Virolution. Frank Ryan

through rough intercourse, or during the delivery of a baby – and also in the mother’s milk during breast-feeding. The virus finds its way into the blood, from where it discovers its primary host cells, mainly cells involved in the immune system, known as helper T-lymphocytes – the technical term is CD4+ T cells – but it will also multiply in other cells, such as the white blood cells known as macrophages, and in various other tissues and organs of the body, especially the testes. After entering the T-lymphocyte, the virus uses its own enzyme, reverse transcriptase, to convert its viral RNA genes to the equivalent DNA genes, and then it inserts its entire genome, in this DNA form, into the chromosomes of the lymphocyte. This process, which is typical of all retroviruses, was discovered by the Nobel Laureate, Howard Temin, who called this DNA form of the virus the “provirus”, which also includes the dynamo regulatory regions known as LTRs. It stays in the chromosomes for the lifetime of the infected cell, and is reproduced within the chromosomes every time the infected cell divides to form daughter cell offspring.

      Here, in the chromosomes of the lymphocyte, the provirus acts as the template for the production of daughter viruses, which emerge from the lymphocyte cell fully competent to spread to other cells, and through the bloodstream, to the organs of reproduction, from where the virus spreads, through mating, to infect other individuals. In actuality, there are several different strains of HIV-1, which follow different patterns of invasion – if you like, different patterns of behaviour in relation to their hosts. The latter explains much of the early bigotry and confusion, such as we read in And the Band Played On, since the strain usually seen in America and Western Europe is spread in the main by homosexual intercourse and contaminated needles and syringes, and through blood products, offering an easy platform for prejudice, while the much greater epidemics in Africa, and increasingly in Asia, are caused by strains that spread in the main through heterosexual intercourse and the various mother-to-child mechanisms.

      I’m afraid that there is nothing judgemental or moralistic in the arrival of a plague such as AIDS. Like all viruses, HIV-1 is essentially amoral. We now recognise many similar immunodeficiency viruses in nature – indeed, I will present evidence for numerous such viral epidemics during our own human evolution – and the preferred, and usual, route of spread is through heterosexual intercourse. The proclivity towards homosexual friendships, and spread through needles, blood products and syringes, merely reflects opportunism, the western strain of the virus responding to the fact that there were new evolutionary avenues to be exploited. If any societal lesson is to be learnt from AIDS, it is that it was inappropriate to apply human notions of morality or behaviour to plague viruses.

      Even today, despite the billions that worried governments have thrown at it, the disease remains incurable, though the sufferer’s life can be greatly improved and prolonged by anti-viral therapy, and most of the terrible secondary infections can now be prevented. By now perhaps 30 million people worldwide have died from AIDS, and yet still, in 2007, the United Nations estimated that another 30 million people were currently infected, more than 2 million of whom were children. In another projection, published a year earlier, the UN predicted that HIV would infect 90 million people in Africa alone, resulting in as many as 18 million orphans.

      Why, we might wonder, has a disease caused by such a simple entity as a virus, its genome amounting to no more than three genetic domains encoding perhaps the equivalent of ten genes, proved such a terrible adversary?

      In my view, the answer is simple: the AIDS pandemic is an evolutionary phenomenon. And evolutionary phenomena can be exceedingly hard to stop. That long history of similar invasion of the animal lineage by similar retroviruses is likely to be significant. It means that the retroviruses have a long evolutionary experience, with highly adapted behavioural patterns, so that when the AIDS viruses first encountered humanity, they were pre-evolved to behave exactly as they did. In this sense the pandemic in humans, if not exactly predictable, might at least be seen as potentially unsurprising. And while some might find this statement outrageous, I shall endeavour to defend it.

      Viruses are very small, on average a thousand times smaller than bacteria. From the genetic perspective, they are relatively simple. But this should not seduce us into underestimating viruses in their biological roles, which, as we shall see, extend in a very important way to evolution. How then might we explore this important evolutionary perspective? Perhaps it would be a good idea to examine exactly where viruses such as HIV-1 and HIV-2 came from.

      In 1995, an article published some eight years previously in Scientific American – amid the full sound and fury of the emerging AIDS pandemic – caught my attention. The authors were Professor Max Essex, head of the department of cancer biology and chairman of the Harvard AIDS Institute, and his doctorate student, Phyllis J Kanki.² The title of the paper was “The origins of the AIDS virus”. If the title were not sufficiently intriguing, there was a subtitle that began with the words, “The AIDS virus is not unique”. As the subtitle and the body of the text went on to explain, the now notorious HIV-1 had relatives in people as well as rainforest monkeys and apes. Most provocative of all, studies by Essex and his co-workers indicated that some of these related retroviruses had arrived at an evolutionary accommodation that enabled them to live in a disease-free coexistence with their animal hosts.

      What could cause viruses as terrifying as HIV-1 to change behaviour to this remarkable extent? This was a question guaranteed to fascinate me, so I made contact with Professor Essex, who was kind enough to agree to an interview with me.

      By the spring of 1995, having digested the thinking of Terry Yates and Joshua Lederberg, and having interviewed many other leading virologists in the UK and Europe, from fields as diverse as botany, zoology and molecular biology, I was close to assembling what amounted to a jigsaw of understanding that came from adding the stories and views of these many experts into a single picture. By this stage I believed that our medical approach to the problem was inevitably skewed by our vocational, if entirely natural, concerns for humanity. Viruses had no such concerns. Thus, if I were to search for the evolutionary explanation for the emergence of plagues such as AIDS, I would have to abandon such vocational thinking, however deeply ingrained, and adopt a neutral stance that for me, as a doctor, felt curiously alien. I was obliged to ask myself this question: Is something very important going on in the world of plague viruses, something profound, which, if we could only grasp and define it, would give us a radically different perspective – a new level of understanding? So it was that, in February 1995, I made arrangements to return to America, where I planned to visit other experts at Harvard and Yale, and where I hoped to interview Essex among those based at Harvard. Unfortunately he was flying out of the country during the few weeks I would be in America, so I arranged a preliminary interview by phone two days before leaving England, to be followed up by a face-to-face meeting in the hustle and bustle of Washington National Airport.

      Given my own earlier researches on the immune response to blood-borne viruses, I was very much looking forward to the prospect of talking to an investigator who shared my interest in immunity, and who had been a pioneer in linking animal and human retroviruses to the arrival of AIDS, and to the devastation of the immune system that gave rise to so many of its key symptoms and problems. During those heady years of fear and confusion, when AIDS was first challenging the world of medicine, he had also been one of the first to point to a retrovirus as the likely cause.

      ‘Why,’ I asked him, ‘had he become so involved with viruses?’

      In fact, as he now explained to me, he had entered into a career in Veterinary Medicine because he was interested in viruses as a possible cause of chronic diseases, and cancer in particular. ‘At the time I was training, which was in the late 1960s, it was already clear that some forms of naturally occurring cancer were caused by viruses in animals, but it wasn’t yet clear in people, and there was debate about whether it would turn out to be true in people.’

      We talked for a few more minutes about his earliest research, on diseases caused by retroviruses.

      ‘Two or three viruses were discovered in our laboratory during the time I was there, in either cats or monkeys, and it made a very solid case that long-term retroviruses – because they happened to be retroviruses – really could cause chronic diseases, such as leukaemias and certain other cancers. But then, as we were studying those parameters, we