Red In Tooth And Claw
issue 169 - March 1987
Jungle ethics -
Red in tooth and claw
Nowhere is the 'profit before health' motive more starkly revealed than
in the intense competition between scientists and drug companies to find a
cure for AIDS. This competition, Mark Pownall argues, has hindered research.
And while millions are gained on the stock market on the strength of misleading
rumours, the 'magic bullet' for the AIDS virus remains as elusive as ever.
AIDS is big business. Pharmaceutical and biotechnology companies are gearing up their research and development on anti-AIDS products in the scramble for the jackpot of million-dollar profits which will flood into the coffers of any company developing a successful treatment or vaccine. Arthur Gottlieb, the president of one relatively small company, Imreg inc., has predicted that a successful AIDS treatment could attract between 300,000 and 1,000,000 users in the United States (where the majority of AIDS victims who could afford an expensive treatment live).
Gottlieb points out that an AIDS treatment is likely to be needed for life - making it a long-term money spinner comparable to insulin for diabetics and anti-hypertensive drugs for high blood pressure - currently two of the pharmaceutical industry's biggest profit makers.
Getting on for 50 corporations are now working on AIDS testing kits, anti-AIDS drugs and vaccines against Human Immunodeficiency Virus (HIV) in pursuit of the $1,000 million likely to be spent annually on AIDS products by 1996.
But in the midst of this frenzy of competitive commercial research and development - best guesses are that around 20 different drugs are being tested for the treatment of AIDS but the number is increasing all the time - the truth remains that at present there is no 'cure' for AIDS, nor a hope of one.
Even the best drug currently on offer - azidothymidine (AZT), the much-trumpeted 'AIDS wonder drug' - is unlikely to prove widely effective. No current drug destroys the virus whose mechanism of infection makes it a difficult customer to deal with. AZT acts by blocking an enzyme, reverse transcriptase, which is necessary for viral replication, but infected human cells remain infected.
The companies in the forefront of AIDS research have not been slow to point to 'promising' results of the drugs in early trials. For bullish statements can help boost a company's standing on the international stock exchanges, where the latest wild hopes and rumour affect share prices every bit as much as a scientifically rigorous double-blind placebo-controlled trial (the gold standard doctors use to test the worth of a new drug - see box). Last year alone rumours of promising research results for antibodies to HIV, which causes AIDS, inflated share prices of drug companies by more than $50 million.
It is interesting to note, for example, that the first article to appear about AZT, made by Wellcome, in the British national press was an uncritical account of early trials in The Observer newspaper. The prominent front-page story was written not as might be expected by the newspaper's health correspondent, but by Melvyn Marcus, the newspaper's city editor in charge of covering the finances of private industry. That article, whispered into Marcus's ear by Wellcome sources, did no harm at all to prices of Wellcome's shares.
That story, and others like it, helped boost Wellcome's shares during 1986 by about a third. The spectacular rise - which gives the company a value of about $4,250 million - rides mainly on hopes for AZT. Compared to other British pharmaceutical companies Wellcome is valued at nearly twice what might otherwise be expected.
This neatly illustrates the commercial pressures on the drug industry. One drug - in an extremely early stage of development - can mean massive gains of hundreds of millions of dollars in capital for shareholders. Such gains mean that competition is fierce, and information which could help competitors is, far from being shared openly in medical and scientific journals to advance the search for a fast cure, jealously guarded and kept secret as long as possible.
The competition also means that over-enthusiasm by a company for a drug it is developing can lead to bitter disappointment if rigorous trials prove it is ineffective. There is a conspiracy of optimism which feeds such hopes. The collusion happens between drug companies with their obvious commercial interest in good news about a new drug, scientists and doctors who depend for research grants, publication in prestigious journals and career advancement on positive rather than negative results; and on the media who are only too happy to publicise 'AIDS breakthroughs', but who are less keen to report drug failures.
The public interest in AIDS and the probable reward of a Nobel Prize for the eventual discoverer of an effective treatment or vaccine means it is not just market-geared companies who are competing - it is scientists themselves.
Competition has hampered at least one publicly funded AIDS laboratory. Poor management and lack of direction at the US Centers for Disease Control (CDC) AIDS laboratory in Atlanta, caused dissatisfaction and low morale among researchers there, an investigation reported.
The CDC is one of the premier Government-funded laboratories doing AIDS research in the US, so the report is worth examining in some detail.
In the few months preceding the announcement in October 1986 of the appointment of an independent panel of enquiry into the CDC from the US National Academy of Sciences, seven of 13 scientists in the laboratory doing AIDS research had either left, transferred elsewhere or been fired.
The investigation followed allegations of sabotage of experiments, 'purposeful minor tampering' linked to 'dissatisfaction and distrust'. 'Unusual incidents did in fact occur', the panel reported.
The laboratory was only 'moderately productive'. 'No team spirit has been forged. and the demands of challenging fast-moving AIDS research have generated internal competition rather than uniting individuals', reported the enquiry panel.
The report identified the authorship of scientific papers as one of the main bones of contention at the centre. When a scientist is credited at the top of a paper his standing among other scientists increases. Critics of the Atlanta AIDS lab say that some senior scientists undeservedly received credits for some papers at the expense of others.
Given this intense competition between scientists even within one laboratory, it is hardly surprising that a World Health Organization (WHO) call for open and cooperative research towards an AIDS vaccine has been ignored.
WHO had been hoping to formulate a common way of conducting trials so that results could be evaluated quickly with the best available scientific resources. Clinical trials in Zaire are reported to involve the use of an AIDS vaccine in already infected individuals and are aimed at preventing the development of AIDS itself (only between 30 and 40 per cent of those infected with the virus go on to develop AIDS). Initial safety tests appear not to have been carried out.
According to Dr Jonathan Mann, head of the WHO AIDS programme, secret trials followed by an announcement that company X's vaccine works would be 'a nightmare'. There would then be intense pressure to use the new vaccine. But an inadequate or dangerous vaccine could cause 'tremendous damage'.
The WHO call for co-operation follows efforts by the US Public Health service last year to initiate collaborative research on an AIDS vaccine. But we have still to see whether the drug companies ahead in the vaccine game will allow anyone else a peek at their hand.
If more collaborative research - between countries, between research institutions and between individual scientists - fails to develop, then a 'cure' for AIDS will remain as far off as it is now.
Mark Pownell is a freelance journalist specialising in medical issues. He is a regular contributor to Hospital Doctor magazine.
Suramin looked every inch the 'promising' anti-AIDS drug. The substance had been developed by scientists at the laboratories of the huge West German pharmaceuticals and chemicals plant Bayer and trials had shown that, in the test tube at least, it inhibited replication of the virus and hindered certain properties of the virus that caused it to kill cells.
But trials in actual AIDS patients soon found that the drug produced little improvement. Only one of nearly 100 patients tested in the trial improved - the condition of 70 others actually deteriorated.
The drug also caused toxic side-effects, harming the kidneys, liver and adrenal glands. Clinical trials were abandoned soon after.
The placebo effect - when an inert substance exerts a therapeutic effect - is a powerful medicine, and scientists have developed the placebo-controlled trial to ensure that a new drug has some activity over and above the placebo; the 'dummy pill'.
To avoid the influence of expectations on result neither the doctor nor the person in the trail taking the medicine knows whether a patient is taking the drug on trial or the placebo - the trial is then siad to be 'double-blind'. These trials are the basis on which regulatory authorities like the Food and Drug Administration in the US or the Committee on Safety of Medicines in the UK grant, or do not grant, licenses for drugs.
But this system has come under attack, AIDS, it is suggested, is something else. For example, Theodore Weiss of the US House of Representatives told a Congressional hearing 'There are legitimate concerns about the need to collect valid scientific data in controlled tests, but people with AIDS do not have the luxury of waiting for months to collect treatment in a controlled trial or for the results of those trials.' He called for a easing of restrictions to allow 'compassionate' use of potential AIDS drugs.
At the same hearing one AIDS patient declared: 'It makes no sense to restrict the availability of drugs when a person is terminal.'
Placebo-controlled trials on AZT were halted after it was found to prolong life by a few months in a selected group of patients. A board of scientists declared that further placebo trials with AZT would be unethical - even though research without such trials would proceed more slowly.
Perhaps the best solution is to allow people with AIDS to decide for themselves. Volunteers willing to participate in controlled trials could probably be found - those willing to forgo a possibly beneficial treatment for themselves so that scientific knowledge can advance quickly and other sufferers in the future might benefit.
Resentment simmers between the world's two most prestigious AIDS researchers over who first discovered the virus which causes the disease. In January 183 Professor Luc Montagnier and colleagues at the Pasteur Institute in Paris isolated a virus from a patient with a condition that often precedes AIDS, which he called LAV (lymphadenopathy associated virus). He published a paper on his discovery in May 1983.
A year later Dr Robert Gallo of the US National Cancer Institute published a paper describing an AIDS associated virus Human T-cell Leukaemia Virus (HTLV) which he said, as the Paris team had said, was a third member of the HTLV group of viruses. For this reason Gallo called his virus HTLV-III, a name which the predominately English-speaking scientific world, and later the public, picked up.
LAV and HTLV-III are in fact virtually identical. The French team therefore argue that they were the first to identify the AIDS virus and should be credited with its discovery.
The unseemly squabble is of fundamental concern to the scientists. Priority of publication is part and parcel of the competitive ethos of research at the boundaries of knowledge. Who gets there first - by as little as days or weeks - can decide who gets the resources, and n the end who gets the Nobel prize, science's ultimate accolade.
The dispute concerns more than glorification of the scientists involved, however. The patent rights of AIDS testing kits, and millions of dollars of royalties, go to the team which patents the procedures for isolating the AIDS virus.
The relationship between the two groups has continued to remain sour; a court case over the patent rights and errors about giving due credit to the other's work has made sure of that.