AIDS
HIV - A necessary factor but not a sufficient explanation?

By Beverly Griffin

Nov. 1991

One crucial and fundamental principle seems to have got lost in the debate that has followed the announcement on American television in 1984 - by Margaret Heckler, the then Secretary of Health and Human Services - that an American scientist, Dr. Robert Gallo, had discovered the virus which causes AIDS. This principle underlies the very basic philosophy that governs science and says, "does the experiment which suggests an answer actually prove it, or can there be some (still-hidden) alternative solution? How solid are the data, how solid the interpretation?" Almost as if driven by a whirlwind, the key question in the HIV/AIDS saga soon became not "how certain are we about the sole causative role of this virus in a syndrome that may represent not one, but a multiplicity of diseases" but rather, "who first discovered the virus and to whom should the credit go"? This question rapidly degenerated from a debate into a petty squabble over priorities, where the weight of evidence - scientific, journalistic, judicial - now appears to support the claims of the protagonist, the French virologist, Dr. Luc Montagnier. In this fight, for that is what it became, one clear loser has been science itself. TIME magazine had an article on this subject which stated boldly that the general public has become disillusioned by the antics of scientists and questions even the motives of many of us, and whether we should continue to be funded from the public purse.

Scientists themselves are concerned over laboratory implications that have arisen regarding the isolation of HIV, where it would now appear that the more virulent strain isolated by Montagnier was reisolated in the Gallo laboratory and in another laboratory not so far from the Lancet office, and in each case was initially claimed to be independent, new viral isolates. This violates another basic principle of science, that is, the strict requirement for careful, accurate experimentation and continuous monitoring for errors due to the "human factor". In neither case mentioned can either adequate stringent experimental precautions or control have been exercised. Speed, often the enemy of science, seems to have prevailed, and the ultimate loser is once again science itself.

The final - one hopes not fatal - nail in the scientific coffin in this perturbed field has come from an irresponsible misuse of statistics. By 1985, a consultant venereologist in the UK, with few facts in hand, made the bold statement that the Aids (AIDS) virus could produce a self-sustaining epidemic and lead to a pandemic throughout the cities and villages of the third world. The terms AIDS and the virus (now HIV) were already by then being used indistinguishably. Based on government figures, the Royal College of Nursing published a report that said there could be one million AIDS sufferers (in the UK) by 1991. Similar use was made of the same figures by a London clinician to say that the 118 known cases of AIDS in Britain (in 1985) could be expected to rise to 1500 by the end of 1986. By extrapolation, this would produce the "million figure by 1991". The Polish government appointed an army general to head a task force to combat the killer disease.

Here a digression is motivated, because the appropriation of the data, leading in this case to an unprecedented level of apprehension in our age, resulted in "predictions" that fortunately have not yet been fulfilled. A hundred years ago (1883), Mark Twain described the hazards of extrapolation in his book "Life on the Mississippi". Taking statistics on changes in the length of the Mississippi River observed to occur with time he stated "Now, if I wanted to be one of those ponderous scientific people and 'let on' to prove what had occurred in the remote past by what had occurred in a given time in the recent past, or what will occur in the far future by what has occurred in late times, what an opportunity is here". Using the available figures, he wrote " ...just a million years ago next November, the lower Mississippi River was (or would have been) upwards of one million three hundred thousand miles long and by the same token, seven hundred and forty-two years from now will be only a mile and three quarters long, and Cairo (Illinois) and New Orleans will have joined their streets together." Twain's cynical denouncement was that, "There is something fascinating about science. One gets such wholesale returns of conjecture out of such a trifling investment of facts." In the case of HIV and AIDS, statistics have not been treated with caution either.

Does anyone remember the more conservative, responsible voices from 1985? From two London microbiologists: "It would be irresponsible to produce guidance (on AIDS) until an infectious microorganism is identified; the means by which it causes disease are understood; the risk groups identified; the routes of transmission within and outside these special groups discovered, and effective means of limiting these factors are found. It is only now becoming obvious that infection with the virus does not usually give rise to Aids (AIDS) - when it does, and when it does not, have yet to be clarified." From a haematologist: "The tragedy of a new and generally fatal disease affecting mainly young adults must not be minimised, but the epidemiology of the disease, as so far defined, seems to be very different from that of the plagues of the Middle Ages and it is important to keep the risk factors in perspective." From a German virologist: "There is no evidence that it (AIDS) is spread through casual contact with an infected person. It is primarily a sexually transmitted disease."

Since 1985, the dominant voices have been those that categorically define HIV as "the AIDS virus" with only scant evidence behind them. In a talk delivered to the 636th meeting of the Biochemical Society (UK) by Montagnier in 1990, two statements stand out from the first paragraph of the text. One, "the AIDS epidemic continues to spread at a serious pace." Does it? What are the figures? The second, "AIDS is caused by a virus and, like other viral diseases, it is transmissible." It is obvious that direct experiments cannot be carried out with HIV, but in the absence of a good animal model, how is the latter statement defended? The point is, it apparently doesn't have to be defended. The assumption was made in 1984 that HIV caused AIDS and this has scarcely been challenged since. Montagnier's statement was chosen here, but hardly a day passes when one does not read the words "the AIDS virus", meaning HIV, in reputable scientific journals or, by all means, the press, where "it sells more papers than bingo."

What is the other side of the coin? Well, Peter Duesberg, a retrovirologist, has argued lucidly since 1987 that the available data support no causative role for HIV in AIDS. Were the subject not so emotive, or defended so strongly by certain pressure groups and vested interest, he might have hoped to receive a sympathetic hearing, at least from his scientific peers. The question seems an open one. Duesberg could be totally wrong, or possibly correct. However, there is a compromise which would say he could be partly wrong and partly right. HIV may play a role in the diseases we call AIDS but not such an important one as has been foisted upon it. That is the voice of caution expressed in 1985 in the three statements quoted above. That is also the voice of a group of scientists and concerned individuals, mainly from the USA, who recently submitted an open, signed letter to the well-known American and UK journals, Science and Nature, saying: "It is widely believed by the general public that a retrovirus called HIV causes the group of diseases called AIDS. Many biomedical scientists now question this hypothesis. We propose that a thorough reappraisal of the existing evidence for and against this hypothesis be conducted by a suitable independent group. We further propose that critical epidemiological studies be devised and undertaken."

In steadfastly maintaining his position, Duesberg and his standing as a scientist have been undermined, and in Nature he was pilloried in an article to which he was allowed only limited reply. That scarcely seems "cricket" but this is not the issue. If he is totally wrong, he may deserve some of the criticism that has been heaped upon him, but the point is, we don't really know if HIV causes AIDS, nor have we really seriously tried to find out. There are alternative explanations for the frequency of AIDS observed in haemophiliacs who received HIV-contaminated blood, or the Romanian orphans where "virtually all children in this exposure group had histories of numerous admissions to hospital and had received many intramuscular injections before being diagnosed as having AIDS." If a detailed study of bovine viruses in fetal bovine serum (used in cell culture) has produced a list consisting of parainfluenza type 3-like virus, bovine herpesvirus-1, bovine enterovirus type 4, bovine diarrhoea virus, bovine papova virus, etc, how little do we know about what viruses, or other pathogens, might be transmitted by injection with human blood, or vaccines produced from cells that have been propagated in tissue culture in the presence of bovine serum? Recently, even Montagnier himself has been hedging his bets in reporting that Mycoplasma, a common microorganism in tissue culture material, could be involved in the aetiology of AIDS.

The signs are that things are changing. Maybe in 1992 it won't be totally heretical to query, rather than assume, the direct casual relationship between HIV and AIDS. An article in Science this year, analyzing the data, says that the infection rate of HIV (in the USA) which grew rapidly in the early 1980s, peaked in the mid- 1980s and has subsequently declined markedly. If HIV is indeed the causative agent for AIDS, then the disease should also decline in a noticeable way over the next few years. Thus, some answers may be automatically forthcoming.

The weakness in the diagnosis of HIV infection has always been a problem. It is indirect and what is measured is not, as desired, presence of the virus itself or viral antigens, but antibodies to HIV that is, the response to the provocation, not the provocation itself. Recent data from the PHLS Virus Reference Laboratory in the UK (in Lancet) have proved particularly disturbing in suggesting that the current commercial tests have been made so sensitive that false positive results are easily obtained. In arriving at meaningful conclusions about the role of HIV in AIDS, it is obvious that the testing procedures themselves must be critically assessed. Arising from this method of virus analysis, the reports from two separate investigations over the past few months have produced in themselves sufficient cause for concern to stimulate a "rethink" on the role of the virus in the disease. One of them concerns the UK vaccine trials where, working with the simian equivalent (SIV) of HIV, when the control experiment was eventually carried out, both SIV-infected human T-cells, and uninfected control cells, produced high levels of antibodies to what had been hitherto considered viral-specific antigens. This was an unexpected, startling finding. In similar experiments, two Canadian scientists found that mice which had not been exposed to HIV, but had been exposed to T-cells from another strain of mice, made antibodies to two antigens thought to be specific to HIV. According to a report in New Scientist, the proponents of the virus causal role say that none of the new research questions the link between HIV and AIDS, but rather raises questions about how the virus causes the disease. This pushes the new data hard. One could argue that because of the nature of the assay used, many AIDS patients, past and present, could even be HIVnegative. Do we know?

AIDS is with us. It is a tragic and thought-provoking disease. It creates moral, legal and medical problems. When it hits the innocent, or the specially talented and thus newsworthy, it affects all of us. It may be that HIV infection is crucial to the disease, either directly causing it, by expression of a viral gene, or generating a lethal immune response. It could also be acting as a principal cofactor, together with other, as yet not convincingly identified agents, perhaps by an immunosuppressive route. It may be only a marker, not a cause of disease. What is patently obvious is that we urgently require a better assay for the presence and expression of the virus than we have at present. We need to gather meaningful statistics on the numbers of AIDS patients, particularly in Africa, and not confuse the term HIV, or antibodies to it, with AIDS. We need to direct some of the vast sums of money being spent on HIV research to answering the question raised by middle-of-the-roaders (not all of whom can be branded as "flat-earthers"), does HIV cause AIDS? If not, we need to pursue alternatives with haste. *

Beverly E. Griffin is Director of the Department of Virology, at the Royal Postgraduate Medical School, Hammersmith Hospital, in London.