Virolution. Frank Ryan

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Virolution - Frank  Ryan

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paid attention to the disease … the virus was already pandemic to the nation.

      RANDY SHILTS1

      Viruses have caused some of the great epidemics that project like tombstones through the fabric of human history. The quotation above is from the prologue of a book that chronicles the arrival of the AIDS pandemic in America, and the ensuing hue and cry of blame, prejudice, bewilderment, laudable dedication on the part of a few doctors and scientists and heartbreaking failings on the part of some politicians and key institutions, all conspiring to delay or limit the necessary response. It might seem counter-intuitive for me to suggest that even from such a grotesque tragedy we have discovered an important level of enlightenment. But this is speaking with hindsight and few, if any, understood the implications of this new, and utterly alien, organism when it first arrived on American shores in 1978.

      In time we noted how, unlike smallpox, or pandemic influenza, the symptoms of AIDS conspired to mask its very arrival. It came among us stealthily, almost silently: the first entry of the virus into a new victim was all too often unrecognised, causing no more than a mild rash or fever – in half its victims causing no symptoms at all. After invasion, the virus continued to mask its presence, often hiding for years inside the blood cells known as lymphocytes, so that its victims remained none the wiser. Yet, even while hiding, it could be transmitted to other victims, through blood, through other bodily fluids, and particularly through sexual intercourse, heterosexual or homosexual. This parasite, and yes, I do suggest, aggressive symbiotic partner, is devoid of pity or prejudice, embracing all races, all ages from newborn to senility, and either gender. Meanwhile, throughout its period of silent invasion, the virus mutates at an extraordinary speed inside each infected person so that, some two or three years after first infection, the original strain of virus is no longer recognisable amongst the competing swarms of millions of different mutating progeny.

      AIDS shocked society to its very core. Like a shudder come back to haunt us from the nightmares of smallpox and bubonic plague in the history books, it heralded a new face among Bunyan’s Men of Death. This plague was contracted in the main by sex amongst the young, and it was unlike any plague of old in the subtle and sinister way that it directly infected and killed the very immune cells that might best fight it off. Before the modern antiviral treatments, this destruction of the immune cells of the victim allowed all manner of secondary horrors to invade, so people drowned in amoebae, normally inconsequential germs from tap water that invaded their bowels and spread into their internal organs; or strange viruses, such as the cytomegalovirus, hopped a ride in a vicious parody of their normal patterns of infection. The skins of sufferers were showered with purple-bluish cancers. Bizarre forms of leukaemias coursed their bloodstreams. Every surface of their bodies, both skin and internal, was tormented and disfigured by an anguish of afflictions. It was a vision of hell the equal of anything dreamed up in Dante’s Inferno. To make matters even worse, the plague could be passed from a mother to her children, so the horror was handed down, like some nightmarish legacy, to the next generation. This was a particular problem in developing countries, when either one or both parents died, leaving the sick children to be cared for by devastated grandparents, or handed over to ill-equipped orphanages, or abandoned altogether.

      There are two causes of the AIDS pandemic, related retroviruses known as the human immunodeficiency viruses, HIV-1 and HIV-2. Perhaps at this stage I should explain that retroviruses are a large and complex family of viruses, all of which have in common the fact that their genes are made not of DNA, as are all other life forms other than viruses, but of its sister molecule, RNA. The retroviruses infect virtually every animal species, from the simplest of marine invertebrates – such as sea slugs – to primates, including humans. As part of their normal infectious life cycle, they need to inject their viral genes into the nuclei of their hosts, so it is vitally important to understand just how they do so. Retroviruses usually spread through mating, or from mother to baby in a variety of ways. The HIV-1 virus is transferred in the pre-ejaculate male fluid and in the vaginal fluids that help to lubricate normal sexual intercourse, in semen, in blood – for example, through contaminated needles, contaminated blood transfusions, 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

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