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| Believe in Evolution and Go To Hell [adaptivecomplexity's column] Posted: 24 May 2008 04:57 PM CDT If education can help attitudes about evolution, we have a lot of educating to do. Maybe it was my Scientific Blogging T-shirt, or my anti-Bush bumper sticker, but something motivated a member of the church near my children's day care to hand me this well-reasoned, tightly argued attack on evolution:  |
| Community Sites for Scientists and Physicians: The List [ScienceRoll] Posted: 24 May 2008 03:33 PM CDT I’ve already come up with lists of the best medical places in Second Life; the best medical wikis and the best services with medical videos/animations. So it’s time to dedicate another one to community sites created for scientists and physicians. This idea came to my mind when I read the post of Bora Zivkovic.
Let me know if you know more.         |
| The web as platform: A science Data Commons [business|bytes|genes|molecules] Posted: 24 May 2008 12:50 PM CDT
Cameron proposes a model in his post. As Cameron notes, repositories already exist for most data types and the majority are open. Where the Google’s and Amazon’s can jump in is to enable these repositories, especially with next-gen sequencing and other data types pushing the scientific communities knowledge and capabilities. Very rightly though he pushes the idea of long tail science, i.e. not repositories for structures, etc, but all the information we are streaming out of our labs. What will be the infrastructure that will handle these days. The problem, as Cameron notes, is data capture and perhaps most important, data re-use, for which capturing the associated metadata is critical, and having tools that allow you to consume the data are even more critical. There are a lot more details in the post. My preference would be that these are driven by need and intention rather than by formal committees. The internet provides protocol standards, the Semantic Web stack is essentially complete. In various scientific domains we have efforts on data formats and standards. As we start playing around with the data, the ones that resonate will bubble to the top. The key is to make sure that we as a community come together to realize that this needs to be done. The technology will follow. Image via Wikipedia Technorati Tags: Open Data, Data Commons, Scifoo, Cameron Neylon  |
| Your personal health: Google Health, HealthVault and HIPAA [business|bytes|genes|molecules] Posted: 24 May 2008 11:42 AM CDT Fred has a great post on why HIPAA should not be applicable. I will add the following, especially in the wake of GINA. People need crutches. Knowing there is a regulation there that addresses their fears in some ways is important. PHRs are not only going to be significant for our own health and wellness, but they can become part of a greater good, the development of therapeutics, or trying to understand disease. To enable all that, data ownership is the first key (we should own our data), and data access is the second. This latter one is the crutch people are looking for (most dont understand the former) Technorati Tags: HIPAA, PHR, Google Health, HealthVault  |
| A legal matter [genomeboy.com] Posted: 24 May 2008 09:25 AM CDT Andrew Yates of Think Gene takes issue with my impassioned defense of GINA:
How about this: It is theoretically wrong because we know that we are more than our genes and because we have a long paper trail of misguided and inappropriate social engineering supposedly based on genes. How are we more than our genes? I received my Health Compass data from Navigenics the other day (I hope to post about this soon). Of the 17 conditions for which I received reports, heritabilities ranged from 0.13 (glaucoma) to 0.8 (Crohn’s). Most were in the 0.6 range. My lifetime risks, excluding all phenotypic data other than gender, ranged from 0.02% (lupus) to 41% (obesity). The latter is a bummer, of course, but it’s hardly deterministic (my current BMI is 26, FWIW). The heritability of schizophrenia is on the order of 0.8–yet somehow we still haven’t found a single major susceptibility locus. Meanwhle, we have genotyped tens of thousands of people to find loci that contribute to height. Well, guess what: there are 54 and counting, each affecting height by an average of 2-3 mm (the standard deviation for height in the population is 7 cm). To exclude a pilot because he carries a highly penetrant mendelian allele for narcolepsy is one thing, but it’s a rare thing. Genetic discrimination may be rare, too, but given the Burlington Northern precedent, given the military’s recent misapplication of genetics, given the entire ugly history of 20th-century eugenics, am I prepared to believe that government and corporate bureaucracies can be trusted to sort the wheat from the chaff and get “objective” genetic testing right without giving those getting tested some explicit legal protection? Not yet. |
| DNA Video: DNA Jewelry [Eye on DNA] Posted: 24 May 2008 03:03 AM CDT Two young women at UC Davis Picnic Day 2007 make DNA jewelry. This would make a great party activity! |
| Posted: 23 May 2008 11:31 PM CDT A team of scientists at Cold Spring Harbor Laboratory (CSHL) has discovered new details about how a simian strain of the AIDS virus replicates. The findings are significant because they suggest new strategies to prevent replication, and because they are applicable to human strains of the virus, which, despite the persistent efforts of scientists over two decades, can only be slowed by drug treatments but neither cured nor prevented. Jacek Skowronski, Ph.D., CHSL associate professor, led a team that studied a virulent strain of simian immune-deficiency (SIV) virus called SIVsm/mac, named for two species of monkeys in which it occurs, sooty mangabeys and macaques. The team included members of Dr. Skowronski's CSHL lab and researchers at Stowers Institute for Medical Research in Kansas City, Missouri, and the Skirball Institute of Biomolecular Medicine in New York City. Like versions of the virus that occur in humans, SIV viral particles, or virions, are composed of a few fundamental parts. At their heart are two identical but separate strands of RNA surrounded by a protective envelope of roughly 2,000 proteins called a capsid. This tiny, conical capsule, in turn, is surrounded by multiple defensive rings, somewhat like the walls of a medieval city. Immediately surrounding it is a protective protein shell, or matrix, and beyond it a formidable double-walled viral envelope. Poking through the outer envelope are the viral equivalent of grappling hooks, protein molecules designed to lock onto receptors on the surface of the unfortunate cell that the virus will attach to and then invade.
Viruses Hijack Living Cells to Reproduce
Viruses, unlike cells, are not living things. They must penetrate a living cell and commandeer its internal machineries in order to reproduce. HIV and its simian cousin SIV are members of a viral subspecies called retroviruses that invert the usual reproductive procedure. Their genetic raw material is not DNA but rather RNA, and before they can begin to replicate, they must first convert their RNA into DNA, using a special enzyme that they encode, called reverse transcriptase. Once its RNA has been reverse-transcribed into DNA, the virion, having invaded a cell whose genetic material consists of DNA, can shed its protein coat and immediately proceed to integrate its newly converted DNA — containing 9 genes — into the host cell's DNA. In this way the virion effectively hijacks the cell and reproduces itself whenever the cell reproduces. Dr. Skowronski has devoted years to the study of various molecular factors — think of them as assistants — that immune-deficiency viruses employ to perform a range of essential tasks. The idea behind his approach is to understand with great precision all of the details of the processes by which the virus lives and propagates, as a means of identifying points of vulnerability, where drugs might be inserted to foul up the works. In the research just completed, results of which appeared in PLoS Pathogens on May 9, Skowronski and his team focused on a so-called accessory protein called Vpx (Viral protein x). Prior studies had shown that Vpx was produced by simian, as well as a subset of human, immunodeficiency viruses, and was somehow active at the heart of their reproductive processes in a subset of immune cells called macrophages. The question was how, and to what effect.
How Vpx Enables the Virus to Replicate
Macrophages are central players in the mammalian immune system. Immune-deficiency viruses are devastating because they specifically seek out, invade, and commandeer the machinery of these particular cells — macrophages, dendritic cells, helper T-cells — which protect the mammalian system from foreign invaders. Skowronski and colleagues knew from prior work that Vpx was a key enabler: it somehow facilitated an "early event" in the viral life cycle that helped the virus invade macrophage target cells. Recent studies had further shown that Vpx proteins in both monkey and human viruses promoted the process of reverse transcription that underlies the conversion of viral RNA to DNA. In their study, which consisted of several steps, the CSHL team showed that when the vpx gene (the gene that encodes the Vpx protein) was deliberately deleted, the virus went about reverse transcription "very inefficiently." "This suggests that the Vpx protein is key to the process by which the virus infects macrophages," Dr. Skowronski comments, "and further, that it seems to be acting either before and/or during the reverse transcription process." This new view of Vpx's role contrasts with a prior hypothesis that it was involved in the transporting of genetic material that had already undergone reverse transcription. The team's experiments revealed that the Vpx protein in the SIVmac virus binds to a complex of three cellular proteins that in turn engage a molecular machinery involved in the degradation of proteins. Thus, the team revealed for the first time not only that Vpx interacted with this system — called the ubiquitin-dependent proteosomal protein degradation mechanism — but also identified precisely the way it does so, via a series of intermediate steps. "The net result," says Dr. Skowronski, "is that we show how Vpx enables efficient reverse transcription in the simian virus, and in so doing, overcomes an innate block that otherwise prevents viral replication." By implication, this suggests a strategy by which a future drug might interfere with the reproductive machinery of the virus to prevent or limit is ability to spread. "There are no guarantees, of course, that such an approach will work," Dr. Skowronski says, "but unless we understand molecular mechanisms such as this one that empower this remarkable virus, we are not likely to devise a means of stopping it." Source: Cold Spring Harbor Laboratory Josh says: I just skimmed the paper, but it seems that the protein prevents an E3 ubiquitin ligase from targetting the viral proteins for degredation by the proteasome. This will definitely be a drug target in the future. I think the “cure” for HIV will be a cocktail of medications that all target different parts in the viral replication and infection pathway. |
| GINA Series: Irrational Bureacratic Risk Abhorance [Page 1] [Think Gene] Posted: 23 May 2008 11:00 PM CDT
“It’s not fair…” but why? Irrational Bureaucratic Risk Abhorrence The problem with institutionalized testing is that institutions tend to be irrationally risk adverse. This leads to social inefficiency and destabilizing stratification. The problem is that people confuse what’s probable with what’s true. Quick Quiz: Research shows that mutation X is strongly correlated with low intelligence. I am intelligent. I have mutation X. How intelligent am I? And here’s the problem: how does society learn about one’s intelligence? am I admitted to school? employed? funded? will the guardian bureaucrats of society’s fine institutions be willing to risk their admission statistics and resources to learn how successful I could be? Historically: NO. Thus, social injustice. But maybe you think something silly like that institutions can or even try to reward aptitude, effort, and loyalty despite unrelated negative evidence like genetic test scores. So how about this one: Guess who gets fired, not promoted, or not hired. But you say: oh Andrew, drug use is a choice and genes aren’t and also Regan said drugs are bad because I learned that in DARE and so your example isn’t relevant. Well, expression of intelligence is a choice too. The historical norm is that otherwise highly qualified people are neglected because they don’t have the right genes… I mean parents. Irrational risk-adverse discrimation is the rule because people believe “rational” means “justifiable when challeged.” Our challenge is to create policy to check that rule. GINA does. |
| Lederberg Workshop Rest of the Story [The Tree of Life] Posted: 23 May 2008 10:56 PM CDT When I left off in my notes the first day of the workshop was basically ending. After the session ended, the speakers and the members of the Institute of Medicine Forum on Microbial Threats went out to dinner at a restaurant in Cleveland Park. A few of us walked over to the Metro together and talked along the way. Thankfully, I did not get lost, as (1) I grew up in the DC area (2) I worked around the corner from where the workshop was held for a summer 20 years ago and (3) Julian Parkhill from the Sanger Center was with us and I had sadly gotten very disoriented with him when I was at a NIH Human Microbiome meeting in Bethesda which is actually where I grew up. The dinner was quite good and I had some good conversations with various folks about microbes and their lives as well as about science in general. Sometimes these types of events are a bit much for me but for whatever reason the whole dinner event was very pleasant. And this was despite the fact that I still had not even started working on my talk for the next day. Finally, as some people were getting coffee Stanley Cohen and a few others said they wanted to head back to the hotel so a gaggle of us left, and went back. I then spent a few hours making an outline of my talk and finding some slides and worrying about what I was going to say. I was going to be the last talk of the meeting -- in essence wrapping things up. Normally I do not get stressed about such things but here I was at this workshop in honor of one of the greatest biologists of the 20th century. And many scientist's I really really respect were to be in the audience. To give those who know an idea of how big a deal I thought this workshop was - I wore a suit for both days of the meeting. Now, I have not worn a suit in probably two years. But it just seemed natural to do it here. Anyway, with all of these things together it was a big deal to me to give the closing talk of the workshop. And so I slept very little piecing together a talk that I hoped would honor Lederberg and make people glad they stayed until the end. On a side note, I never met Lederberg. But I was trained in microbiology by one of his students - Ann Ganesan who worked as a Senior Scientist in Phil Hanawalt's lab where I did my PhD. Ann was amazing -- the grand guru of microbiology and I learned a great deal from her. And thus I felt a connection to Lederberg even if I did not know him. And finally, after very little sleep, I headed out for day 2 of the workshop. And day 2 was as good or better than day 1. There was Stanley Cohen talking about Lederberg and plasmids, Julian Davies (one of my all time favorite speakers) discussing antibiotic resistance, Jo Handelsman talking about functional metagenomics and microbial commensals in insects, Steven S. Morse talking about emerging diseases, Peter Daszak from the Consortium for Conservation Medicine, Mark Woolhouse talking about the ecology of human pathogens, and then me. All of the talks before me were quite excellent. Thoughtful. Insightful. Entertaining. (I do not think I have ever been at a meeting like this - I normally cannot sit through more than a few talks in a day). Lederberg would have been proud. And then me. I think I did a good job with the wrap up. A lot of the talks for the day had been about how we can use an understanding of the past to help predict the future. And I talked about the original of novelty and how understanding how new functions originate can certainly help us understand the present (e.g., analyzing genome sequences) and I tried to bring in examples from all the other talks at the meeting (ahh .. one of those times where having my laptop and modifying my slides during the day was a good thing). And then there was a brief discussion session where some really good questions/suggestions came up and then it was over. But I did come back inspired. Lederberg was such an incredible scientist and person. His legacy hopefully lives on. |
| Posted: 23 May 2008 10:45 PM CDT
Via the Science Commons blog, I learned about efforts at the Coriell Insititute to provide what they are calling research in a box. The goal is to create an eCommerce sample site that allows researchers to acquire samples and information easily, within a framework designed for the transfer of such information. Science Commons materials transfer license, also used by iBridge Network, plays a role in making the technology transfer as seamless as possible. In the future, organizations like 23andme, personalized health records, etc can also be sources of information for research. The question is if we can develop frameworks which protect patient privacy, are able to address informed consent and make the data available to researchers and clinical trials (including commercial entities). The ability to develop these frameworks will require dialog between patients, healthcare providers, academia and industry, and transparency in the processes and frameworks. My hope is that Science Commons can continue to play a role here in bringing all these entities together to enable the future of medicine. I’d like to point out that the scenario being painted above is somewhat simplistic. With the number of stakeholders, potential downstream revenue sharing issues, etc, a lot of dialog will be required, but we need leadership and that’s what I am alluding to. Image via Wikipedia Technorati Tags: Science Commons, Biobanking, Materials Transfer, Personalized Medicine, Coriell Institute  |
Recently, President Bush signed GINA, the Genetic Information Nondiscrimination Act, into law. GINA makes it illegal for employers or health insurers to discriminate based on genetics. Virtually the entire genetics community has 
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