Transapient Musings of an S6 Archailect

May 28 (Bloomberg) -- Francis Collins, who led the U.S. government effort to decode the body's DNA blueprint, will step down as head of the National Human Genome Research Institute effective Aug. 1, the agency said.

Collins, 58, helped identify the gene linked to cystic fibrosis in 1989, and in 1993 helped identify DNA tied to Huntington's disease. That same year, Collins was named head of the Human Genome Project and, in 2001, the project published a first draft that identified all 2 billion or so letters that make up the human genetic code.

By providing access to the full catalogue of human genes, scientists have been able to identify variations linked with common and inherited diseases. Researchers have used those results to create medicines such as Tarceva, the Genentech Inc. lung cancer drug developed after a DNA mutation was found to be linked to the tumors. Variations in more than 100 genes have been linked to about 20 diseases, researchers have said.

"The study of the human genome has completely transformed medical research, and is on the way to transforming clinical practice,'' Collins said in a telephone interview today, when asked what he is proudest of from his tenure at the National Institutes of Health.

Alan Guttmacher, the institute's current deputy director, will become acting director on Aug. 1, said NIH director Elias Zerhouni in am e-mailed statement announcing Collins' decision to leave the agency.

`No Heir Apparent'

Bert Vogelstein, professor of oncology and pathology at the Johns Hopkins School of Medicine in Baltimore, said there is "no heir apparent, no one who can easily swoop into the void'' left by Collins' departure. " Francis has both the scientific credentials and an amazing ability to bring people together,'' Vogelstein said. ``He could really explain what was important in understandable terms.''

In the late 1990s and early 2000s, Collins' institute raced against a private company, Celera Genetics, led by Craig Venter, to be the first to publish the genome. A full analysis was completed by Collins' group in April 2003.

Collins, who grew up on a small farm in Virginia and was home-schooled until the sixth grade, got an undergraduate degree in chemistry from the University of Virginia, a doctorate in physical chemistry for Yale University and medical degree from the University of North Carolina. He served on the faculty at the University of Michigan until joining the NIH in 1993.

While at Michigan, he collaborated with researchers at the Hospital for Sick Children in Toronto, Canada, on the gene for cystic fibrosis and Huntington's.

`Insights'

Collins' work at the institute made him "an extraordinary leader in developing tools and applications and insights into what makes us who we are,'' said W. Ian Lipkin, a professor of epidemiology at Columbia University's Mailman School of Public Health in New York, in a telephone interview.

Lipkin was the first to identify the West Nile Virus in the U.S. using genetic technology, and recently isolated one of the causes of a malady killing honeybees using gene sequencing technology created by Roche Holding AG.

"What's not as well-known is that he set the stage for a whole series of projects which followed on the heels of the human genome sequence, and now are probably some of the most valuable studies ongoing in biomedical research,'' Vogelstein said. "The whole idea of having several labs undertake these projects is a different way of doing biomedical science, and you can largely attribute that to Francis as the leader.''

As a computational scientist (and with both a physical and a life science background), that such arguments still happen is appalling. IMO, all scientists, especially those remotely connected to theory and/or computational science should be given the opportunity to learn some formal software engineering and computer science principles (for physical chemists, bioinformaticians, etc is should be mandatory to do some courses). Everything I know, which is not much, is self taught. It’s the princples and practices that are important, not the specifics. Have seen way too much noodly, unmaintainable code and bad hacks over the years (including my own).

Perhaps things have changed, but apparently not that much, and given attitudes towards software engineering in academia, I seriously doubt it.

According to the hygiene hypothesis, reduced exposure to infections in early childhood - owing to diminishing family size and improvements in living standards and personal hygiene, for example - may increase the risk of allergic and autoimmune disease. This concept is supported by epidemiological and clinical reports documenting increased incidences of inflammatory bowel diseases, colon cancer, asthma, type 1 diabetes and multiple sclerosis over the past 50 years in societies with improved medical care and hygiene (for example, Europe, the United States and Japan) but not in undeveloped countries. However, the application of major interventions, including vaccination, sanitation, and antibacterial and antiviral therapies, often does not permit discrimination between infectious and non-infectious microorganisms and has undoubtedly led to changes in human association with the microbial world as a whole. The hygiene hypothesis does not address humanity’s primary relationship with bacteria: the harbouring of multitudes of microbial species during commensalism. A new study just published shows that symbiotic bacteria residing in the mammalian gastrointestinal tract produce molecules that mediate healthy immune responses and protect the host from inflammatory disease. The authors propose that the mammalian genome does not encode for all functions required for immunological development but rather that mammals depend on critical interactions with their microbiome (the collective genomes of the microbiota) for health.

A microbial symbiosis factor prevents intestinal inflammatory disease
Nature 453: 620-625, 29 May 2008
Humans are colonized by multitudes of commensal organisms representing members of five of the six kingdoms of life; however, our gastrointestinal tract provides residence to both beneficial and potentially pathogenic microorganisms. Imbalances in the composition of the bacterial microbiota, known as dysbiosis, are postulated to be a major factor in human disorders such as inflammatory bowel disease. We report here that the prominent human symbiont Bacteroides fragilis protects animals from experimental colitis induced by Helicobacter hepaticus, a commensal bacterium with pathogenic potential. This beneficial activity requires a single microbial molecule (polysaccharide A, PSA). In animals harbouring B. fragilis not expressing PSA, H. hepaticus colonization leads to disease and pro-inflammatory cytokine production in colonic tissues. Purified PSA administered to animals is required to suppress pro-inflammatory interleukin-17 production by intestinal immune cells and also inhibits in vitro reactions in cell cultures. Furthermore, PSA protects from inflammatory disease through a functional requirement for interleukin-10-producing CD4+ T cells. These results show that molecules of the bacterial microbiota can mediate the critical balance between health and disease. Harnessing the immunomodulatory capacity of symbiosis factors such as PSA might potentially provide therapeutics for human inflammatory disorders on the basis of entirely novel biological principles.

Related:

Thinking about BioBarCamp, listening to Chris Messina talking about DiSo, Barcamp and open projects in general and all consumed by the cloud and web services. Over the past year, we’ve built a fairly cool group of bio and data geeks distributed all over the world. We have different skills, different backgrounds and different knowledge bases. Question is, are there enough of us to achieve the kind of bursty success that has driven efforts like OpenID, OAuth, DiSo, Wordpress, etc in the tech/web world? Can we come up with simple tools and protocols that have the same impact on bioinformatics, cheminformatics, molecular modeling and perhaps life science discovery in general?

What can you do with the API? Among other things you can upload patient medical records and get patient medical data to provide additional, personalized, functionality. This is clearly targeted at developing an ecosystem around the Google Health system. Google Health supports CCR (or at least a subset), and in theory, companies can set up services that allow hospitals/health systems to communicate with Google Health, and hopefully some day, enable health data portability between health systems.

Will be interesting to see how the API gets used? How will any privacy concerns be overcome? Who will the early adopters be? We will have to wait and see.

The possibility of fusing a mechanical device with the human brain becomes a reality.

Ladies and gentleman, I would like to introduce you to a new piece of technology. Lo and behold, the brain prosthesis. Wait. Did I just say brain prosthesis, as in an artificial replacement of the mind? Yes, that’s right; the brain prosthesis is going to be used to replace the damaged parts of our brain.

Hundreds of individuals who have lost their body parts due to traumatic injuries or congenital defects have already chosen to get artificial replacements. To elaborate, a patient may want to get a synthetic limb because of a missing arm or an ocular prosthesis because of a damaged eye. However, never would we ever consider replacing a damaged brain. But according to scientists at the University of Southern California in Los Angeles, a silicon chip could be used to replace the hippocampus, part of the forebrain involved in forming memories. This may provide great hope for people who have suffered from stroke and epilepsy or for those currently battling Alzheimer’s disease. That’s wonderful news.

Currently, Dr. Theodore Berger and his team of colleagues at the university are testing their prosthetic device on a live rat. Their preliminary data showed positive results. They have created a device, successfully mimicking the activity of biological signals in the hippocampal circuit. According to mathematical models, this microchip, incorporated in the brain tissue, matched perfectly with an intact brain slice without the chip. Thus, the researchers’ next step is to use and study animal models.

Could this possibly work? I’m optimistic. Though, it may very well come with complications, both ethically and biologically. First and foremost, our bodies could reject this foreign object. Secondly, ethicists will certainly raise valid arguments over the procedure that will tamper with the patients’ identities. Most importantly, the role of the human brain is intricate. It is where we interpret our conscious thoughts and emotions. But at a time where accidents and diseases will inevitably rob our memories, sometimes we need these recollections that shape who we are. Hence, research in this field, combining neuroscience and technology, should continue.

Nevertheless, I wonder how many people out there would want this procedure if it does work and if it is going to be given a green light. If drugs can’t fully work, maybe biomedical engineering can help revolutionize medicine. Perhaps scientists can replace other parts of the brain. A scary thought. I’m also curious to know if the current prosthesis would really help a victim of Alzheimer’s disease, because there will still be the presence of amyloid plaques and neurofibrillary tangles in the brain. I guess we’ll have to stay tuned.

New York put together a draft plan for how to spent $600 million over 11 years to foster stem-cell research and is seeking input through June 20. You can read the plan and leave comments at the link above.

Below, I'll provide the budget breakdown for the plans for New York and the California Institute of Regenerative Medicine.

Here a clip from the press release:
“According to the draft Strategic Plan, the state will utilize the
funding to support innovative basic, translational and clinical research that builds on the potential of stem cells to detect, treat and cure human diseases. New York’s legislation creating the stem cell research initiative expressly forbids the use of state funding for human reproductive cloning.”

The plan was developed over 6 months by staff and board members of New York State Stem Cell Science (a group within the state’s health department) plus other experts. It gives ranges of spending over its first 5 years. Of the $300 million to be spent over this time, research will get 65-80% of the funds, scientific training 4-10%, infrastructure development 10-15%, administration and consideration of societal, ethical, and legal issues will both receive 3 to 5%.

For comparison, the California Institute of Regenerative Medicine issued a strategic plan in 2006, which also forbids reproductive cloning. Its budget is complicated because the funding comes from bonds with provisions for issuing loans, and the $3 billion budget assumes $52 million over ten years in capitalized interest. Overall, the budget estimates that 3% of the $3 billion funds over ten years will go for general administration, 3% for grants administration, 1% for issuing bonds and litigation, 9% for facilities, and 82% for research. The $2,377.5 million allocated for research includes funds for a journal and web portal ($1.9 million), public outreach ($4.5 million), and assessing impacts on society and the economy ($27.8 million), with the vast majority of funds aimed at grants for scientists and scientific training.

Because of the federal funding ban, US states are emerging as independent entities within the stem-cell research enterprise. Our related content includes a news feature on what states are doing to coordinate their efforts, a scientist’s perspective on how the fragmented funding environment strains the scientific enterprise, and a scientist’s perspective on shepherding international efforts to advance stem cell research.

Tue, 03 Jun 2008