|Year : 2006 | Volume
| Issue : 1 | Page : 5-10
The origin of HIV and AIDS: An enigma of evolution
Sarosh M Katrak
Emeritus Professor, Grant Medical College & Sir JJ Group of Hospitals and Consultant Neurologist, Jaslok Hospital & Research Centre, Mumbai, India
Sarosh M Katrak
Department of Neurology, Jaslok Hospital and Research Center, 15 Dr. G Deshmukh Marg, Mumbai 400026
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Katrak SM. The origin of HIV and AIDS: An enigma of evolution. Ann Indian Acad Neurol 2006;9:5-10
The AIDS epidemic officially began on the 5th of June 1981. On that day Gottlieb et al. published the first report titled "Pneumocystis Pneumonia - Los Angeles". In late 1983, Professor Luc Montagnier and his team at the Pasteur Institute, Paris, discovered the virus and called it lymphadenopathy associated virus - LAV. Nearly a year later, Professor Robert Gallo and his team from NIH discovered the same virus and called it Human T-cell lymphotropic virus - HTLV III and claimed to be the discoverer of human immunodeficiency virus (HIV). This resulted in a bitter controversy between the French and the NIH group. In March 1987, this controversy was resolved when the US President Ronald Reagan and the French Prime Minister Jacques Chirac announced Luc Montagnier and Robert Gallo as the co-discoverers of the HIV.
Gaetan Dugas, a French Canadian air steward, was born in February 1953. It is reported that he entered Toronto gay scene in 1971 or 1972. It was assumed from several reports that he had 250 partners per year for the next decade and was the first person to introduce HIV in USA from elsewhere. In December 1979, he developed lymphadenopathy, in 1980 Kaposi sarcoma and full blown AIDS in 1981. He died in March 1984 and was posthumously called patient "O" but mistakenly this was interpreted as patient zero in the cluster study.
The AIDS pandemic began in India in the mid 1980s. In 1986, 12 commercial sex workers (CSW) tested HIV positive in Madras (Chennai). UNAIDS - 2004 report on global AIDS epidemic report that there were 5.1 million people around the world living with HIV in 2003 and this has increased to 5.134 million in 2004. In the state of Tamil Nadu, which has the highest prevalence rate of HIV, 50% of CSWs have tested HIV positive and the prevalence of HIV positivity among IV drug users (IVDU) had risen from 26% in year 2000 to 64% in the year 2003. Hence, the epidemic is still not under control in India.
I saw my first patient with neurological complications of HIV in the year 1991 [Figure - 1]. In mid-1991, he presented with chronic inflammatory demyelinating polyneuropathy (CIDP) in a facio-scapulo-humeral distribution. Early in 1992, he developed cardiomyopathy followed by cardio-embolic right hemiplegia, pulmonary tuberculosis, constant diarrhea, severe weight loss and cachexia. This resembled SLIMS about which I will elaborate later in the oration. In the 1990s, I became interested in the neurological complications of AIDS [Table - 1]. This interest resulted in the publication of two major works., It is during this phase of my work that I got interested in the origin of HIV. The more I read, the more I realized that the origin of the HIV is controversial and that this controversy is not yet resolved. Hence, the title of my talk - an enigma of evolution.
AIDS in the pre-epidemic era
Any theory about the origin of AIDS would have to account for the cases of AIDS in the pre-epidemic era. There are many such cases but I would like to highlight two of the earliest cases of HIV and AIDS . In 1985, researchers started testing blood samples from Congo. These samples were collected by a Belgian and an American doctor who were investigating genetic differences in ethnic groups in Central Africa. Using four different procedures they found only one sample was positive. This sample known as ZR59, was taken from an unidentified African male in the area around Leopoldville (present day Kinshasa, Democratic Republic of Congo) as early as 1959. The second case is that of David Carr, also known as the Manchester sailor. He was a British printer who served in the Royal Navy in the 1950s. In 1958, he was struck by a mysterious illness which had many characteristics of immunodeficiency. He had a pneumocystic carinii pneumonia and evidence of cytomegalovirus infection at various sites. He rapidly deteriorated and died in 1959. A post mortem was performed and his treating doctors, Drs William and Stretton together with their pathologist Dr Leonard published their findings in 1960. Drs Leonard and Stretton had preserved 50 tissue samples and when they read the initial accounts of AIDS they got these samples tested for HIV. All these samples tested positive. This makes David Carr, the earliest known case of AIDS, apparently contracting it several years before "the Man from Leopoldville".
There are six theories of the origin of AIDS.
1. The Heavenly Theory
2. Conspiracy Theory
3. The contaminated oral polio vaccine (OPV) theory
4. The cut hunter theory
5. The contaminated needle theory and
6. The colonialism theory
The first two need not be considered seriously. Many religious groups believe that HIV came from an angry God who was unhappy with gays, IVDUs and promiscuity. There are others who believed that HIV came as a Cosmic debris as part of the tail of a comet - the Heavenly theory. Many believe that HIV was developed by the US army as a weapon of germ warfare, whereas right wing American groups blamed the Soviets for the AIDS epidemic - the Conspiracy theory.
The contaminated OPV theory
Contaminated OPV theory is the most controversial and also the most thought provoking theory. The lead player in this theory was Edward Hooper. This former BBC correspondent had lived in Africa for nearly 5 years between 1981 and 1986. He worked in various capacities as a backpacker, teacher, store keeper, etc. In August 1986 while in Kampala, he heard reports that hundreds of people were dying in the village of Kasensero on the western shores of Lake Victoria, of a mysterious disease which many medical experts believed could be AIDS. He travelled to that village and had a meeting under the only tall tree with the village elders. This mysterious illness involved cough, fever, ulcers in the mouth, sores and constant diarrhea. One common factor was that all of them became thin and shrunken and, therefore, it was called SLIMS - very reminiscent of my first patient [Figure - 1]. Hooper recalled "I still look back on that day with a mixture of sadness and horror". When the village elders were asked how they got the disease, he was told that it was brought by Tanzanian soldiers, traders and women who came to sell their bodies.
The scenario then shifts to the United States. The WABC program "Natural Living with Gary Null" was a radio program in which far out ideas were described. On 31st May 1987, Eva Lee Snead, a San Antonio physician claimed that OPV was contaminated with simian immunodeficiency virus (SIV) from the African "Green Monkey" and that this started the AIDS epidemic. The program was heard by Louis Pascal, a reclusive New Yorker and a nonmedical person who had written a single essay in philosophy anthology. He decided to research this theory. Pascal poured over scientific journals until he was convinced that the kidneys of chimpanzees (and not African Green Monkeys as suggested by Dr. Snead) used for the production of OPV in the campaign against polio in 1950 in Central Africa, were contaminated by a SIV - SV40, which in the 50's was still an undetected virus. The OPV was developed by an acclaimed virologist, Hilary Koprowski, Director of the Wistar Institute in Philadelphia. Pascal also emphasized that there is a link between the vaccination sites and the earliest cases of AIDS in Africa. He carefully drafted out an article and tried to publish it in journals like Lancet, Nature and New Scientist. All he got from the scientific community was rejection or silence. After 5 frustrating years the University of Wollongong, NSW, Australia, published his article in December 1991. Not surprisingly, few noticed it. The title of the article was also interesting: "What happens when science goes bad. The corruption of science and the origin of AIDS - a study in spontaneous generation". In order to understand the further sequence of events, it becomes important to understand a few facts about the genesis of polio vaccine.
In August 1921, the US President Franklin D. Roosevelt was stricken with "infantile paralysis". This started his courageous efforts to eradicate polio. A national foundation for infantile paralysis - NFIP was founded in 1938 and was headed by his long time friend Basil O'Connor. O'Connor started the March of Dimes which raised US$ 25 million per year for two decades. NFIP funded Jonas Salk - Director of Viral Research Laboratory, University of Pittsburg. Inactivated polio vaccine (IPV) had to be injected and thousands of children received this vaccination. On 26th April 1955 - five children injected with IPV developed polio in the same limb that had received the injection - this was called the "Cutter" incidence and shifted the attention from IPV to OPV. The lead players in OPV were Hilary Koprowski and Albert Sabin from University of Cincinnati and Herald Cox from Lederle Laboratories. On 27th February 1950, Koprowski became the first scientist in the world to administer OPV to a human being. In order to get an edge over the others, he started an experimental camp in Lindi, near Stanleyville, Belgian Congo (now Kisengani, Democratic Republic of Congo) to harvest chimpanzee kidneys. These kidneys were used to make an OPV called CHAT. Between 1957 and 1960, this CHAT vaccine was administered to an estimated 300,000 people in the former Belgian colony, now encompassing the Democratic Republic of Congo, Rwanda and Burundi.
The theory of contaminated OPV would have died a silent death were it not resurrected by certain events. On 12th March 1992, Tom Curtis a free lance writer from Texas wrote an article in a magazine, Rolling Stones, outlining a theory about the AIDS epidemic. It was essentially the same hypothesis as described by Louis Pascal in 1987 - five years earlier. Unlike Pascal's article, this one drew widespread attention through a major wire service. Koprowski was furious at the wildest of lay speculations. However, when interviewed by Curtis he could not recall or find documentary evidence as to whether his group at Wistar had used African green monkey, Asian macaque or chimpanzee kidney cells. Wistar Institute appointed a panel of experts who presented their findings in an eight page report, not in a scientific journal but at a press conference in October 1992. This report exonerated the CHAT vaccine. Promptly, Koprowski and Wistar sued Tom Curtis and the Rolling Stone magazine for defamation. The matter was settled out of court when the latter issued a clarification stating "it was never intended to suggest that there was scientific proof that the vaccine caused AIDS".,
In June 1992, Hooper read Curtis' article and was convinced about the contaminated OPV theory. He pursued this theory with increased vigor and became its most ardent supporter. He contacted Curtis and Pascal and got all their research data. Through his research on the polio vaccine, he came across the name of Professor William Hamilton. Professor Hamilton was an evolutionary biologist who had won many prestigious awards. He was fascinated by the evolutionary aspects of AIDS and intrigued by the contaminated OPV theory. He felt that the Wistar panel's report was "scientifically weak" and at best preliminary. However, what bothered him most was the scientific community's rejection of the contaminated OPV theory and refusal of scientific journals to publish Pascal's work. He had already written several letters to journals but most of them were unpublished and, therefore, he encouraged and guided Hooper to pursue his research.
For the next seven years, Hooper tenaciously researched the contaminated OPV theory. In his pursuit, he taught himself molecular biology, virology, primatology and other disciplines. His research began in 1986 and culminated in a 1070 page book called "The River - a journey back to the source of HIV and AIDS" published in December 1999. He reviewed thousands of pages of medical records, scientific papers and government documents, conducted more than 600 interviews, at times with hostile people, who called him "obstinate, over zealous and belligerent". Still as one of his detractors said, "he is without question, an earnest man consumed by a mystery of undeniable import". In this book, he gives compelling circumstantial evidence that CHAT was contaminated with SIV and caused the AIDS epidemic. He showed that there was a high degree of correspondence between the CHAT vaccinations sites and early evidence of AIDS in Africa. He screened records of HIV positive blood samples collected in Africa before 1981. Forty seven of fifty two samples came from CHAT vaccination sites. All the samples were taken within 100 miles of vaccination sites including the village of Kasensero, where in August 1986 he had first learnt about SLIMS.
The publication of 'The River' sparked off more bitter controversy and vehement rejection from Koprowski and Wistar. Bill Hamilton decided to put an end to this controversy and organized the Royal Society conference on "Origins of HIV and the AIDS epidemic" from September 11-12th, 2000. Hooper's theory came under intense scrutiny. Beatrice Hahn and her group from the University of Alabama, showed that the SIV from 3 West African chimps were clearly related to HIV-1, whereas one from Central Africa (Camp Lindi's chimps) did not correlate with HIV-1. Hence, based on the genetic makeup of one chimpanzee, they felt that the Wistar vaccine was not contaminated by chimpanzee SIV (SIV-cpz). Betty Korber and her group from Los Alamos National Laboratory, used Nirvana, the world's most powerful super computer and traced the origin of HIV-1 (Eve HIV-1) to 1930 with a range from 1910 to 1950. John Beale , a vaccine expert stated that only one viral particle in 10,000 billion could survive the process of heating, freezing, drying and enzyme stripping involved in the manufacturing process. Hooper was unfazed and stoutly defended the theory. The controversy still persists.
The cut hunter theory
The process of viral transfer from animals to humans is known as zoonosis. It is now generally accepted that HIV is a descendant of the SIV because certain strains of SIVs have a homology to HIV-1 and -2. The virulent HIV-1 has its closest counterpart in SIV of the chimpanzees (SIV-cpz) and the more benign HIV-2 in the SIV of the sooty mangabeys (SIV-sm). The basis of this theory is that SIV-cpz and SIV-sm were transferred to humans as a result of these primates being killed and eaten, a practice know as "bushmeat hunting". While being butchered, their blood got into the cuts and wounds of the hunter. These SIVs then adapted to the hunter's body and then over a period of time transformed into HIV-1 or -2. Every time a SIV passed from a chimpanzee to man, it would develop in a slightly different way and produce a slightly different strain. The fact that there are several different early strains of HIV, each with a slightly different genetic makeup, would support this theory. Secondly, in Africa, retroviral zoonosis is still occurring, as postulated in the article by Wolfe et al. Discoveries such as this, have led to a call for an outright ban on bushmeat hunting. The timing of the AIDS epidemic, according to this theory is attributed to urbanization and regional commerce, which facilitated conditions for sexually transmitted diseases. However, the emergence of the AIDS epidemic in the mid-70s could not be explained by this theory alone as bushmeat hunting and hence SIV zoonosis has been going on for centuries.
The contaminated needle theory
The lead role in this theory was played by Preston Marx, a virologist in primate research, who had worked extensively on SIV. During a number of trips in the northern and eastern parts of Sierra Leone, Marx collected blood samples from sooty mangabeys and also from the villagers who hunted the primates. In his laboratory in the United States, he found that the mangabey blood samples tested positive for SIV and that the blood samples from a few of the villagers contained both HIV and SIV genes. He was convinced that retroviral zoonosis must have been going on for centuries but he was not sure of what "kick started" the epidemic of HIV and the timing of the epidemic in the mid-70s.
Now serendipity plays a hand. On a flight from New York to New Orleans, he noticed a passenger reading an article by one of his colleagues in Manhattan. The passenger, Ernest Drucker, was a professor at New York's Albert Einstein College of Medicine, who told Marx that he had been studying the role of unsterile needles in the upsurge of AIDS among heroin users in Asia, South America and West Africa. Marx was captivated by this theory and felt that retroviral zoonosis and the re-use of unsterile needles, as practiced in Africa in the mid-50s could have spread HIV from person to person and ignited the epidemic. Hence, he proposed the theory of serial passage.
The theory of serial passage
The process of serial passage commences when a person exposed to SIV, through retroviral zoonosis, receives an injection. When the same needle is used to inject another individual, the SIV gets transferred and infects the second person. This person then receives another injection with a new needle which is re-used on a third patient. This procedure gets repeated and with each passage the SIV adapts and grows stronger to the human immune system. The virus is thus serially passaged through several persons by contaminated needles and this process eventually transforms the benign SIV into the virulent HIV. This transformed HIV is virulent enough to be transmitted through sexual contact and thus started an epidemic.
The history of the hypodermic syringe and needle in Africa bears testimony to this theory. Post World War II, penicillin was introduced as an antibiotic. In 1943, 21 million units, were produced which increased to 120 million units in 1949. In the 1950s, WHO and other agencies launched massive health programs in Africa. Poverty and limited resources compelled the re-use of syringe and needles. In the years 1917-1919, six syringes were used to vaccinate 90,000 people. From 1952 to 1957, the UNICEF campaign against yaws used 12 million injections of penicillin in Central Africa. The data from the Bulletin of the WHO - 2000, shows that between 20 and 60% of primary health centers in some of the poorer countries of Africa still use unsterile needles. The use of unsterile needles exponentially increased the opportunity for serial human passaging of SIV and "kick started" the benign SIV into "overdrive" and generated the virulent HIV. Marx demonstrated experimentally that the SIV became 1000 times more pathogenic when serially passaged through just three monkeys. This theory is less flawed than the contaminated OPV and the cut hunter theories. The only explanation it lacked was the latent interval between the use of unsterile needles and the emergence of the HIV epidemic.
The colonialism theory
The colonialism theory is based on the cut hunter theory premise but is more thorough and specific. Joseph Conrads' novel regarding the colonial rule in Belgian Congo, "Heart of Darkness", was as much fact as fiction and described the horror of the official policies in the Congo. The Belgian colonial rule under King Leopold was very harsh and cruel. It is estimated that more Africans died as a result of colonial practice in French Equatorial Africa and Belgian Congo between 1880 and onset of World War II, then had been taken from Africa as slaves in the preceding 400 years. The first census in 1920s estimated that the population in the two colonies, at that stage was 15 million. Census recorders reported that about another 15 million had died in the preceding two decades. A fatality of 50% far exceeds even the 35% fatality rate of the plague in Europe. The state of the colonies was such that they had a poor diet, poor sanitation and exhausting labor demands. The well meaning but ill equipped doctors, trying to protect workers from various rampant diseases, faced an uphill task. Re-use of syringes and unsterile needles was rampant and to appease the laborers, sex workers were officially encouraged. The transfer of pathogens under such circumstances was inevitable.
This theory which is a combination of the cut hunter and contaminated needle theory was proposed by Jim Moore, an anthropologist, together with two of his postgraduate students, Amit Chitnis and Diana Rawls. The harsh colonial rule with all its ramifications, expedited the "serial passage" of SIV through humans and "evolved" the virulent HIV. This theory, like the contaminated needle theory, does not explain the delay of decades between the origin of HIV in the1930s and the widespread epidemic of AIDS starting in the late 50s. However, as Jim Moore argues, did the epidemic explode or did it start as a trickle of one case and doubling in frequency every one to two years? This would require at least a decade for prevalence to build up appreciably to be recognized as a new syndrome. Would overworked colonial doctors be able to pick up this new syndrome amongst all the common infections existing there? "Maybe, the long delay is only an artifact of our perception" reasons Jim Moore.
In conclusion, I would like to state that it is likely that we may never know when and where AIDS actually originated. Scientists become very attached to their pet theories and insist that theirs is the only true answer. Arguments over rival's theories and in defense of their own, have raged continuously and in the case of the contaminated OPV, viciously and at times far beyond the norms of scientific debate. From all the four theories, an obvious general conclusion is that for some puzzling reason, the origin of HIV was not natural. Something spurred the conversion of the benign SIV into the virulent HIV, although humans have been exposed to SIV for thousands of years. It is also worth noting that three out of the four theories involve the inadverant, albeit well intended, medical efforts with what was then the state of the art health program and technology. Lastly, I would like to conclude with the first few lines of the foreword by Professor Bill Hamilton for The River. These words have made a lasting impression on me and I would like to share them with you.
"Every time two people put their heads together, TRUTH suffers; when many put their heads together SHE suffers more... when the heads are great ones and have owners with much to lose (employed in perhaps giant companies or government departments) TRUTH can be made so ill that we should all shiver".
| References|| |
|1.||Centers for Disease Control (CDC). Pneumocystic Pneumonia - Los Angeles. MMWR Morb Mortal Wkly Rep, 1981;30:250-2. |
|2.||Barre-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 1983;220:868-71. [PUBMED] |
|3.||Broder S, Gallo RC. A pathogenic retrovirus (HTLV-III) linked to AIDS. N Engl J Med 1984;311:1292-7. [PUBMED] |
|4.||Hooper E. "A Mysterious Microbe": Early evidence of AIDS in North America. In The River: A Journey Back to the Source of HIV and AIDS. Penguin books, London, UK 1999. p. 67-9. |
|5.||Velhal GD, Bichile SK. Human immunodeficiency virus infection - trends and problems. J Assoc Phys India 1999;47:261-2. [PUBMED] |
|6.||A global overview of the AIDS epidemic. 2004 Report on the global AIDS epidemic. http://www.unaids.org/bangkok 2004. |
|7.||Katrak SM, Shembalkar PK, Bijwe SR, Bhandarkar LD. The clinical, radiological and pathological profile of tuberculous meningitis in patients with and without human immunodeficiency virus infection. J Neurol Sci 2000;181:118-26. [PUBMED] [FULLTEXT]|
|8.||Katrak SM. Neurological manifestations of AIDS. In Neurological Practice - An Indian Perspective. Ed. N. H. Wadia, Elsevier: New Delhi; 2005. p. 52-73. |
|9.||Carlsen W. Quest for the origin of AIDS. Controversial book spurs search for how the worldwide search for the scourge of HIV began. San Francisco Chronicle, Sunday January 14th 2001: p. A1, A14-5. http://www.sfgate.com |
|10.||William G, Stretton TB, Leonard JC. Cytomegalic inclusion disease and Pneumocystis Carinii infection in an adult. Lancet, 1960;2:951-5. |
|11.||Hooper E. Frozen in space: A rural epicenter in Africa. In The River: A Journey Back to the Source of HIV and AIDS. Penguin Books, London, UK. 1999. p. 31-51. |
|12.||Pascal L. What happens when science goes bad. The corruption of science and the origin of AIDS. A study in spontaneous generation. University of Wollongong Science and Technology Research Programme, Working paper no. 9, December 1991, University of Wollongong, NSW 2522, Australia. |
|13.||Hooper E. The race to conquer polio: early research and inactivated polio vaccine. Oral polio vaccine. In The River: A journey Back to the Source of HIV and AIDS. Penguin Books, London, UK. 1999. p. 194-217. |
|14.||Curtis T. The origin of AIDS. Rolling Stones 1992;626:106-8. |
|15.||Hooper E. What happens when science goes bad. In The River: A Journey Back to the Source of HIV and AIDS. Penguin Books, London, UK. 1999. p. 227-35. |
|16.||Hooper E. Correlation with early HIV and AIDS. In The River: A Journey Back to the Source of HIV and AIDS. Penguin Books, London, UK. 1999. p. 740-57. |
|17.||Gao F, Bailes E, Robertson DL, Chen Y, Rodenburg CM, Michael SF, et al. Origin of HIV-I in pan troglodytes. Nature 1999;397:436-41. [PUBMED] [FULLTEXT]|
|18.||Korber B, Muldoon M, Theiler J, Gao F, Gupta R, Lapedes A, et al. Timing the ancestor of the HIV-1 pandemic strains. Science 2000;288:1789-96. [PUBMED] [FULLTEXT]|
|19.||Moore J. The puzzling origin of AIDS. Am Sci 2004;92:540-7. |
|20.||Wolfe ND, Switzer WM, Carr JK, Bhullar VB, et al. Naturally acquired simian retrovirus infections in central African hunters. Lancet 2004;363:932-7. [PUBMED] [FULLTEXT]|
|21.||Dicko M, Oni AQ, Ganivet S, Kone LP, Jacquet B. Safety of immunization injections in Africa: Not simply a problem of logistics. Bull World Health Organ 2000;78:163-9. |
|22.||Marx PA, Alcabes PG, Drucker E. Serial human passage of simian immunodeficiency virus by unsterile injections and the emergence of human immunodeficiency virus in Africa. Phil Trans R Soc Lond B 2001;356:911-20. [PUBMED] [FULLTEXT]|
|23.||Chitnis A, Rawls D, Moore J. Origin of HIV Type 1 in Colonial French Equatorial Africa? AIDS Research and Human Retroviruses. 2000;16:5-8. [PUBMED] [FULLTEXT]|
[Figure - 1]
[Table - 1]
|This article has been cited by|
||Cellular & molecular basis of HIV-associated neuropathogenesis
| ||Sharma, D., Bhattacharya, J. |
| ||Indian Journal of Medical Research. 2009; 129(6): 637-651 |