Oct. 29, 1999 ITHACA, N.Y. -- Natural solutions to human diseases, from Alzheimer's to cancers, might lie within the genomes of whales, bats and other mammals, a leading genetic researcher believes. Treatments, from drugs to therapies, might result from mapping the thousands of mammalian genomes.
"Genetic resistance to infectious diseases like hepatitis, papilloma, herpes and AIDS is an area where genomics is just getting started and will have a huge future," Stephen J. O'Brien, chief of the Laboratory of Genomic Diversity for the National Cancer Institute, said at a lecture at Cornell University.
O'Brien, who is an Andrew D. White Professor-at-Large at Cornell, was talking about comparative genomics, a new field that studies the evolution of genomes. His study of the genomes of various mammals has led him to the conclusion that there are natural solutions to many human diseases.
A review of the field, "The Promise of Comparative Genomics in Mammals," by O'Brien and nine of his colleagues appeared in the Oct. 15 edition of the journal Science.
Hospitals, O'Brien noted in his talk at Cornell, "are full of people that have diseases for which we have only symptomatic treatment infectious diseases or degenerative diseases, like Alzheimer's, muscular dystrophy, multiple sclerosis and cancers." But species that have survived, he noted, likely have been exposed to the same kinds of diseases. "In their genomes are often solutions to the same kinds of problems that we have."
His views on natural solutions to human diseases, he said, are based on the belief that all mammals share a common ancestor. It is almost certain, he said, that about 165 million years ago, probably in Eurasia, "a modest rat-sized creature with squared forelimbs adapted for travel, sprawling hind-limbs reminiscent of lizards or turtles and an unusually potent genome began an evolutionary divergence from reptiles, culminating in panoply of mammalian descendants who would one day dominate the planet."
The 4,600 to 4,800 species of mammals living today, he said, comprise about 28 orders. "Encrypted in the genomes of surviving species are novel genes, lost genes, modified genes and reorganized genes." Mammals each contain between 70,000 and 100,000 genes. Comparative genomics, he said, is revealing valuable information about the disease defense mechanisms that have protected these species from extinction.
"One of the things that has influenced my thinking," said O'Brien, "is what happens when a fatal infectious disease gets into a species. It can either kill a species or the species will survive. If the species does survive then one or two things can happen: The virus can become attenuated, or mutate, into some sort of quiescent thing, the "Andromeda Strain" model, if you will; or the virus does not change its virulence but simply kills off all the genetically sensitive individuals, and the genetically resistant ones survive."
In trying to understand what is responsible for this survival and how it might apply to humans, O'Brien and his colleagues have been searching for what he called human genetic restriction genes. About two years ago, several were found. As a result, he said, "we might find genetic answers to things like resistance to AIDS and resistance mechanisms that we can translate directly."
Following O'Brien's talk, Charles Aquadro, professor of molecular biology and genetics at Cornell, noted that comparative genomics offers "clear opportunities to understand how species have responded to challenges in the environment, from parasites to viruses." Knowledge of how other organisms have solved such problems, he said, can be applied to the human genome in the development of drugs, therapies and treatment regimes. "This research can point to genes that help us understand the pathways of defense," he said.
Other authors of the Science article were: Marilyn Menotti-Raymond, William J. Murphy, William G. Nash, Johannes Wienberg and Rosco Stanyon of the Laboratory of Genomic Diversity; Neal G. Copeland and Nancy A. Jenkins of the Mammalian Genetics Laboratory, Advanced BioScience Laboratories, National Cancer Institute; James E. Womack of the Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University; and Jennifer A. Marshall Graves of the Department of Genetics and Evolution, LaTrobe University, Melbourne, Australia.
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