Pandemics. Having raised their heads every century or so to spread primal panic and horror on a continental scale, they were something we believed ourselves well rid of by the mid-twentieth century. By vaccine and vitamin, sanitation and antibiotic, humans had pushed back the terrors of globe-spanning disease in the first world and had every reason to expect that, if a new bug should dare raise its head, it would be summarily identified and executed before it had a chance to penetrate Main Street. Then, on 5 June 1981, we had the first inkling of how wrong, how very wrong, we were.
On that day, the Center for Disease Control announced five cases of severe immunodeficiency in Los Angeles, a number that grew to 270 by year’s end. Previously healthy individuals were being felled by advantageous diseases that their immune systems should have had no trouble dispatching. These cases of catastrophic immune system failure, at first seemingly limited to homosexuals and heroin users, soon spread into all communities the world over, as 270 cases became 20,000 by the end of 1985, became 300,000 by 1990, and today stands at 70 million infected individuals across the world.
As the first disease reports trickled through the medical community, there was a grim and general realisation that not only did we not know how to combat this disease – we did not even know what it was. One man, however, had a hunch. His name was Willy Rozenbaum and he believed the symptoms of this new disease matched up with one discovered in 1980 by Gallo, Hinuma and Yoshida: Human T Lymphotropic Virus (HTLV). In 1982, he went to the Pasteur Institute to find somebody experienced enough in retrovirus analysis to test his theory. He was soon passed along to the laboratory of Jean-Claude Chermann, where a tiny group of researchers was studying the role retroviruses play in certain forms of leukaemia, a group that included the woman destined to discover the culprit behind AIDS and to dedicate the next decades of her life to coordinating the world’s resources to eradicating it: Françoise Barré-Sinoussi.
Born in Paris in 1947, her family was of Parisian extraction stretching back generations, but her most prized memories were of vacation trips to the countryside where she could wander and observe plants and animals by herself, or compete in pet snail races with her cousin (whenever her snail lost, she felt it must, of course, be due to a terrible snail illness, and set herself the task of diagnosing the malady). She knew that she wanted to do something with the ‘living’ sciences, but could not decide between pure biology and medicine. Reasoning that a degree in biology would take less time and therefore be cheaper for her parents, she ultimately decided on biology, her head full of dreams of stimulating laboratory work.
Imagine her disappointment, then, when her first years were focused almost entirely on theory, with virtually no laboratory work at all. After two years, she was ready to leave the university and join a laboratory tech training college just to finally have practical research work to do, when fate intervened in the form of the college president. He told her that, having already finished two years at the university, it was inadvisable to stop now to join his school’s programme. For her own good, he turned her down, and so it was back to the university, and theory.
But Barré-Sinoussi was not one to accept defeat so easily. She spread a wide net, looking for laboratories who would take her while she continued her university studies, and in 1970 she found a spot in the small but well-regarded laboratory of Jean-Claude Chermann, a virologist working on retroviruses that caused leukaemia in mice. In spite of her lack of laboratory experience, Chermann took her into his laboratory family and acted as her mentor. She spent as little time as possible actually in class in order to spend more at Chermann’s laboratory and learn all the tools and tricks of a retrovirologist.
All of which begs the question, what is a retrovirus? Remember that there are two main carriers of genetic information: DNA and RNA. Most living things keep a permanent copy of their genetic structure in the form of double-stranded DNA and use single-stranded RNA for various tasks in the creation of proteins and regulation of the cell.
Retroviruses, however, carry RNA, not DNA, as their primary genetic source. When they invade a cell, they make DNA copies of their RNA and insert those copies into the host DNA. The host cell then believes the foreign DNA is part of its own code, and happily copies it over and over again, creating new copies of everything needed to make a swarm of new retroviruses, which will invade new healthy cells, thereby triggering a biological chain reaction. As infectious agents, retroviruses are particularly nasty as the process that produces viral genetic copies is notoriously imprecise, generating progeny viruses with mutational variations that immune systems have difficulty keeping up with.
Barré-Sinoussi received her PhD in 1975 and continued at the Pasteur Institute, researching retroviruses until the fateful day when Rozenbaum’s challenge made its way to her desk. A momentous decision had to be made: would she work on the assumption that the disease agent was HTLV, and proceed through the established steps laid out for its identification, or would she start from step one and push her way through the various methods and tactics for identifying a new infective agent? Not entirely convinced by Rozenbaum’s claim, she opted for the latter, securing on his advice some samples from a patient exhibiting symptoms of swollen lymph nodes that often marked the onset of the new disease.
Analysing the samples, she noted the presence of reverse transcriptase which betokens retroviral activity, but simultaneously noticed that the T-Cells she was studying were dying out at an alarming rate, too fast to gather the corroborating data she needed. The laboratory team put their heads together and had a brilliant flash of insight – why not go over to the local blood bank and ask them for fresh blood? There would be enough white cells there for the virus to hopefully feed on, which would extend the amount of time they could study the original viral sample.
The trick worked. Retrovirus activity picked up, and new knowledge was gained: whatever this disease was, it clearly had the ability to infect and eventually destroy new white blood cells. Barré-Sinoussi was convinced that what she had was a retrovirus, but was it HTLV? She got in contact with Robert Gallo, one of the original discoverers of HTLV, and asked him for his help. Obligingly, he sent her samples of the HTLV retrovirus and of antibodies that responded to its presence. Using these samples, she discovered that the HTLV antibodies did not interact with her retrovirus, and the antibodies from the original patient did not respond to HTLV. Whatever this new disease was, it was not caused by HTLV.
All this research was carried out at breakneck speed. Rozenbaum had laid out his idea in December 1982. Barré-Sinoussi started testing in January 1983, and her paper identifying HIV was published in May of that year, a startling turn-around built on the cleverness of her colleagues, and the inspired solidity of her retroviral analytic technique. She would go on to win the Nobel Prize in 2008 for the discovery, but in the meantime, there was work to be done.
Africa, where AIDS probably originated, had by and large kept quiet about the epidemic in its midst. Fearful for the political and economic ramifications if the disease were known and its scale laid out, pressure was put on local health services to remain silent about immunodeficiency-related deaths. Part of the task Barré-Sinoussi set for herself, then, was to determine the scope of the African AIDS epidemic and coordinate resources to allow large-scale testing and treatment to be carried out throughout the continent. She travelled across Africa, and eventually south-east Asia as well, assessing the tremendous need for better public education about the causes and transmission of AIDS, and establishing centres that could identify AIDS cases early and administer life-saving anti-retroviral treatments.
It was work of profound importance and substantial frustration. For every government like Thailand or Brazil that worked vigorously with her teams to educate the public and catch early cases before they became fatal, there were governments like Thabo Mbeki’s South Africa which, seizing upon the HIV denialist theories of UC Berkeley biologist Peter Duesberg, declared that AIDS was caused by issues of sanitation, malnutrition and lifestyle, not by the HIV virus. As a result, the government refused to institute early detection or anti-retroviral programmes, ultimately causing hundreds of thousands to die unnecessarily.
Somehow amidst travelling the world in an unflagging attempt to create a stable international approach to AIDS treatment, Barré-Sinoussi’s research carries on, investigating the genetic variations that allow some members of the population to seemingly purge HIV from their system naturally. Unlike normal people infected by HIV, who must take anti-retroviral medication for their entire lives, these ‘elite controllers,’ who make up less than 0.3 per cent of the population, are able to safely stop taking their medication and not experience a relapse of AIDS symptoms. Learning from their biological bag of tricks could hold the key for single-trial medications and perhaps even the long-sought AIDS vaccine.
In the meantime, Barré-Sinoussi can point with satisfaction to the sharp increase in anti-retroviral treatment resulting in no small part from her efforts in working with foreign governments to create public health policies based on good science but still responsive to local concerns and methods. In 2002, fewer than 400,000 people in developing countries were receiving anti-retroviral treatment. Ten years later, thanks to Barré-Sinoussi and others like her, that number had grown to 6.5 million individuals. In Africa, without treatment, 40 per cent of infected mothers passed HIV directly to their babies, a number that now stands at less than 5 per cent.
There are people who have done so much good, who have so unambiguously made the world a better place by the work of their mind and heart, that finding the words to sum their lives is an impossible task. If Françoise Barré-Sinoussi were just the researcher who discovered HIV and is looking into genetic causes of HIV resistance, or just the voyager who went into the heart of the countries most impacted by AIDS to evaluate what needed to be done to stop the omnipresent suffering, or just the organiser assembling experts from the world over to concentrate financial and intellectual resources in the fight against AIDS, or even just the spokesperson who uses her platform to educate the first and third worlds about what is being done, and what yet remains to be done, it would be enough to earn thanks. But she is all of those people at once, and before that, dumbstruck awe is all one can reasonably feel. Words are too small to express the thanks we owe, too small by half.
FURTHER READING:
Francois Barré-Sinoussi’s memoir/report on the history and future of AIDS treatment, Pour un Monde Sans SIDA: Un Combat Partagé (2012) is delightful and inspiring. It is all done in an interview format and I would say about a third of the book is devoted to her life and work, and the other two-thirds to investigating the world AIDS situation, and promising lines of research in new treatments and potential cures. It is in French, but the vocabulary is nowhere so technical as to be opaque, so a casual French reader should not have too much trouble with it.
Barre-Sinoussi's story is also one of 140 stories of women in Medicine I told in A History of Women in Medicine and Medical Research, available on Amazon and from Pen and Sword books US or UK!
