The DNA Network |
George Will: Why Are We kicking Talent Out of the US? [adaptivecomplexity's column] Posted: 10 Jul 2008 08:31 PM CDT Continuing my science policy blogging streak (we'll get back to real science here soon, I promise!), it's worth noting Washington Post columnist George Will's recent piece about our "perverse national policy of expelling talented people." If you've spent any time recently around America's science PhD programs, you'll have heard about the problem: we bring talented people in from all over the world, train them to do great science, and then make it impossible for them to get a job here, even when US companies and universities want to hire them. As George Will writes, this creates yet one more incentive for US companies to send their operations outside of the US:
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Fascinating correlations or elegant theories? [The Seven Stones] Posted: 10 Jul 2008 06:47 PM CDT Chris Anderson, Editor-in-Chief of Wired , wrote a few weeks ago a provocative piece "The End of Theory: The Data Deluge Makes the Scientific Method Obsolete", arguing that in our Google-driven data-rich era ("The Petabyte Age") the good old "approach to science —hypothesize, model, test — is becoming obsolete", leaving place to a purely correlative vision of the world. There is a good dose of provocation in the essay and it was quite successful in spurring a flurry of skeptical reactions in the blogosphere, FriendFeed-land and lately in Edge's Reality Club. I know that it is a bit late to write a post on this but this debate reminds me of the bottom-up vs top-down dialectic in (systems) biology. The tradition in molecular biology has been to focus on molecular mechanisms–a series of molecular events–that explain given biological functions. With detailed knowledge on the properties of an increasing number of components, bottom-up mechanistic descriptions–or models–can be constructed, which account for the experimental observations. Of course, the purpose of models, at least for insightful ones, is more than merely providing mechanistic descriptions. As William Bialek writes, "Given a progressively more complete microscopic description of proteins and their interactions, how do we understand the emergence of function?" (Aguera y Arcas et al, 2003). There is therefore some subsequent subtle transition from description to insight, from model to theory, from detailed and specific to simple and general (watch Murray Gell-Mann's TEDTalk on "Beauty and truth in physics"). Theories are elegant. On the other hand, high-throughput technologies (microarrays, proteomics, metabolomics, ultra high throughput sequencing, etc...) are indeed profoundly changing molecular biology and flooding the field with experimental data like never before. Currently, only part of this data can be explained within the context of mechanistic models. Still, and this is probably Chris Anderson's main point, it turns out that if the data is rich enough, one can exploit it by looking at the data globally, from the 'top', to reveal statistical patterns and correlations. Even if there is no mechanistic explanations (yet) for these correlations, they may reveal new worlds, novel structures and detect relationships between processes that were considered before as unlinked. Correlations are fascinating. Correlations resulting from data-driven analysis may well in turn stimulate new mechanistic investigations and hopefully new understanding. On Edge, Sean Carroll summarizes it all: "Sometimes it will be hard, or impossible, to discover simple models explaining huge collections of messy data taken from noisy, nonlinear phenomenon. But it doesn't mean we shouldn't try. Hypotheses aren't simply useful tools in some potentially-outmoded vision of science; they are the whole point. Theory is understanding, and understanding our world is what science is all about." BUT, what is true for fundamental science is not obligatorily a rule for more applied fields, where the priority might less be on understanding than on acting. In particular, in medically related fields, top-down data-driven correlative approaches represent a pragmatic approach to obtain predictive models without waiting for still elusive fully mechanistic models that would encompass the entire complexity of human physiology (Nicholson, 2006). As often in science, as in other human activities, different but complementary views are championed by people with different temperaments: there are those who like to build an edifice piece by piece and those who want to explore new territories. I think–I hope–that progresses in systems biology on both fronts, top-down and bottom-up, demonstrates that there is no need to turn this complementarity into an opposition. |
Presentations of the Week [ScienceRoll] Posted: 10 Jul 2008 03:11 PM CDT I’ve recently come across two interesting slideshows I must share with you. The first one was presented by Jean-Claude Bradley at the Scholar2Scholar conference at Drexel University. He introduced Web2.0 then described how developing anti-malarial agents could be done on blogs and wikis. The second one belongs to Peter Bihr and focuses on social media in higher education (via). |
Badass Scientist of the Week [Bayblab] Posted: 10 Jul 2008 12:22 PM CDT In keeping with last week's badass scientist of the week, I present to our readers Dr. Werner Forsmann, Nobel prize winning cardiologist, and badass scientist (and possibly inspiration for Dr. House). Dr. Forsmann pioneered the technique of cardiac catheterization, a process by which a cable is inserted through an artery or vein into the heart. Conventional wisdom was that this would be certainly fatal, and Dr. Forsmann was forbidden from trying the technique by his department head. He decided to try the technique on himself. When his assistant protested, he tied them to a table, in order to prevent an alarm being raised. He then gouged his own arm, placed a urinary catheter (designed for something quite different) into one of the veins he located, pushed it up his arm and into his heart. To seal the deal, he then walked up a flight of stairs (holding the catheter in place) to the x-ray department, and ordered an x-ray of his chest, to prove the location of the catheter. He was subsequently fired. And fired again from his next position. Having become disillusioned with cardiology, and having now practiced with the urinary catheter, he changed specialties to urology, and became a country doctor. He was awarded the Nobel prize in 1956. |
Molecular Movies and Animations [Bitesize Bio] Posted: 10 Jul 2008 10:54 AM CDT In a recent issue of Cell, there’s an interesting commentary on Molecular Movies… Coming to a Lecture Near You. The article got me thinking - wouldn’t it be useful if there were more skilled graphics and animation experts at the disposal of researchers? Conveying the information content of your average proposal, report, lecture, or public exposure moment in a way that gets and keeps the attention of the non-expert is something that comes very difficultly to the average scientist. I know it does for me, not being experienced in anything beyond PowerPoint and Adobe Illustrator. It strikes me that with the notoriety of molecular biology and microbiology, there must be a market for graphics editors interested in shopping their skills around - graphics freelancing, as it were. As the Cell article focuses on movies and animations, that would perhaps be top tier. But even a well-done and customized schematic would be an extremely useful addition to any journal manuscript, symposium talk or poster, laboratory website, or research proposal. Okay, I notice some such multimedia utilizing nice graphics for presenting molecular biology and microbiology, but I rarely hear about research proposals including a request for a small allocation of funds for paying a graphics editor for 20 hours of work. I also rarely hear about a graphics editors circulating business cards at any gathering of researchers who might be interested in getting a funding or publishing advantage (and there are plenty of those). |
Posted: 10 Jul 2008 09:49 AM CDT A few months ago I wrote about a recent spate of measles cases in North America. After years of low immunization rates, the same thing has been happening in the United Kingdom, to the point where measles is once again endemic after more than a decade of halted spread. Fourteen years after the local transmission of measles was halted in the United Kingdom (UK), the disease has once again become endemic, according to the Health Protection Agency (HPA), the public health body of England and Wales. In an update on measles cases in its weekly bulletin last week, the agency stated that, as a result of almost a decade of low mumps-measles-rubella (MMR) vaccination coverage across the UK, 'the number of children susceptible to measles is now sufficient to support the continuous spread of measles'Current vaccination rates in the UK are well below the 95% desired to maintain herd immunity. Of over 50 lab-confirmed measles cases in Scotland so far this year (there have been 461 in England and Wales), only 2 of them were imported from overseas. Measles is no longer endemic to Canada and the USA, but remains endemic in many other countries. If the current anti-vaccination movement continues to flourish, how long will it be before it returns to our shores? [via Respectful Insolence] |
Am I Left-handed or Right-handed? 23andWe Wants to Know. [BUZZYEAH » My Genome] Posted: 10 Jul 2008 09:00 AM CDT Why does 23andWe want to know? It's for their featured research project titled "Handedness". According to 23andMe, little is known about why people become left-handed or right-handed. They think they can help the science community figure out what genetic component is linked to handedness by polling the 23andMe community and comparing their answers against their genetic data. Here are the questions I was asked for the Handedness survey: Questions 1-3: Questions 4-6:
Questions 10-12: It's no surprise that my 23andWe results tell me I'm "Pure right-handed": And, now I raise my right fist in salute to right-hand power. See this post over at The Spittoon for more on the interesting lefties vs righties battle. |
HEALTH Highlights - July 10th, 2008 [Highlight HEALTH] Posted: 10 Jul 2008 08:57 AM CDT
This article was published on Highlight HEALTH. Related articles |
Is Helix Health a Top Competitor in DTC Genomics? [Think Gene] Posted: 10 Jul 2008 08:40 AM CDT No. Why?
Helix’s non-classification as a competitor isn’t a slight, it merely does not compare well with Navigenics, 23andMe, and deCODEme because it sells services (time), not product. unit profit by size of business
Services business begin profitable at full capacity (because people do not work at a loss) but do not scale well because experts have limited time to sell. So consulting businesses like Helix Health may achieve consistent, moderate returns, but they don’t have the potential for monopolistic growth that leads to huge exits. Thus, consulting businesses rarely raise venture capital funding which depend on a few huge exits before their fund’s horizon for profitability. So deCODEme, Navigenics, and 23andMe are “all or nothing” fence-swingers, while Helix Health is not. So the “crossing the chasm” argument applies less to Helix because its survival doesn’t depend on reaching a general market. Bottom line: if every American ordered a 23andMe test, 23andMe would be Google. If every American tried to schedule an appointment at Helix Health, there would be a very long line. |
Physician 2.0 Award at the Medicine 2.0 Congress [ScienceRoll] Posted: 10 Jul 2008 03:15 AM CDT I will attend the Medicine 2.0 Congress taking place in Toronto this September, 4-5. I will talk about web 2.0’s role in medical education and how to build an online reputation. Moreover, I will be in the Medical Bloggers’ Panel as well. If you plan to attend it, register at the site of the congress and let’s meet there. Now here is a great idea from MDPIXX and the organizers.
Click here for further information. |
Forget Lincoln-Douglas - How about a Lincoln-Darwin debate? [The Tree of Life] Posted: 10 Jul 2008 02:43 AM CDT In case you did not see it - it is worth seeing the discussion of Lincoln vs. Darwin in Newsweek (How Darwin and Lincoln Shaped Us). They set up the discussion by pointing out that they had the same birthday. They say Lincoln was more important. Not going to argue but not sure they are right. My favorite section on this article: This questioning spirit is one of the most appealing facets of Darwin's character, particularly where it finds its way into his published work. Reading "The Origin of Species," you feel as though he is addressing you as an equal. He is never autocratic, never bullying. Instead, he is always willing to admit what he does not know or understand, and when he poses a question, he is never rhetorical. He seems genuinely to want to know the answer. He's also a good salesman. He knows that what he has to say will not only be troubling for a general reader to take but difficult to understand—so he works very hard not to lose his customer. The book opens not with theory but in the humblest place imaginable: the barnyard, as Darwin introduces us to the idea of species variation in a way we, or certainly his 19th-century audience, will easily grasp—the breeding of domestic animals. The quality of Darwin's mind is in evidence everywhere in this book, but so is his character—generous, open-minded and always respectful of those who he knew would disagree with him, as you might expect of a man who was, after all, married to a creationist. |
Anton is just round the corner [business|bytes|genes|molecules] Posted: 09 Jul 2008 11:24 PM CDT
I must admit that D.E. Shaw makes me go green around the gills. He was a computer science professor at Columbia University, founded a very successful hedge fund (he doesn’t run it full time any more), is the money behind a company that makes some great molecular modeling software, and is the chief scientist at a computational scientific research company. That he also publishes single author theoretical papers is just plain unfair. One of the cooler projects at D.E. Shaw Research is Anton; “a specialized, massively parallel supercomputer designed to execute MD simulations hundreds of times faster than has been possible to date.” Yesterday, the New York Times carried an article on Anton. I have argued in the past that general-purpose machines are ideally used to solve a certain set of problems, the majority of problems that most of us are interested in. I have also argued that molecular simulation was stuck in a rut. Anton is a special purpose machine and essentially is designed to solve problems that are not simple solved by having bigger faster machines, but actually thinking about what would be needed to solve a specific problem; atomic resolution, millisecond scale simulations, essentially 1000 times |
Updating how the US Government Gets Its Advice [adaptivecomplexity's column] Posted: 09 Jul 2008 10:58 PM CDT Over the last few years, we've seen some bitter political arguments over the role of US Government scientists, political appointees, and the manipulation of technical reports. I'm not going to wade into that fight here, except for one point: occasionally we hear the argument that government scientists are employees of the executive branch, and that they are therefore legitimately subject to the efforts of the President and his appointees to get everybody on board with the President's agenda. For many positions in the federal government, that argument is correct. If you work for the executive branch, ultimately the President is your boss. But in many cases, especially ones that concern some government scientists, there is a limit to what the President and his political appointees can do, because the role of those scientists has been established by law. Congress has sensibly written several laws to ensure that the government can get sound, unbiased technical advice, free from political manipulation. |
Now some comments from Raoul, the organic farmer [Tomorrow's Table] Posted: 09 Jul 2008 10:32 PM CDT Rather than another story about Me, the blogger here is a link to an interview conducted by The US News and World Report with my coauthor and husband, Raoul. In it, he discusses our book "Tomorrow's Table: Organic Farming and the Future of Food." Have you ever wanted to know what an organic farmer has to say about genetically engineered crops? Here is your chance. |
A great vegetarian recipe from Raoul and Pam [Tomorrow's Table] Posted: 09 Jul 2008 10:30 PM CDT Raoul and I included several recipes in our book Tomorrow's Table. Amazon posted one of these on the product page for the book. I would attach it here, if I only knew how. Instead, here I append an excerpt from the book that describes how we prepare this recipe and explains why some of the ingredients are GE and some are certified organic. First, we generally eat as much as possible from the farm basket Raoul brings home every few days. We like the variety, freshness, and ease that comes from eating off the farm. At home on weekdays, we like to prepare the food quickly, and we want it to be colorful (we figure if there are a variety of colors on the plates, then we are getting enough vitamins) and tasty. The tofu is made from certified organic soybeans that are processed into the familiar white square blocks in a factory a few miles away. After I finish preparing the tofu, I turn on the stove to high and pour in a few tablespoons of olive oil. The oil is not certified organic but it was on sale and locally made. The low cost appeals to me and so does eating locally grown foods because it supports our neighboring farmers. The olive oil is definitely not GE because there are no GE olives on the market. Despite this fact, the label on the bottle says "GE-free." It is a hopeful marketing ploy that is often seen at our local food co-op where many consumers associate GE with massive farms, pesticide runoff, and high fertilizer use. Yet genetic engineering is not the cause of these types of farms. The industrialization of agriculture, with the associated high inputs of pesticides and fertilizers, proceeded quite contentedly for years before the advent of GE, fueled mainly by governmental agricultural policies that do not put high priority on social and environmental costs. Ironically, much of the food labeled "GE-free" may have been imported from afar, grown with toxic pesticides, or be less nutritious than the local fare. In contrast, food that is GE may be locally grown without pesticides, and someday, be more nutritious than crops grown from non-GE seed. I pull out another pan, turn a burner to high, pour in some more oil and plop down two of Micaela's corn tortillas, made in a factory ten miles north of here. The ingredients are simple: corn, water, and salt. The corn is not certified organic and the tortillas likely contain trace amounts of Bt protein. We choose them because these are the best tasting tortillas around and they are produced close by our home. It seems to me that these tortillas made from corn from Bt-corn plants fit well within the ecological farming framework we try to support. First, the global environment is being spared more than a hundred million pounds of much more toxic pesticides each year. Second, the tortillas likely contain reduced amounts of mycotoxins as compared to tortillas made from conventional or organic corn. In California's Central Valley, food is abundant, and it is fairly easy to figure out what to eat, especially if you are not overly concerned about the presence of GE ingredients. If there is meaning to be found in each meal, it is not about how the food was genetically modified, but in the freshness of ingredients, the health of the farm workers, the impact on the environment, and the mood and gratitude of the diners. We hope you enjoy the recipe. |
Blogging Back from Boston [Tomorrow's Table] Posted: 09 Jul 2008 10:29 PM CDT I spent the last two days at the Center for Cancer Systems Biology then at a meeting at Center Director Marc Vidal's beach house with his coPIs Joe Ecker, Pascal Braun and David Hill and their staff and scientific advisory board members (Rod Wing, Fritz Roth and Mike Snyder) to learn how to create REALLY LARGE datasets of interacting proteins. The Vidal lab makes these kinds of datasets for yeast and human and now, oh happy day, they are going to tackle rice. This kind of data can reveal candidate functions for many new genes. For example if protein x is known to be important for a defense response and it is found to interact with protein y then that implicates protein y in the same defense pathway. This kind of approach was used to create a human "diseasome" as described in a recent NYT Science times article that is being used to predict which proteins are involved in which disease. In rice, we can use this information to identify new forms of genes (alleles) that can help the rice plant resist disease or tolerate stress. You can see some examples of the rice interactome here. We watched slides and discussed the data in the cabin's living room. From my chair I could consider the view of the broad lawn and beyond, a tangle of flowering shrubs and small trees surrounding a steep bank that dropped down to the Gloucester Bay. During a break, we followed Marc down a footpath lined by rose bushes and granite boulders, to a diving platform near a rocky beach. The water below looked clean and inviting. My plan was to dive in and then swim to the spit of land across the bay and back. I quickly changed my mind after diving into the icey water. We took turns hauling each other out over the seaweed-coated rocks. We returned to the cabin for a short discussion and then moved on to barbequed organic chicken, homemade potato salad, cucumber green salad, roasted asparagus and corn on the cob. And wines. Lots of wine. And ice cream- 6 flavors of Haagen Daz and Ben and Jerrys- to choose from and then bread and cheese and then… Oh oh. I just realized my science blog is being overrun by descriptions of Marc and Roseanne's beach house and good cooking. Sorry about that. Back to business here. The previous day I visited Fred Ausubel's lab at the Dept of Molecular Biology, Harvard Medical School where I learned all kinds of neat and efficient ways to infect Arabidopsis with bacterial pathogens and insect pests. The reason for this is not simply to torture the tiny, gentle, leafy, green plants, but to figure out which varieties are resistant to pathogens. Scientists can then take that information to generate new crop varieties. I also gave a talk about our book "Tomorrow's Table". This was the second time that one of my university hosts asked me to talk about the book rather than my research. Either my research talks have gotten really boring or there is a lot of interest in organic farming, genetics and the future of food. A Whole Foods market is located right next door to the lecture hall, just a few steps away. I wished I had though to recruit some shoppers to my talk. Many of them are interested in these kinds of food things. I don't mean to imply that the medical students weren't interested, after all about 50 showed up, but I do wonder if they were more interested in my brief discussion of the enhanced risk of prostate cancer in farmworkers exposed to pesticides than to the discussion of Raoul's organic farm. If you are interested in what I had to say, check out Anna Kushnir' blog post here: Anna is a newly minted Harvard PhD and blogger for Nature Networks. Aside from Jonathan Eisen, whom everyone has met, this is the first time I have met a blogger. On this trip I had the pleasure to meet Rob Paarlberg for lunch. You should check out his excellent book called Starved for Science (with a forward by Norman Borlaug and Jimmy Carter). After lunch we stopped by the Harvard Coop bookstore to sign books at my publishers request. The salesclerk helping us was very nice enthusiastic and said he had 24 books in stock "Right up front". The three of us looked in front, and then on the side aisles and then in the back. I am still not sure if they ever found them. Ah the life of famous authors. |
Posted: 09 Jul 2008 10:28 PM CDT Oxford University Press has posted a conversation on their blog between Robert Paarlberg (who recently published Starved For Science) and I (co-author of Tomorrow's Table). We debate how to best ensure a safe food supply with the least amount of damage to the environment. This is a series that OUP will be publishing all week. Please check it out! |
Walle and Paul Ehrlich [Tomorrow's Table] Posted: 09 Jul 2008 10:27 PM CDT Professor Paul Ehrlich and the makers of the new film Walle have a lot in common. They see the need to "shift our dominance away from malignant" (please see Stewart Brand's review of the lecture below) and toward the benign, the living and the beautiful. They also both discuss the ways in which humans will need to evolve socially and culturally to make this happen. In the movie Walle, humans have fled an earth that is no longer habitable. There are great scenes of stuff (calling to mind the George Carlin riff) piled as high as the abandoned skyscrapers nearby. In Ehrlich's world, we are well on the way to an equally dismal fate. With the warming of the earth's atmosphere and the accumulation of toxic chemicals in our soils we are destroying humanity's life support system-the climate food and water we need to survive. Ehrlich's lecture, entitled "The Dominant Animal: Human Evolution and the Environment " was one of a series of Seminars About Long Term Thinking hosted by the Long Now Foundation. The fabulous Long now Foundation aims to provide counterpoint to today's "faster/cheaper" mind set and promote "slower/better" thinking. Today I recycled some stuff and hung my clothes out to dry. Here is founding board member Stewart Brand's summary of the event: "To track how humans became Earth's dominant animal, Ehrlich began with a photo of a tarsier in a tree. The little primate had a predator's binocular vision and an insect-grabber's fingers. When (possibly) climate change drove some primates out of the trees, they developed a two-legged stance to get around on the savannah. Then the brain swoll up, and the first major dominance tool emerged---language with syntax. About 2.5 million years ago, the beginnings of human culture became evident with stone tools. "We don't have a Darwin of cultural evolution yet," said Ehrlich. He defined cultural evolution as everything we pass on in a non-genetic way. Human culture developed slowly-the stone tools little changed from millennium to millennium, but it accelerated. There was a big leap about 50,000 years ago, after which culture took over human evolution---our brain hasn't changed in size since then. With agriculture's food surplus, specialization took off. Inuits that Ehrlich once studied had a culture that was totally shared; everyone knew how everything was done. In high civilization, no one grasps a millionth of current cultural knowledge. Physicists can't build a TV set. Writing freed culture from the limitations of memory, and burning old solar energy (coal and oil) empowered vast global population growth. Our dominance was complete. Ehrlich regretted that we followed the competitive practices of chimps instead of bonobos, who resolve all their disputes with genital rubbing. "The human economy is a wholly-owned subsidiary of the Earth's natural systems," said Ehrlich, and when our dominance threatens the ecosystem services we depend on, we have to understand the workings of the cultural evolution that gave us that dominance. The current two greatest threats that Ehrlich sees are climate change (10 percent chance of civilization ending, and rising) and chemical toxification of the biosphere. "Every cubic centimeter of the biosphere has been modified by human activity." The main climate threat he sees is not rising sea levels ("You can outwalk that one") but the melting of the snowpack that drives the world's hydraulic civilizations--- California agriculture totally dependent on the Sierra snowpack, the Andes running much of Latin America, the Himalayan snows in charge of southeast Asia. With climate in flux, Ehrlich said, we may be facing a millennium of constant change. Already we see the outbreak of resource wars over water and oil. He noted with satisfaction that human population appears to be leveling off at 9 to 10 billion in this century, though the remaining increase puts enormous pressure on ecosystem services. He's not worried about depopulation problems, because "population can always be increased by unskilled laborers who love their work." The major hopeful element he sees is that cultural evolution can move very quickly at times. The Soviet Union disappeared overnight. The liberation of women is a profound cultural shift that occurs in decades. Facing dire times, we need to understand how cultural evolution works in order to shift our dominance away from malignant and toward the benign. In the Q & A, Ehrlich described work he's been doing on cultural evolution. He and a graduate student in her fifties at Stanford have been studying the progress of Polynesian canoe practices as their population fanned out across the Pacific. What was more conserved, they wondered, practical matters or decoration? Did the shape of a canoe paddle change constantly, driven by the survival pressure of greater efficiency, or did the carving and paint on the paddles change more, driven by the cultural need of each group to distinguish itself from the others. Practical won. Once a paddle shape proved really effective, it became a cultural constant." --Stewart Brand |
Is Organic Farming simply an ideology or is it better than conventional farming? [Tomorrow's Table] Posted: 09 Jul 2008 10:26 PM CDT Please see a discussion on these questions and more on the Nature Network. Read the 27 comments on this blog to hear what some science bloggers have to say. |
Freedom from Hunger- science can lend a helping hand [Tomorrow's Table] Posted: 09 Jul 2008 10:25 PM CDT Each year an estimated 15 million hectares of rice lands (a region half the size of Italy) in South and Southeast Asia are inundated by flash floods. In Bangladesh, during the monsoon, roads are so wet that they become waterways for homemade sailboats rigged with cloth, jute, and bamboo. Such lands are home to an estimated 140 million people of whom 70 million are living on less than $1 a day, the highest concentration of poor people in the world. Here, losses of rice production can be over $1 billion per year. This number, however does not capture the human suffering caused by the catastrophic crop losses where people get about two-thirds of their total calories from rice. Although rice is the only cereal that can withstand some flooding, most rice varieties will die if submerged for too long. There are a few rare exception and these are of great interest to rice breeders. One of these is the traditional Indian rice variety, FR13A. This rice plant has an unusual and agronomically important trait- the seedlings are able to withstand fourteen days of submergence. It is, however, low yielding and no longer widely grown. FR13A originated in the state of Orissa, in eastern India, bordered on the east by the Bay of Bengal. Hindu temples dating to the thirteenth century are scattered through the area. Today most of the people there still speak the ancient dialect of Oriya, and the majority are still rice farmers. For over fifty years, breeders tried to use FR13A as a parent plant to introduce the submergence tolerance trait into high yielding, tastier varieties favored by rice farmers in other parts of Asia. Frustratingly, the resulting new varieties were of poor quality. The main reason for thisbreeding failure was that, because they were not really sure which genes were needed or where in the genome they were located, the breeders accidentally introduced other genes that reduced the overall quality of the rice. In 1996, Dave Mackill, a scientist at the International Rice Research Institute who had been studying this problem for 10 years, asked if I would use my expertise in rice genetics to help him identify the submergence tolerance gene from FR13A. Within a couple of years after joining my lab, the husband and wife team of Kenong and Xia Xu were able to locate the submergence tolerance trait to a very small region of one of the rice chromosomes. Computer programs allowed us to predict the function of the genes in this region, one of them, an ethylene responsive transcription factors, was of particular interest. Based on what we knew about this gene, we hypothesized that it might act as a master switch to regulate complex functions of the plant. It was as if Kenong and Xia had been able to unravel a ball, woven from 42,000 silken threads all of a slightly different hue, and to pull out one thread, interlaced but distinct from the others. Unlike weavers, geneticists cannot determine if the thread they hold is the one they want simply by looking at it; instead they need to test it by weaving it into another pattern—in this case another rice plant that normally cannot survive floods. So that is what we did. We genetically engineered (GE) this single thread, carrying the submergence tolerance trait, into a rice variety that normally would die in a flood. We wanted to know if incorporation of this one gene would allow the plant to survive. To test this hypothesis, we transplanted the young GE seedlings and then submerged them for over two weeks. After 10 days, we could see that only a few of the control rice plants lacking the gene survived the flood and these were weak, spindly and very pale. The flaccid appearance is typical of plants that have drowned, lacking the air and sun- light needed to function. It was unlikely that this group of plants would survive much longer. We then looked at the row of GE plants that carried the genetic information from the submergence tolerant Indian variety. If we had identified and introduced the correct gene, the plants would have survived the extended time underwater and recovered. I hurried over and gently touched the bright green leaves of the first plant. My eyes quickly traveled down the row. They were alive. It was as though the rice plants had been able to hold their breath until the water was gone. Our work represents the latest genetic change in the rice plant, which was first cultivated along the Yangtze River 6000 years ago. Since that time, hundreds of thousands of rice varieties have been developed. It is likely that FR13A was selected by Orissan farmers because it could survive the floods particular to that area. It was then handed down from one generation to the next, prized then, as now, for its submergence tolerance. We now know that the submergence tolerance trait is found not only in the Orissan variety, but also in two traditional varieties from Sri Lanka. It appears that ancestors of the Sinhalese, who originated from Orissa and migrated to the island twenty-five hundred years ago, transported these precious rice grains over thousands of kilometers. Perhaps as geneticists, we are acting as humans have always done: learning the secrets of the sacred and ancient and passing that knowledge to others, who will then use that information in a new and unexpected way. The submergence tolerance gene has now returned to southern Asia in another new form. With the use of marker-assisted breeding (a kind of hybrid between conventional breeding and genetic engineering) Dave and coworkers have introduced this gene into rice varieties that are adapted to habitats in South and Southeast Asia. These genetically modified plants can withstand fourteen days of submergence, and they yield and taste the same as their parent variety that is popular with local growers. Last fall Dave assessed the productivity of these varieties on farm trials in Bangladesh. The weather in Asia last year was ferocious. Monsoon rains inundated countries from the Philippines to Nepal. Super typhoons slammed into China and Japan. All of this was bad for rice. And what's bad for rice is especially bad for Bangladesh. Jon Hamilton, a National Public Radio correspondent, recently interviewed farmers who had planted sub1 rice. This is his report: "Gobindra Chandra Rai is a farmer whose field had been under water just a few weeks earlier. He says that when the floods came, the whole area was submerged up to about waist high. The government gave farmers in Gobindra's village seedlings with the flood-resistance gene, but most hadn't planted them in time. When the monsoon floods came early, Gobindra was the only one that had. So he and his neighbors watched Gobindra's field anxiously. The field was under water for eight days. Gobindra says that usually after eight days, the crop would be damaged. But the sub-1 rice is still thriving. He tends to it carefully. If a stalk is leaning, he straightens it. If a leaf is muddy, he squeezes it clean between two wet fingers. Gobindra says his neighbors are amazed by what they've seen in his paddy. Standing in a semi-circle in front of a shed made of bamboo and corrugated sheet metal, they line up to talk about Gobindra's rice. Men stand up front. Women farther back. And little boys climb on anything tall enough to give them a better look. Many of the farmers can't read or write. But when it comes to rice science, they're at the cutting edge. And every single one in Gobindra's village now plans on planting the sub-1 variety." Xu, K., Xu, X., Fukao, T., Canlas, P., Maghirang-Rodriguez, R., Heuer, S., Ismail, A.M., Bailey-Serres, J., Ronald, P.C., Mackill, D.J. (2006). Sub1A is an ethylene-response-factor-like gene that confers submergence tolerance to rice. Nature, 442(7103), 705-708. DOI: 10.1038/nature04920 |
Posted: 09 Jul 2008 10:24 PM CDT Dear Governor Jindal, As scientists from across the country and members of the Public Affairs Committee of the American Society of Plant Biologists, we are concerned about the passage of bill SB 733 in the Louisiana legislature. In particular, we are concerned that this bill may represent an attempt to introduce religion into science classes. Teachers already try to promote critical thinking skills; thus, why is there a need for a bill to "to create and foster an environment within public elementary and secondary schools that promotes critical thinking skills, logical analysis, and open and objective discussion of scientific theories being studied including, but not limited to, evolution?" Science, as you know as one of the few governors with an undergraduate degree in biology, is based on the interpretation of actual data. Denying the validity of evolutionary theory requires either a complete lack of knowledge of the data and science behind this theory, or purposely ignoring that data and science. It is true that scientists still debate the mechanistic details of the evolutionary process. That is the nature of science: to seek to understand a process in ever greater detail. In the past 150 years, our understanding of the mechanistic details of how evolution occurs has increased tremendously. For example, Darwin did not know the molecular basis of heredity, and it was not until the late 1940's through the early 1950's that DNA was found to be the genetic material. However, the occurrence of scientific debates about the mechanistic details of the evolutionary process does not cast any doubts on the validity of evolutionary theory. In science, a "theory" is not a hunch or a guess, it is an idea that is continually scrutinized with respect to all of the data that scientists accumulate. Over the past 150 years since Charles Darwin published 'On the Origin of Species,' all of the data collected has provided additional support for the validity of the theory of evolution. Indeed, evolution is as clearly and strongly supported by the data as any theory in science. Simply put, there is no controversy whatsoever about the validity of evolutionary theory among honest scientists who are familiar with the data; rather, there is complete agreement that evolution has been the process that has resulted in, to quote Charles Darwin, the "endless forms most beautiful" that live on our planet. As Governor you are in a position of leadership. Your leadership could guide Louisiana down a path where science is taught in science classrooms and scientific issues are discussed within the framework of actual scientific data. We hope that you will not let Louisiana sanction a path designed to mislead students about what science is and how it works. The students of your state deserve the opportunity for a proper science education. Sincerely, Gary Stacey, Chair, University Of Missouri Richard Amasino, University Of Wisconsin Sarah Assmann, Penn State Daniel Bush, Colorado State University Roger Innes, Indiana University James N. Siedow, Duke University Ralph S. Quatrano, Dean of the Faculty of Arts & Sciences, Washington University in St. Louis Thomas D. Sharkey, Chair Dept. of Biochemistry, Michigan State University David E Salt, Purdue University Mary Lou Guerinot, Dartmouth College Roger Hangarter, Indiana University Robert L. Last, Michigan State University Richard T. Sayre, Ohio State University Robert L. Last, Michigan State University Peggy G. Lemaux, University of California, Berkeley Pamela Ronald, University Of California, Davis C. Robertson McClung, Dartmouth College cc Louisiana legislature |
Do-it-yourself genomics: bad advice is bad advice [Omics! Omics!] Posted: 09 Jul 2008 10:11 PM CDT GenomeWeb's frequently entertaining Daily Scan notes that Wired magazine has a wiki which gives instructions on how to explore your own genome, including how to do your own genetic testing by home-PCRing your DNA and sending it to a contract lab for sequencing. It isn't a very good idea, but that doesn't mean people won't try it. Doing a simple PCR really is pretty easy; I've done it in a hotel ballroom (proctoring a high school science fair sponsored by Invitrogen). Instructions for homebrew thermocyclers are surely out there; a number were published in the early days of PCR. But that doesn't mean getting good results is easy. Sticking to a purely technical level, are Wired's instructions very good? I'd say no. I suppose I should even register to edit the wiki, but at the moment I'll limit myself to pointing out some of the technical issues that are ignored or glossed over (the material I quote below may well change, since it is a wiki). The first obvious area is primer design. Wired's instructions are pretty simple Designing them may be the hardest step. Look up the DNA sequence flanking your genetic marker of interest in a database like dbSNP. Pick a segment that is about 20 bases long and slightly ahead of the marker. That is your forward primer. Pick another 20ish base sequence that is behind the region of DNA that you want to study. Use a web app of your choice to find its reverse complement. Alas, this will frequently be a recipe for disaster. As for my own qualifications for making that claim I will state that (a) I regularly design PCR amplicons in my professional life and (b) I have a much greater appreciation for my ignorance about how PCR can go awry than the average biologist. Leading the list of pitfalls is designing a primer with too low a Tm -- if those 20 nucleotides are mostly A & T, it won't work well. Second would be if the two primers will anneal to each other; you'll get lots of primer-dimer and little else. Equally bad would be a primer that can prime off itself. Third would be if the primers aren't specific to your targeted region of the genome. Prime off a conserved Alu piece and you are in real trouble. The really silly part about this advice is that there are free primer design programs all over the internet, and some of the sites will perform nearly all of the checks mentioned above. The rules for placement are much trickier than suggested. If you are going to sequence (and you might be sequencing heterozygous DNA; see below), then you really need the primers to be at least 50 nucleotides away from what you care about -- there is a front of unincorporated dye which often drops the quality any closer than this. Even more of a concern is the sequence data itself. Wired makes it sound easy Once that's done, you can buy sequencing equipment and do it yourself, or send the sample off to any one of many sequencing companies and they will do it for about five dollars. If you are sequencing uncloned PCR products, then you are sequencing a population. If you are heterozygous for a single nucleotide, that means that nucleotide will read out as a mix -- two overlapping peaks of perhaps half height. A deletion or insertion ("indel") will make the trace "double peaked" from that spot on. Those are the best case scenarios. If you had poor quality amplification (due to badly designed primers or just a miserable to amplify region), all those truncated PCR products will be in the sequencing mix as well -- further degrading your signal. If your SNP is in a region expanded due to copy number variation, then life is even harder. Which gets to another point: Wired seems to be ignorant of copy number variants. Their testing recipe certainly won't work there. The idea of untrained, emotionally involved individuals trying to interpret good genetic data is scary enough (Wired's example of celiac disease, as pointed out over at DNA and You, is a particularly problematic one); scarier is to overlay lots of ambiguity and error due to sloppy amateur technique. Hopefully, few will have the energy & funds to try it. |
Do we know nothing about the origins of the first living systems? [adaptivecomplexity's column] Posted: 09 Jul 2008 09:42 PM CDT Over at the Panda's Thumb, Nick Matzke weighs in on how scientists should respond to Creationist criticisms that we know nothing about abiogenesis - the origins of the first living systems from non-living systems. Matzke correctly says that the typical response is two-fold: scientists will say that a) sure, we don't know much about it, but we're working on it, and b) it has nothing to do with the main field of evolutionary biology. Matzke says that
I agree with much of what Matzke has to say, but disagree with him that it's wrong for scientists to say that origins of life/abiogenesis research is a substantially different field from mainstream evolutionary biology. |
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