A Short History of a Catastrophe
30 YEARS IN 30 MINUTES
Dr. Anthony Fauci, the longest serving director of the National Institute of Allergy and Infectious Diseases, spoke at Georgetown University on September 7. He told the audience that he would cover the 30-year history of the AIDS pandemic in 30 minutes, and he did.
Fauci was introduced by Dr. Mark Dybul, his former research fellow and now a distinguished scholar at Georgetown’s O’Neill Institute for National and Global Health Law. One thing about Fauci that is not always captured in his many public accolades, Dybul said, is that “he is singularly focused, whether in the laboratory or the clinic or in the public arena, on saving lives and caring for others.” That’s what has made him so effective as a key scientific advisor to the last five presidents.
THE FIRST REPORTED CASES
No matter how good your training, no matter how much energy you have, began Fauci, sometimes things happen that are simply beyond your control.
“I just happened to be in a position 30 years ago this past summer that allowed me to step into the beginning of what no one knew at the time would turn out to be one of the most transforming public health catastrophes in the history of our civilization.”
Fauci was a senior investigator with the National Institute of Allergy and Infectious Diseases when the now famous Morbidity and Mortality Weekly Report (MMWR), June 5, 1981, from the US Centers for Disease Control and Prevention, landed on his desk. It reported an unusual situation, five gay men, all previously healthy, from Los Angeles who presented with pneumocystis pneumonia. As one of the few researchers devoted solely to human immunobiology, he knew this condition only occurs in people who are immunosuppressed.
THIS IS SOMETHING NEW
The next month’s MMWR report cited an additional 26 gay men, all previously healthy, from Los Angeles, New York City, and San Francisco, who not only had pneumocystis pneumonia but also Kaposi’s sarcoma. Kaposi’s sarcoma is another opportunistic condition seen in people with compromised immunity.
Fauci knew this was something new, something clinicians had never seen before. He immediately began to focus on this mysterious new disease, to the dismay of his mentors and advisors, who warned him it was a bad career move.
History proved otherwise.
THE FIRST THREE YEARS
Fauci described that early period as “three years worth of serious darkness.” He took care of patients, not having identified the causative pathogen that totally destroyed the immune system, being only able to palliate symptoms, and then watching the patients all die. “It was like living in an intensive care unit all day long. It was very stressful.”
But then, scientifically, things really started to happen. In 1983, Luc Montagnier and his colleagues at the Pasteur Institute in France identified a virus in patients with gay-related immune deficiency syndrome. In 1984, Robert Gallo established definitively that a RNA retrovirus, HIV, causes AIDS.
Retroviruses were not a common focus of research back then. A retrovirus is so named because it propagates itself in a backward way. In order to replicate itself, it must hijack a cell’s DNA. The retrovirus goes from RNA back to DNA using an enzyme called reverse transcriptase. Once it makes a DNA copy of itself, it can then turn the host cell into a virus factory.
THE TIP OF THE ICEBERG
Now that the infectious agent was identified, antibodies to the virus could be detected, because in spite of the fact that HIV targeted and dismantled the immune system, an immune response was triggered. The first payback on research investment was the development, in 1985, of the HIV test.
Now the blood supply could be screened, and that was critical.
The other payback was the ability to do epidemiological screening, to test people for infection. “This was a shocker,” Fauci said. “It told us that the cases we were seeing trickling in from the big cities were the tip of the iceberg of who was really infected. The numbers were astounding. We know now that the median time between first infection and clinical illness is about 10 years, which meant that the people we were seeing had far advanced disease.”
That meant that hundreds of thousands in the United States and millions of people worldwide who were not yet sick were HIV-infected.
How to measure the size of the catastrophe? It went from those initial five and then 26 patients to extraordinary numbers, about 65 million cumulative infections, 30 million deaths, about 34 million people living with HIV, 2.6 million new infections a year, 1.8 million deaths.
TRANSLATION AND TRANSFORMATION
The development of a drug to combat a retrovirus loomed as a monumental challenge. By 1986, scientists could describe the nature and shape of HIV proteins as well as key molecules on the immune system cells that HIV infects. They understood the process by which HIV multiplies and infects new cells.
National Cancer Institute investigators under the direction of Dr. Samuel Broder worked with the Burroughs Wellcome & Company to identify a drug, AZT that suppressed HIV replication.
Fauci points out that we now have over 30 drugs, approved by the US Food and Drug Administration, which when used in combination, have completely transformed this disease. So go back the first picture we started with, he says, where the median survival was 6 to 8 months. Now, if a 20 year old, newly-infected person comes into the clinic today, and you start them on triple combination medication, you can mathematically model that that person will live an additional 50 years.
“So it’s gone from 6 to 8 months to 50 years,” he says. “That has to rank among the short list of major accomplishments in the translation of basic research into a clinical benefit.”
By Frank Reider, GUMC Communications