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The genomic revolution will transform medicine but will require the use of complex mathematical algorithms, the study of simple organisms, and possibly even a better understanding of what it is about former president Bill Clinton's genetic makeup that allows him to eat pizza and cheeseburgers while maintaining low cholesterol. Those were just a few of the speakers' opinions at a session of "The Impact of Genes and Genomes on Medicine and Society," a Health Sciences-sponsored symposium held Oct. 16 and 17 on the Morningside campus as part of Columbia's 250th anniversary celebration.

"Genomes contain a lot of information about disease, and the information is sitting there in databases, if we only knew how to extract it," said speaker Dr. Eric Lander, a geneticist at the Whitehead Institute for Biomedical Research and MIT and a leader of the Human Genome Project.

As an example of how genomic information can uncover clues to even complex diseases, Dr. Lander spoke about a powerful new technique that was used recently to identify genes linked to Type 2 diabetes. The analysis sifted through huge datasets from the Human Genome Project and from DNA microarrays, which recorded the activity of 22,000 genes inside muscle cells of people with diabetes. The data-crunching determined that only one set of genes explain the greater insulin resistance in diabetics, but surprisingly, those genes are not related to insulin. Instead, the genes are related to a cell's energy production and point to its mitochondria as a major factor in diabetes.

Though some scientists are delving into the massive datasets from the Human Genome Project to better understand disease, Dr. Cori Bargmann, a neuroscientist at the University of California, San Francisco, said small, simple organisms like the fruit fly Drosophila are also important resources, even for understanding human behavior. For example, 30 years ago, the first person to make inroads into the genetic influence on behavior, Dr. Seymour Benzer at Caltech, discovered mutations in the Per gene of flies that altered the fly's circadian rhythms. Subsequent work by others on people with Advanced Sleep Phase Syndrome – those who wake up at around 3 a.m. and fall asleep around 6 p.m. – revealed that a mutation in the same gene is responsible for the human disorder.

Epidemiologist Dr. Roy Anderson of Imperial College, London reminded everyone that infectious diseases are the leading cause of death worldwide and that the genomes of most infectious pathogens are now known. The evolution of infectious disease organisms is speeding up, Dr. Anderson said, in part because of the 1,000-fold increase in the contact rate among people since 1918, the year the "Spanish flu" spread around the world. The challenge for infectious disease researchers now is to understand the interplay between the genome of the pathogen and the host, which may help in the development of vaccines against rapidly evolving pathogens like HIV and malaria parasites.

Genomes may also help in the discovery of new ways to treat diseases caused by a collision of genes and the environment, such as one in which people regularly consume cholesterol-laden diets. Nobel Prize winners Drs. Michael Brown and Joseph Goldstein of the University of Texas talked about their role in discovering how one receptor in liver cells controls the level of cholesterol in blood and the phenomenal impact statins have had on the 30 million people with atherosclerosis who have taken the cholesterol-lowering drugs.

As for Bill Clinton, he was just one example of how complicated the study of genomics can get. "Not all people with low cholesterol are eating low-fat diets," Dr. Brown said as he presented a slide of Mr. Clinton enjoying a slice at a pizzeria. "Clearly, there are a lot of genetic influences that control our response to this challenge, and if we can understand Bill Clinton's genes, we may understand other influences on cholesterol."

Other notable speakers at the symposium included Sydney Brenner of the Salk Institute and Jeffrey Sachs, director of the Earth Institute, who addressed the impact of genomic science on evolution and society. Video highlights and transcripts of the event will be available in November on the Columbia 250 web site (http://c250.columbia.edu/).

—Susan Conova


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