The Italian Researcher Working to End the AIDS Epidemic
Massimo Pizzato has spent the last 15 years studying a protein that could neutralise the deadly disease and eventually render it harmless.
This article originally appeared on VICE Italy
When I arrive at CIBIO, the University of Trento's Centre for Integrative Biology, exactly one week has passed since Massimo Pizzato's findings were first published in Nature magazine. A discovery he thought would only be considered important by experts in the scientific field, has now gained the attention of countless media outlets. The lab's phone has been ringing constantly and Pizzato appears to cringe every time it does, as if all those requests for interviews, comments and statements were his own private torture.
"All this attention makes me feel uncomfortable, I don't want to be looked at like I'm all smoke and mirrors," he tells me in a low and measured tone, as I sit in his office – a small room on the second floor of the aseptic, ultra-modern CIBIO headquarters. " Vanity Fair just called," he exclaims. "What can Vanity Fair possibly have to do with all of this?"
Pizzato's research deals with a key challenge in modern medicine: studying HIV and searching for a treatment. Despite a generalised tendency to see it as something belonging to the past, HIV is still a problem: There are nearly 37 million HIV-positive people worldwide. In 2014, an estimated 2 million were newly infected with HIV while 1.2 million died from AIDS. The problem is still far from being solved, even though the availability of treatments to fight and control the rate of infection and the disease's progress have reduced the emergency somewhat.
Can you believe it? I have been studying a protein for 15 years.
Pizzato's research has taken every second of the last 15 years of his professional life, making him shuttle in and out of four countries and two continents – with his only purpose that of thoroughly studying one single protein.
"Right after my PhD I went to Harvard, and that's where I entered this field," he recalls. "There I found people interested in understanding how this specific protein worked in the process of cell infection by HIV. Of course that protein was known to be important but nobody knew why, at the time." After Harvard, Pizzato returned to Italy, where he became a researcher. However, as he rapidly realised, pursuing a career in Italy would mean ditching his research – as there was little funding or interest from most institutions – which was something he wasn't willing to do. So he quit his academic career and started going from one lab to another, from London to Geneva to, finally, Trento in Northern Italy. "In Trento, the research started progressing faster. Here I found a sort of blessed spot, in terms of both funding and freedom. Our situation is very different from the Italian academic world."
In broad terms, Pizzato's findings can be described as follows: the HIV virus is composed, among others, by a protein called Nef—which stands for "Negative factor." For many years the actual role of this protein remained an enigma: when the virus was grown in vitro and deprived of the protein, nothing seemed to change. "But it's highly unlikely that such a small virus, after thousands of years of evolution, generates and carries some useless RNA segment. Nef had to have a function," he explains. "It was discovered, in fact, that in rare cases of patients infected with HIV who did not possess the Nef protein — mostly patients with hemophilia who had received a transfusion of infected blood—symptoms of AIDS were slower than usual to appear, and these people could live up to 15 years without any problem. The only difference was the absence of this protein."
"The aim of my research was to understand why the HIV virus without Nef became unable to infect a cell. In the end, we found that the answer was another protein, called SERINC5. The infectivity is reduced drastically where SERINC5 is present and Nef lacking. Which means that SERINC5 forces the virus to produce an antidote: Nef is the result of an adaptation of the virus to a cellular defense. Indeed, a bunch of other retroviruses did the same thing HIV did, developing different proteins like Nef. Which means SERINC5 is a cellular defense mechanism against retroviruses, a form of defense we were totally unaware of."
By increasing the SERINC5 concentration in the cells, it might be theoretically possible to prevent HIV from infecting them and HIV could in fact become harmless. It seems like we now have a weapon to neutralize HIV, even though we don't really know how this weapon works. To quote Pizzato, "The virus has still won the battle. But what we've done here is understood how it was able to win."
For some reason, we often expect the place where something significant happens to be itself significant. In some way, the CIBIO headquarters meet the expectations. A large university complex committed to scientific research, the building sits on the side of a hill in the countryside, surrounded by vineyards. Once inside, however, the complex is downright ordinary: its hallways are as bare-looking as those of any other Italian university, its laboratories don't differ much from any other laboratory I've been in. It doesn't have any special aura or particular atmosphere – it's simply a place conceived and designed for work and study.
It's not hard to understand why someone like Pizzato feels perfectly at ease in this context. During the three hours I spent with him, the thing that struck me the most was his disarming humility. Being in the spotlight not only made him feel uncomfortable but also nervous. He agrees to be photographed without saying a word, but with just one look you can see he is unsure of the situation. It's like he doesn't consider himself worthy of all this attention.
Pizzato was born and raised in Marostica, a very small town near Vicenza — and his humble roots seem to have contributed to his current persona and made him feel different from or inferior to his peers, especially his colleagues. This could be the reason why he demands so much of himself and is prone to belittle his important breakthrough. When talking about HIV, though, he lights up. His posed, immobile persona starts gesturing, he becomes passionate and even his voice warms. Which might seem odd to someone who knows the full trajectory of his career since HIV research was not actually Pizzato's first choice as a field of study.
"After my PhD, what I was most interested in was the chance to use retroviruses for therapeutic purposes, as vectors for gene therapy – by inserting a gene into a retrovirus you can cure certain conditions. This is the reason that I first started studying retroviruses, but I almost immediately realised our knowledge has not improved enough for this method to succeed, because retroviruses themselves were still a sort of question mark for us." Thus, his interest shifted to how retroviruses can infect organisms, and in particular why HIV is such an epidemic – this shift makes sense and was most likely almost mandatory given that back in the 1990s – when Pizzato was finishing his post doc – the HIV pandemic was in full swing.
"At the time HIV was the problem. Now we don't talk about it that much but a social interest for this matter still exists, and the storm raised by our study confirms it," he says. "And in a sense, the general reaction was a revelation to me, a very positive one. I've been contacted by many people who suffer from this condition, which made me very happy, because it made me understand clearly that what I'm doing has a real impact in real life."
All the passion that this humble scientist has poured into a 15-year-long research project on a tiny protein becomes exceedingly clear to me after hearing the awe in his voice as he says that sentence. He is well aware that, from an external point of view, the time and effort he put into such a specific field of study may seem completely absurd to many people. "Can you believe it? I have been studying a protein for 15 years," he repeats several times, almost incredulous himself.
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The truth is, Pizzato's field of study is so complicated that such a fragmentation is inevitable. Each of his colleagues studies a tiny aspect of HIV, and our knowledge evolves a little every time one of them achieves the tiniest result. This helps to explain why the sensational reaction on the part of the press after the announcement of Pizzato's breakthrough made him feel awkward – even though there are certainly some who would have revelled in all the media attention.
It goes without saying that the pressure to be published in reputable journals and gain attention and recognition is intrinsic to the academic environment, and there's much more at stake than just a scientist's vanity. Scientists' careers and the continued existence of their laboratories depend on it – not to mention their ability to push forward with important work that may not always deliver immediate results.
We walk in silence out through a long, bare corridor, covered with pictures of microorganisms and human body parts. "I have met several geniuses, and that's why I know that I'm not one of them," Pizatto says suddenly. "This is part of the reasons this whole situation seems so absurd to me," he says, referring to his recent rise to fame. I try to argue that most likely our society's idea of genius is just a cliché, and that in most cases results come from dedication and perseverance, rather than some mystical intelligence. But in the end, I don't think he agrees – maybe because beneath all that rational science, he still feels like there was some magic involved.
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