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The History Mystery of HIV/AIDS and Genetics

by Tom Grayson

If you want to control where you're going, you may want to review how you got where you are.

That was the primary message delivered by Dr. Stephen J. O'Brien of the National Institutes of Health (NIH) concerning the AIDS epidemic, a virus that has killed over 25 million people since its identification in 1981.

Often called the Indiana Jones of Genomes due to his worldwide travels investigating disease and evolution, O'Brien spoke to genetics students from various universities at New Jersey's Burlington County College.

O'Brien's life work is dedicated to the discovery and assessment of AIDS Restriction Genes (ARG). This work has led to a shift in the scientific reasoning associated with HIV/AIDS and therefore the development of new diagnostics, prevention, therapies, and vaccines.

"I had been living on the strength of my rhetoric, not data," said O'Brien. But science is now providing the data to support his team's belief that ARGs and AIDS-defining conditions are crucial elements in the fight against HIV/AIDS.

As chief of the Laboratory of Genetic Diversity at NIH, O'Brien led a team conducting a study on high-risk individuals in hopes that a common denominator would surface among those resistant to the HIV virus. Their research focused on a protein that sits on the surface of immune cells. HIV docks at this protein to get into our cells.

For many resistant individuals, the common denominator was a genetic defect in this protein, known as Δ32. This defective protein blocks HIV entry into cells of resistant individuals.

Wrapped in all this science is a history lesson. Appearing on both PBS's "Nova" and the Discovery Channel, O'Brien set forth the idea that many of those who survived the Black Plague of Europe in the mid-14th century had such fortune because they carried Δ32 in their genomic sequence.

Having both harmful and beneficial effects, Δ32 is a defect that affects the human immune system. As for HIV, the carrying of Δ32 is believed to be a great benefit. It is hypothesized that natural selection allowed those with Δ32 to survive the Black Plague, an epidemic that killed between one-third and two-thirds of Europe's population. The survivors then passed on this genetic mutation to future generations. In theory, this same strength through natural selection is why so many people of European decent are resistant to HIV/AIDS.

The Plague attacked Europe but spared Asia and Africa the same level of devastation. While this was fortunate for Asians and Africans then, the same cannot be said for these populations today.

Since the agent of Black Death, Yersinia pestis, docks at the same protein as HIV, Asians and Africans were not given the opportunity for natural selection to eliminate the non-Δ32 population in return for a more resistant population today. As a result, a high percentage of these populations do not carry Δ32. This genetic mutation, combined with risk factors resulting from social norms, has led to HIV/AIDS being more prevalent in Asian and African populations.

"O'Brien's work is most impressive because he utilizes evolutionary links between humans and wild life, such as cheetahs and pandas, to draw inferences regarding human disease and treatment," said Laura Grayson-Roselli of Grayson Scientific Consulting. "He has also illustrated that previously disparate fields of study, such as virology, evolution, conservation genetics, and history can work in unison to help solve today's problems."

As O'Brien writes in his book, Tears of a Cheetah, predictions as to the value of this research are risky, but he believes "if one could forecast a payoff for our investment in AIDS restriction genes, it would be a translation of the gene's mechanism into innovative and effective therapies that would mimic natural stalls on HIV and AIDS." Furthermore, he states that the discovery of a gene that is necessary for a fatally infectious disease to progress is an ideal target for pharmaceutical research.

Armed with this ever-evolving knowledge of where we stand on the genetic timeline, where do we go from here? Researchers like O'Brien are working to ensure its quickly toward eradicating one of Mother Nature's most deadly diseases.

Dr. Stephen J. O'Brien of the Laboratory of Genetic Diversity at NIH discusses the effects of genetic evolution on HIV/AIDS. O'Brien is referred to as the Indiana Jones of Genomes due to his world travels exploring the connections between virology, evolution, genetics, and history.
Dr. Stephen J. O'Brien of the Laboratory of Genetic Diversity at NIH discusses the effects of genetic evolution on HIV/AIDS. O'Brien is referred to as the Indiana Jones of Genomes due to his world travels exploring the connections between virology, evolution, genetics, and history.