SfN 2009: The attention of owls
Sudden movements and sounds can trigger a battle between neurons in the brain, and the winners get to decide where an animal will look, according to new research. Read the full story on Nature News.
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Sudden movements and sounds can trigger a battle between neurons in the brain, and the winners get to decide where an animal will look, according to new research. Read the full story on Nature News.
Jibril Hirbo hails from a tiny mountaintop town called Marsabit, in northern Kenya. Now, as a population geneticist, Hirbo has completed perhaps the largest-ever genetic study of people from Kenya and other East African nations.
The study, he reported yesterday, examined 1,500 people from 66 ethnic groups in East Africa, roughly doubling the number of African populations studied to date. The study provides valuable data about human evolution. For instance, it strengthens the evidence that the “out of Africa” event, in which humans left the continent to colonize the rest of the world, occurred in East Africa sometime within the past 100,000 years. And the data will help clarify the migration and mixing events that connect Africa’s diverse ethnic groups.
Hirbo says, the results are especially interesting to people from his own ethnic group, the Burgee, a group of about 10,000, many of whom now live in southern Ethiopia. He remembers that as a child, people in his town started to suffer from increasing rates of diabetes and cancer, and they weren’t sure why. Some blamed it on witchcraft, or on caste, thinking that these were diseases of the lower classes. But then, respected members of the community started dying from these same diseases. So the caste explanation couldn’t be right.
That’s what motivated Hirbo to become one of only two people from his primary school to go to college, and the only one to get a doctoral degree. At first, he wanted to become a medical doctor, to try to understand the reason behind the illnesses that plagued his neighbors. But along the way, his goals changed. He wanted to understand the genetic variation that might predispose some to disease and grant others immunity. He is now a graduate student working with Sarah Tishkoff of the University of Pennsylvania in Philadelphia.
African genetics have not been nearly as well studied as genetics of Europeans and other western populations. But the few studies that have been done so far, such as Hirbo’s, confirm that Africa harbors more genetic diversity than Europe, because humanity’s original genetic diversity was slowly lost as humans migrated away from Africa to colonize the rest of the world.
Tishkoff says that population studies like Hirbo’s are important for understanding both human history and genetic characteristics that might affect people’s propensity to get disease and respond to drug treatments. And the Africans who participate in the studies hope to learn something about their own histories, Hirbo says.
For that reason, Hirbo and Tishkoff both have plans to travel back to Africa to share what they have found. “I grew up in a small village where people narrate oral traditions and myths about their origins, and so when you tell people you want to know about the traditions based on blood, that’s what they understand, and they really get excited about the results,” Hirbo says.
And it’s no longer true that Hirbo’s old friends and neighbors in Marsabit believe that disease is a result of witchcraft. Now they know, Hirbo says, that disease is “a problem of blood.”
Posted on behalf of Chris Gunter
Believe it or not, some people are complaining that now the ASHG meeting has too much genomics. This comes after years of dire warnings that the society was ignoring genomics at its own peril. Friday morning featured yet another all-genomics platform session, with multiple talks on sequencing whole human genomes.
Matthew Bainbridge of Baylor made crowd laugh by saying all we need is an assay with 100% sensitivity and 100% specificity. In the meantime, he’s using a method of sequencing a genome on two different platforms and comparing the results. He and others at the Baylor College of Medicine extended their work on personal genomes by sequencing in a family with a form of ataxia not due to a triplet repeat mutation, as many ataxias are. As in several talks at the meeting, Bainbridge and colleagues captured the sequence of the exome (or entire set of expressed genes) from key members of a pedigree, and by comparison of genetic variants were able to pinpoint the one gene they think carries the responsible mutation.
In the same session, Stephan Schuster of Penn State discussed the genome sequence of four Kalahari bushmen. He claimed that these were the first genome from non-pastoralists, so they were likely to have different metabolism than other sequenced genomes. Two points stood out for me: first, he addressed the motivation on the part of the Kalahari for participating in the project, as they are fully consented for the full genome sequence data to be freely released. “Desired outcome for Bushmen: they hope that via this project their unique position among today’s human population will be documented and they will benefit thru inclusion in ongoing pharmacological studies.”
Second, Schuster showed a maximum likelihood evolutionary tree of the few whole human genomes currently available. The branch groupings were determined not by the actual evolutionary history but by the method of sequencing used to generate the data. Thus “we are comparing apples to oranges,” he said, “and need to come up with a new set of rules for whole-genome phylogenies.” The crowd agreed as there was much murmuring and furious typing. Schuster proposed a number of reasons why this would happen; solutions include standardizing SNP calling between platforms and agreeing on minima for sequencing coverage.
This brought to mind the presidential address from Ed McCabe earlier in the week – McCabe related his own experience with proprietary algorithms created by companies to analyze the data produced with their technologies. He said that one of his trainees had written an abstract for last year’s meeting and was about to send it off. As a double-check, she reran the analyses first, and got completely different results. The company had changed the algorithm without telling them. When they contacted the company, he and the trainee were told essentially “yes we know there are some problems with the new update but we figure once more people use it and know about the problems, some one out there will come up with a solution.” McCabe therefore encouraged ASHG members to become more involved with the society’s Corporate Responsibility Task Force, launched in 2009 to handle issues just like these.
More details are in the February 2009 issue of the ASHG newsletter.
Posted on behalf of Chris Gunter
In 2006 I blogged from ASHG’s career development session and hate to say that not much has changed.
Back then I said “The session was kicked off by Bill Lindstaedt, Director of the UCSF Office of Career and Professional Development. He delivered the depressing news first: the median age of first tenure-track positions is 38; the median age of receiving a first NIH research grant R01 is 42; and only 4% of such grants go to first-time investigators.”
Bill showed the same or very similar stats this time:
--Only 11% of students/post-docs say they are “confident” in their career goal.
--Growth in new biomedical PhDs 35 or younger is increasing at rate of 59.4% from 1993-2001; growth of jobs was 6.7% in same time.
--For biomed PhDs 35 or younger: ~13% in tenure-track faculty positions. Now PhDs are 42 age at time of first major NIH award; 44 for MD-PhDs.
--% of biomed PhD’s in biotech/pharma: 1997 = 27.3%; 2001 = 31.6%.
For the last statistic, I was quite disappointed that no data were given beyond that. I have to think that the explosion in genomics has at least continued the increase of 1% a year, making it now nearly 40% of “biomedical PhDs” who are in biotech/pharma. If that’s the case, I wonder, why don’t we have more rotations with biotech companies? For example, at the HudsonAlpha Institute for Biotechnology, where I work now, we have multiple internships for students in high-school and college to gain experience at a biotech company. I know other places have similar programs – why not make it mandatory for graduate education if it’s almost equally likely a career option as an academic job?
Bill Lindstaedt also commented: “There is a bit of hand-wringing from students and postdocs I meet with” from “option paralysis.” He showed a video of two people stuck in escalator who just stand there and yell for help instead of just walking up the rest of the way, and says an individual development plan, which he advocates that one completes, is the way to get off the escalator. Everyone should have “a written plan for professional career progression,” he suggests.
One other written plan, and my second modest proposal: Twitter. Oh I know you might scoff, but I sat next to a post-doc who didn’t know about the session until she saw me mention it on Twitter, and she found it very useful. Following the career development session, we had the first ASHG “Tweetup,” organized via Twitter and word-of-mouth. In addition to science writers and lab scientists, we had reps from three of the most cutting-edge genomics companies show up: PacBio, Knome, and Complete Genomics. Clearly they understand the importance of social media, as well as the importance of PhDs going into biotechnology.
Anyone wanting to follow the conference as a whole can use this link.
Everyone wants to find the genes that "make us human." The problem is, when we find them, how will we know?
A talk last night by Raymond Clarke of the University of New South Wales in Australia posed this dilemma. Clarke and his colleagues, Zhi Fang of the University of New South Wales and Zhongming Zhao of Vanderbilt University in Nashville, Tennessee, believe they have found a new gene that could have been crucial to the development of human language. Unlike FOXP2, the most famous "language gene," Clarke and his coworkers believe their gene regulates the development of the human larynx - the tissue in the human throat that allows us to speak. (FOXP2, in contrast, is involved in brain development).
Clarke and his colleagues have studied a family that has an inherited speech impairment caused by a malformed larynx; the worst affected members of the family can hardly speak above a whisper. Clarke's group traced the root of the problem to a broken gene on chromosome 8. The gene, which Clarke's group calls tospeak, is not transcribed into a protein. Rather, Clarke's group claims, it contains a regulatory element called an "enhancer" that promotes the transcription of another gene, growth and differentiation factor 6 (GDF6), which, when mutated in mice, causes malformations in the larynx and joints that look similar to those seen in the family affected by the speech problem.
Clarke says tospeak is unique to primates - humans and their relatives, such as chimpanzees - and doesn't exist in its exact current form in other mammals. That raises the question of how he can be sure that it does what he thinks it does. Usually, scientists can check this out by knocking out the gene in mice, and watching what happens. But if the gene doesn't exist in mice, this isn't possible. And since mice don't speak like humans do, it's not clear what good it would do to engineer mice containing the gene. Clarke was challenged on this point by the audience: how do you know that you're not just seeing some other genetic perturbation that affects GDF6? How do you really know tospeak is involved? Clarke appeared apologetic: "I'm sorry; I can't put it in a mouse," he said.
This is not a dilemma unique to tospeak; any other gene responsible for "uniquely human" traits will be similarly difficult to study in other model organisms. There is another way to check them out, however; part of the rationale for sequencing the genome of another human species, the Neanderthal, was that it would help shed light on human evolution and uniquely human traits.
Clarke, in fact, said that he had asked the scientists studying the Neanderthal genome for any information they had about tospeak. "They declined," Clarke said, "and said they would publish their data within the month." That drew murmurs of disapproval from the audience.
It's surely a coincidence that Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, is both a leader of the Neanderthal genome project, and has made his reputation with studies on what had previously been the only really famous language gene - FOXP2.
One of the major themes of this meeting is personalized medicine - the promise that some day, doctors will be able to tailor treatments for all of us based on our genetic makeup. Scientists and researchers are excited about the future prospects of personalized medicine, but there are also huge questions about how useful it will really be. Social scientists are wondering: can patients can handle genetic information? Will they overreact upon learning they have some small increase in risk for a disease? Or will the information wash over them like the myriad public service announcements exhorting us to eat right and get more exercise - messages that, apparently, most of us have learned to ignore?
Researchers are starting to get some answers on these questions by studying patients in Detroit, Michigan's Henry Ford Health System in a study called the Multiplex Initiative, funded by the U.S. National Human Genome Research Institute. In it, doctors offer a bundle of genetic tests to healthy patients aged 25-40. They then follow the patients to see who goes on to take the tests - which are packaged together in a so-called "multiplex" assay that surveys risk variants in 15 different genes - and what they do with that information. This multiplex test simulates, on a much smaller scale, the consumer genetic tests sold by private companies, which survey hundreds or thousands of risk variants across the genome.
So far, the NHGRI's data hints that some of the worst fears about genetic testing might not come to fruition.
For instance, NHGRI's Colleen McBride said that one of the strongest factors that predicts which patients choose to take the multiplex test was how much the patient believed that behavior contributes to overall risk of disease. Those who believed more strongly that behavior contributes to disease - that smoking, not just genetic makeup, affects the risk of lung cancer, for example - were more likely to get tested. McBride's interpreted this finding to mean that the patients wouldn't believe that they were powerless to do anything about their disease risk if they got a "high risk" test result. And, conversely, they might be more motivated to change their behavior by a multiplex test result.
And Robert Reid of Group Health Cooperative in Seattle said that patients who took the multiplex test made slightly more visits to their primary care doctors in the 18 months after getting their test results than they had in the 18 months prior to taking the test. But even though the increase was significant, it was still a small increase in sheer number of visits. What's more, the number of screening tests ordered on the patients didn't increase after the genetic tests were completed.
And McBride noted that of the patients who got tested, only 11 percent actually discussed their results with their doctors; an additional 14 percent planned to.
According to Reid, this contradicts the fear that patients will overreact to their genetic tests results, causing wasteful spending on a glut of unnecessary follow-up medical work. "We are certainly not finding a stampede of visits to primary or specialty care following multiplex testing," he said.
So it seems - at least from this very preliminary data - that people are better at using genetic information to inform their health decisions than some might have feared. If the finding holds up, it will correlate well with other studies of reactions to genetic testing, such as a study published earlier this year, which found that genetic testing for Alzheimer's disease risk didn't hurt patients' mental health.
There was, however, some data to suggest that other concerns about genetic testing might be more salient. For instance, the patients who eventually got the multiplex test were more likely to be white than black, perhaps substantiating the fear that testing will not reach everyone equally.
It's hard to say what this means for the personal genomics tests sold to consumers, though. The Multiplex Initiative requires patients to at least visit a web site, prepared by the project, that is intended to be educational rather than promotional. The site even gave reasons why patients might decide against testing, and described the limitations of the tests. That's different in a pretty important way from the information provided by personal genomics companies: the companies obviously believe that the tests are useful - and are motivated to convince consumers that this is, indeed, the case. So it's unclear whether the lessons from the Multiplex Initiative will apply to the "wild west" of commercial personal genomics.
Scientists have discovered a site containing the most extensive evidence seen so far in Mexico for the Clovis culture. The find extends the range of America's oldest identifiable culture, which roamed North America about 13,000 years ago. Read the full story on Nature News here.
A newly discovered crater on Mercury may have been geologically active as recently as a billion years ago. Read the full story on Nature News here.
Posted on behalf of Rex Dalton
The oldest dwelling structure in Utah -- dated to 3,000 years ago -- was reported this week, offering a glimpse of ancient life in the Great Salt Lake Basin.
The pit house structure was located near a river bed in the highly developed Salt Lake City region after a team of scientists persevered for years to study the location without project funding. Some now fear the potentially important site may be lost to development, with but a plaque to mark the location.
In a lecture at the annual meeting of the Geological Society of America, Kathleen Nicoll of the University of Utah in Salt Lake described enlisting students from local elementary and high schools to help survey the site’s rich artifacts. "It is easier to get on the Oprah Winfrey Show than to get funding for this type of work,” says Nicoll.
Such dwellings across the United States are drawing scrutiny as researchers employ more widely available sophisticated techniques to test pollen, bones and artifacts to answer questions about paleoenvironments and inhabitants. “This is a very important time for understanding the transition to agriculture in the Southwest, when people became more sedentary,” says Nicoll.
The location is between the Jordan River and a Denver & Rio Grande Railroad right-of-way, which is now eyed as a route for a light-rail transit system.
In the 1990s, the pit house was identified during an environmental survey for construction of a prison. When that plan faded, the site -- across the river from a golf course -- was also eyed as a possible housing development. And some residents want a park. What becomes of the location will be determined by this three-way debate.
Nicoll said radiocarbon dates from within the pit house and adjacent sediments found repeated occupations from 1,500 to 3,000 years ago.
Remnants of the pit house were found just a few centimeters below the surface, after surveys of the terrace identified 30,000 artifacts within an area of nearly 40 hectares. “I found that sixth grade students are very good at counting artifacts,” says Nicoll.
In the future, the team plans to study plant or artifact samples to learn more about the diet of the people of the time.
Some of the oldest dwellings in the West have been located in valleys east of the Sierra Nevada Mountains in California and in Colorado.
Mark Stiger of Western State College in Gunnison, Colorado, and David Meltzer of Southern Methodist University in Dallas have studies underway on multiple dwellings. One mountain camp site may date to the age of the Folsom people, about 10,400 years ago, Stiger noted
Nicoll’s study is under peer review at the journal Catena.
Posted on behalf of Rex Dalton
The fast-sinking idea that a comet struck North America 13,000 years ago, killing off the Clovis Paleo-Indians and triggering the Younger Dryas cold snap, was again undermined by geochemical tests released this week.
A US-Belgium team has reported that it can find no evidence of a comet impact at seven sites and in sediments in two ocean cores corresponding to when the object reportedly exploded over the North American ice sheet. Francois Paquay, a doctoral student at the University of Hawaii in Honolulu, reported the team’s results at the annual meeting of the Geological Society of America in Portland, Oregon.
There was no rise in iridium at the Clovis sites, no change in other platinum group element levels that would be altered by an impact, and no concurrent iridium rise in cores from the Guaymas Basin in the Gulf of California and the Caribbean Sea south of Tortuga, he said.
“There is nothing; there was no impact,” says Paquay, whose co-authors are Philip Claeys, a prominent researcher on impacts at the Free University of Brussels, and Greg Ravizza of Hawaii.
Findings from the study are at the heart of an article now under peer review at the Proceedings of the National Academy of Sciences.
Earlier this month, PNAS published a study by researchers led by Todd Surovell of the University of Wyoming at Laramie; they were unable to find the abundant levels of magnetic spherules purported to be remnants of the explosion.
Proponents of the comet theory insist their idea has validity. One author of the original theory, Richard Firestone of the Lawrence Berkeley Laboratory in California, wrote in an email: “The authors of the recent papers that found nothing have an agenda to disprove our work and to keep anyone else from publishing positive results. This and the previous paper are examples of sloppy research.”
But among those who study extraterrestrial impacts, there is little support for the theory. The GSA report is likely to only accelerate the level of criticism.
For instance, Paquay found in examining the ratios of isotopes of osmium, a platinum group element, there was no change at the studied sites. And there was no change in the examined levels of the cores, drilled years ago as part of the Integrated Ocean Drilling Program. All the study results were confirmed in two independent laboratories, Paquay added.
Nature reporter Erika Check Hayden (twittername @patsycat21) will be covering this year's American Society of Human Genetics meeting in Honolulu, Hawaii, from 20-24 October. Check back here for her coverage, as well as guest posts from Chris Gunter (@girlscientist), director of research affairs at the HudsonAlpha Institute for Biotechnology in Huntsville, Alabama, and former Nature editor extraordinaire.
In the Field is where you can find diary entries from the most exciting science events. Get daily reports from Nature reporters scouring conference floors or covering field missions. Keep us bookmarked, sign up for RSS feeds, or watch the homepage of Nature News to see when we’re hitting a conference.
The stimulation of a tiny number of neurons can evoke entire memories, new research in mice suggests. Read the full story on Nature News here.
There are heaps of posters and presentations this year about optogenetics — the technique developed just a few years ago at Stanford by Karl Deisseroth and Ed Boyden, in which neurons can be engineered to respond to light. There's even a section of the press book on optogenetics. If this had been a year ago, I might have rolled my eyes and thought, "optogenetics is so 2005", but it looks like the technology is riding on its second wave: it's out there, people trust it, and now labs are using it in quite creative ways and actually discovering new things about the brain. A few people at the conference are already murmuring about a Nobel for optogenetics.
The hottest thing I saw so far was a poster by Matteo Rizzi and Kate Powell from Michael Häusser's lab at University College London. The group put the light-sensitive protein channelrhodopsin (ChR2, the most commonly used protein for optogenetics that's sensitive to blue light) under the control of the promoter for c-fos, a gene that is expressed by recently activated neurons. This way, they could specifically hit neurons that had been involved in a behavior or task. It's a great new tool that they used to generate a very exciting result, which you can read about on Nature News.
Posters all over the place were using optogenetics' fast, cell-type specific control to learn more about various circuits, and of course Boyden, now at the MIT Media Lab, and Deisseroth had many posters and gave a number of talks (I only had time for a few posters — there were more than 3,000 posters today alone). A couple of Boyden's posters were working out how to do simultaneous optogenetic simulation and electrophysiological recordings — many people thought this couldn't be done, as the light source would cause too much noise. Turns out all you need to do is shield the light source or shield the electrode.
Deisseroth is also doing a lot of work on other light-sensitive proteins, which would respond to a color other than ChR2's blue. These include NpHR, which is sensitive to yellow; VChR1, which is sensitive to yellow but has the opposite effect of NpHR; OptoXR, which activates second messenger signaling; and a newcomer called GtR3, which is inhibited by blue light. Given the progress already made with ChR2, it's very exciting to imagine the ingenious ways people will use these various proteins to further dissect neural circuits.
In a first for the SfN conference, the director of the NIH -- who ultimately holds the purse strings for most of the people here -- made an appearance and addressed the crowd. Francis Collins began his talk with a facetious reference to some of the criticism he's fielded since his appointment just months ago.
"Those of you who have been reading the blogs might expect me to begin with a benediction, I assure you I have no intention of doing that," he said. "I won't ask you to pray for anything, except perhaps the FY2011 budget.”
Collins highlighted the increases to NIH funding in the stimulus bill, the hope for the new Challenge Grants and progress with establishing NIH guidelines for human embryonic stem cell research. He also stressed the importance of the NIH blueprint for neuroscience research, which includes the human connectome project.
He then continued preaching to the choir, listing the themes NIH thinks are important for neuroscience, such as translating basic discoveries to treatments, incorporating genomics, being interdisciplinary, etc. I doubt any of the neuroscientists here got any new ideas from his presentation, but Collins' presence was symbolically important. Knowing that the government thinks this work is a priority is a welcome change for these folks.
Functional MRI has been getting a bad rap lately, with recent papers and posters critical of fMRI analyses receiving a frenzy of media attention. These have generated a harsh reaction from the public; many journalist friends of mine have declared they'll never write about an fMRI study ever again.
Sure, some people are seduced by the pretty pictures and like to think they let scientists “see our thoughts”, and this fantasy should be nipped in the bud. But while fMRI has its limitations, it's a valuable technique that, when performed correctly, can give neuroscientists a unique insight into the brain.
SfN gave me a nice opportunity to get an fMRI veteran's perspective on the state of fMRI in science and the public. John Gabrieli at MIT has been working in the field since the early years (fMRI only came about in the early 90's), and has written and spoken extensively on the power and limitations of the technique. Here he participated in the “Meet the Experts” series, where he gave a presentation about the technique to a small group of mostly post-docs and students over breakfast.
He noted that the flashy colorful pictures of brain activation are statistical maps — not actual changes in blood flow. For example, if you have a very powerful visual stimulus, like a flashing light, the signal in the visual cortex would change by about 3%. Same for the BOLD signal in the motor cortex when you wave your arms around wildly. But for most interesting activities — thoughts, feelings, desires, memories — a signal change of half of 1% would be “a really good day”, he says. He points out that if we had been doing imaging before the famous patient H.M., we would have no idea the hippocampus was involved in memory formation; “we would have spent 20 years thinking the hippocampus was not involved in memory, because in dozens of memory tasks we couldn't get hippocampus.”
Gabrieli says this super-weak signal means we're actually missing a lot of stuff, and are at a far greater risk for false negatives than we are for false positives. People only get into trouble with false positives when they try to overcompensate for this low signal, and Gabrieli detailed ways to avoid this trap.
Gabrieli also spoke about some of the newer uses for fMRI, beyond just trying to see “where” things happen in the brain. For example, if scientists could find brain activation patterns in young people that were associated with the later development of diseases like schizophrenia or depression, they could use fMRI as a far more accurate predictor of psychiatric disease than genetic testing, which is extremely limited.
Another hot area of fMRI research is “real time” fMRI, in which a subject's fMRI signal feeds back to what they see. For example, if a certain area of the brain is active when the subjects are ready to remember a picture, the fMRI can wait until this brain region is active before presenting the picture. A few people have already started thinking about clinical applications of “real time” fMRI, such as enhancing learning, behavioral therapy and giving people “control” over their auditory cortex to stop tinnitus.
The massive annual conference of the Society for Neuroscience hit the ground running today in sunny and crisp Chicago. It's only day one and the conference center is already clogged with neuroscientists. Attendance is supposedly around 30,000 this year — a staggering number, but down from the conference's peak a few years ago in Washington, D.C. when attendance almost hit 35,000 (and when travel budgets were a bit more generous).
30K-plus is still a decent number, but apparently not big enough to take over the McCormick Place convention center — just next door from the conference, McCormick was hosting open auditions for season 5 of America's Got Talent, and a dense and enormous stream of aspiring stars and their parents snaked around the conference center for most of the day.
There are plenty of other reporters here blogging and tweeting away, including Greg Miller at Science, DrugMonkey, the folks Tweeting with #sfn09 and eight "official" SfN bloggers. The latter is SfN's admirable effort to actively integrate live blogging into their conference. Of course, plenty of people manage to blog and Tweet without the "official" designation, and it's unclear whether this will actually impact coverage — but at least SfN is embracing social media, as opposed to clamping down (which has its pros and cons).
Nature reporter Lizzie Buchen will be covering this year's Society for Neuroscience conference from Chicago. Look for updates from her on all things brainy from 17-21 October.