineage identified first in the HK97 bacteriophage has now been found in viruses from all three domains of life. Viruses have evolved unique mechanisms for infecting cells dependent on their hosts, but the capsid proteins seem to share common structural features. “The basic argument is that capsid proteins with the same fold share common ancestry, even when, as is often the case, they no longer share any detectable sequence similarity,” commented Roger Hendrix, a viral evolution specialist at the University of Pittsburgh, PA, USA. He explained that the idea is that the adaptation to different host environments led to fundamental sequence changes in ancestral viruses as new functions were acquired, but that there was no corresponding selective pressure to alter the fold of the capsid. “The simple interpretation of this is that there were viruses with some resemblance to modern viruses before cells started to divide into the three current domains and some of the then-existing viruses stuck with and coevolved with each of the three emerging cellular domains,” he said.He cautioned, however, that another explanation for the common fold could be that at some stage in evolution, after the three cellular domains of life split, a virus jumped across the domains, spreading the common fold. This is not likely to have occurred recently because the cells of the different domains have diverged so far that such a viral jump would be difficult, though it could have occurred only shortly after life split into three domains and cannot be ruled out.A third possible explanation for the common fold would be that it coevolved in parallel in each of the three domains, but this is less likely to have happened, according to Hendrix. “Co-evolution is a formal possibility but […] unlikely since I think it would imply that some protein folds are ‘ideal'' and selected in certain viruses of all three domains but not others,” he said. “There are too many successful ways to make a viral capsid for this to make sense, at least to me.”At any rate, the evidence does indicate that diverse viruses were around at the time of the last common ancestor of the three domains of life and contributed to their evolution through their ability to mutate quickly and donate genes to host genomes. As such, the work being done to untangle viral evolution by studying modern viruses is very much related to the advances being made with molecular fossils to probe our way back towards the origins of life.     

Visual perceptual difficulties and under-achievement at school in a large community-based sample of children

Introduction

Difficulties with visual perception (VP) are often described in children with neurological or developmental problems. However, there are few data regarding the range of visual perceptual abilities in populations of normal children, or on the impact of these abilities on children''s day-to-day functioning.

Methods

Data were obtained for 4512 participants in an ongoing birth cohort study (Avon Longitudinal Study of Parents and Children; ALSPAC). The children''s mothers responded to questions designed to elicit indications of visual perceptual difficulties or immaturity, when their children were aged 13 years. We examined associations with standardised school test results in reading and in mathematics at age 13–14 years (SATS-KS3), accounting for potential confounders including IQ.

Results

Three underlying factors explained half the variance in the VP question responses. These correlated best with questions on interpreting cluttered scenes; guidance of movement and face recognition. The adjusted parameter estimates (95% CI) for the cluttered-scenes factor (0.05; 0.02 to 0.08; p<0.001) suggested positive associations with the reading test results whilst that for the guidance-of-movement factor (0.03; 0.00 to 0.06; p = 0.026) suggested positive association with the mathematics results. The raw scores were associated with both test results.

Discussion

VP abilities were widely distributed in this sample of 13-year old children. Lower levels of VP function were associated with under-achievement in reading and in mathematics. Simple interventions can help children with VP difficulties, so research is needed into practicable, cost-effective strategies for identification and assessment, so that support can be targeted appropriately.     

The Development of Purpose During Adolescence

While there has been much research on adults' abilities to detect deception, there have been very few studies examining both children's and adults' abilities to detect children's real, spontaneous lies. The present study asked both children and adults to make judgments of children's true and false reports. Participants (N = 156) were shown videotaped sessions of children who were either spontaneously lying or telling the truth. Results indicate that both children's and adults' accuracy for detecting children's true statements was below chance. However, older children were significantly better at detecting lies than both younger children and adults.