AIDS & HIV

A human virus causing human deaths.  Animal experiments have proved a waste.

The spread of AIDS threatens one of the biggest potential epidemics in living memory.  Lives lost to it number over 12 million, including 2 million children. It has revolutionised sexual activity and torn through some social groups with terrifying effects.  Caused by a virus which targets the defence mechanism of the body, HIV and AIDS are claimed to be another area where animal research is vital.  Yet the animal models have failed to replicate the human system, and have been unable to produce any advances, while human study and scientific endeavour has enabled understanding of the illness and attempts to combat it.

How the HIV virus works

The HIV virus targets the part of the human immune system called the 'acquired' immune response.  This comes into effect when foreign bodies start infiltrating cells.  White cells circulate the blood ready to fight infection.  Killer T-cells are organised by helper T-cells to identify and overcome uninvited viruses and bacteria.  This magnificent system learns from experience, and when confronted with a previous opponent recalls the previous methods to defeat it.

HIV brings this incredible defence system to ruin.  The helper T-cells are hijacked by the virus.  New viral material is bred which kills the helper cell as the virus replicates and moves on to new cells.  Hidden inside the helper T-cells, the virus is immune to attack by the body's defence system.  The helper T-cells diminish in number and effectiveness, and the acquired immune system fails.

Human study

Understanding the illness and developing treatments has been possible thanks to the study of humans and the use of scientific techniques.

The helper T-cells vulnerable to attack have a receptor called the CD4 receptor, which enables the HIV virus to attach itself and transfer it's contents into the cell.  Less common HIV strains require other receptors.  Studies on human cultures revealed this and enabled us to build a picture of the progression of the illness [1].  Identifying the nature of the linkage of the HIV virus with the helper T-cell identified a possibility for blocking the virus and therefore a potential for vaccine development [2].  Observing human patients showed HIV infection clustering in the lymph nodes, leading to the discovery that critical parts of the development of AIDS occur in lymphoid tissue [3]

The first HIV medications

Work by Dr David Ho of New York's Aaron Diamond AIDS Research Centre was based on human study.  His team concluded that replication was rapid from the start of infection.  His work persuaded doctors to disregard animal results, which showed slow replication, and start treatment sooner, rather than waiting for symptoms.  Studying the cells outside the body identified three enzymes vital to the replication of HIV. This enabled researchers to target the replication and led to the use of AZT.  Originally a cancer drug, it was found in 1985 to hamper the metabolism of HIV in a test tube experiment.  Patients were rapidly given the drug without animal tests [4].

Drugs to inhibit Protease, one of the three enzymes vital to HIV were designed on computer and tested in human cell culture [5].  They also bypassed animal tests. Reverse transcriptase (another of the vital enzymes) was targeted by numerous drugs developed in an identical manner [6].  Antivirals took a similar path.  A noted primate experimenter admitted animal experiments played no part, and that "...there is no predictive animal model for HIV infection in humans." [7]

Learning from human clinical experience with cancer that attack from several directions was possibly more effective gave suggestions for AIDS therapies.  Mathematical modelling aided the design of these strategies, which proved effective.  Clinical researcher David Ho developed combinations including protease inhibitors with other medications, administered at an early stage in the progression of the disease.  The successes were startling and lead to the establishment of early treatment programmes which prevent progression of HIV to AIDS.  His work, based entirely on human studies and test tube research reduced the risk of death by 62% and the incidence of HIV progressing to AIDS by 73% [8].

More studies of humans have tried to identify why HIV has progressed more quickly in some patients than others and has identified factors. The role of vitamins and minerals, different HIV mutations and the behaviour of them, body chemistry, genetic factors, active proteins, and other factors have been identified, many of which have lead to the development of more contributing treatments.

Failed animal models 

At the same time, research has also been conducted on animals.  At the start of this work, it would have been obvious to most that these monkey-centred experiments were likely to yield nothing and create a wasteful diversion of funding and other resources.  Human studies had provided the advances in our understanding of the intricacies of the human immune system, largely through the observational work of Dr Good in 1952 [9].  Previous work involving monkeys to study a virus had been conducted on polio, which had suffered many setbacks delaying the introduction of the vaccine.  The primate study had wrongly indicated the route of infection to be nasal, which was believed for years until the correct route, via digestion, was identified [10].

No naturally occurring HIV infected primate has ever been discovered. SIV (Simian Immunodefieciency Virus, as opposed to Human Immunodefieciency Virus) has infected primates, but the virus is different.  And as human studies have shown, small differences in the structure of the virus affect significantly its activity and threats. Viruses are known to be specific to each species.  Pigs carry the swine 'flu virus, but humans can die if infected with it.  A child with measles is affected, yet their dog is not at threat, fearing instead canine distemper, a virus which won't affect the humans.  And humans can and do die of AIDS. Monkeys do not.

Still attempts were made to create a monkey model of human AIDS.  HIV has been given to thousands of chimpanzees without AIDS developing, leading to increased doses of the virus being given, with still no development, due to differences in the immune systems of the two species.  A major difference is that chimpanzees have higher incidences of killer T-cells in their blood compared to humans.  Also there are less helpers (the target of the HIV virus) per thousand killer cells than in humans.  This high incidence of killer T-cells provided a strong level of resistance [11]. Humans produce killer T-cells which don't exist in chimps [12]. More defensive antibodies are produced, (and they are produced earlier) by B-lymphocytes in chimps compared with humans [13]. While in humans the HIV virus spreads to the saliva, plasma, and even the cerebral spinal fluid, in chimps it's confined - apparently exclusively - to the white blood cells [14].  Humans infected with HIV often develop cancers, infections, and changes in the central nervous system, while the chimp merely has symptoms similar to 'flu [15].

Research has spread to other monkeys, yet their immune systems have been found to be even more different from ours.  Cats have been said to suffer from a feline equivalent (FIV).  It binds to a different receptor, is transmitted by saliva not sex, and induced FIV does not develop into a deficient immune system [16].

As with all animal-based experiments to study human diseases, HIV research has been hampered by the twin problems of differences in diseases and disparities in the way they are dealt with by the animal in question.  In the case of HIV, the immune system of man is not comparable to any other species, and the virus to which it is compared is dissimilar. One percent differences in viruses are significant in determining the activity of a virus, yet HIV and SIV are considered roughly 60% similar [17].

Criticism of HIV research in animals has come from many angles, and even animal experimenters have been unable to deny it's failure.  A director of Yerkes, one of the largest American research primates centre admitted "I don't see much coming out of the chimp work that has convinced us that that is a particularly useful model." [18] Leading AIDS researcher Dr Mark Feinberg spoke of AIDS vaccine development when he asked: "You find five or six years from now that it works in the monkey, and then you test it in humans and you realise that humans behave totally differently from monkeys, so you've wasted five years." [19]  ACT UP San Francisco, the pressure group fighting for the more action to combat AIDS recognised the failure of vivisection in finding treatments for HIV infection.  In 1995 they agreed by consensus to support a ban on animal based research [20].

Despite these failures, the interests that have made money from vivisection lobby for it's continuation and have succeeded in diverting colossal sums of money from research into self-perpetuating animal projects which at best have been useless.  Meanwhile clinical researchers like Claude Reiss and David Ho conduct dedicated work to make inroads on treatments and hopefully a vaccine.

 

 This is one illness of many that serves as an example of the failure of animal experiments.  See more here.

References

1  Nature, 1984;312:767-8
2 Reuters Feb 4 1998. Nature 1998;393:648-659, 705-711, 830-831. Science 1998;208:1949-1953
3 Nature Medicine, Vol 1 1995, p1320
4 Proc Natl Acad Sci USA 1985;82:7096-7100. Nature Vol 398 p380 1999 & 1987;325:773-778
5 Science 1996;272:1882-3  & 1990;247:454-456. Nature 1987;325:773-8
6 Antimicrobial Agents and chemotherapeutics 1991;35:1386-90. Proc Natl Acad Sci USA 1985;82:7096-7100. Science 1990;248:358-361
7 Michael Wyand, in AIDS research and human retroviruses 1992;8:349-356
8 BMJ 1997;315:1194-1199
9 Dr C Ray Greek & Dr J Swingle Greek "Sacred Cows & Golden Geese" Continuum 2000, p186
10 Flexner, S, Lewis,PA 1910 Journal of Exp Med vol 12 p243. Flexner S, Clark PF 1912-3 Proc Soc Exp Biol Med Vol 10 p1. Paul, JR 1971 A History of Poliomyelitis, Yale University Press p245, p385, Op Citation
11 J Med primatol 1989;18:343-355. Intervirology 1989;30 (suppl 1):51-58. J Virology 1990;64(6):2751-8. Animal Models in AIDS. Amsterdam Elsevier Science Publishing BV, 1990 pp27-40
12 Science 1984;226:549-552. Nature 1991;352:434-436. J Immunology 1990;144(8):2992-2998
13 Intervirology 1989;30(suppl):51-58
14 J Med primatol 1989;18:343-355
15 Antiviral Research 1992;19:81-109. Clinical infectious Diseases 1993;17 (suppl 1):S230-S235. Aids Research Review, New York, Marcel Decker, 1991. FASEB Journal 1989;3:2593-2606
16 Trend in Biotechnology 1995;13:142-150
17 Dr C Ray Greek & Dr J Swingle Greek "Sacred Cows & Golden Geese" Continuum 2000, p192-3
18 The Scientist Vol 13, no16, p7, Aug 16 1999
19 Dr C Ray Greek & Dr J Swingle Greek "Sacred Cows & Golden Geese" Continuum 2000, p183
20 ACT UP Publication April 1997