Today, psychologists are studying the genetics of brain function, engineers are using mathematics to design cancer therapies and clinicians are tapping into anthropological methods to analyze the spread of infectious disease. In the 21st century, science no longer adheres to the strict boundaries that once demarcated the traditional fields of study.

“The most interesting questions are at the intersections of what were once distinct fields,” says chemist Molly Shoichet from the University of Toronto in Canada.

But navigating these intersections can be a tricky business, especially for young scientists struggling to make a name for themselves in not just one, but multiple fields.

“Right now, we’re at a crossroads,” says Melissa Riddle, chief of the Behavioral and Social Sciences Research Branch at the NIH’s National Institute of Dental and Craniofacial Research in Maryland. “Most people will agree that, in order to tackle the really big questions, you need an interdisciplinary team and each person needs some ability to think across disciplines. But my impression is that the structure of academia still doesn’t lend itself completely to interdisciplinary work.”

This structure – which still relies heavily on the traditional idea that researchers belong to one field and one academic department – can make life difficult for students and postdoctoral researchers. How can they know how best to satisfy their drive for research across boundaries while ensuring that they develop the type of credentials that will lead to success within the existing academic structure?

Just explaining the nature of interdisciplinary work to other researchers can be difficult, says University of Florida postdoc Krishanu Mukherjee,whose research has ranged from agricultural science and molecular biology to genomics and computer science. “When I’m looking for a job, people get confused, because I have publications in all these different areas,” he says.

“Everyone says they want interdisciplinary research, but people don’t really know what bin you fit in,” agrees engineer Dionne Aleman of the University of Toronto. Her background is in industrial engineering, but she now uses mathematical methods in a variety of medical applications: to design radiation therapy plans, to predict the spread of pandemic diseases and to match bone marrow donors more effectively.

Overcoming obstacles

Researchers from traditional disciplines often make hiring and funding decisions, which can make things difficult for interdisciplinary researchers, she adds. “You end up caught between two fields and nobody can understand you.”

But the payoff of learning to deal with these obstacles can be great, says Aleman. “In some ways, it makes it a lot easier for you to get your work out there and have people know what you’re doing, because you have twice the audience who’s willing to listen to you,” she says.

One of the most important skills for young interdisciplinary scientists to acquire is the ability to speak the languages of multiple disciplines, says Greg Evans, who studies air quality at an interdisciplinary center at the University of Toronto. “The language often differs significantly among research disciplines,” he says. This means that interdisciplinary researchers “need to become skilled communicators, familiar with the language of both so that they can serve as an effectiveinterface to facilitate communication between the groups”.

Understanding another discipline isn’t limited to learning its terminology. “The culture often differs significantly among research disciplines or even research groups. These differences can be seen in how groups operate, identify research questions and approach problems,” adds Evans. It is important for successful interdisciplinary scientists to “become sensitive to differences in the values and motivations of the different groups they are working with”.

Working with people who have been trained in different disciplines can be challenging for many scientists, says Jaimie Meyer, a postdoc at the Center for Interdisciplinary Research on AIDS at Yale University. She uses many social science methods from her background in anthropology in her current work studying the health outcomes of HIV-infected prisoners after their release. With any interdisciplinary project, “people are coming at it from different perspectives,” she says. “You need to be open-minded about it.”

Not only are these skills important for scientists to develop, they’re also important qualities to look for in a research group before joining, says Eliza Congdon of the Semel Institute for Neuroscience and Human Behavior at the University of California, Los Angeles. Her neuropsychological research involves both neuroimaging and genetics studies. During the interview, she found that researchers from both areas “were aware of the issues in each other’s studies and fields. I could tell that they had put a lot of time into discussing it”.

It’s also important to consider the extent to which a particular group or institution will allow truly interdisciplinary work. “A lot of departments say they’re interdisciplinary but they’re really not,” Congdon says. For some, interdisciplinary interactions might be limited to shared lab meetings or collaborations in which each group performs its own analyses.

Congdon belongs to two separate labs and fully participates in both the neuroimaging and the genetics components of her work. While she considers her primary field to be psychology, she designs her studies with genetics in mind and participates in those aspects as well. “It’s not just an afterthought, an analysis performed by someone else and tacked on,” she says.

Breadth versus depth

But aligning yourself with a primary discipline continues to be important when looking for postdoctoral positions and, later, faculty jobs, says Aleman. “You need to be able to classify yourself as belonging to one field with interests extending into another.”

Riddle, who is also a member of the NIH’s interdisciplinary research consortia, believes that there is still tension between having depth and having breadth. “You still need to have expertise in your one field,” she says.

David Zingg, director of the University of Toronto Institute for Aerospace Studies, agrees. Postdoctoral researchers must “develop deep expertise in at least one discipline”, he says. “Students looking for postdoctoral positions in interdisciplinary fields should ensure that they will gain sufficient depth in a specific discipline, while working with researchers who specialize in other disciplines and gaining some broader knowledge of the other disciplines.”

Working across too many different areas can be demanding, agrees Congdon. “You run the risk of spreading yourself too thin. The key is to understand what your strength is,” she says. “Every interdisciplinary project needs experts. You need to recognize and develop your expertise, while still training in the other aspects of your projects.”

Some aspects of traditional research are changing to allow better integration of interdisciplinary work, Riddle says. For example, some universities are trying to acknowledge interdisciplinary work explicitly during tenure review. But it remains a challenge to figure out how to train interdisciplinary scientists.

“Training programs need to figure out how to train across disciplines,” she says. While designing such a program for an individual researcher may be straightforward, doing so for an entire cohort of students or postdocs is much more difficult – and raises questions about whether interdisciplinary training will, by nature, take longer than training in more traditional disciplines.

Finding satisfying interdisciplinary positions remains daunting but worthwhile, says Mukherjee. “People still have to be open-minded,” he says, “but I think it’s the future.”

Spurred by financial support from investors and public funding, careers in environmental sciences abound. Among scientists from all sorts of backgrounds – biology, chemistry, geology, physics, oceanography, computer science – there’s now a “huge trend in the direction of environmentalism”, says Michael Lassner, vice president of trait discovery at plant genetics company Pioneer Hi-Bred International in Johnston, Iowa. In everything from alternative energy sources and sustainable agriculture to basic research into our planet’s climate, he says, “we’re seeing a lot of creativity – training a lot of people and actually getting people to change fields”.

Energy, food and Arctic ice

Looking for alternative and renewable energy sources is a rapidly growing area of environmental science, says Meredith Hastings of the Environmental Change Initiative at Brown University in Providence, Rhode Island. “With the different issues our society is facing, anything related to energy is interesting, exciting and pressing right now,” she says. Researchers in academia, government and the private sector are involved in myriad efforts to find cheap energy sources that do not increase carbon emissions or have the potential to inflict environmental disasters such as the Gulf oil spill.

Changes in energy policy over the past decade or so have already created new jobs in many states. California, Wisconsin and Massachusetts, among others, have voluntarily adopted more restrictive energy regulations than those mandated by the federal government, and regulatory jobs in state and local governments will probably increase further as more states follow suit, Hastings says. To help meet this need, many consulting firms have recently opened environmental consulting branches that try to help businesses make decisions about how to meet regulations or how to avoid having a particular environmental impact.

Agricultural science also underlies many scientists’ efforts to work toward a sustainable future. Much research in this area focuses on technologies that improve yield when crops face different types of adversity. ĐÓ°ÉÔ­´´s at Pioneer, for example, are working to engineer plants that re resistant to disease, drought and flooding.

One of the most successful areas of agricultural research and development revolves around insect-tolerant plants. Farmers have to use less insecticide with these crops, which is good both for the environment and for the farmers’ bottom line. Pioneer scientists are now moving a droughttolerant line of crops from the research phase to product development, Lassner says, which should give farmers more reliable yields from year to year.

Studying Earth’s systems

Although many environmental scientists work in applied research like energy and agriculture, some are engaged in the basic research that helps us understand how our planet works – what we could call “yet to be applied” research.

Søren Rysgaard of the University of Manitoba in Winnipeg studies what happens in Arctic waters as the ice caps melt. When the freshwater sea ice melts, the salinity of the surrounding ocean decreases, which can affect microorganism populations and have a domino effect on local food webs.

Rysgaard and his colleagues are building models of complex feedback systems between Arctic ice caps, atmosphere, fjords and ocean circulation – and how all of this is altered by climate change.

Rysgaard has scientists from many different disciplines working with him on these complex environmental analyses, including atmospheric chemists, physicists, oceanographers, biologists and computer scientists. “Everything is connected: the ocean affects the climate system, temperature feeds back to influence ocean composition, and phytoplankton affect cloud formation in the atmosphere,” he says. “As we do our research, we come up with questions that can only be answered by someone next door.”

In terms of climate research, he believes that interdisciplinary work is the only way to go: in recent years, many new discoveries have been made at the borders between disciplines.

“Because of the inherent need for cross-discipline research in environmental work, there’s a lot of discussion about the best way to educate future environmental scientists,” Rysgaard says. Older environmental scientists have usually been educated in a traditional discipline such as biology, chemistry or geology, he says, but today’s students have the opportunity to study environmental sciences more broadly from the beginning of their education.

The tendency in both academia and the private sector, however, still seems to be to seek out students who have a solid background in any physical science discipline. “Just being trained in science gives you the skills and the viewpoints you need,” says Hastings. “In most environmental research, you’re applying knowledge that you’ve learned in a different context.”

Lassner believes that the most successful environmental scientists will combine both generalist and specialist knowledge and approaches. “ĐÓ°ÉÔ­´´s today have to be specialists, but they also have to be able to integrate approaches from a lot of different disciplines,” he says. “Having a broad perspective on experimental approaches is necessary to be successful today.”

Learning to view environmental problems from other perspectives is especially important for mid-career scientists who may be moving from a classical discipline to something more broad and systems-based. “You might be trained in, say, chemistry and you might be focused on a laboratory project, but when you’re in the field, you don’t have control of the elements,” says Hastings. “You have to take a system approach. You have a piece that you want to understand in detail, but you have to remember that it’s connected with a lot of other things that are happening in the environment.”

“Burgeoning environmental scientists will still be required to specialize in order to get a PhD,” Lassner says, “but the people I admire the most are the ones that aren’t too set in one way of thinking or one way of doing something.

“Learn about other approaches, learn about how to stretch the bounds of your thinking, and apply new approaches to old problems.

Most grad students begin their search by targeting groups that work in a similar field, but think about stretching yourself further, says Brian Mayer, a postdoc at Lawrence Livermore National Laboratory in Livermore, California. “Seek out the chance to broaden your scientific experience,” he says. Mayer’s work applies solid state nuclear magnetic resonance spectroscopy to art conservation, which is a departure from his graduate training. “Looking for an institution that was willing to take a risk and allow me to develop a breadth of new knowledge wasn’t easy, but I felt that finding this type of environment is necessary to grow as a scientist,” he says.

Looking at publication records is an important next step, says Stephanie Colvin, a grad student at Indiana University School of Medicine in Indianapolis. She recommends finding out how frequently your investigator publishes their work, and in what type of journals. “Does this investigator put themselves as first author frequently, or does he or she give the graduate students and postdocs the credit?” she says.

Thomas Adams, a postdoc in chemical engineering at the Massachusetts Institute of Technology (MIT) in Cambridge, agrees: “A strong publishing record is really good in the sense that your own papers are more likely to get published and noticed with that group’s name on it, too.”

Who’s who?

The details of a group’s publication record may also tell you something about how they work together, says Ryan Widau, a grad student at Indiana University. When searching for his postdoc at the University of Chicago, Widau paid attention to the number of authors on the publications “as a means to gauge the collaboration within a laboratory”.

Laura Thomas, a postdoc at the National Institute of Mental Health in Bethesda, Maryland, focused on the same priority: “I was more interested in doing my postdoc in a lab that had a common focus and was not too individualistic and competitive.”

“It is important to understand the dynamics of the research group,” agrees Carolyn Seto, a postdoc in chemical engineering at MIT. “You are spending at least a year with this group, and you will make the most productive use of your time if you are in an environment in which you feel comfortable working.”

The work environment will also likely extend outside of your individual research group, and you may want to look for a place that has a “strong, networked postdoctoral community”, says Lauren O’Donnell, a postdoc at Fox Chase Cancer Center in Philadelphia. “Navigating your postdoc can be an intense experience.”

Among all of the relationships you will have with other scientists as a postdoc, the most important one will probably be with your direct advisor, so getting this relationship right is a must. “You want someone who understands and treats you as a person, not as a slave,” says Maria Aronova, a postdoc at the National Institute of Biomedical Imaging and Bioengineering in Bethesda. “This heavily influenced my choice of a postdoc mentor.”

A mentor should understand and appreciate your professional goals, says O’Donnell, whether those include teaching, industry, an alternative career or a classic academic position.

While assessing a mentor’s style can be difficult when you’re interviewing, says Sara Howden, a postdoc at the Morgridge Institute for Research at the University of Wisconsin in Madison, you’ll usually be able to meet with lab members as part of the interviewing process. “This provides an excellent opportunity to ask other postdocs and grad students about the group’s dynamics and the day-to-day running of the lab,” she says.

And don’t discount your impressions of other members of the group, adds John Bochanski, an astronomy postdoc at MIT. “Try to seek out another postdoc to bounce ideas off of,” he says. “Your supervisor may be busy or out of town, but if you can think out loud with another peer, it will make the research process a lot easier – and you may even get a friend out of it.”

Show me the money

Evaluating your chances for funding in a particular field is an essential part of picking a postdoc position, says Steven Smith, a postdoc studying HIV at the National Cancer Institute (NCI) in Bethesda. First, it’s important to pick a research project in an area that has solid funding. “I learned from my grad school days to pick a disease that has worldwide effects and is of extreme importance,” he says.

Beyond the field or project in general, the type of institution and the history of a specific investigator can tell you a lot about your funding chances. “I knew that by doing a postdoc at the National Cancer Institute, I would not have to worry too much about funding,” says Caroline Davis. “They have a good record of securing grants.”

For his part, Widau checked out potential labs’ funding through the National Institutes of Health (NIH) database and only seriously considered labs with multiple sources of funding.

It’s also important to check out the resources an institution has to offer. For Bochanski, working at MIT was appealing because the school has access to the Magellan telescopes in Chile – a major resource for his research into low-mass stellar astronomy. “Being able to use world-class facilities for my own research puts me at a distinct advantage compared with smaller schools, where I would need to apply for telescope time among a national pool,” he says.

No matter where you decide to apply, start to think about options as early as possible in your graduate career. “I wish that I would have started the postdoc search much earlier than I did. I would recommend emailing large labs up to a year in advance,” says Widau.

Thomas recommends treating the entire process as a learning experience. “Visit multiple labs, even ones you aren’t sure you’d want to join,” she says. “The more information you gather about what type of lab, mentor and environment you do or do not want to be in, the more informed a decision you can make.”

And don’t ignore considerations of how your choice will affect your life outside of science, Mayer says. “Being able to live in the Bay Area has helped to maintain my sanity when away from the lab bench.”

Expanding your horizons might even present an opportunity to live and work in an entirely different country. “I strongly recommend looking at labs overseas for potential postdoc positions,” says Howden, who is from Australia. “I think working overseas not only looks great on a CV but is also an incredible experience that often gives you a much greater perspective on life.”

According to Tom Carew of the University of California, Irvine, and the current president of the Society for Neuroscience, advances come in two flavors: technical and conceptual. “And often, the former feeds the latter,” he says. Below, we look at a few of the most exciting developments in neuroscience.

Imagine that

Imaging technologies have been around for a while, but have only recently reached a level of maturity that allows meaningful insight into real-time brain function. Functional magnetic resonance imaging (fMRI), for example, was first used by researchers to show off their skills, says Carew. Today, however, fMRI can provide detailed quantitative analyses of brain activation patterns and show how those patterns change across time and space.

Many conceptual advances have followed, but one that stands out for Carew is an appreciation of the aging brain. Imaging has shown that there seems to be a reduction in communication between neuronal networks across vast areas of the brain. For example, the entire parietal cortex might not effectively communicate with the entire frontal cortex. Such large-scale communication problems seem to account for many of the variances in cognitive impairments that accompany aging, Carew says. “It seems to be a signature of the aging brain.”

Imaging advances have also illuminated basic functions of a normal, healthy brain, says Nora Volkow, director of the National Institute on Drug Abuse in Bethesda, Maryland. Researchers have moved on from a simplistic perception of certain brain areas being ‘responsible’ for certain behaviors, she says. Instead, imaging studies have revealed that “networks function in coordinated ways to generate behaviors”.

Imaging is now even being used directly in treatment. By watching activity levels in their own brains via fMRI scans, patients can learn to control activity in pain-related circuits and reduce the amount of pain that they experience.

And imaging technologies are constantly being pushed further, especially to finer and finer resolution, Volkow adds. Some researchers are now using imaging techniques to visualize gene expression in live organisms. “We can do things that we never thought we’d be able to do.”

Modify this

Another research hotspot involves the control of the brain by epigenetic effects. Studies of how epigenetic modifications, such as DNA methylation and histone deacetylation, control gene expression have been common in fields like cancer and metabolism for about a decade. Recently, however, researchers have realized that these molecular mechanisms are important in the brain, too. As these epigenetic changes control gene expression in the brain, they may be involved in neuroplasticity and perhaps disrupted in certain diseases.

MicroRNAs are one type of epigenetic modification getting quite a bit of attention right now. These molecules, which usually control gene activity by inhibiting protein translation, were discovered in the early 1990s, but were studied mainly in relation to cancer and metabolism. Today, their role in brain function is starting to become clearer. It’s been shown that blocking a certain microRNA at synapses can improve long-term memory. “These kind of studies are opening our minds to steps of modulation and regulation that weren’t appreciated,” Carew says.

Volkow finds epigenetic modifications fascinating from the perspective of therapeutic intervention. “In the past, psychiatric medications have targeted specific receptors in the brain, either increasing or decreasing their activity,” she says. “But epigenetic studies introduce the possibility of changing brain function by directly controlling gene expression.” In fact, it’s possible that some drugs used to treat neurological or psychiatric disorders may already work this way. Both lithium, which is used to treat bipolar disorder, and valproic acid, an antiepileptic also used to stabilize mood, seem to work at least partly by influencing histone acetylation.

Next steps

According to Salvatore Carbonetto of McGill University in Montréal, many of today’s most exciting questions in neuroscience address one basic question: how does the normal brain function? And answering such large, fundamental questions may require a new model for how research is conducted, especially in the US, he says, adding that the single-investigator model likely won’t work for big problems that require a lot of personnel and resources. “I think that model has to be modified to stimulate cooperation among labs,” he says. “It’s going to take some new thinking about teamwork and virtual labs that are linked by computers and meet every day.”

Neuroscience in general would also likely benefit from drawing in scientists educated in fields other than biological sciences. “We need to attract mathematicians, physicists and engineers to neuroscience to give us new ways of thinking,” Carbonetto says. He hopes that fresh insight from other fields could help address some of neuroscience’s biggest problems. For example, the brain contains billions of neurons and trillions of synapses. “We’re not going to be able to map out every connection. We need more holistic views of how the brain functions.”

As for what exactly the next big thing in neuroscience is likely to be, that’s the million-dollar question. Some techniques and ideas that have exploded today would have seemed impossible five years ago. “I’m excited that I can’t answer that question,” says Carew. “It could come from anywhere.”

Collaborative consortia

During the 20th century, the number of children’s hospitals in the US and Canada mushroomed. While many children are still treated at normal hospitals, families often choose pediatric hospitals when facing rare but serious childhood conditions. Today, many children’s hospitals continue to treat their patients as they grow into adulthood – a testament to advances in research and care.

Because of pediatric research advances, “there are kids alive today who, a few decades ago, would not have been alive,” says Edward McCabe, chair of pediatrics and physician-in-chief of Mattel Children’s Hospital UCLA. “They’re even living into adulthood and having families. It’s amazing the changes we’ve seen.”

Some of this progress came out of collaborative networks of researchers focusing intense effort on specific problems. For example, pediatric oncology consortia originally formed several decades ago have led to huge advances in treating childhood cancers, says James Hendricks, president of Seattle Children’s Research Institute in Washington. “Ten or 15 years ago, pediatric cancer had a mortality rate of close to 50 or 60 per cent. Now it’s more like 10 or 15 per cent. This is a direct result of the work of that consortium.”

Legislation currently in Congress could allow the formation of new collaborative centers devoted to other children’s diseases. The National Pediatric Research Consortia Act, introduced in both the Senate and the House of Representatives in March 2007, would authorize 20 such centers. In a hub-and-spoke model, a central children’s hospital plus other aligned institutions would cooperate to address a particular problem, with annual NIH funding of $2.5 million for each center and its partners.

Such collaboratives encourage focus and a core support system on which to build, says Arnold Strauss, director of the Cincinnati Children’s Research Foundation and chair of pediatrics at Cincinnati Children’s Hospital Medical Center in Ohio. “That is a major push for all of us interested in research in pediatrics.”

Many researchers hope that the funding atmosphere will improve with the Obama administration in office. The president’s economic stimulus plan will provide an additional $10 billion to NIH over two years, which has caused “a great deal of excitement in the research community”, Hendricks says. For example, Seattle Children’s went from a typically monthly submission of 20–25 NIH grants to 106 grants submitted in April for stimulus dollars. “Of course, the competition is going to be stiff,” he says. “But I think it demonstrates that the research community is really interested in trying to make something out of the stimulus dollars.”

Research prospects

The excitement around improved support stems partially from the feeling that researchers are poised to make major inroads into pediatric illnesses. “I think it’s the best time ever to study pediatric disorders and prevention,” Strauss says. The tools to study congenital birth defects and to pinpoint genes underlying genetic disease should allow rapid advancement in treating those illnesses, he says.

At UCLA, researchers are studying the benefits of nanotechnology in pediatric medicine, McCabe says. “We’re trying to make sure that diagnostic and therapeutic approaches at the nanotechnology level are safe and effective for children.”

UCLA also has faculty working on developing non-invasive stents and valves for kids with congenital heart disease. Although such devices are now commonplace for adults, developing safe and effective child-sized devices has been a longstanding problem.

In addition, children’s hospitals and pediatric departments are putting a lot of effort into vaccine development, basic and clinical autism research, and prevention of premature birth, as well as investigating many diseases that affect adults, including obesity, type II diabetes, and hypertension, which are believed to begin in childhood. “Most adult diseases start in childhood and, if we don’t learn how to treat them in childhood, it’s not going to change,” says Strauss.

Overcoming obstacles

Concern remains that advances in pediatric medicine will continue to suffer from a lack of financing, however. In fact, many scientists and doctors who focus on children’s health feel that pediatrics is consistently shortchanged when compared with adult diseases – in part because these tend to be widespread, while many childhood disorders are severe but rare.

Increased difficulties since the recession are forcing some pediatric departments and children’s hospitals to downsize. Charles Irwin, professor and vice chair of pediatrics at the University of California, San Francisco (UCSF) School of Medicine, suspects that UCSF will cut back on the number of researchers they employ, mainly because they won’t be able to afford to supplement the salaries of their investigators whose federal grants may cover only 50 per cent of their salaries.

While this may be a common theme at state-funded institutions, not all children’s hospitals are reacting in the same way. For example, Seattle Children’s Research Institute is currently expanding facilities and recruiting 10 new scientists this year. Because other institutions are struggling financially, more scientists than usual may be willing to move, says Hendricks. “Now is the time to go out and try to find the best candidate.”

A similar strategy is in place at Cincinnati Children’s Hospital. “We get really good people from other places that aren’t doing so well,” says Strauss. “We’re adding research staff at a pretty significant pace and I anticipate that we’ll continue to do that.”

To help with funding, pediatrics at the University of California, Los Angeles (UCLA) looks to foundation money, says McCabe. “We’re trying to keep everybody going, because we’ve got a strong research program,” he says. “We know it will be harder to rebuild it than to try to keep it going through the difficult times.”

Pediatric researchers are clearly passionate about the work they do, despite the current funding challenges. “I recognize that everybody wants to scrimp, but it’s important to recognize that we can change the futures of the children who we claim are our future,” says Irwin. “We just need to invest in it appropriately.”

Researchers at the University of Chicago, US, developed a statistical test to find genomic regions that evolution has favoured over the last 15,000 years or so – when modern humans dealt with the end of the last ice age, the beginning of agriculture, and increased population densities.

Many of the 700 genes the researchers identified – especially those involved in smelling, fertility, and reproduction – are also suspected of having undergone natural selection during the divergence of humans and chimpanzees millions of years ago.

But some of the newly identified genes fall into categories not previously known to be targets of selection in the human lineage, such as those involved in metabolism of carbohydrates and fatty acids.

Milk lovers

“It’s reasonable to suspect that a lot of these are adaptations in response to new diets and agriculture,” says team member Jonathan Pritchard.

For example, gene variants that improve the digestion of lactose have become more common, presumably since the domestication of cattle provided a ready source of milk. And in some Europeans, genes giving a lighter skin have increased in frequency, as populations have moved north to regions where there is less sunlight to generate vitamin D.

The researchers analysed the genomes of 209 people from Nigeria, East Asia, and Europe. They found widespread signals of recent selection in all three populations.

Only one-fifth of the 700 genetic regions identified were shared between at least two of the groups – the rest were unique to single populations. That supports the idea that the adaptations are recent, Pritchard explains.

Huge list

The statistical test is a “powerful way of looking for selection in the genome”, says Michael Hammer of the University of Arizona in Tuscon, US. It looks for certain patterns of DNA – called linkage disequilibrium – that show a gene variant is young. It then identifies those that appear at high frequencies, which suggest they have been selected for.

Definitive proof that the gene variants are being favoured in the human genome will require detailed analysis of the changes they cause in proteins and how this affects fitness. But Hammer says “they’ve given us a huge list of candidates”.

Nonetheless, there are likely to be many more, says Peter Andolfatto of the University of California, San Diego, US: “The genes being mapped here at best probably account for only a small fraction of the targets of recent selection in the human genome.”

Identifying the gene variants that are under selection may one day help medicine, Pritchard adds. That is because individuals with a newly evolved gene variant may be better adapted for modern human conditions and less susceptible to certain diseases. Understanding the differences could help guide future therapies.

Journal reference: Public Library of Science Biology (vol 4, p e72)

Women who used birth control pills had a 40% lower risk of being diagnosed with MS for several years afterwards than those not taking the pills, found a study by Álvaro Alonso at Harvard School of Public Health, US, and colleagues.

Previous studies of the long-term likelihood of developing MS found no protective effect of oestrogen, says Alonso, but “our study had more precise information on the use of oral contraceptives, so it has been possible to see this short-term effect”.

Oestrogens influence immune responses and so may affect autoimmune diseases like multiple sclerosis, in which immune cells attack and destroy the insulating fatty layer around nerve cells that allows fast transmission of neural signals. Studies in mice have shown that oestrogens ameliorate a disease similar to MS.

Risks after birth

Alonso and colleagues compared data on 106 UK women who were diagnosed with MS between 1993 and 2000 with 1001 age-matched controls who had no signs of MS. These women’s anonymous medical records also indicated if and when they had taken oral contraceptives.

Alonso found that women who had taken contraceptives in the previous three years were 40% less likely to be diagnosed with MS than were those women who had not taken any oestrogen-based pills.

The researchers also found that women were more likely to be diagnosed with MS within six months after a pregnancy than they were at other times. This makes sense if increased oestrogen deters disease onset, the authors say, as the body’s oestrogen levels are particularly low after pregnancy.

Oestrogens in birth control pills are likely conferring only a short-term reduction in risk of MS diagnosis, Alonso says, because the previous work of some of his colleagues showed that contraceptives “don’t change the risk of having the disease in the long term”.

Low probability

If researchers can figure out exactly how oestrogen affects MS, they may gain insight into “what went wrong” in the body that caused the disease to develop, says Rhonda R Voskuhl at the University of California, Los Angeles, US.

However, “no one will want to take birth control pills to prevent themselves from getting MS,” Voskuhl says, “because the probability of getting MS is so low.” About one in 1000 people in the western world will develop MS.

Alonso’s results are “promising, but we have to be careful,” she adds. “Clearly, what has to be done is a placebo-controlled trial: design it and do it and see what happens, as opposed to just looking back at records.”

Journal reference: Archives of Neurology (vol 62, p 1362)

The drugs seem to work through a pathway not involving the chemical dopamine, which surprised the researchers since dopamine deficiency is the cause of Parkinson’s.

These results may lead to the discovery of “other systems that can replace or substitute for the very important action of dopamine”, says study author Marc Caron of Duke University, US.

Dopamine transmission in a region of the brain called the striatum is essential for normal movement. Parkinson’s results when dopamine-producing neurons in this region die.

The best current treatment for the condition is a chemical called L-Dopa – a natural precursor to dopamine. L-Dopa works well for patients in the early stages of the disease, but its effectiveness diminishes with time, and it can actually cause involuntary movements.

Unknown system

To screen for other types of drugs, Russian scientists Tatyana Sotnikova and Raul Gainetdinov, working with the team at Duke University, studied mice altered to possess no brain dopamine. They show classic symptoms of Parkinson’s disease including muscle rigidity, problems initiating movement, and resting body tremor.

When the researchers treated these mice with high doses of different types of amphetamines, their movement problems dramatically improved. The most effective compound was methylenedioxymethamphetamine (MDMA) – commonly known as Ecstasy.

This result was surprising, because amphetamines are thought to affect movement through the dopamine system. But since these mice have no functional dopamine system, an unknown mechanism must be at work.

The authors suggest proteins called trace amine receptors may be involved. Amphetamines interact with these receptors, but very little is known about their physiological role in the brain.

Ecstasy-Parkinson’s links

Some previous research has hinted that Ecstasy might actually cause symptoms of Parkinson’s disease, although the best-known study was retracted when the researchers discovered they had administered the wrong drug.

Prompted by British stuntman Tim Lawrence’s claim that his Parkinson’s symptoms were relieved by Ecstasy, a study in marmoset monkeys confirmed some anti-Parkinsonian effects the drug. And work by Werner Schmidt and colleagues at the University of Tübingen, Germany, has shown similar results in rats.

The Duke University researchers used a very different approach and a very different method, Schmidt notes, but they “reached the same conclusions as we did”.

“We have to be cautious not to be too suggestive, so that every Parkinson’s patient doesn’t run to the street corner,” Caron warns.

The researchers plan to base further work around the structure of amphetamines, Caron says, to find or create other compounds that might have similar anti-Parkinsonian effects.

Journal reference: Public Library of Science Biology (vol 3, p e271)

“We have a vaccine system here that looks really promising,” says Thomas W Geisbert, at the US Army Medical Research Institute of Infectious Diseases in Maryland.

Lassa haemorrhagic fever is endemic to several countries in West Africa and is estimated to infect more than 200,000 people each year, killing a few thousand. That makes it a much bigger public-health problem than Ebola or Marburg, says Susan Fisher-Hoch of the University of Texas at Brownsville, US. Treatment with an anti-viral drug is sometimes effective, but only if given soon after disease onset.

The Lassa virus is transmitted to humans from rodents, and people can also pass it to each other. In the past few years, several travellers returning to Europe or the US from Africa have been found to be infected with Lassa, but they have not spread the disease to others.

The risk of Lassa fever spreading outside of Africa is probably quite small, says Geisbert, unless the virus mutates into a more transmissible form. But “where it’s endemic, it really matters,” adds Fisher-Hoch.

Protective envelope

The vaccine trial was led by Geisbert and Steven Jones of the Public Health Agency of Canada in Manitoba. First, they obtained the genetic sequence for the surface glycoprotein that forms Lassa’s outer protective envelope. Then they put this into an altered form of another virus, called vesicular stomatitis virus (VSV), where it was also expressed on the surface.

The researchers immunised four macaque monkeys with this Lassa vaccine and injected two control monkeys with their vaccine for Ebola Zaire instead. After 28 days, all six macaques were injected with a lethal dose of Lassa virus.

The two control animals developed fever, rash and anorexia, and succumbed to the disease less than two weeks after virus exposure. But the four vaccinated monkeys “showed no clinical evidence of illness at all”, says Geisbert. They developed strong immune responses against Lassa, including both antibody and white blood cell responses, he notes.

The Lassa VSV vaccine is a good candidate for use in humans, Geisbert believes. That is because VSV does not cause severe side effects, as do some other virus vehicles, and the vaccine confers protection after only one injection.

“This is clearly the vaccine that’s needed for Lassa fever,” says Fisher-Hoch. But she also notes one potential problem, which is that many viruses, including HIV, are being inserted into VSV for use as vaccines. If VSV is used to deliver too many vaccines, it is possible that some people will develop immunity against VSV itself, and the vaccines will no longer work in those populations.

Journal reference: Public Library of Science Medicine (vol 2, p e183)

“Stress can influence different features of the immune response in different ways, sometimes improving and sometimes suppressing” this response, says Monika Fleshner, of the University of Colorado at Boulder, US. While chronic stress suppresses “nearly every feature of the immune system,” acute stress can enhance some features, she says.

Firdaus Dhabhar and Kavitha Viswanathan at Ohio State University, US, injected mice with a small amount of protein called keyhole limpet hemocyanin (KLH), which triggers the body’s immune response in a way similar to many proteins, according to Dhabhar. Half of the mice were put in small, unfamiliar wire cages for two and a half hours immediately before receiving their immunisations, while the other half stayed in their regular cages.

Nine months later, the researchers injected the animals with KLH at a different skin site. Mice that had been confined before being immunised developed much more skin inflammation than did the non-stressed mice – a sign that their bodies’ immune systems responded more intensely to the new injections. The researchers show that many more immune cells rushed to the injection sites in mice that had been stressed.

Mounting a defence

The researchers think that acute stress somehow encourages activity of immune cells called memory T cells. Memory T cells remain in the body after infection or vaccination and “remember” the chemical components of the invader. If short-term stress enhances the activity of memory T cells after a KLH vaccine, then these cells will mount a better defence when KLH is injected again.

But according to Bruce Rabin at the University of Pittsburgh Medical Center, US, acute stress is unlikely to enhance human immune responses. “In humans, even a short stressor is suppressive to the immune system,” he notes.

Fleshner differentiates between mild and severe stressors: In mice – and probably in humans – short-term stressors can impair the immune response if they are severe, she says. Mild stressors like being placed in an unfamiliar cage activate a different stress response than severe stressors like being shocked, she says.

Journal reference: American Journal of Physiology – Regulatory, Integrative, and Comparative Physiology (DOI: 10.1152/ajpregu.00145.2005)