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June 2007 Posts
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Minnesota Gene Pool Blog

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June 29, 2007

Podcasts and videos from U of M PH genomics courses are online

Podcasts and video from the Public Health Genomics courses at the 2007 Public Health Institute at the University of Minnesota (May 21-June 8, 2007) are now available.

This year, three new one-credit courses on public health genomics were offered as part of the 2007 Public Health Institute sponsored by the School of Public Health at the University of Minnesota. The courses covered many areas relevant to public health, including science, controversies, ethics, and possibilities. Outstanding guest faculty and engaging discussion between presenters and participants were part of every session. Many of the lectures and class discussion can now be downloaded as podcasts. As students learned more about the role of genomics in public health, they used their developing knowledge to contribute to the Public Health Genomics article on Wikipedia , to posts on the Minnesota Gene Pool Blog and the GeneForum website.

As one of the instructors of the course, I was very, very impressed with the high caliber of participants from diverse backgrounds that participated in the courses. Having participants who brought such accomplishment in other fields and areas of study and were so engaged added to the depth and richness of the experience for everyone.

The capstone and grand finale of the three week Public Health Institute was the Public Health Roundtable that was keynoted by Muin Khoury, MD, PhD, Director of National Office of Public Health Genomics at CDC. Dr. Khoury is one of the primary thought leaders in the field of public health genomics and he did not disappoint with this lecture--it was truly mind-expanding.

Respondents to Dr. Khoury’s thought-provoking comments were provided by Catherine McCarty PhD, MPH, Senior Epidemiologist and Interim Director of The Center for Human Genetics - Marshfield Clinic Research Foundation; Betsy Hirsch, PhD, Professor of Laboratory Medicine, Director of the Cytogenetics Laboratory, University of Minnesota; and Brian Van Ness, PhD, Professor and Chair, Department of Genetics, Cell Biology, and Development, University of Minnesota. The video of the Public Health Roundtable event is available online.

The annual Summer Public Health Institute , offered through the University of Minnesota School of Public Health, provides professionals with a unique opportunity to immerse themselves in a chosen field of study – for a single day or for three weeks. The Summer Public Health Institute has something for everyone practicing in or studying public health or in fields related to public health. Opportunities exist to build or expand professional knowledge and expertise, learn best practices, broaden career options, network with other professionals or explore a new area of interest.

June 13, 2007

The Genome is Messier Than We Thought

It turns out that there are more and more surprises coming out of studying the human genome. I guess that fact that we don't have that many more genes than a round worm or a fly should have been a harbinger of the discoveries to come.

It turns out that many of our ideas about gene transcription and regulation, chromatin and replication, and evolutionary constraint may have to be revised. Work recently published by the ENCODE Consortium, which is made up of some 35 groups in 80 organizations, is rocking the Central Dogma of Biology with their findings.

Read more about this in a report in The GenomeWeb Daily News today.

June 8, 2007

Rethinking “holistic� medicine

Guest blogger Devavani Chatterjea reflects on moving to a more holistic understanding of health and disease that works to improve the health the whole person--not just the parts.

For decades, the culture of research in cellular and molecular biology has been reductionist. In the 1980s, graduate students often built their academic career on a single gene that they painstakingly cloned or copied from their organism of study (mouse, fruitfly, zebra fish, worm or chicken). Once the gene was identified as “novel� (in other words, no one had seen it before), they then set about trying to understand how it worked, what kind of protein it made and where and when, what other proteins the protein interacted with, what happened to a genetically engineered mouse, fly, chick or worm when you took this protein away, what happened if you gave it too much of this protein. If the findings were interesting, answers to each of the above questions would be shared with the scientific community in a published paper; the most interesting answers might even be picked up by the popular press and if said graduate student decided to pursue a lifetime of laboratory research, the answers were also the basis for applications for further studies about the gene, its family members, another closely related gene, etc. The concluding sections for the application, particularly if it was an application to a national health agency, invariably read that research into this gene needed support because it was important for human health. Exactly how it was important was never clarified for most of those genes. For the ones that did have a dramatic effect in a lab animal model of cancer, diabetes or arthritis, biotech companies bought up the molecules, erected walls of patents around them and plugged them into 12-15 years of directed drug development research and layers of clinical trials to eventually bring them to market. These wonder drugs worked wonders for some people but not for all and side effects were always present, often serious; that was how it went. In fact, for most purposes, that is still how it goes.

Patients who have serious autoimmune diseases, cancers or life-sapping infections often turn to “holistic care� to supplement these medications – bodywork, dietary changes, herbal supplements, meditation practices – because they feel a need to treat their whole selves and not just a mass of cancerous tissue that is growing in their bodies or a particular disease process that is destroying their joints.

Fast-forward 20 years and the picture looks very different in the research laboratories. The “one graduate student-one gene� or “one research lab-one gene family� model is not so prevalent anymore. Hundreds of genomes have been sequenced and so has ours. The nucleotide sequence of all our DNA is known – the genes and the filler whose functions we still don’t know. We have no excuse any longer to turn away from the problems and the sheer mind-boggling wonder of “systems biology.� We cannot think of genes, organs, organ systems and by extension diseases in isolation. The interaction of any gene of interest with other genes, with the environment (think of family, air quality, stress, food as just a few examples), with epigenetic mechanisms (the forces within our bodies that shape the physical and functional attributes of genes without changing their sequence) is at least theoretically available for a biochemical readout and therefore, we excitedly extrapolate, to intervention, health promotion and disease reduction.

The idea of personalized medicine/intervention is not necessarily new. The success of Herceptin for treating women with a particular kind of breast cancer but not other kinds has been often held up both as an example of the intelligent design of clinical trials to speed up drug development as well as a model of delivering medicine to the patients who need it and not to those who will not benefit from it. Avoiding ineffective drug administration and adverse drug reactions is seen as one of the greatest benefits of genomic medicine perhaps because we know this can be done already.

More mysterious are the workings of those promised magic bullets – stem cells. Evolution has given us adult stem cells most likely as protection against cancer (which is caused by the aberrant and excessive proliferation of cells; stem cells contain potential for regeneration that is usually tucked away in a quiet niche within the body; low rates of division mean lower chances of cancer production; stem cells only divide when they need to replenish) but now we can perhaps foresee a future where these stem cells can be harnessed to reverse disease processes and build new organs. But for either of these two examples – personalized drug therapy or stem cell therapy – and for countless other applications we have only begun to imagine, genomic medicine forces us to be holistic. We have to consider the body (and in fact the mind) as a whole – not just the disease process, not just the organ transplant. When a therapeutic medication or a stem-cell transplant lands in the living landscape of our bodies, the whole landscape is perturbed and the balance of health/disease or perhaps wellness/illness reflects that perturbation as a whole. How do we read this perturbation? How will we begin to respond to it? The DNA scans of Ethan Hawke’s character in the film GATTACA do not seem quite so science fiction-like anymore. James Watson of the Crick/Watson/Franklin trio who elucidated the structure of DNA just had his genome sequenced and while the rest of us don’t yet have a way to order a whole genome scan, already there are start-up corporations promising us that they will help us make sense of that genomic information when we do. Of course, for genomic medicine to be feasible, even human genomic biology to be understood, Dr. Watson’s genome alone won’t do. We will need a diversity of genomes, analytical capacity to mine the huge volume of genomic data and then of course, parallel work at laboratory benches to understand the biology, the integrative biology that arises from the complexity and diversity of the genomic landscape. The ethical, social and political intricacies of how these data will be stored, handled, accessed and interpreted have only begun to be considered. Not only will these issues have to be considered but in reality they have to be resolved to at least a working level so that this sticking point does not prevent the

And so we come anew to a holistic approach – to biology and to the understanding, maintenance and promotion of health of our species and our environment. Like the proverbial blind men feeling the parts of an elephant, we have been working on reductionist approaches to biology undoubtedly with many remarkable achievements and stunning successes along the way. But now the path goes into uncharted territories and armed as we are with the best that technology has to offer today, we will also need fresh perspectives. Perhaps some of the most valuable insights and perspectives can be found in traditional models of health promotion and therapeutic intervention that have long considered the whole body rather than single biochemical mechanisms. Modern western medicine and various indigenous medical practices have often been wary and skeptical of each other. Perhaps it is time for this mistrust to give way to fertile exchanges. Although much of older, traditional modes of medical intervention has yet to be “validated� using modern biochemical tools, the systemic understanding of biology and living systems may prove to be a forum where the two kinds of medicine can finally begin to come together. The task, at the outset, seems daunting, almost impossible. And therapeutic drugs are only the tip of the iceberg. Ideas such as nutrigenomics (the effect of the dietary environment on the genomes of individuals and populations), generalized gene-environment interactions, neurochemistry of biological responses, stress/mindfulness-related bioresponses all have correlates in many traditional forms of medicine such as ayurveda, traditional Chinese medicine and many other indigenous traditions. Genomic medicine raises the tantalizing possibility that the old and new languages of wellness, illness and cures will begin to be understood across boundaries of tradition and modernity. Holistic medicine will acquire a whole new meaning in the genomics era.