Oct 08 2008
The Nobel Prize in Medicine was awarded this week to two French virologists, Françoise Barré-Sinoussi and Luc A. Montagnier, for discovering the AIDS causing virus, the Human Immunodeficiency Virus (HIV). They will share half the prize of 1.4 million dollars, the other half going to three Dr. Harald zur Hausen for discovering the human papilloma virus and its relation to cervical cancer.
The prize comes 25 years after Barré-Sinoussi and Montagnier, working at the Pasteur Institute in Paris, published their paper identifying what was later called HIV. The last quarter of a century has proven their discovery to be a triumph of science-based medicine. The Nobel committee is correct, in my opinion, in waiting such long periods of time before granting such recognition. It reflects that fact that, even in a fast-paced arena of science such as medicine, it takes time for the meticulous process of science to work itself out. It takes decades to garner the perspective necessary to tell the difference between a crucial breakthrough and a false lead.
The story of HIV encapsulates the power and potential success of a reductionist approach to understanding and treating disease. HIV was detected and described shortly after AIDS was recognized as a distinct clinical entity. Soon papers were published showing that HIV is a retrovirus – a specific type of virus that makes DNA from its RNA (using an enzyme called reverse transcriptase) and then inserts that DNA into the DNA of its host. Retroviruses use this mechanism to hijack the reproduction machinery of the host cell, which then makes millions of copies of the virus until the cell bursts with them, sending them forth to infect new cells.
In the case of HIV, the cells it infects are CD4 cells – white cells that play an important role in the immune system. By killing CD4 cells HIV makes a preemptive strike against the immune system allowing it to survive immune attack. This weakening of the immune system is what leads to AIDS, which results in increased susceptibility to infection. So-called opportunistic infections (ones that would typically not take place in an immune-competent host) are the hallmark of AIDS.
It was later discovered that HIV has regions that mutate very rapidly, allowing the virus to change throughout the course of an infection of a single host. This further allows it to hide from the host’s (now weakened) immune system.
The story of HIV, which is still unfolding, allowed researchers to design treatments for HIV and AIDS – ones that would target HIV specifically. The first treatment, AZT, from very crude. In fact, AZT was nothing more than a failed cancer drug, but it inhibits the action of reverse transcriptase. The drug therefore interferes with the life-cycle of HIV. While AZT did work to prolong the life of patients with HIV/AIDS, it was not very effective, tended to develop resistance, and had many side effects. But this was just the first attempt at treating HIV with an off-the-shelf drug.
Within about a decade pharmaceutical companies were developing the next generation of anti-HIV drugs. These efforts eventually led to HAART – Highly Active Anti-Retroviral Therapy – a cocktail of drugs that attacks HIV at multiple points in its life-cycle. With HAART HIV patients are surviving much longer than prior to the availability of this therapy.
Current therapies are far from a cure, but newly diagnosed HIV patients can now except to live for decades, and are likely to live long enough to benefit from future advances.
Dr. Montagnier is optimistic about the future. He predicts that an effective HIV vaccine might be available within 4 years. Predicting future developments is always risky. While an HIV vaccine is plausible, it has proven to be technically very difficult. The primary stumbling block has been the virus’s ability to mutate during an infection – evading the immunity granted by a vaccine. However, researchers are now trying to target the more stable regions of the virus with vaccines, those regions critical for HIV’s function, which should result in a more effect vaccine. The history of science has taught us that not everything pans out the way we expect – and so there will be no substitute for clinical trials to see if any putative vaccines work. But there is reason for cautious optimism.
Science is certainly not a panacea, and it is difficult and messy work. But it is a powerful tool. Recently there has been much popular attention paid to non-reductionist approach to medicine. There is both good and bad in this. Medicine is the very human practice of healing individual patients – patients that need to be viewed in their entirely. When I was going through medical school at Georgetown, this was referred to as the biopsychosocial model of medicine, treating the patient as a person with biological, psychological, and sociological factors to consider.
In the past decade, however, this approach has been hijacked and rebranded as “holistic” medicine. In my opinion, this is a double deception. First, it pretends as if good and ethical mainstream scientific medicine was not already “holistic.” This is not to suggest that the practice of medicine cannot be improved, but it is simply a fiction to pretend that mainstream scientific medicine did not understand and incorporate the principles of the whole-patient approach. The term holistic was used to create a false dichotomy – that between scientific medicine and the new approach that was being sold as whole-patient oriented. But the new approach (so-called CAM or integrative medicine) was not, in fact, distinguished by being holistic. Rather it was only distinguished by being non-scientific.
Mainstream medicine was falsely painted as non-holistic and reductionist, when it is holistic and reductionist. What the public was sold (under the name of holistic healing) was something that was not holistic and not reductionist. CAM is often not holistic because it does not take the biopsycosocial model – it often does not consider what science knows about biology and accepted models of psychology and sociology. Rather it often simply substitutes a very narrow philosophy as a single approach to all disease – a decidedly non-holistic approach.
It also often rejects the benefits of a reductionist understanding of biology and disease. Worse than throwing the baby out with the bathwater, it threw the baby out with the baby.
Our science-based reductionist understanding of HIV had lead directly to improved quality and duration of life for those infected with HIV. Carl Sagan said it best, “Science delivers the goods.”We can combine that with compassion for individual patients and personalized attention to their medical, psychological, and social needs. The health care system does not always have the resources to do this optimally, but that is the ideal model we strive for.
Finally, I applaud the Nobel committee for maintaining their dedication to science and not succumbing to the latest fads. The medical community should follow their lead.
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