After the year of the dumpster fire

2020 has been one of the craziest and strangest years we have lived through. Now that it’s over, it’s an opportunity to show gratitude for all the good things. Subject Categories: S&S: History & Philosophy of Science

I moved to New York City the year of the attacks on September 11, 2001, one of the bleakest moments in the history of the United States. I was also in New York City when Superstorm Sandy hit in 2012. Luckily, much fewer people died due to the storm, but it was incredibly disruptive to many scientists in the affected area—my laboratory had to move four times over a period of 6 years in the storm’s aftermath. These were awful, tragic events, but 2020 may go down in the record books as one of the most stressful and crazy years in modern times. Not to be outdone, 2021 has started terribly as well with COVID‐19 still ravaging the world and an attack on the US Capitol, something I thought I’d never see in my lifetime. The unnecessary deaths and the damage to America’s “House of the People” were heartbreaking.While these events were surely awful, nothing will be as crushing as the deaths of family members, close friends, and the children of friends; perhaps, it is these experiences—and the death of a beloved dog—that prepared me for this year and made me grateful, maybe even more than usual, for what I have. But in the age of a pandemic, what am I particularly grateful for?I''m ridiculously grateful to have a job, a roof over my head, and food security. The older I get, the more I see illness and injury affect my colleagues, family, and friends, I increasingly appreciate my good health. I am grateful for Zoom (no, I have no investment in Zoom)—not for the innumerable seminars or meetings I have attended, but for the happy hours that helped to keep me sane during the lockdown. Some of these were with my laboratory, others with friends or colleagues, sometimes spread over nine time zones. Speaking of which, I’m also grateful for getting a more powerful router for the home office.I''m immeasurably grateful to be a scientist, as it allows me to satisfy my curiosity. While not a year‐round activity, it is immensely gratifying to be able to go to my laboratory, set up experiments, and watch the results coming in. Teaching and learning from students is an incredible privilege and educating the next generation of scientists how to set up a PCR or run a protein gel can, as a well‐known lifestyle guru might say, spark serious joy. For this reason, I’m eternally grateful to my trainees; their endless curiosity, persistence, and energy makes showing up to the laboratory a pleasure. My dear friend Randy Hampton recently told me he received a student evaluation, thanking him for telling his virtually taught class that the opportunity to educate and to be educated is something worth being grateful for, a sentiment I passed onto a group of students I taught this past fall. I believe they, too, were grateful.While all of the above things focus on my own life, there are much broader things. For one, I am so grateful to all of those around the globe who wear masks and keep their distance and thereby keep themselves and others safe. I am grateful for the election of an American president who proudly wears a mask—often quite stylishly with his trademark Ray‐Ban Aviators—and has made fighting the COVID‐19 pandemic his top priority. President Biden''s decision to ramp up vaccine production and distribution, along with his federal mask mandate, will save lives, hopefully not just in the United States but worldwide.This Gen‐X‐er is also especially grateful to the citizens of Generations Y and Z around the world for fighting for social justice; I am hopeful that the Black Lives Matter movement has got traction and that we may finally see real change in how communities of color are treated. I have been heartened to see that in my adopted home state of New York, our local politicians ensure that communities that have been historically underserved are prioritized for COVID‐19 testing and vaccinations. Along these lines, I am also incredibly encouraged by the election of the first woman who also happens to be of African and Asian heritage to the office of vice president. Times are a changin''...While it is difficult to choose one, top thing to be grateful for, I would personally go for science. I am stoked that, faced with a global crisis, science came to the rescue, as it often has in the past. If I had to find a silver lining in COVID‐19—albeit it would be for the darkest of clouds—I am grateful for all of our colleagues, who despite their usual arguing, quickly and effectively developed tests, provided advice, epidemiological data and a better understanding of the virus and its mode of infection, and ultimately developed therapies and vaccines to save lives. The same can be said for the biotech and pharmaceutical industry that, notwithstanding its often‐noted faults, has been instrumental in developing, testing and mass‐producing efficient and safe vaccines in blistering, record time. Needless to say, I have also much gratitude to all of the scientists and regulators at the FDA and elsewhere who work hard to make life as we once knew it come back to us, hopefully in the near future.Once again, thank you for everything, Science.     

Work life balance?

There is no perfect recipe to balance work and life in academic research. Everyone has to find their own optimal balance to derive fulfilment from life and work. Subject Categories: S&S: Careers & Training

A few years ago, a colleague came into my office, looking a little irate, and said, “I just interviewed a prospective student, and the first question was, ‘how is work‐life balance here?’”. Said colleague then explained how this question was one of his triggers. Actually, this sentiment isn''t unusual among many PIs. And, yet, asking about one''s expected workload is a fair question. While some applicants are actually coached to ask it at interviews, I think that many younger scientists have genuine concerns about whether or not they will have enough time away from the bench in order to have a life outside of work.In a nutshell, I believe there is no one‐size‐fits‐all definition of work–life balance (WLB). I also think WLB takes different forms depending on one''s career stage. As a new graduate student, I didn''t exactly burn the midnight oil; it took me a couple of years to get my bench groove on, but once I did, I worked a lot and hard. I also worked on weekends and holidays, because I wanted answers to the questions I had, whether it was the outcome of a bacterial transformation or the result from a big animal experiment. As a post‐doc, I worked similarly hard although I may have actually spent fewer hours at the bench because I just got more efficient and because I read a lot at home and on the six train. But I also knew that I had to do as much as I could to get a job in NYC where my husband was already a faculty member. The pressure was high, and the stress was intense. If you ask people who knew me at the time, they can confirm I was also about 30 pounds lighter than I am now (for what it''s worth, I was far from emaciated!).As an assistant professor, I still worked a lot at the bench in addition to training students and writing grant applications (it took me three‐plus years and many tears to get my first grant). As science started to progress, work got even busier, but in a good way. By no means did I necessarily work harder than those around me—in fact, I know I could have worked even more. And I’m not going to lie, there can be a lot of guilt associated with not working as much as your neighbor.My example is only one of millions, and there is no general manual on how to handle WLB. Everyone has their own optimal balance they have to figure out. People with children or other dependents are particularly challenged; as someone without kids, I cannot even fathom how tough it must be. Even with some institutions providing child care or for those lucky enough to have family take care of children, juggling home life with “lab life” can create exceptional levels of stress. What I have observed over the years is that trainees and colleagues with children become ridiculously efficient; they are truly remarkable. One of my most accomplished trainees had two children, while she was a post‐doc and she is a force to be reckoned with—although no longer in my laboratory, she still is a tour de force at work, no less with child number three just delivered! I think recruiters should view candidates with families as well—if not better—equipped to multi‐task and get the job done.There are so many paths one can take in life, and there is no single, “correct” choice. If I had to define WLB, I would say it is whatever one needs to do in order to get the work done to one''s satisfaction. For some people, putting in long days and nights might be what is needed. Does someone who puts in more hours necessarily do better than one who doesn''t, or does a childless scientist produce more results than one with kids? Absolutely not. People also have different goals in life: Some are literally “wedded” to their work, while others put much more emphasis on spending time with their families and see their children grow up. Importantly, these goals are not set in stone and can fluctuate throughout one''s life. Someone recently said to me that there can be periods of intense vertical growth where “balance” is not called for, and other times in life where it is important and needed. I believe this sentiment eloquently sums up most of our lives.Now that I''m a graying, privileged professor, I have started to prioritize other areas of life, in particular, my health. I go running regularly (well, maybe jog very slowly), which takes a lot of time but it is important for me to stay healthy. Pre‐pandemic, I made plans to visit more people in person as life is too short not to see family and friends. In many ways, having acquired the skills to work more efficiently after many years in the laboratory and office, along with giving myself more time for my health, has freed up my mind to think of science differently, perhaps more creatively. It seems no matter how much I think I’m tipping the balance toward life, work still creeps in, and that’s perfectly OK. At the end of the day, my work is my life, gladly, so I no longer worry about how much I work, nor do I worry about how much time I spend away from it. If you, too, accomplish your goals and derive fulfillment from your work and your life, neither should you.     

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.”     

Decoding the genetics of rare disease: an interview with Monkol Lek

Monkol Lek, Assistant Professor at Yale University School of Medicine, and Associate Editor at Disease Models & Mechanisms, dedicates his research to finding a genetic diagnosis and improving treatments for rare disease patients. As he originally studied computer engineering at the University of New South Wales in Sydney, Australia, he now utilises computational methods to optimise large-scale genetic studies, provide globally accessible resources for genetic research communities and, importantly, resolve diagnostic odysseys for rare disease patients. Monkol completed his PhD in Prof. Kathryn North''s lab at the University of Sydney, studying the genetics of muscle strength and performance, and then continued his investigation of muscle disease in Prof. Daniel MacArthur''s lab at Massachusetts General Hospital and the Broad Institute. During his postdoc, he led several large-scale studies aimed at distinguishing pathogenic from benign variants, including the Exome Aggregation Consortium (ExAC) project ( Lek et al., 2016). Monkol established his own lab at Yale University School of Medicine, which continues to improve the diagnosis and treatment of rare muscle disease, and also focuses on underserved populations, whose genetic mutations are not as well characterised as those of European ancestry. In this interview, Monkol discusses how his own diagnosis with limb girdle muscular dystrophy has shaped his career and what he envisions for the future of genetic research in rare disease.

You have a very unique career path – could you tell us a little bit about that? My first degree was in computer engineering. When I first went to university, I studied the hardware and software of computers. I really liked the software aspect of the degree, and so I worked for IBM as a software developer when I finished university. However, during the last few years of university, I noticed that my muscles were getting weaker. My university was on a big hill, with classes at the bottom and top of the hill, and I had to stand up for about 3 h a day while commuting on public transport. It started becoming obvious that I had something wrong with my muscles because I felt totally exhausted at the end of the day. It was frustrating, because I felt that my performance at university was impacted by something that had nothing to do with my ability to think. So, I went from doctor to doctor to try to find out what was wrong with me. As a lot of doctors are not trained in rare diseases, they didn''t consider a rare disease diagnosis. Then one doctor did a blood test for creatine kinase (CK), which is leaked into the bloodstream when muscle is damaged. In healthy people, high levels of CK are detected in the bloodstream after they''ve done intensive exercise, like a marathon. If someone hasn''t done something like that, but they have high levels of circulating CK, it could be an indication that there''s something wrong with their muscles. As I had high levels of CK in my bloodstream, I then went to a neurologist, which was when I got a clinical diagnosis. At that point, they didn’t know the root cause of the problem, but they knew that I have a muscle disease based on several tests, including a nerve conduction test.I received this clinical diagnosis during my time in IBM, and that''s when I became dissatisfied with my job, because I felt that I was using all my talents to make a very big, international company richer. I was also becoming frustrated when visiting the neurologist every 6 months, as all they would tell me was that my muscles were getting weaker, which I already knew. I began to think that not much was happening in the neuromuscular disease field if that''s the best they could offer me. I wanted to know what the root cause of my disease was and if there were any treatment options. I came to the conclusion that no one would care about my disease more than I would, because I''m the one that has lived with it every day of my life.That''s when I decided to leave IBM and pursue a career in researching muscle disease. It didn''t go down well with my parents and friends, because I was leaving a well-paid job to go back to university to get paid nothing for an unknown number of years. If I had known my chances of success – completing a meaningful PhD, doing a meaningful postdoc and landing a faculty position – I wouldn''t have gone on this journey. I have been very fortunate, but I wasn''t always in the right place at the right time.When I finished my undergraduate degree in bioinformatics and physiology at the University of New South Wales, I started a PhD in Melbourne, but it didn''t work out, because not all supervisors are perfect. My wife and I then returned to Sydney, where my wife bumped into one of the professors from our undergraduate degree. She explained that we''d had a bad experience in Melbourne with our PhDs, but our passion was still to do muscle research. The professor''s daughter was researching muscle disease in Kathryn North''s lab at the University of Sydney, and she invited us to visit the lab. I was offered an opportunity to do my PhD in Kathryn''s lab, but I was initially reluctant as it was a diagnostic lab, and I was more interested in developing therapies for people with muscle disease. However, I thought I could still learn a lot about muscle physiology and, in the long term, I''m glad that I received training and mentorship from Kathy''s lab. Also, if I hadn''t done my PhD there, I wouldn''t have met Daniel MacArthur, my future boss. He was a very talented student in Kathy''s lab, who taught me a lot about scientific communication among other things, and I taught him some coding skills. He left to work on the 1000 Genomes Project in Cambridge, UK, but I kept in contact with him to get his advice on my project.When I was finishing my PhD, Daniel asked if I wanted to join the lab he was setting up in Massachusetts General Hospital and the Broad Institute. His lab was going to study common loss-of-function mutations in human populations using large datasets from the 1000 Genomes Project, but he offered me a project investigating neuromuscular diseases. As soon as I submitted my PhD thesis, I started working in his lab. This was perfect timing, because it was 2012, when exome sequencing had recently been published in the context of rare diseases (Ng et al., 2010) and, more importantly, it was becoming affordable, in terms of research. I waited over 10 years for a genetic diagnosis, so my goal was that no one should have to wait that long in the future.Through collaboration with our former PhD lab, Daniel and I used samples from undiagnosed patients to find answers for Australian families. The first family had two affected girls with undiagnosed nemaline myopathy, who had been on a diagnostic odyssey for about 9 years. It was amazing how quickly we progressed from receiving the samples to identifying the novel gene, LMOD3, associated with their disease (Yuen et al., 2014). This was part of my main project during my postdoc – working on gene discovery in neuromuscular diseases and finding answers for patients that have been waiting years and years to get a genetic diagnosis (Ghaoui et al., 2015; O''Grady et al., 2016).The project that most people know me for is the ExAC project, which was initially my ‘side’ project during my postdoc. The idea was to create a big database of all rare variants that we see in the general population, so we can better interpret the rare variants that we see in rare disease patients. When we were creating it, we thought that it may be useful to other researchers around the world. Therefore, we tried to ensure, through data-use agreements and consent processes, that we could share as many of our findings as possible. I''m happy to say my side project was quite successful. After that, I led other projects, including an analysis group in the Centre for Mendelian Genomics, to expand that framework and idea across all rare diseases, not just neuromuscular diseases (Baxter et al., 2022).I was having a lot of fun at the Broad Institute, and I was co-author on a lot of high-impact papers. However, the reason I left the Broad Institute was that I wanted to be involved in the full journey for the patients. Sometimes scientists don''t understand that getting a genetic diagnosis is not the end of the journey for a patient. After the diagnosis they want to know what treatment options are available. Yale gave me the opportunity to continue doing the gene discovery and analytical work that I was doing at the Broad Institute, plus the capability of doing experiments with mouse models to investigate gene replacement therapies and other therapeutic approaches.

“I waited over 10 years for a genetic diagnosis, so my goal was that no one should have to wait that long in the future.”

How has being both a researcher and a patient affected your career? When I was first diagnosed, there was a neurologist who discouraged me from researching my own disease and this became the basis of my TEDx talk, because I thought it was very condescending. I thought, “Just because I have this disease, it doesn''t mean that I have a low IQ”. However, this experience motivated me more. I discussed it with Kathy before starting my PhD, and her encouragement and enthusiasm was refreshing. At the time, in the early 2000s, people hadn''t accepted the idea of patients researching their own disease. Things have changed since then, mainly because there are more examples of it now (Branca, 2019), but at the time, it was really hard for me to progress in science. I always thought that people were looking at me with sympathy, and I felt like I had to achieve twice as much to get the same respect as someone else who wasn''t as talented or didn''t work as hard as me. It was frustrating, but in everyday life people still correlate physical disability with intellectual disability. For example, if my wife is pushing me in the wheelchair in public, no one ever directs a question to me because they assume that the physical disability comes with mental disabilities. There are well-known examples of scientists with physical disabilities, like Stephen Hawking, but it is still challenging in academia when you have a physical disability and people make certain assumptions about you.On the other hand, just before starting at Yale, my collaborators at the University of Massachusetts took a skin biopsy from me. With this skin biopsy, they created induced pluripotent stem cells, and, using CRISPR, they corrected my disease-associated gene variant in the cultured cells. They then published this in a Nature article, in which fig. 1 is the experiment in which they corrected my mutation (Iyer et al., 2019). Are there specific skills or knowledge you learned while working in computer engineering that have helped shape and develop your research today? When I started my PhD, there was an increase in how much genetics research, and biological research in general, relied upon big data. It can be very challenging to work with big data if you''re a biologist without a background in computer science. You can go online to teach yourself to an extent, but it gives you an advantage to learn the theory behind a lot of algorithms and other aspects of software engineering, in a formal setting. It makes the difference between building tools that take a week to analyse a set of data and building tools that take a few minutes to analyse the same data. If you can analyse the data more quickly, you can explore different possibilities and ideas much more quickly. You can''t learn everything online, and having a firm foundation of knowledge can enable you to work with big data in an efficient way.The other thing that you learn from computer science is a certain mindset when approaching problem solving. This is because you have to debug code frequently and, due to this fast pace, you learn quickly. This helped me to troubleshoot problems in biological research quickly.

“Getting a genetic diagnosis is not the end of the journey for a patient. After the diagnosis they want to know what treatment options are available.”

What do you think are the key challenges for rare disease research and diagnosis moving forward? I now have a greater appreciation of the challenges because I see it from two points of view: one as a researcher in a group and one as a PI, who leads the research. The diagnosis rate for rare disease is about 50%, so there are still 50% of patients with a disease that has an unknown genetic cause. The gold standard requirement for associating a new disease gene with a novel phenotype is that it presents in multiple unrelated families (MacArthur et al., 2014). However, when you work with rare diseases, there is the issue of small sample numbers. One challenge for basic scientists is creating good collaborations with physician scientists across the world to enable you to create a large enough dataset.The other challenge is the cost of research for these diseases with unknown genetic cause. The 50% of cases for which we know the genetic cause are no longer considered an area of research, as clinical genetic services can now diagnose these patients. To diagnose the remaining patients, you have to use more expensive technologies, such as long-read sequencing.The last thing is the interpretation of rare variants. Although the ExAC project helped with this, there is still a challenge. For example, if a patient has a rare genetic variant, this doesn''t necessarily mean it is the cause of their rare disease. This is because even healthy people have rare variants. So, we have a massive interpretation challenge in rare disease genetics, which can be overcome by creating a laboratory model system with that genetic variant to investigate it further. However, if you had 1000 variants to consider, it''s not going to scale as an animal model. So, an important question is how can we interpret these variants in a scalable manner? This is one of the main driving forces behind the new Subject Focus, ‘Genetic variance in human disease: decoding diversity to advance modern medicine’, that we are launching in DMM. You have led and coordinated several studies involving very large cohorts. From your experience what are the key components of a successful study? I think the key to a successful large cohort study with unsolved rare disease patients, is the amount of structured phenotype data you can collect. This requires a good collaborator, who has the time to prepare that data in a meaningful way, which makes it easier to find other families with the same rare disease. The other thing is to have the ability to recontact patients and collect different samples from them, because we''re moving to a more multi-omics world. Therefore, we need the ability to go beyond just collecting DNA samples. Also, we''re in a world where we''re starting to link data to electronic health records, which allows the collection of deeper and richer phenotype data that enable associations to be made between families.In addition, you can''t work in isolation. In order for us to make a meaningful impact, we need to work with groups that have specialties outside of our own. For instance, we collaborate with groups that specialise in the interpretation of non-coding variants. This is important as variants in these regions could hold the answers for some of those unsolved cases.Another key aspect to a successful study is collaboration with statistical geneticists because some of the more complicated questions are best asked by them. Some of these questions go beyond monogenic diseases. We are seeing convergence between genome-wide association studies, looking for many variants, each with very small contributions to a disease, and studies of Mendelian disease that are looking for one gene that causes disease. The field has to start looking at diseases in the middle of this spectrum, which requires statistical geneticists. This is because you need to make sure that your conclusions are correct. For instance, if you''re asking whether a rare disease is caused by a combination of two genes, then you must have a robust statistical model to show that these variants aren''t presenting together by chance. You have to prove that those two variants are acting in concert, instead of independently, to cause this disease. My colleagues at Yale published a great paper that demonstrated this concept (Timberlake et al., 2016).Lastly, it is important to forge meaningful collaborations beyond academia. A lot of my colleagues are being funded by industry collaboration, and a lot of these companies have access to more samples than we do in academia. You can also collaborate with large biobanks, such as the UK Biobank, which has a rich set of phenotype data and also the ability to recontact patients (Glynn and Greenland, 2020). The FinnGen project is a recent public–private collaboration that combines genetic data with electronic health records from Finnish biobank participants to improve disease diagnosis and treatment (Kurki et al., 2022 preprint). So, working with biobanks and industry is another way of increasing sample numbers, which is the biggest challenge in rare disease research.

“We don''t want to create disparity in terms of health, especially in the context of genetics, which will continue to become more prominent in modern medicine.”

You dedicate a lot of your research towards patients in underserved populations, such as East Asian populations, whose genetic mutations are not as well characterised as those of European ancestry. Can you explain the importance of this? One of the reasons that it took over 10 years for me to get a genetic diagnosis was because the gene that causes my disease was first reported as not commonly associated with disease in populations of European ancestry. The problem with biomedical research is that when people read that, they think it applies to everyone, even patients who have non-European ancestry. Although the gene that causes my disease aligned with my muscle disease phenotype, it wasn''t sequenced because of this assumption. They only decided to sequence this gene once they did linkage analysis of my family, and this was the only gene associated with neuromuscular disease in the linkage region they identified. This is the reason why we need to have good data on all populations. The ExAC and gnomAD studies that I worked on acknowledged that we need good allele frequency data for populations of East Asian, South Asian, Latino and African ancestry, because we don''t want to create disparity in terms of health, especially in the context of genetics, which will continue to become more prominent in modern medicine.If you want to deliver the best healthcare, you have to realise that some variants and diseases are more common in certain populations, such as Tay-Sachs disease, which is common amongst the Jewish community, and sickle cell anaemia, which is more prevalent in populations of African ancestry. By understanding these differences, we can actually find a genetic diagnosis a lot quicker. If it''s not a de novo variant, and is instead a variant inherited in the population, and if you''ve made the discovery in East Asians, there is a better chance of identifying more incidences of this variant in the population in which it was first discovered.I think it''s also good for validation of data, because if you had discovered a potential disease-causing variant and you find that this variant has a frequency of 1% or higher in a non-European population, then it''s impossible for it to be the cause of a rare disease, regardless of its frequency in a European population (Lek et al., 2016).     

Joan Heath interviews Suzanne Cory and Joan Steitz: a female perspective of science in the swinging ‘60s

Prompted by the occasion of International Women''s Day, Joan Heath and DMM reunited Professors Suzanne Cory and Joan Steitz via Zoom to discuss their extraordinary careers and joint experiences in science. They also delve into past and present challenges for women in science, and discuss the role of scientists in a post-pandemic world.

Suzanne Cory, Joan Steitz and Joan Heath (from left to right) As one of Australia''s most eminent molecular biologists, with a school in Melbourne bearing her name, Professor Suzanne Cory has been both Director of The Walter and Eliza Hall Institute of Medical Research in Australia (WEHI) and President of the Australian Academy of Science. She earned her PhD at the Medical Research Council (MRC) Laboratory of Molecular Biology (LMB) in Cambridge, UK, with postdoctoral training at the University of Geneva. She continues her research at WEHI as an honorary distinguished research fellow, investigating the genetics of the immune system in the development of blood cancers and the effects of chemotherapeutic drugs on cancer cells.Joan Steitz – currently Sterling Professor of Molecular Biophysics and Biochemistry at Yale University, and for 35 years the recipient of a Howard Hughes fellowship – is best known for her seminal work in RNA biology. She was the first female graduate student to join the laboratory of James Watson at Harvard University and proceeded with her postdoctoral training at the MRC LMB in Cambridge. Her pioneering research delved into the fundamental mechanisms of ribosome and messenger RNA interactions, as well as RNA splicing, heralding the phenomenon of alternative RNA splicing. A recipient of many awards and honours, she is also involved in international projects aimed at supporting women in science.Host Joan Heath heads a laboratory at WEHI in Australia. She received her undergraduate degree from the University of Cambridge, followed by her PhD at the Strangeways Research Laboratory also in Cambridge, then just across the road from the MRC LMB. After postdoctoral positions in bone biology and osteoporosis research, Joan joined the Ludwig Institute for Cancer Research where she became a laboratory head, and changed her focus to cancer research using zebrafish to identify genes that are indispensable for the rapid growth and proliferation of cells during development. She joined the WEHI in 2012. There she showed that the same developmental genes are also required by highly proliferative, difficult-to-treat cancers, including lung, liver and stomach cancer, paving the way for translational research targeting these genes in novel cancer therapies. Joan H: How long have you two known each other? Suzanne: I was calculating that this morning and I was astonished because it seems like only yesterday, but it has been 55 years since we met in Cambridge. It has been a voyage in science and a voyage in the world because we have always made a point to meet up in beautiful places and go hiking. That is how we''ve been able to renew our friendship over all these years. Joan H: Where were you when you first met? Joan S: We both were working at the MRC LMB in Cambridge, England. Suzanne was doing her PhD and I arrived slightly later for a postdoc.Suzanne: We had a pre-meeting in the sense that Joan, Jerry Adams (my future husband) and Tom Steitz (Joan''s husband), were all graduate students together in Harvard. So, when Joan and Tom came to Cambridge, it was natural that we would all start doing things together. And Joan and I ended up sharing a lab bench.Joan S: The reason that I did a postdoc in the mecca of X-ray crystallography was that I had married a crystallographer – and there was no other place that he could possibly go. They very much wanted to have my husband at the Cambridge MRC lab, but there wasn''t a clear plan for me. Francis Crick suggested that I do a literature project in the library, but I knew that theory was not my forte in comparison to experiments. I started talking to the many people working in the lab and found a project that no one wanted, because it was so challenging. But it was a very interesting problem, so I decided to take it on – and it turned out to be a great project.Joan H: That''s amazing. You were obviously determined to overturn other people''s expectations of you.Suzanne, even now, it''s extremely unusual for a young person to leave their home country to do their PhD. It''s still a brave thing to do but all those years ago it was really courageous. You told me that you ended up there because you wrote a simple letter, which was a complete shot in the dark.Suzanne: It certainly was. During my master''s degree at the University of Melbourne, I became more and more interested in doing science and decided I would do a PhD. But I had a counteracting desire to travel and see Europe. So I decided that I would do my PhD overseas to give myself the opportunity of travelling. I had fallen in love with DNA during my undergraduate studies. So, I wrote a letter to Francis Crick in Cambridge, and asked if he would take me on as a PhD student. Much to my amazement, I eventually got a letter back saying yes. I think that my professor of biochemistry might have also visited Cambridge while he was travelling and spoken up for me. However, I was still extraordinarily fortunate that Francis had agreed because there weren''t many PhD students in the LMB at that time. It made such a difference to my entire life. I look back on that letter and think, “How did you have the audacity to write that letter and aim to go to that laboratory?”. I think it was partly naivety.Joan H: That''s a lesson for everyone, to go for your dreams, and don''t assume people won''t take notice of you. It is more difficult now, when scientists receive hundreds of e-mail applications from prospective PhD students in their inbox. You would have written a letter with a stamp on it that probably took three weeks to arrive, but it just shows you that you should be audacious. Did you have a different experience to Joan when you arrived? Was there a proper project already lined up for you?Suzanne: I was interviewed by Francis Crick and Sydney Brenner, who were the joint directors of the department. They decided that I would work on the structure of the methionyl-tRNA that puts methionine into internal positions in polypeptides. After they described the project – which involved doing counter-current distribution fractionation of bulk tRNAs, in which I had no experience whatsoever – Sydney in his very characteristic monotone said, “Do you think you''re up to it?”. I sort of gulped to myself and said, “Yes, I think I could do that”. I then went to Brian Clark''s laboratory, who was going to be my PhD supervisor, and started the project. Like always in life, if you learn from people and just go from one day to the next, you actually get there in the end.Joan H: So, persistence was key. Were there many other women at the LMB at the time?Suzanne: I don''t remember any female scientists who had official senior positions. There were certainly some strong female scientists there, but I don''t think they were given the recognition or the status that they actually deserved.Joan S: Later, some were given more recognition, crystallographers in particular, but not so much the molecular biologists.Suzanne: I think, as women, we both pioneered in that department.Joan H: Given the fact that you both agreed to take on projects you had very little previous experience with and that the male supervisors thought you weren''t going to have the mettle to carry it through, once you were there, did you feel that you had to work the whole time? Or did you still manage to have lots of fun and partake in opportunities that Cambridge had to offer at the time?Joan S: We certainly partook in a lot of those things. My husband and I got interested in antique furniture, antique paintings, and used to scour the countryside for little antique shops. We saw lots of England, then a little bit of Scotland and Wales. It was wonderful. A real adventure.Suzanne: I worked really hard most of the time that I was in Cambridge, as the work was very exciting. But I would take holiday periods, camping and youth hostelling all over Europe with a girlfriend from Melbourne and later, travelling with Jerry. We also would go to London for the opera and looking for amazing clothes on Carnaby Street and Chelsea Road (this was the Beatles era, late 60s). Jerry once came back with a purple velvet suit, which was his prized possession for many years. There was lots of fun but also lots of work.Open in a separate windowJoan Steitz, Tom Steitz, Jerry Adams and Suzanne Cory (from left to right) in the Swiss Alps, 1970. Image courtesy of Mark Bretscher. This image in not reproduced under the terms of the Creative Commons Attribution 2.0 Generic license. For permission to reproduce, contact the DMM Editorial office. Joan H: Can you remember the first moment in that part of your career that gave you the most pleasure? Joan S: I worked on a project for about a year, and it turned out that I was doing the wrong fractionation method to get the material that I needed to analyse. Then I had a conversation with Sydney Brenner telling him that I was going to give this one more try with a new method, and then I was going to give up. I remember Sydney saying, “Sometimes, like with a bad marriage, you have to give experiments one last try before you give them up.” Then I tried again, and it worked. This is often the case in science, that you try something new, that''s a little bit different, and it makes all the difference. Then you''re running.Suzanne: The same thing happened to me. I was labouring away on the counter current distribution machines fractionating methionine tRNA, with the goal of sequencing it by the laborious procedure recently published by Robert Holley. However, Fred Sanger, in the department upstairs, had invented a totally new method for sequencing using ³²P-labelled RNA. I desperately wanted to try this, so I managed to persuade my supervisor that we should change techniques. That change was key to my future because the approach was successful. I still remember to this day exactly where I was in Cambridge, walking on a Sunday afternoon, when the last piece of the puzzle dropped into place in my mind, and I had the entire sequence. In that moment, I was extremely joyful, because I knew I had my PhD and that I had succeeded. So that was my eureka moment.Joan H: Obviously, these were extremely productive years, and you''ve mentioned several Nobel Prize winners in your midst. It must have been the most inspiring environment, which I''m sure had a big impact on what you did next. By this stage in your career, were you already feeling ambitious or was it still your scientific curiosity that was driving your path?

“I expected that I would go back to the United States and be a research associate in some man''s lab […]. Then it turned out that people were more impressed than I thought and started offering me junior faculty jobs.”

Joan S: I had gotten a lot of recognition for having sequenced a piece of mRNA, using the same methods that Suzanne used to sequence tRNA. However, I had no expectations, because I had never seen a woman as a science professor, or head of a lab. I expected that I would go back to the United States and be a research associate in some man''s lab, and maybe they''d let me guide a graduate student. Then it turned out that people were more impressed than I thought and started offering me junior faculty jobs.My husband had already secured a junior faculty job in Berkeley before we even went to England, so we went back there after two years. My husband went to the chair of the department in Berkeley and put down letters on his desk of job offers that both of us had received for independent, junior faculty positions from several universities. The Chairman then said to Tom, “But all of our wives are research associates in our labs, and they love it”. This tore at my pride, as there had been a couple of universities that offered us both faculty jobs, and Berkeley was only offering one. So, we didn''t stay at Berkeley, and we came to Yale, which was wonderful.Suzanne: It''s really amazing to think that they gave you up. How foolish they were.Joan H: They''ve lived to regret it a million times over. Suzanne, at that point were you ready to climb this very difficult ladder?Suzanne: Like Joan, I didn''t have any expectations. For me, it was a matter of being able to continue discovering things in science. Jerry had already arranged to start a postdoc in Geneva. So, I applied for a postdoctoral fellowship, and obtained one. We went off together to Geneva to start our married life, and that was the beginning of us doing science together, which we''ve done ever since. I think without Jerry guiding me at that stage in my life, I would have probably drifted out of science. I don''t think I had the scientific confidence to ever think that I would be running a lab. For me, it was just continuing a voyage of discovery; and being lucky to end up in a wonderful scientific partnership and, through that partnership, my confidence grew over the years. Joan H: How many years after your postdoctoral training was it before you looked around your environment and had the confidence to think that you could be a lab or department head or could run an Institute? Joan S: I would say that confidence just grew. Tom and I were part of a departmental overhaul that involved hiring about six new people at Yale. We all stuck together, supported each other and were very collegial even though we worked in different areas. I think the collegial nature of the department in Yale helped me gain confidence. It was very scary at first because I didn''t know if I could write grants or direct people.Suzanne: Cambridge had an incredible influence, certainly over me, and I''m sure over Joan, Tom and Jerry, too. We looked around and saw all these amazing Nobel laureates, but also all these very ambitious, talented postdocs from around the world. I don''t think anyone thought about being the head of a department at that stage. We were simply striving to make discoveries and we gave each other mutual confidence, and stiff competition, too.The other thing that Cambridge gave us, was a new technology. For Joan and me, it was RNA sequencing. Being able to do that technology opened doors all around the world. I now always advise young people to go to the best place in the world to train in your chosen subject and acquire a new technology, because that will open the door to many opportunities in the future.Jerry and I made some excellent discoveries in Geneva, which were published in front-rank journals. Then it was time to move to full independence. I really wanted to go back to Australia but, as Jerry is an American, it was not at all obvious that he should take the big leap of moving to the bottom of the world and starting a lab there. I owe him a tremendous debt because he decided that he would take that risk.Earlier, whilst on our honeymoon, we had visited various labs in Australia. Although WEHI was an institute for immunology, a field we knew little about at that stage, it had the same atmosphere as the LMB in the sense that everyone was striving at the frontiers of science and competing with the rest of the world. We decided this was the only place in Australia that we would work at and that we would attempt to persuade the new director Gus Nossal that he needed molecular biologists. We had an interview with him in Switzerland and he offered us jobs as postdocs. Again, we were probably very naive and audacious but we told him we didn''t want to be postdocs – we wanted to run our own lab. And he agreed and we launched our fledgling lab together in 1971. What drove us was always discovery, rather than career ambitions.Joan H: You''ve both described these amazing sets of circumstances that were challenging but, nevertheless, very satisfying. However, a lot of things have since changed. What do you think are the main remaining barriers to women in science?Joan S: There is an important phenomenon called social identity threat, or stereotype threat, that I think still impedes women in proceeding in their careers. The phenomenon is described by cognitive psychologists as a reaction that all people experience if they feel that they are part of an undervalued minority. And so, by definition, since there are fewer women in science than there are men, women are being subjected to stereotype threat. Cognitive psychologists have studied the physiological manifestations of this, including increased heart rate and perspiration but, psychologically, they''ve also documented that cognitive learning and memory are impaired when one has these feelings.I first learned about this in 2007 and I looked back and realized why, for 30 years, when I''d been on committees as the only woman amongst ten men, I wouldn''t dare say anything – because I was frightened stiff. Men undergo this response, too, if they''re put into the situation of being undervalued. If you understand why you''re reacting the way you''re reacting and know that this is a normal human response, I think it helps you to overcome your own feelings of insecurity and allows you to go ahead. I always tell young women who I''m rooting for in science about this, because I want them to know that they will very likely end up feeling this way, and it''s a normal human response.

“One thing I sometimes get frustrated about is that we often need men to change things […] but what we really need are women in those high-level positions, so that they can be the champions of change.”

Joan H: There are other terms describing other relevant phenomena, such as unconscious bias, imposter syndrome and champions of change. One thing I really relate to is imposter syndrome. I''ve listened to webinars on this topic and they all reach a similar conclusion that we all feel the same. On the one hand, at the end of the webinar, you do feel somewhat elated to know that it''s not just you, and that it''s normal. But, on the other hand, it doesn''t really change things. It''s a recognition of what we feel, and we all get some help from that, but you really need opportunities to change things at a higher level. One thing I sometimes get frustrated about is that we often need men to change things, leading to this concept of male champions of change. I admire those men; but what we really need are women in those high-level positions, so that they can be the champions of change. Not having 50% of university departments and medical research institutes run by women still limits our full potential.Joan S: I certainly agree with you, Joan. It''s very important to have realistic role models. Suzanne being head of the WEHI for all those years has engendered all sorts of admiration.Joan H: During that period, Suzanne not only did fantastic science but our Institute doubled in size.It''s transformative when you have women making up 50% of people around the table. It''s no help just having a token female because that poor person''s not going to be able to change everything on her own. In American scientific institutions, are there any firm quotas for female scientists and other people that are underrepresented in science?Joan S: In recent years there has been a push in that direction. Sometimes it''s successful and sometimes it''s not. It is very different now compared to when there was no consciousness that this was unfair or that things could be better if we had real representation.Suzanne: I agree with both of you in everything that''s been said. While reflecting at this moment, what it says to me is that what''s really needed is societal change, and that we need to give courage to girls from the very earliest age. It should come naturally, they shouldn''t feel inferior, and others should not look at them as inferior. They should expect to have careers as well as families, be able to manage both and have somebody alongside them who helps them manage both.I think that affirmative action for women in science is necessary because the pace of change has been so slow. However, I also think quotas can be detrimental to the cause of women, in the sense that it''s then possible for people to say you only made it because there was a quota – which is very destructive. If I look back on our careers in science, it is clear that things have changed tremendously. Today there are more opportunities for women because many universities and institutes are bending over backwards to equalise things. The downside of this is that talented men may miss out on positions because of this policy and the pendulum could swing back.Joan H: The evidence shows that when more women are involved in things, those things go better. For instance, boards that have more women on them are more productive. Obviously, what you alluded to is there are lots of fantastic male scientists as well. The real issue here is there''s not enough funding to go round to support all the great men and women. But there are clearly enough good women around to be represented at the 50% level, without disproportionately disadvantaging male scientists.Joan S: Men and women are now operating on a more even playing field, which doesn''t mean that the men are missing out. They''re just in a more-competitive situation – as they should be. Joan H: Suzanne previously covered the specific advice she would give to young female researchers. Joan, do you have any other suggestions? Joan S: I encourage them to try lots of different things in science, and when they find something that really grabs them, then go for it and be persistent. We all know that science is very up and down. But if you keep pushing when you''re in a trough, it will always go back up again and you will succeed. That''s harder for a young person, who hasn''t experienced these troughs, to understand.Joan H: Yes, and the period when women scientists start having children is the hardest part. It''s still a choice that some women make, to take some years off and come back with a less ambitious plan for their career. Obviously, things like maternity leave payments and so on are improving but there''s no question that, in most circumstances, the research will slow down during that period.Suzanne: What I say to young women at that stage of their careers is that you have to be very focused, you must spend the time that you do have in a very focused manner, so that you can be the most productive you can be. But you have to be supported at home by your partner. If you''re both scientists it''s easier because you can appreciate why the other person is rushing into the lab late at night, for example, but for most people, that''s not true. So, what is really important is equal sharing of responsibilities from both partners when young families are around. And I think employers need to give both of those partners a longer time to achieve the kind of papers that they need to progress in their careers. That''s a period when it is much harder to be productive, and we need to continue to support people during that difficult phase of their careers because we''ve invested so much in them. They have so much to offer to science and to society, so to let them slip out at that stage is a great waste.Joan H: Let''s change tack a little bit and think about some of the broader challenges in science. What do you think the COVID-19 pandemic has taught us about the importance of clear scientific communication and real engagement with the community?Joan S: Whenever I talk to people about this, I very clearly make the point that it was decades of fundamental research that led to the development of the COVID-19 vaccine. If it hadn''t been for those fundamental discoveries in how cells and mRNA work, it would never have only taken 63 days from sequencing the virus to phase one clinical trials at Moderna. I try to point out to people that all the different discoveries coming in from different angles made that possible. I personally find it absolutely remarkable that all that knowledge could be harnessed, so very quickly. I''ve been doing fundamental research my entire life and I never expected to see it materialise in the way it has. It''s a wonderful reward. Joan H: Do you think this has resulted in the community appreciating scientists more? Joan S: I don''t think we''re far enough downstream to know that. In the US, there has been a congressional vote to abandon our maintenance of vigilance and preparedness for future pandemics – which seems ridiculous. Now we have all these procedures set up, all we have to do is maintain them for the next one. Whereas, if we just let go of these procedures, we''ll have to start over again for future pandemics. I guess we''re not good enough at communicating some of these things at this point.Joan H: Millions of people died from the virus and yet, if we hadn''t had the vaccines, the scale would have been even more horrific. If we were able to convey this information effectively to the public, then, hopefully, people would recognise that – as well as spending a fixed percentage of the gross domestic product on defence, for example – we should spend at least the same amount on science. Not only for pandemics but for tackling climate change and other pressing issues. I like to think this is an auspicious time but I don''t know whether we are really taking advantage of it.Suzanne: The pandemic has brought science and scientists to the forefront, and there has been a period of great respect for scientists having developed the vaccine. It''s an absolute miracle that it was done so fast and effectively. We''re very fortunate but, as Joan said, that was not luck. It was through investment in basic science for decades. We have to keep conveying this message, to our politicians in particular, so that they will keep supporting all kinds of scientists, because we never know what''s around the corner.Joan H: Certainly, people like Anthony Fauci in the US and Catherine Bennett in Melbourne, spoke eloquently and had a real talent for communicating things clearly and in a nutshell. That''s not something we''re all good at and it''s not something that is easy to train into people either. I think we all need to try to capture the attention of the community at large, by speaking plainly. I don''t think people understand that scientists are underfunded and could do so much more if funding was more generous.

“All I can say to young people is, if you really love science and have a passion for it, keep trying – because you will succeed if you put your whole heart and soul into this career path.”

Suzanne: I think the general public has no appreciation of how tenuous the life of a scientist can be, and how we are losing so many great minds entering the field because young people just finishing their PhDs look with dismay at how hard it is to support a career in science and get enough funding. There''s a tremendous waste of talent. All I can say to young people is, if you really love science and have a passion for it, keep trying – because you will succeed if you put your whole heart and soul into this career path.Joan H: This has been an absolutely fantastic discussion and it''s such a delight to talk to women who, after all these years, are still as passionate as ever and are pursuing their scientific subjects with the same vigour as they have all along.Suzanne: It''s been wonderful to talk with you, Joan, and I hope that we see each other soon, no matter what continent. And thank you, Joan Heath for getting us together and giving us this opportunity.     

It's a Wonderful Life: A Career as an Academic Scientist

Many years of training are required to obtain a job as an academic scientist. Is this investment of time and effort worthwhile? My answer is a resounding “yes.” Academic scientists enjoy tremendous freedom in choosing their research and career path, experience unusual camaraderie in their lab, school, and international community, and can contribute to and enjoy being part of this historical era of biological discovery. In this essay, I further elaborate by listing my top ten reasons why an academic job is a desirable career for young people who are interested in the life sciences.Students are attracted to careers in academic science because of their interest in the subject rather than for financial reward. But then they hear messages that make them think twice about this career choice. It is difficult to find a job: “Hear about Joe? Three publications as a postdoc and still no job offers.” The NIH pay line is low: “Poor Patricia, she is now on her third submission of her first NIH grant.” Publishing is painful: “Felix''s grad school thesis work has been rejected by three journals!” Academic jobs are demanding: “Cathy has spent her last three weekends writing grants rather than being with her family.”Such scenarios do take place, but if you think that this is what a career in academic science is about, then you need to hear the other side of the story. And this is the purpose of this article—a chance to reflect on the many good things about the academic profession. In the classic movie It''s a Wonderful Life, George Bailey is at the point of despair but regains his confidence through the wisdom and perspective of a guardian angel, Clarence. Doubt and setbacks also are bound to happen in science (as is true of other careers), but pessimism should not rule the day. It is a great profession and there are many happy endings. I would like to share my top ten reasons of why being an academic professor is a “wonderful life,” one that bright and motivated young people should continue to aspire to pursue.     

Crop shortages

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

After 2 years of a pandemic,students are struggling to find strong reference letters

Writing and receiving reference letters in the time of COVID. Subject Categories: Careers

“People influence people. Nothing influences people more than a recommendation from a trusted friend. A trusted referral influences people more than the best broadcast message.” —Mark Zuckerberg.

I regularly teach undergraduate courses in genetics and genomics. Sure enough, at the end of each semester, after the final marks have been submitted, my inbox is bombarded with reference letter requests. “Dear Dr. Smith, I was a student in your Advanced Genetics course this past term and would be forever grateful if you would write me a reference for medical school…” I understand how hard it can be to find references, but I have a general rule that I will only write letters of support for individuals that I have interacted with face‐to‐face on at least a few occasions. This could include, for example, research volunteers in my laboratory, honors thesis students that I have supervised, and students who have gone out of their way to attend office hours and/or been regularly engaged in class discussions. I am selective about who I will write references for, not because I am unkind or lazy, but because I know from experience that a strong letter should include concrete examples of my professional interactions with the individual and should speak to their character and their academic abilities. In today''s highly competitive educational system, a letter that merely states that a student did well on the midterm and final exams will not suffice to get into medical or graduate school.However, over the past 2 years many, if not most, students have been attending university remotely with little opportunity to foster meaningful relationships with their instructors, peers, and mentors, especially for those in programs with large enrollments. Indeed, during the peak of Covid‐19, I stopped taking on undergraduate volunteers and greatly reduced the number of honors students in my laboratory. Similarly, my undergraduate lectures have been predominantly delivered online via Zoom, meaning I did not see or speak with most of the students in my courses. It did not help that nearly all of them kept their cameras and microphones turned off and rarely attended online office hours. Consequently, students are desperately struggling to identify individuals who can write them strong letters of reference. In fact, this past spring, I have had more requests for reference letters than ever before, and the same is true for many of my colleagues. Some of the emails I have received have been heartfelt and underscore how taxing the pandemic has been on young adults. With permission, I have included an excerpt from a message I received in early May:Hi Dr. Smith. You may not remember me, but I was in Genome Evolution this year. I enjoyed the class despite being absent for most of your live Zoom lectures because of the poor internet connection where I live. Believe it or not, my mark from your course was the highest of all my classes this term! Last summer, I moved back home to rural Northern Ontario to be closer to my family. My mom is a frontline worker and so I''ve been helping care for my elderly grandmother who has dementia as well as working part‐time as a tutor at the local high school to help pay tuition. All of this means that I''ve not paid as much attention to my studies as I should have. I''m hoping to go to graduate school this coming fall, but I have yet to find a professor who will write a reference for me. Would you please, please consider writing me a letter?I am sympathetic to the challenges students faced and continue to face during Covid‐19 and, therefore, I have gone out of my way to provide as many as I can with letters of support. But, it is no easy feat writing a good reference for someone you only know via an empty Zoom box and a few online assignments. My strategy has been to focus on their scholarly achievements in my courses, providing clear, tangible examples from examinations and essays, and to highlight the notable aspects of their CVs. I also make a point to stress how hard online learning can be for students (and instructors), reiterating some of the themes touched upon above. This may sound unethical to some readers but, in certain circumstances, I have allowed students to draft their own reference letters, which I can then vet, edit, and rewrite as I see fit.But it is not just undergraduates. After months and months of lockdowns and social distancing, many graduate students, postdocs, and professors are also struggling to find suitable references. In April, I submitted my application for promotion to Full Professor, which included the names of 20 potential reviewers. Normally, I would have selected at least some of these names from individuals I met at recent conferences and invited to university seminars, except I have not been to a conference in over 30 months. Moreover, all my recent invited talks have been on Zoom and did not include any one‐on‐one meetings with faculty or students. Thus, I had to include the names of scientists that I met over 3 years ago, hoping that my research made a lasting impression on them. I have heard similar anecdotes from many of my peers both at home and at other universities. Given all of this, I would encourage academics to be more forthcoming than they may have traditionally been when students or colleagues approach them for letters of support. Moreover, I think we could all be a little more forgiving and understanding when assessing our students and peers, be it for admissions into graduate school, promotion, or grant evaluations.Although it seems like life on university campuses is returning to a certain degree of normality, many scholars are still learning and working remotely, and who knows what the future may hold with regard to lockdowns. With this uncertainty, we need to do all we can to engage with and have constructive and enduring relationships with our university communities. For undergraduate and graduate students, this could mean regularly attending online office hours, even if it is only to introduce yourself, as well as actively participating in class discussions, whether they are in‐person, over Zoom, or on digital message boards. Also, do not disregard the potential and possibilities of remote volunteer research positions, especially those related to bioinformatics. Nearly, every laboratory in my department has some aspect of their research that can be carried out from a laptop computer with an Internet connection. Although not necessarily as enticing as working at the bench or in the field, computer‐based projects can be rewarding and an excellent path to a reference letter.If you are actively soliciting references, try and make it as easy as possible on your potential letter writers. Clearly and succinctly outline why you want this person to be a reference, what the letter writing/application process entails, and the deadline. Think months ahead, giving your references ample time to complete the letter, and do not be shy about sending gentle reminders. It is great to attach a CV, but also briefly highlight your most significant achievements in bullet points in your email (e.g., Dean''s Honours List 2021–22). This will save time for your references as they will not have to sift through many pages of a CV. No matter the eventual result of the application or award, be sure to follow up with your letter writers. There is nothing worse than spending time crafting a quality support letter and never learning the ultimate outcome of that effort. And, do not be embarrassed if you are unsuccessful and need to reach out again for another round of references—as Winston Churchill said, “Success is stumbling from failure to failure with no loss of enthusiasm.”     

Commentary: Personal Renewal

After John Gardner''s presentation on “Self-Renewal” to THE WESTERN JOURNAL OF MEDICINE Editors'' Meeting, ^* Joseph Murphy, MD, Special Editor for Wyoming, asked the former Secretary of Health, Education, and Welfare, “Where are you in your life''s cycle?” Dr Gardner, who is 80 years old, answered, “When Chief Justice Oliver Wendell Holmes, Jr, was in his 90s, he was asked a similar question and said, `I''m like a race horse cantering along after the race is over, cooling down.'' Well, I''m nowhere near cantering! I''m still in the race, pushing the world.” race, pushing the world.”John Gardner, who received his undergraduate degree from Stanford and PhD from the University of California, Berkeley, taught at the college level for several years before he joined the Carnegie Foundation. As president of Carnegie Corporation and Carnegie Foundation for the Advancement of Teaching, he began to “push the world” toward education and in 1964 received the country''s highest civilian honor, the Presidential Medal of Freedom. He has also pushed it toward political reform by founding Common Cause, toward grass-roots political action by founding the Urban Coalition, toward leadership training by founding the White House Fellows program, and toward volunteerism by founding the Independent Sector (a coalition of for-profit and not-for-profit organizations and foundations). His books, including Excellence, Self-Renewal, No Easy Victories, and On Leadership, have pushed readers to new understanding of themselves and of organizations to higher levels of creativity and energy to get important work done. His current research focuses on discovering and defining the characteristics of healthy, vital communities. His call to “keep on keeping on,” indeed, to push the world, leads to constructive change. Active people become effective people, infused with the energy and optimism that good hard work inspires. I think you will find this paper as invigorating to read as it was to hear.     

The Novel New Jersey Eyewitness Instruction Induces Skepticism but Not Sensitivity

In recent decades, social scientists have shown that the reliability of eyewitness identifications is much worse than laypersons tend to believe. Although courts have only recently begun to react to this evidence, the New Jersey judiciary has reformed its jury instructions to notify jurors about the frailties of human memory, the potential for lineup administrators to nudge witnesses towards suspects that they police have already identified, and the advantages of alternative lineup procedures, including blinding of the administrator. This experiment tested the efficacy of New Jersey’s jury instruction. In a 2×2 between-subjects design, mock jurors (N = 335) watched a 35-minute murder trial, wherein identification quality was either “weak” or “strong” and either the New Jersey or a “standard” instruction was delivered. Jurors were more than twice as likely to convict when the standard instruction was used (OR = 2.55; 95% CI = 1.37–4.89, p < 0.001). The New Jersey instruction, however, did not improve juror''s ability to discern quality; rather, jurors receiving those instructions indiscriminatingly discounted “weak” and “strong” testimony in equal measure.     

More than a blog

Blogging is circumventing traditional communication channels and levelling the playing field of science communication. It helps scientists, journalists and interested laypeople to make their voices heard.Last December, astrobiologists reported in the journal Science that they had discovered the first known microorganism on Earth capable of growing and reproducing by using arsenic (Wolfe-Simon et al, 2010). While media coverage went wild, the paper was met with a resounding public silence from the scientific community. That is, until a new breed of critic, science bloggers, weighed in. Leading the pack was Rosie Redfield, who runs a microbiology research lab in the Life Sciences Centre at the University of British Columbia in Vancouver, Canada. She posted a critique of the research to her blog, RRResearch (rrresearch.fieldofscience.com), which went viral. Redfield said that her site, which is typically a quiet window on activities in her lab got 100,000 hits in a week.Redfield said that her site, which is typically a quiet window on activities in her lab got 100,000 hits in a weekThis incident, like a handful before it and probably more to come, has raised the profile of science blogging and the freedom that the Internet offers to express an opinion and reach a broad audience. Yet it also raises questions about the validity of unfettered opinion and personal bias, and the ability to publish online with little editorial oversight and few checks and balances.Redfield certainly did not hold back in her criticism of the paper. Her post said of the arsenic study: “Lots of flim-flam, but very little reliable information. [...] If this data was presented by a PhD student at their committee meeting, I''d send them back to the bench to do more clean-up and controls.” She also opined on why the article was published: “I don''t know whether the authors are just bad scientists or whether they''re unscrupulously pushing NASA''s ''There''s life in outer space!'' agenda. I hesitate to blame the reviewers, as their objections are likely to have been overruled by Science''s editors in their eagerness to score such a high-impact publication.”Despite the fervor and immediacy of the blogosphere, it took Science and Felisa Wolfe-Simon, the lead author on the paper, nearly six months to respond in print. Eventually, eight letters appeared in Science covering various aspects of the controversy, including one from Redfield, who is now studying the bacteria in her lab. Bruce Alberts, editor-in-chief of Science, downplayed the role that blogging played in drumming up interest in the controversial study. “I am sure that the number of letters sent to us via our website reflected a response to the great publicity the article received, some of it misleading [...] This number was also likely expanded by the blogging activity, but it was not directly connected to the blogs in any way that I can detect,” he explained.Bloggers, of course, have a different take on the matter, arguing that it was another example of a growing number of cases of ''refutation by blog''. The blogging community heralds Redfield as a hero to science and science blogging. By now, more traditional science media outlets have also joined the bloggers in their skepticism over the paper''s claims, with many repeating the points Redfield made in her original blog response.Jerry Coyne, an evolutionary geneticist at the University of Chicago in the USA, writes the blog Why Evolution is True (whyevolutionistrue.wordpress.com), which is a spinoff from his book of the same name. He said that bloggers, both professional scientists and journalists, have been gaining a new legitimacy in recent years as a result of things such as the arsenic bacteria case, as well as from shooting holes in the 2009 claims that the fossil of the extinct primate Darwinius masillae from the Messel Pit in Germany was a ''missing link'' between two primate species (Franzen et al, 2009). “[Blogging has] really affected the pace of how science is done. One of the good things about science blogging, certainly as a professional, is you''re able to pass judgment on papers instantly. You don''t have to write a letter to the editor and have it reviewed. [Redfield] is a good example of the value of science blogging. Claims that are sort of outlandish and strong can be discredited or at least addressed instantaneously instead of waiting weeks and weeks like you''d otherwise have to do,” he said.“... you''re able to pass judgment on papers instantly. You don''t have to write a letter to the editor and have it reviewed”Perhaps because of the increasingly public profile of popular science bloggers, as well as the professional and social value that is becoming attached to their blogs, science blogging is gaining in both popularity and validity. The content in science blogs covers a wide spectrum from genuine science news to simply describing training or running a lab, to opinionated rants about science and its social impact. The authorship is no less diverse than the content with science professionals, science journalists and enthusiastic amateurs all contributing to the melting pot, which also has an impact on the quality.Carl Zimmer is a freelance science journalist, who writes primarily for the New York Times and Discover Magazine, and blogs at The Loom (blogs.discovermagazine.com/loom). “Most scientists have not been trained how to write, so they are working at a disadvantage,” he said. “[Writing for them] would be like me trying to find a dinosaur. I wouldn''t do a very good job because I don''t really know how to do that. There are certainly some scientists who have a real knack for writing and blogs have been a fantastic opportunity for them because they can just start typing away and all of a sudden have thousands of people who want to read what they write every day.”Bora Zivkovic, who is a former online community manager at Public Library of Science, focusing mainly on PLoS ONE, is one of those scientists. A native of Belgrade, he started commenting in the mid-1990s about the Balkan wars on Usenet, an Internet discussion network. He began blogging about science and politics in 2004 and later about his interest in chronobiology, which stems from his degree in the topic from North Carolina State University. He still combines these interests in his latest blog, Blog Around the Clock (blogs.scientificamerican.com/a-blog-around-the-clock). Last year, Scientific American named Zivkovic its blog editor and he set up a blogging network for the publication. “There isn''t really a definition of what is appropriate,” he said. “The number one rule in the blogosphere is you never tell a blogger what to blog about. Those bloggers who started on their own who are scientists treasure their independence more than anything, so networks that give completely free reign and no editorial control are the only ones that can attract interesting bloggers with their own voices.”“The number one rule in the blogosphere is you never tell a blogger what to blog about”Daniel McArthur, an Australian scientist now based in the UK, who blogs about the genetic and evolutionary basis of human variation at Genetic Future (www.wired.com/wiredscience/geneticfuture), and about personal genomics at Genomes Unzipped (www.genomesunzipped.org), said that it is difficult to define a science blog. “I think it''s semantics. There are people like me who spend some time writing about science and some time writing about industry and gossiping about things in the industrial world. Then there are the people who write about the process of doing science. There are many, many blogs where [...] the content is much more about [the blogger''s] personal voyage as a scientist rather than the science that they do. Then there are people who use science blogging as an extra thing that they do and the primary purpose of their blog is to add political advocacy. I think it''s very hard to draw a line between the different categories. My feeling is that science bloggers should write about whatever it is they want to write about .”The ability to distribute your opinion, scientific or otherwise, online and in public is raising difficult questions about standards and the difference between journalism and opinion. Sean Carroll, who writes for the physics group blog Cosmic Variance (blogs.discovermagazine.com/cosmicvariance), is a senior research associate in the Department of Physics at the California Institute of Technology in the USA. “Some blogging is indistinguishable from what you would ordinarily call journalism. Some blogging is very easily distinguishable from what you would ordinarily call journalism,” he said. “I think that whether we like it or not, the effect of the Internet is that readers need to be a little bit more aware of the status of what they are looking at. Is this something reputable? Anyone can have a blog and say anything, so that one fact is both good and bad. It''s bad because there is a tremendous amount of rubbish on the Internet [...] and people who have trouble telling the rubbish from the good stuff will get confused. But it''s also good because it used to be the case that only a very small number of voices were represented in major media.”Zimmer contrasts the independence of blogging with traditional journalism. “You really get to set your own rules. You''re not working with any editor and you''re not trying to satisfy them. You''re just trying to satisfy yourself. In terms of the style of what I do, I will tend to write more—I think of [my blog posts] as short essays, as opposed to an article in the New York Times where I''ll be writing about interviewing someone or describing them on a visit I paid to them. One of the great things about a blog is that it''s a way of making a connection with people who are your readers and people who are following you for a long time.”One of the world''s most popular scientist bloggers is Paul Zachary Myers, known as PZ, a biology professor at the University of Minnesota in the USA. He blogs at Pharyngula (scienceblogs.com/pharyngula), a site named for a particular stage in development shared by all vertebrate embryos. “Passion is an important part of this. If you can communicate a love of the science that you''re talking about, then you''re a natural for blogging,” he explained. “[Pharyngula] is a blog where I have chosen just to express myself, so self-expression is the goal and what I write about are things that annoy me or interest me.”“Passion is an important part of this. If you can communicate a love of the science that you''re talking about, then you''re a natural for blogging”Myers'' blog, which is driven by a mix of opinion, colourful science writing, campaigning against creationism and an unflinching approach to topics about which he is passionate, draws about 3 million visitors a month. He said his blog attracts more traffic than other blogs because it is not purely about science. “I do a lot of very diverse things such as controversial religious stuff and politics, and whatever I feel like. So I tap into a lot of interest groups and that builds up my rank quite a bit. I''d say there are quite a few other science blogs out there that are pure science blogs, but pure science blogs—where they just talk about science and nothing but science—cannot get quite as much traffic as a more broadly based blog.”In an example of his sometimes-incendiary posting, Myers recently took on the Journal of Cosmology regarding an article on the discovery of bacteria fossils in a meteorite. He said that the counterattack got personal, but that he usually enjoys “the push back” from readers. “That''s part of the argument. I would say that everyone has an equal right to make their case on the web. That''s sometimes daunting for some people, but I think it''s part of the give and take of free speech. It''s good. It''s actually kind of fun to get into these arguments.”Beyond the circus that can surround blogs such as Pharyngula, scientist bloggers are debating whether their blogging counts as a professional activity. Redfield said that blogging can be taken into account among the outreach some governments now require from researchers who receive public funds. She said that some researchers now list their blogging activity in their efforts to communicate science to the public.Coyne, however, does not share his interest in blogging with other senior faculty at the University of Chicago, because he does not believe they value it as a professional activity. Still, he said that he recognizes the names of famous scientists among his blog readers and argues that scientists should consider blogging to hone their writing skills. “Blogging gives you outreach potential that you really should have if you''re grant funded, and it''s fun. It opens doors for you that wouldn''t have opened if you just were in your laboratory. So I would recommend it. It takes a certain amount of guts to put yourself out there like that, but I find it immensely rewarding,” he said. In fact, Coyne has had lecture and print publishing opportunities arise from his blogs.“It opens doors for you that wouldn''t have opened if you just were in your laboratory [...] It takes a certain amount of guts to put yourself out there like that...”Redfield said she finds blogging—even if no one reads her posts—a valuable way to focus her thoughts. “Writing online is valuable at all levels for people who choose to do it. Certainly, by far the best science writing happening is in the community of writers who are considered bloggers,” she said.In terms of pay, science blogging usually remains in the ''hobby zone'', with pay varying widely from nothing at all to small amounts from advertising and web traffic. ''GrrlScientist'', an American-trained molecular evolutionary biologist based in Germany, who prefers to go by her nom de blog, has been blogging for seven years. She writes the popular Punctuated Equilibrium blog (www.guardian.co.uk/science/punctuated-equilibrium) for The Guardian newspaper in the UK, as well as Maniraptora (blogs.nature.com/grrlscientist) for the Nature Network, and is co-author of This Scientific Life (scientopia.org/blogs/thisscientificlife) for the science writing community Scientopia. She said she earns a small amount from ad impressions downloaded when her blog is viewed at The Guardian. On the other end of the scale is Myers, who declined to disclose his income from blogging. “It''s a respectable amount. It''s a nice supplement to my income, but I''m not quitting my day job,” he said.Yet bloggers tend not to do it for the money. “I know that when I go to give talks, the fact that I have the blog is one of the first things that people mention, and lots of students in particular say that they really enjoy the blog and that they''re encouraged by it,” Carroll explained. “Part of what we do is not only talk about science, but we act as examples of what it means to be scientist. We are human beings. We care about the world. We have outside interests. We like our jobs. We try to be positive role models for people who are deciding whether or not this is something that they might want to get into themselves one day.”The rise of the science blogosphere has not all been plain sailing. Although the Internet has been hailed as a brave new world of writing where bloggers can express themselves without interference from editors or commercial interests, it has still seen its share of controversy. The blogging portal ScienceBlogs was the launchpad for some of the best and most popular writers of the new generation of science bloggers, including Myers and Zivkovic. But an incident at ScienceBlogs shook up the paradise and raised journalistic ethical quandaries.In July 2010, a new site, Food Frontiers (foodfrontiers.pepsicoblogs.com), appeared on ScienceBlog, sponsored by PepsiCo, the makers of the popular drink. The blog featured posts written by the beverage maker''s representatives and was blended in with the other blog content on the portal. “Pepsi''s blog looked like my blog or PZ''s blog,” Zivkovic explained, “with no warning that this was paid for and written by Pepsi''s R&D or PR people [...] talking about nutrition from a Pepsi perspective, which is a breach in the wall between advertorial and editorial. The moment the Pepsi blog went live, about 10 bloggers immediately left.” He said that the journalist-bloggers in particular pointed to a break of trust that would sully the reputation of ScienceBlogs writers and confuse readers.In his final blog at the site, titled ''A Farewell to Scienceblogs: the Changing Science Blogging Ecosystem'', Zivkovic nailed the danger of the ''Pepsigate'' incident to the validity of the blogosphere. He wrote: “What is relevant is that this event severely undermined the reputation of all of us. Who can trust anything we say in the future? Even if you already know me and trust me, can people arriving here by random searches trust me? Once they look around the site and see that Pepsi has a blog here, why would they believe I am not exactly the same, some kind of shill for some kind of industry?” (scienceblogs.com/clock/2010/07/scienceblogs_and_me_and_the_ch.php). Myers, who at the time was responsible for more than 40% of the traffic at ScienceBlogs, went ''on strike'' to protest. In the aftermath, the Pepsi blog was pulled.Redfield raises another interesting word of caution. “Most scientists are extensively worried about being scooped, so they''re scared to say anything about what''s actually going on in their lab for fear that one of their competitors will steal their ideas,” she said. In this context, social networking sites such as ResearchGate (www.researchgate.net; Sidebar A) might be a more appropriate avenue for securely sharing ideas and exchanging tips and information because it enables users to control who has access to their missives.“... they''re scared to say anything about what''s actually going on in their lab for fear that one of their competitors will steal their ideas”

Sidebar A | ResearchGate—social media goes pro

Whenever she is looking for ideas for a research project, biologist Anne-Laure Prunier, who works in the Department of Cellular Biology and Infection at the Institut Pasteur in Paris, has recently turned to ResearchGate (www.researchgate.net), the scientists'' version of the social networking site Facebook. “Every time I have used ResearchGate, I found it really useful,” she commented.ResearchGate, based in Berlin, Germany and Cambridge, USA, is a free service that launched in January 2009. It was co-founded by Ijad Madisch, who earned his MD and PhD from the University of Hannover''s medical school in Germany and is a former research fellow at Harvard Medical School. He explained that his goal in starting the network was to make research more efficient. “During my research in Boston, I noticed that science is very inefficient, especially if you''re doing an experiment and trying to get feedback from people working on the same problem. You don''t have any platforms, online networks where you can go and ask questions or if you''re trying to find someone with a specific skill set. So I decided to do that on my own.”As a result, the site offers researchers functionality similar to Facebook—the modern template for social networking. Through ResearchGate, members can follow colleagues, be followed by those interested in their research, share their conference attendance and recent papers—their own or those that interest them—and most importantly, perhaps, ask and answer questions about science and scientific techniques.“You can get in touch with a lot of different people with a lot of different backgrounds,” Prunier explained. “When I have a very precise technical question for which I don''t find an answer in my institute, I turn to ResearchGate and I ask this question to the community. I have done it three times and every time I have gotten a lot of answers and comments, and I was able to exchange information with a lot of different people which I found really useful.”By May 2011, ResearchGate had reached one million members across 192 countries. The largest numbers of registrations come from the USA, the UK, Germany and India. Biologists, who are second only to medical doctors on the site, make up more than 20% of members. In addition to blogging, ResearchGate is just one example of how the Internet—originally invented to allow physicists to share data with one another—is changing the way that scientists communicate and share information with each other and the public.Carroll, on the other hand, who has been blogging since 2004, said that physicists are very comfortable about publicly sharing research papers with colleagues online. “The whole discussion gets very heated and very deep in some places about open access publishing. Physicists look on uncomprehendingly in fact because they put everything for free on line. That''s what we''ve been doing for years. It works.” But he said they are more cautious about blogging for a general audience. By contrast, he believes biology is especially well-suited to being blogged. “[Biologists are] actually more comfortable with talking to a wider audience because biology, whether it is through medicine or through debates about creationism or life on other planets or whatever, gets involved with public debate quite often.”Zivkovic agrees: “PZ [Myers] and me and a number of others are interested in reaching a broad lay audience, showing how science is fun and cool and interesting and important in various ways. Connecting science to other areas of life, from art to politics and showing the lay audience how relevant science is to everyday life”. Even so, he pointed out that although blogging is popularizing science with the public, there is a less-mainstream sphere serving professional scientists as a forum for surviving the cut and thrust of modern science. “There is a strong subset of the science blogosphere that discusses a life in science, career choices, how to succeed in academia [...] A lot of these are written by people who [...] believe that if their real names were out there it could jeopardize their jobs. They''re not interested in talking to lay audiences. They are discussing survival techniques in today''s science with each other and providing a forum for other young people coming into science.”Ultimately, whether you read popular science blogs, trawl deeper for survival tips, or write your own, the science blogosphere is expanding rapidly and is likely to do so for years to come.     

A sustained passion for intracellular trafficking

I am honored to be the first recipient of the Women in Cell Biology Sustained Excellence in Research Award. Since my graduate school days, I have enjoyed being part of a stimulating scientific community the American Society for Cell Biology embodies. Having found myself largely by accident in a career that I find deeply enjoyable and fulfilling, I hope here to convey a sense that one need not have a “grand plan” to have a successful life in science. Simply following one''s interests and passions can sustain a career, even though it may involve some migration.     

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.”     

Meet the IUPAB Councilor—Hans-Joachim Galla

As one of the twelve Councilors, it is my pleasure to provide a short biographical sketch for the readers of Biophys. Rev. and for the members of the Biophysical Societies. I have been a member of the council in the former election period. Moreover, I served since decades in the German Biophysical Society (DGfB) as board member, secretary, vice president, and president. I hold a diploma degree in chemistry as well as PhD from the University of Göttingen. The experimental work for both qualifications has been performed at the Max Planck Institute for Biophysical Chemistry in Göttingen under the guidance of Erich Sackmann and the late Herman Träuble. When E. Sackmann moved to the University of Ulm, I joined his group as a research assistant performing my independent research on structure and dynamics of biological and artificial membranes and qualified for the “habilitation” thesis in Biophysical Chemistry. I have spent a research year at Stanford University supported by the Deutsche Forschungsgemeinschaft (DFG) and after coming back to Germany, I was appointed as a Heisenberg Fellow by the DFG and became Professor in Biophysical Chemistry in the Chemistry Department of the University of Darmstadt. Since 1990, I spent my career at the Institute for Biochemistry of the University of Muenster as full Professor and Director of the institute. I have trained numerous undergraduate, 150 graduate, and postdoctoral students from chemistry, physics, and also pharmacy as well as biology resulting in more than 350 published papers including reviews and book articles in excellent collaboration with colleagues from different academic disciplines in our university and also internationally, e.g., as a guest professor at the Chemistry Department of the Chinese Academy of Science in Beijing.

     

Do Pressures to Publish Increase Scientists' Bias? An Empirical Support from US States Data

The growing competition and “publish or perish” culture in academia might conflict with the objectivity and integrity of research, because it forces scientists to produce “publishable” results at all costs. Papers are less likely to be published and to be cited if they report “negative” results (results that fail to support the tested hypothesis). Therefore, if publication pressures increase scientific bias, the frequency of “positive” results in the literature should be higher in the more competitive and “productive” academic environments. This study verified this hypothesis by measuring the frequency of positive results in a large random sample of papers with a corresponding author based in the US. Across all disciplines, papers were more likely to support a tested hypothesis if their corresponding authors were working in states that, according to NSF data, produced more academic papers per capita. The size of this effect increased when controlling for state''s per capita R&D expenditure and for study characteristics that previous research showed to correlate with the frequency of positive results, including discipline and methodology. Although the confounding effect of institutions'' prestige could not be excluded (researchers in the more productive universities could be the most clever and successful in their experiments), these results support the hypothesis that competitive academic environments increase not only scientists'' productivity but also their bias. The same phenomenon might be observed in other countries where academic competition and pressures to publish are high.     

To Crowdfund Research,Scientists Must Build an Audience for Their Work

As rates of traditional sources of scientific funding decline, scientists have become increasingly interested in crowdfunding as a means of bringing in new money for research. In fields where crowdfunding has become a major venue for fundraising such as the arts and technology, building an audience for one''s work is key for successful crowdfunding. For science, to what extent does audience building, via engagement and outreach, increase a scientist''s abilities to bring in money via crowdfunding? Here we report on an analysis of the #SciFund Challenge, a crowdfunding experiment in which 159 scientists attempted to crowdfund their research. Using data gathered from a survey of participants, internet metrics, and logs of project donations, we find that public engagement is the key to crowdfunding success. Building an audience or “fanbase” and actively engaging with that audience as well as seeking to broaden the reach of one''s audience indirectly increases levels of funding. Audience size and effort interact to bring in more people to view a scientist''s project proposal, leading to funding. We discuss how projects capable of raising levels of funds commensurate with traditional funding agencies will need to incorporate direct involvement of the public with science. We suggest that if scientists and research institutions wish to tap this new source of funds, they will need to encourage and reward activities that allow scientists to engage with the public.     

Life in a Three-dimensional Grid

There have been two sharp demarcations in my life in science: the transition from fine arts to chemistry, which happened early in my career, and the move from New York to Stanford University, which initiated an ongoing collaboration with the physicist Harley McAdams. Both had a profound effect on the kinds of questions I posed and the means I used to arrive at answers. The outcome of these experiences, together with the extraordinary scientists I came to know along the way, was and is an abiding passion to fully understand a simple cell in all its complexity and beauty.