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Ashley's Biggest Takeaways

• The U.S. Centers for Disease Control and Prevention (CDC)’s Morbidity and Mortality Weekly Report first reported on a cluster of unusual infections in June of 1981, which would become known as AIDS.
• Evidence suggested that the disease was sexually transmitted and could be transferred via contaminated blood supply and products, as well as contaminated needles, and could be passed from mother to child.
• All hemophiliacs of this generation acquired AIDS (15,000 in the U.S. alone).
• The fact that the microbe was small enough to evade filters used to screen the clotting factor given to hemophiliacs indicated that the etiologic agent was a virus.
• AIDS patients had low counts of T-lymphocytes called CD4 cells.
• By 1993, the most likely virus candidates included, a relative of hepatitis B virus, some kind of herpes virus or a retrovirus.
• Howard Temin discovered reverse transcriptase, working with Rous sarcoma in the 50s and 60s. His work upset the Central Dogma of Genetics, and at first people not only did not believe him, but also ridiculed him for this claim.
• Research conducted by David Baltimore validated Temin’s work, and Temin, Baltimore and Renato Dulbecco shared the Nobel Prize for the discovery in 1975.
• Robert Gallo of the U.S. National Institute of Health (NIH), discovered the first example of a human retrovirus—human T-cell lymphotropic virus (HTLV-1).
• Françoise Barré-Sinoussi worked on murine retroviruses in a laboratory unit run by Luc Montagnier, where she became very good at isolating retroviruses from culture.
• In 1982, doctors gave lab Montagnier’s lab a sample taken from a with generalized adenopathy, a syndrome that was a precursor to AIDS.
• Barré-Sinoussi began to detect evidence of reverse transcriptase in cell culture 2 days after the samples were brought to her lab.
• Barré-Sinoussi and Luc Montagnier were recognized for the discovery of HIV with the 2008 Nobel Prize in Physiology or Medicine.

Featured Quotes:

“When I was working on the first edition of Germ Theory around 2010, I went to an American Society for ������ý meeting where Françoise Barré-Sinoussi spoke. She was 1 of 2 individuals that spoke at that meeting, and when the session was over, I was sitting the row or 2 behind her.”

“Knowing that she worked at the Institute Pasteur, I went up to her, introduced myself and told her what I was doing. And I had asked her whether Pasteur had any influence on her life. And she thought for a moment, and she gave me a very good quote, which I ended up using in the book.”

“I think when you win a Nobel Prize, you are now forever known as a Nobel Laureate, and that is a distinction that is unlike any other award. In fact, when you talk to someone and ask a Nobel Laureate, if they'd be willing to talk with you, it's a little intimidating. But after I started researching and talking to her about her life's work, it was especially noteworthy [to learn] how early influences helped shape her life and her discovery.”

“I still teach the history of medicine to our medical students, and one of the themes that I try and bring to seminars is to understand how change occurs in science and in medicine. We know of groundbreaking discoveries, and we think of them as always known, or that when they were discovered everyone accepted them as…true. But it's surprising how often groundbreaking discoveries are not accepted well, and sometimes the discoverers themselves suffer when they're trying to convince their colleagues that they're right.”

“We always have to keep an open mind when we hear someone present a new discovery, as to whether what we thought we knew was really true, and we can learn that from looking back at history.”

“In the first year or 2 of this, AIDS was a clinical diagnosis. In other words, if you had certain opportunistic infections, or you had a certain unusual cancer called Kaposi sarcoma, you met a clinical definition of AIDS. But what I think made it really terrifying was that once diagnosed with AIDS, pretty quickly, the mortality of people with AIDS was determined to be essentially 100%.”

“Many people have described [the discovery of reverse transcriptase] as being one of the most important findings of the 20th century in genetics. The idea of this reverse process of the from the Central Dogma of genetics, it really forced you to have quite an open mind about how viruses and genetics itself can work.”

“After the discovery of the reverse transcriptase, there was a big search in humans, in particular, to find whether or not there were retroviruses. And during the 1970s that search was basically futile. No one found anything, and it wasn't until 1981 that a man working at the National Institutes of Health—a man named Robert Gallo—found the first retrovirus in humans. It was called human T cell lymphocytic lymphoma trophic virus rather, or HTLV.”

“In her Nobel speech, [Françoise Barré-Sinoussi] commented about what it was like being a woman, one of the few women at the Pasteur Institute. What she wrote, and I'm quoting here,
 

‘At the end of my Ph.D., before going for my postdoc, I met the assistant to the director of the Pasteur Institute, to ask him if I could apply one day for a position at the Pasteur Institute. The guy looked at me and said, ‘As a researcher, no way, women never have done anything in science, you had better think immediately to revise your career plan.’ ‘That has been a driving force for me to demonstrate to males what we can do. The guy at the Pasteur Institute, by the way, called me back many years later and said, ‘I would like to congratulate you, not only for what you did in the discovery of the AIDS virus, but also because you have a lot of courage.’’

“Dr. Barré-Sinoussi became adept at detecting reverse transcriptase in cell cultures. It's a tricky business, and she became quite adept at it. So that was kind of her role in the lab.”

“It's really interesting in that regard, because I remember asking her, when was she sure that she had it? Because remember, this was a single patient, the patient didn't actually have AIDS, although the syndrome was very much associated with people getting AIDS. And this is what she told me:

‘Yes, we were sure, but we could not really write that. Because if you want to make sure that the virus was a cause of disease, you had to let cumulate evidences that we did not have ourselves enhance at the time, so we could not write that it was the cause of [AIDS]. But we were sure.’”

“Well, she told me the reaction was quite mixed. There were some people who didn't believe it—didn't think that they had it—and others that were very excited about it. And remember, the data that she presented was really quite early, they hadn't had a lot of opportunity to test for this virus in a large number of samples and people with AIDS, but they had characterized it to a good degree.”

“Well, I think there's another reason why people were a bit mixed in their acceptance of this initial data and the initial publication, because in that same issue of Science, Dr. Gallo published 2 papers, asserting that it was HTLV-1 that was causing AIDS. And because of the force of Dr. Gallo and his lab, a lot of people paid attention to that.”

“On April 23 1984, Margaret Heckler, who was then the Secretary of Health and Human Services, held a press conference. And at that press conference, she said, ‘The probable cause of AIDS has been found by our eminent Dr. Gallo.’ And he described a virus, which he called HTLV-3. About a week or so after this press conference, he had a paper published in Science, where he described HTLV-3.”

“And this was really an important issue. Who discovered it first? One of the problems that came out of this is that 1 day after this press conference, Gallo applied for a patent in the U.S. Patent Office for a lab test to detect HTLV-3, even though the Pasteur investigators had applied for a patent in the U.S. office 4 months earlier. So now it's become a real disagreement. The Pasteur investigators challenged Gallo's patent later that year, and that's when things got really ugly.”

“I've read this in some journalistic accounts of the era that the 2 men [Gallo and Montagnier] had what 1 journalist called ‘Titanic egos,’ and their egos simply got in the way of all of this. They simply would not let this go. And they got so heated at each other that the dispute became so bitter, and the 2 men literally wouldn't be in the same room.”

“I think that was a very difficult time for [Barré-Sinoussi] because she knew Dr. Gallo, she knew the people in the lab, and she wanted to continue to collaborate. The ego was not a big part of her life. She really did not want to pursue that end of it. But because it had gotten so bitter, she was just simply not allowed to communicate with Gallo’s lab.”

“In 1987, [the dispute] went all the way up to the President of the ������ý States, Ronald Reagan, and the Prime Minister of France, who had to finally sign off on an agreement that settled this, where there was a 50/50 split in both the monies and the prestige of who gets credit for the discovery.”

“We've kind of forgotten the desperation that was occurring around the time of her discovery. And I think seeing the AIDS patients was very motivating for her. She mentioned that, it is was motivating for her to show males what females could do, but I think this was even more motivating.”

“I think one of the sadder parts is that the controversy over who discovered HIV tended to overshadow the importance of the discovery itself. And that's an important lesson. In fact, when you read over the 2003 article that Gallo and Montagnier wrote in the New England Journal of Medicine, they said, ‘Many lessons can be drawn from this early intense period, and most suggest that science requires greater modesty.’”

Links for the Episode:

From the ancient worlds of Hippocrates and Avicenna to the early 20th century hospitals of Paul Ehrlich and Lillian Wald to the modern-day laboratories of François Barré-Sinoussi and Barry Marshall, Germ Theory brings to life the inspiring stories of medical pioneers whose work helped change the very fabric of our understanding of how we think about and treat infectious diseases.

The 2nd edition of Germ Theory, which will include chapters on Françoise Barré-Sinoussi, Barry Marshall and Tony Fauci, will publish in Spring 2023.



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• HIV/AIDS
• Podcast
• Host-Microbe Biology

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