Virus hunter: Luc Montagnier, pictured here in front of an electron micrograph image of the HIV virus.

Credit: Photolibrary

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In 1981, a mysterious new disease was described by two doctors in New York and Los Angeles. Some young homosexual men were dying of multiple infections or cancers characteristic of immune system collapse. A few months later, these symptoms appeared in Europe, also in gay men.

By the end of that year, 121 people in the U.S. had died. This was just the beginning of the spread of what was then called the 'gay disease', and I had no inkling that in a few years time I'd play a pivotal part in identifying the elusive cause of the pandemic, and start working towards a cure.

At that time, I was running a laboratory at the Pasteur Institute in Paris searching for viruses that cause cancer. In fact, if I look back through my whole career, I can best define myself as a virus hunter.

While we were mostly unsuccessful in humans, other groups identified examples in animals of viruses that caused cancer, notably retroviruses. These are a particular sort of virus, with an RNA genome, which are able to reverse transcribe their RNA into DNA, and then embed themselves in the chromosomes of host cells, infecting them.

In 1982, along with colleagues at the Pasteur Institute, I made the surprising observation that some breast cancers contain DNA very similar to that of a retrovirus which causes mammary tumours in mice. The same DNA was present in the white blood cells (lymphocytes) of the patient. Since I knew that retroviruses love to replicate in actively multiplying cells, I wondered if it might be present in the lymphocytes.

I started growing a particular kind, called T-lymphocytes, from patients with breast tumours and I hoped that as they replicated, so too would the whole virus. "Chance favours the prepared mind," said Louis Pasteur, and while this approach had so far proven unsuccessful for breast cancer, it turned out to be a pivotal technique in finding the cause of the mysterious new disease.

By end of 1982, there were numerous theories as to the cause of the disease – such as recreational drugs, fungi or bacteria – but little solid evidence. The disease was officially named Acquired Immune Deficiency Syndrome (AIDS) because it was hitting not only gay men, but also haemophiliacs and people who'd recieved blood-transfusions. By now, cases had been detected across the world.

Slowly, it was becoming clear that it was an infectious disease, transmitted by blood and sexual intercourse; but its cause remained a mystery. It was likely to be a virus, as haemophiliacs had been infected by blood that had been filtered, eliminating anything bigger than a virus. But, we asked, which virus was responsible? It was perplexing.

One possible candidate was a human retrovirus, human T-lymphotropic virus (HTLV), which had just been described by a team led by Robert Gallo at the U.S. National Cancer Institute in Washington DC. Japanese researchers had found it associated with a rare form of leukaemia, but it also seemed to depress the immune system.

In order to probe this connection further, I set up a team of researchers to detect this kind of virus in T-lymphocytes grown from AIDS patients; an increasing number of whom were appearing in France. By the end of 1982 – when cases of AIDS had begun to spring up across the world – we were ready to 'catch the big fish'.

Indeed, the day in question was 3 January 1983. A hospital virologist had called me the day before to say she would bring over a biopsy of a swollen lymph node, packed with white blood cells, taken from a patient with early AIDS symptoms. The biopsy, due to arrive in the morning, in fact arrived late, to an empty lab. Everyone had disappeared for lunch – a sacred time for the French. She left the sample in a refrigerator. It was late afternoon by the time I found it and got to work.

The first surprise came after two weeks, when my team mate at the institute, Françoise Barre-Sinoussi, told me she had detected the sensitive reverse transcriptase enzyme signature (see "From RNA to Retroviridae" below) of a retrovirus in the culture medium. I was subsequently able to grow the virus in lymphocyte colonies generated from healthy blood donors, allowing us to study its properties in detail.

The second surprise came at the beginning of February, when Charlie Dauguet, who worked the electron microscope in my lab, brought in some intriguing pictures of the virus. I quickly realised it looked very different from HTLV.

Soon, we were able to isolate the virus directly from the blood of a range of AIDS patients with differing case histories. Though work progressed slowly due to limited funding, our team, now consisting of virologists, immunologists and clinicians, started to amass conclusive evidence that this new virus was the cause of AIDS.

And then came a controversy. The 'father' of HTLV, U.S. virologist Robert Gallo, announced that he believed a variant of HTLV caused AIDS. However, by the spring of 1984, Gallo had changed his mind and gave his support to our theory of a new retrovirus, confirming and extending our results. Both groups accumulated data sufficient to convince the scientific community that the new human immunodeficiency virus (HIV) was the real cause of AIDS.

Other groups then joined us, and the viral DNA was sequenced – a substantial technical challenge at that time. In 1985, the first commercial blood tests were developed in the U.S and France, and their use all but eradicated the transmission of the virus by blood transfusion or blood products.