A) Meet Dr Gallo B) Stop talking about Thabo Mbeki

The first thing you should know about Dr Robert Gallo is that he’s published more papers than there will probably be words in this feature (over 1,300, plus a good few books). The second is that – perhaps as with many innovators – the answer to what stands out in his career may surprise you. His role in the discovery of the link between HIV and Aids was neither the most challenging nor the most groundbreaking, in his view. And when you ask him about the highlights of his career, he doesn’t mention the accolades, not even winning the Lasker Award – twice. (Nobody else has achieved this; it’s the US’s most prestigious award in biomedical research.)

“I have my own views [on what the highlights were],” he says. A major breakthrough was discovering one of the first cytokines, IL-2, which was then known as the ‘T-cell growth factor’ – a protein made by T-cells which also makes T-cells grow. The result was ultimately being able to grow human blood cells in the laboratory. “Some people say that’s number one in my career. For me, the goal was finding and proving that humans were not protected against retrovirus infections. The time I set out to prove this, in the Seventies, it was ridiculed.”

This journey would prove to be life-changing not only for Gallo, but for HIV/Aids patients for decades to come. When Gallo first suspected that humans were not immune to retroviruses – a family of viruses that replicate in a host cell by reversing the usual replication pattern – there had already been several decades of research suggesting the opposite.

“We proved that wrong and isolated a retrovirus that caused a certain type of leukaemia, a human T-cell leukaemia in young adults,” says Gallo. “That virus is known as HTLV-1. A year later, we discovered HTLV-2.”

HTLV remains a public health problem in many parts of the world including Japan, South America and some parts of Africa, and causes fatal neurological disease. But most crucially for what was to come, Gallo and his colleagues noted in their own labs and in literature from Japan that patients with HTLV – even without leukaemia – became immunosuppressed.

“By the time Aids came along, we know that this was transmitted by blood, sex and mother to infant,” he says. “We know that it targeted T-cells and caused mild immunodeficiency.

“We knew that Aids must be caused by another human retrovirus, but one far more able to kill the immune system. Indeed that was the case. The timing of the research into HTLV was much more difficult than HIV because it reproduces less efficiently and there was very strong resistance to me and this idea. I had to prove it over and over. So that, to me, was huge.”

The early work on HIV/Aids ultimately led to some controversy and one of the best-known disputes in modern medicine. Gallo received one of his Lasker Awards in 1986 for “determining that the retrovirus now known as HIV-1 is the cause of Acquired Immune Deficiency Syndrome (AIDS).” Later, however, there were allegations that Gallo’s laboratory had stolen work from a French laboratory; they were initially cleared of wrongdoing but later the matter was reopened. The dispute ended officially in 1987, when the president of the United States and the prime minister of France announced a joint agreement declaring that Gallo and Luc Montagnier – the lead researcher in the French lab – would share credit for the discovery. In 2008, however, the Nobel Prize in Physiology or Medicine 2008 was divided, one half awarded to Harald zur Hausen “for his discovery of human papilloma viruses causing cervical cancer”, and the other half shared by Françoise Barré-Sinoussi and Montagnier “for their discovery of human immunodeficiency virus”. Gallo was left out, a snub he described at the time as “disappointing”.

Today, there is little trace of bitterness visible. Gallo speaks instead of being greatly inspired by receiving the honorary degree from the University of KwaZulu-Natal, which he describes as “one of the great centres at one of the universities that’s doing the most about it” [HIV/Aids] and “doing the most innovative things to control it”. He’s referring here to the CAPRISA programme, and specifically the leadership of Professor Salim Abdool Karim, clinical infectious diseases epidemiologist and Chair of the UNAIDS Scientific Expert Panel, among other leadership positions in the field of medicine worldwide. Karim has advised several governments and the world’s leading agencies in AIDS and global health such as the WHO, UNAIDS, and the Global Fund to fight AIDS, TB and Malaria, and Gallo says further collaboration is on the cards – with both the abovementioned Karim and Professor Quarraisha Abdool Karim, Associate Scientific Director of CAPRISA and laureate of the 2016 L’Oréal-UNESCO for Women in Science Award.

“Getting to know both Karims has been important,” says Gallo. “We’ve had some interactions but not as intimate as would be useful. Now I know their programme reasonably well. A visit [to local clinics] was really worthwhile.”

So can HIV/Aids be eradicated by 2030? The short answer is maybe. “It’s obviously the central question,” says Gallo. “To be objective about it with the knowledge base I have, you can only answer scientifically: yes. You can prevent infection in a significant number of women, and if you pre-treat people with high risk, even if they are not infected, and if they will take the medicine. The epidemic in San Fransisco is greatly declining, and it looks like that is going to work. If we had a partially effective vaccine to combine with this, I’d be confident.”

The key issue, though, is that it’s not just a scientific problem – it’s also social and political and, of course, financial. “We have to do a lot more outreach and testing in terms of getting to the social aspect – the knowledge and compliance to come in and be tested and treated.”

Reaching adolescents, also, is a critical challenge, as is educating populations to discern the difference between clinics and professionals who are competent and those who are not.

The candidate vaccines have potential, says Gallo, but they are still at their early stages. “We have one that is in Phase 1, which means toxicity studies or safety studies, and we have good data in monkeys. I know there is more science to be solved before that is going to be a really good vaccine. But if it’s a little good, coupled with finding people who are infected and getting them on therapy, and using the microbicide approach the Karims are using and pre-treating high-risk people, I think it is conceivable – but it takes will, real political will and a constancy of support. Not ‘maybe this year, maybe next year’. It has to be multi-year support.”

The vaccine Gallo and his colleagues are working on has shown promising data but more time is required. HIV is different not because of its variation but because it’s a retrovirus, Gallo explains.

“All retroviruses integrate their DNA into our chromosomal DNA within a day, and then it’s too late. What this means is that we have to block right at the beginning, so some of the usual approaches to vaccination, like cellular immunity, have less of a role – we have to have antibodies left, we have to have the right antibodies, and we have to block the infection completely.”

Gallo and his team targeted the conserve regions of this very variable outer protein of the virus, what’s known as the envelope protein – normally very hidden – and exposed it.

“It sounds interesting, it sounds intellectually good. And we have the good data in monkeys. However, I also know that anybody’s antibodies to this envelope protein, for reasons we do not know, but which are not unique in biology, do not last very long, so you are talking about maybe three to four months. To be practical you have to boost three to four times a year. So what do we do? If you boost too much, you alter the mean response you’re getting, and you don’t get the efficacy you want. There are still scientific problems we want to solve before we get to stage three, or efficacy studies.”

In the meantime, Gallo is focusing on his work with the Global Virus Network, which he founded in order to link researchers after realising that he stumbled on HIV research by accident.

“I walked into a lecture by public health officials and thought, ‘Maybe we can help’. That shouldn’t be the case,” he says. Now, the GVN has 34 centres in 30 countries, but a great deal of time is also spent on what Gallo calls “scrubbing around for dimes” – trying to get funding. The GVN needs at least a million or two million dollars per year in order to train more virologists, be more involved in advocacy, and for help and response.

And any last words of wisdom on the epidemic? Yes, he says. “Stop reporting on Mbeki.” Regardless of what he says? Yes, regardless of what he says. “Something is wrong there. It’s hurting. It’s so ridiculous and so bizarre that we can’t even discuss it. There must be someone instead who can say something smart.” DM

Photo: Dr Robert Gallo by Tulane Public Relations via Flickr