The New York Times - November 18, 1985
Lawrence K. Altman

Thus far the search has led American research to two African children who in 1963 lived in Upper Volta, now Burkina Faso. On the basis of blood samples that had been frozen and stored since that time, they are believed to have been infected with the AIDS virus or with one similar to it.

This clue and several others have led to what has now emerged as the prevailing thesis in American and European medical circles that the worldwide spread of acquired immune deficiency syndrome began in Central Africa, the home of several other recently recognized diseases.

Disagreement by Africans

The Africans vigorously disagree, and there is some criticism of the validity of the studies on which the theories are predicated. Indeed, controversial new results that point both to and against Africa as the origin of AIDS are fueling the international furor.

The origin is regarded by many as a key factor in the overall search for the cause and cure of AIDS and the prevention of similar epidemics. But a strong stigma seems to have become attached to the origin, in part because of the deadly and insidious nature of the disease and in part because of the taboos associated with practices often found to have caused its transmission.

Some American and European scientists also consider AIDS to be so widespread in Central Africa that they say they doubt it could have been introduced there recently. There is no general agreement among scientists on either side of the Atlantic about whether it is truly new or merely newly recognized.

Virus Mutation Suspected

There are some who feel, however, that AIDS may be a result of a virus mutation, or change, the first such mutation in medical history to have caused a virulent new disease.

These assessments were gathered over the past several weeks from medical meetings and journals and from interviews with more than 50 physicians, scientists and public health officials in Africa, the United States, Canada and Western Europe.

If AIDS is found to be an old but previously undetected disease, doctors need to determine why it suddenly became a worldwide epidemic. But if a virus mutated to create a new disease, and if scientists identify the precipitating factors, they might be able to stop another epidemic like it or even other new ones from breaking out. AIDS is not likely to be the last new disease.

AIDS was first recognized in 1981 in the United States. But if the disease had been detected 15 or more years ago, it might not have been possible for scientists to find the causative virus. They had not yet developed the technology and expertise that led to discoveries that began in France in 1983.

There is widespread belief that it will take at least one year, if not many, for viral historians to provide a firmer understanding of the origin of the disease through molecular-biological tests. Even then, some scientists insist that proof may never be found. Doctors still do not know the origin of the overwhelming majority of human diseases.

But seemingly lost in the controversy is the fact that determining the origins of AIDS could well lead to new medical strategies.

If scientists find that the AIDS virus mutated from an ancestor virus that caused little harm in humans, or is derived from a closely related virus in animals, then a theoretical chance exists that the ancestor virus might be used to develop a vaccine to protect humans. Although inherent risks would have to be overcome, the vaccine might be modeled, for example, on the use of the vaccinia virus from an animal disease, cowpox, to eradicate a human disease, smallpox. As yet, no ancestor has been found.

One theory is that AIDS had long been an undetected disease in a remote area of Africa and then spread when thousands of people moved from rural to urban areas after countries gained their independence. Another is that the AIDS virus's natural home is in an animal, possibly the African green monkey, and that somehow the virus jumped species to infect humans. Knowing the precise location of its origin may help determine whether such animal-to-human transmission occurred.

Clearly no country really wants to learn that it is the original source of AIDS. Health officials in the United States, for example, are reluctant to acknowledge that exports of American blood products may have spread the disease to people elsewhere.

Africans are particularly sensitive about the question. Their countries have been playing a game of geographic buck-passing, with one citing another as the source. In Rwanda and Zambia, many people insisted that AIDS spread from neighboring Zaire. In Uganda, scientists suggest that Slim disease, a local name for AIDS, came from Tanzania.

Generally, however, Africans contend that AIDS originated somewhere else, that it was probably Americans and Europeans who brought it to them. They have repeatedly pointed out in recent weeks their strong feelings that Americans and Europeans who cannot control the AIDS epidemic on their continents are blaming them for an act of nature. They express bitterness about being blamed for a disease they associate with homosexual practices in the United States and Europe. They contend, and most scientists from outside Africa tend to agree, that these practices are uncommon in Africa.

Milimo Punabantu, press secretary to President Kenneth D. Kaunda of Zambia, succinctly expressed this resentment when he called the theories "a propaganda campaign."

"AIDS may have started where you come from," Mr. Punabantu said in denying a request for an interview with Mr. Kaunda about AIDS in Zambia.

In Kenya, President Daniel arap Moi has called foreign news reports about AIDS in Africa "a new form of hate campaign." African doctors, too, argue against the thesis.

In an editorial in the current issue of Medicus, published by the Kenya Medical Association, the editor, Dr. V. A. Orinda, suggested that tourists from abroad introduced AIDS to Africa. Even finding AIDS everywhere in Africa, Dr. Orinda said, "will not necessarily make AIDS an African disease."

"Must there be an African connection for every disease?" Dr. Orinda asked. He was referring to the apparent determinations by scientists that Africa is the origin of three new or newly diagnosed diseases: Lassa fever, Marburg virus disease and Ebola virus infection. No one knows how long these diseases have existed there.

Dr. A. J. Clayton, a Canadian public health official, and some other experts contend that the world has not really seen the birth of a new disease in the past 1,000 years, though all agree that genuinely new ones are in any case rare.

Leading AIDS researchers such as Dr. Robert Gallo of the National Cancer Institute in Bethesda, Md., and Dr. William A. Haseltine of Harvard Medical School and the Dana-Farber Cancer Institute in Boston argue strongly that AIDS began in Africa.

Dr. Gallo has written that other members of the retrovirus family to which the AIDS virus belongs originated in Africa. Retroviruses are so named because they reverse some normal cell-construction processes. He said he "could not conceive of AIDS coming from elsewhere into Africa."

Dr. Haseltine has testified before Congress that, as well as can be determined, AIDS "began about 20 years ago" and "we now know that a spread of the disease in the United States and Europe was preceded by a massive spread of disease in Central Africa." He made the point on the basis of extrapolation from scientific articles, not from direct evidence.

Although now predominant among American and European researchers, the idea that AIDS began in Africa is by no means universal among them. Dr. Peter Piot, professor of microbiology at the Institute of Tropical Medicine in Antwerp, Belgium, says it is not certain where the disease started, and that proving Africa as the place of origin would be difficult. A Jigsaw Puzzle With No Picture In fact, finding the origin now is a bit like trying to do a jigsaw puzzle with only a few pieces in the box, no knowledge of its dimensions and no picture on the cover. As new clues are found in the bush, or in a desert or laboratory, scientists may have to change the basic design of their research. Pieces that now seem to fit may have to be moved elsewhere later.

Researchers often have difficulty pinpointing the introduction of a new microorganism because their methods are of necessity retrospective and indirect. In the case of AIDS, they concentrate chiefly on blood tests done on humans for other purposes in years past and frozen for the day they might yield valuable information.

However, a relatively small number of blood samples have been frozen over the years. In some cases, even if samples were stored for decades, the origins would be missed if there were no specimens from the particular village or tribe where it struck.

Many stored samples have spoiled as a result of the power failures that are not uncommon in third world areas. Opportunities have been lost for other reasons. In Rwanda, a laboratory worker told this reporter he had discarded many blood samples that a predecessor had left when he moved to Europe because he did not know the key to the code that was used to mark them. He also said he needed the freezer to store other perishable materials.

Although scientists the world over are searching freezers for hidden blood samples that might contribute to finding the origins of AIDS, most experts said they believed they were unlikely to find such samples from Africa dating before the 1960's.

As a result of such difficulties, some scientists believe it may never be possible to determine whether AIDS began in Africa or, if not, where it began. Others are cautiously optimistic. Dr. Donald P. Francis of the Centers for Disease Control in Atlanta is one: "We will localize it to areas though I don't think we will be able to say it began in this village in that specific year."

Blood tests that have been done since 1984, when they were developed, on samples that had been stored for years, indicate that the AIDS virus, or one similar to it, was present in Central Africa in the early 1970's and possibly in West Africa in the 1960's.

So far tests of stored blood from Africa showing evidence of the AIDS virus in years past have been reported from four countries: Kenya and Uganda in East Africa, Zaire in Central Africa and Burkina Faso in West Africa. Additional samples from Tanzania are under study.

The earliest clues to possible infection with the AIDS virus, or a closely related one, prior to the AIDS epidemic come from tests of samples collected in 1963 from 144 children in Upper Volta by Dr. Harry M. Meyer. Dr. Meyer's team from the Food and Drug Administration reports finding evidence of the AIDS virus or a closely related one in two children.

A team of American, French and Danish scientists headed by Dr. W. Carl Saxinger of the National Cancer Institute in Bethesda published in the professional journal Science the finding of evidence of the AIDS virus in 50 of 75 blood samples collected chiefly from healthy people in the West Nile district of Uganda between August 1972 and July 1973.

Another study of blood samples from a remote population of eastern Zaire found evidence of the AIDS virus in about 25 percent of 250 outpatients in a local hospital. The study was reported in the British Medical Journal by a team of American, Belgian, Danish and Zairian scientists headed by Dr. Robert J. Biggar of the National Cancer Institute in Bethesda.

Dr. Biggar headed another team of American and Kenyan scientists who reported finding evidence of the AIDS virus in widely varying percentages among six distinctly different regions of Kenya. The frequency was highest, at 50 percent of 99 samples, among the Turkana people living in the remote areas of northern Kenya where little if any AIDS has been reported. The frequency was lowest, at 8 percent of 99 samples, among the Masai. Over all, 22 percent of the 592 samples showed evidence of the AIDS virus. Doubts Abound On Africa Data However, other scientists have criticized these findings because they believe much of the evidence suggesting previous infection with the AIDS virus reflects a large number of nonspecific reactions and so-called false positive reactions due to co-existent infections from malaria parasites and from cross-reactions with other viruses.

Dr. Luc Montagnier of the Pasteur Institute in Paris and Dr. Piot from Antwerp said their teams were unable to confirm evidence of the AIDS virus in proportions as large as 50 percent of the specimens they had examined. True evidence of the AIDS virus was found but the numbers reported in the published studies are in serious question, these doctors said.

Determining an accurate prevalence of reactions to the AIDS virus in African populations is important. If half the Turkana population has been walking around without symptoms but with evidence of infection from the AIDS virus, for instance, then it is imperative to learn whether such individuals had the infection for a long time and survived because they had developed immunity to the disease, or whether they are infected with a different but related and less dangerous virus.

The Kenya study in the International Journal of Cancer was done by members of the Kenya Medical Research Institute and the Kenyan Ministry of Health. But one member of the Kenyan Ministry of Health, who spoke on condition that he not be identified, denied knowledge that his Government had read the final draft and given permission for its publication.

New tests of a different group of samples from about 100 people in Turkana reportedly show evidence of the AIDS virus in less than 2 percent, in drastic comparison to the 50 percent figure cited in the published Kenya report.

Dr. G. Hunsmann and three other doctors who work in Gottingen, West Germany and Ndola, Zambia reported last month in a British medical journal, The Lancet, on tests of 4,000 Africans in seven countries. "It would seem that the epidemic of AIDS in Africa started at about the same time as, or even later than, the epidemics in America and Europe," they said. "Our results do not support the hypothesis that HTLV-III virus originated in Africa."

Dr. Joseph B. McCormick, an expert in Lassa fever and Ebola virus, said his team at the Centers for Disease Control in Atlanta had tested samples of blood collected from people in northern Zaire in 1976 and 1979 as part of a research study on Ebola virus disease. Some of the tests done recently showed evidence of the AIDS virus in the 1970's.

Dr. McCormick said he hoped his team could return to the area to do follow-up studies.

Dr. Montagnier said stored samples had shown the extent of the spread of AIDS in some areas of Zaire where the AIDS virus could be detected in about 10 percent of people compared to less than 1 percent in the mid-1970's.

In testing stored specimens it is difficult to isolate a virus, as opposed to detecting antibodies, as evidence of infection, because the virus, if present, usually dies in the freezing and thawing.

However, researchers at the Centers for Disease Control have recently isolated a virus from samples collected in Zaire in 1976. The virus has not been fully characterized, but from preliminary tests it appears to be different from the AIDS virus, but closely related to it.

Finding an effective treatment, if not a cure, and a way to prevent AIDS unquestionably are high priorities for scientists. Though finding the origin of AIDS may contribute to this quest, nearly all those interviewed in Africa said they had given more thought to the cases they might have missed than to speculation about origin. 'AIDS Is the Talk Of the Town' "AIDS is the talk of the town," said Dr. Evarist Njelesani, who directs medical services in the Zambian Ministry of Health in Lusaka. He added that he could recall a few cases that now appear to have been AIDS that occurred in Ndola where he worked in 1981 and 1982.

But because of the pressing nature of other major health problems in his country - malaria is surging - Dr. Njelesani said he did not have time to pursue the origins of AIDS.

As to the resentment among Zambians over the thesis developed by American and European scientists that AIDS originated in Africa, Dr. Njelesani said: "That's a dicey question. There are a lot of question marks. There is bias from both sides. Naturally, people here say why do we have to be blamed for it."

Dr. Fakhri Assaad of the World Health Organization, said that the agency, based in Geneva, considered the origins of AIDS as one of its lowest priorities. The staff of the organization, a United Nations agency, responds to requests from member countries, he said. However, he added, "The countries have not requested this."

No country in West, Central or East Africa has reported cases of AIDS to the agency. Officials in countries like Zaire, where many experts say an there is an AIDS epidemic, have denied existence of the disease there.

"We have lots of priorities within Africa and our highest is to learn where the disease is there," Dr. Assaad went on. "To study in real depth where the disease started is a low priority in the W.H.O. program but is a fit subject for individual scientists. The only thing we know for sure about AIDS is that the disease as described by C.D.C. appeared nearly simultaneously in the United States, the Caribbean, and Africa."

If AIDS arose in Africa, how did it spread to the rest of the world?

Dr. Gallo, an American expert, is one of many researchers who have speculated on a Haitian connection: the fact that several thousand professional people went from Haiti to work in Zaire in the 1960's and 1970's and brought it home with them.

However, Dr. Warren Johnson of New York Hospital-Cornell Medical Center who coordinates an AIDS research program in Haiti, said he has found no link between cases in Haiti and Africa and that a search had turned up no cases in Haiti before 1978.

Many scientists contended privately that health officials should try to help overcome the political sensitivities of African governments and place a higher priority on seeking the origin of the disease and the way it spread. These researchers criticize the prevailing trend of financing studies that offer the seemingly greatest promise of quick short term pay-offs. Most likely what is needed, these critics say, are long-term financial commitments to scientists willing to take years to complete work that may never yield conclusive results.

The theory that AIDS went undetected as a rare disease in an isolated area of Africa is based in part on the history of the Marburg virus and other infections.

No one knew about these often fatal illesses until they occurred in dramatic outbreaks that forced the world to pay attention.

In 1967, 25 laboratory and other workers in Marburg and Frankfurt, West Germany and in Belgrade, Yugoslavia and an additional six doctors and nurses who cared for them came down with a high fever and severe bleeding. Seven of the 25 died. Workers Handled Monkey Parts Epidemiologists found that the 25 workers had handled some of the kidneys or cells of 500 African green monkeys imported from Africa. Virologists identified a new agent now known as the Marburg virus among the human victims and the monkeys.

Many doctors, including those working on AIDS, believe that the African green monkey is a natural carrier of the Marburg virus. But they could be wrong. Marburg virus experts say these monkeys had been in contact with almost 50 other species of animals in the incubation period and that these monkeys may have acquired the infection from these other animals or from handlers or other humans in Africa.

Another popular theory is that a pre-existing virus mutated to create the new AIDS virus.

Viruses frequently mutate, or change, under laboratory conditions in a favorable way to become less virulent in a process known as attenuation. A mutation that occurred just one time in the laboratory and that could not be repeated created the so-called 17-D strain of yellow fever. It has long served as the basis of the immunization against that mosquito-borne disease.

Although scientists often talk about mutations as if they were common, those interviewed could not cite examples of microorganisms that had mutated to cause an epidemic of a virulent new disease. Dr. Clayton, the Canadian health expert, subscribes to the theory that AIDS "is a successful virus mutation, perhaps the first in recorded written medical history, and that we are thus dealing with a new disease."

Some scientists contend that a major mutation of the influenza virus caused the epidemic that struck the world in 1918-1919. However, others have argued that the unusual severity of that epidemic may have been caused more by the virulence of secondary infections from staphylococcal bacteria than by such a mutation.

The AIDS virus tolerates many changes among the genes in its envelope, or outer coat. However, the virulence of the virus has not been firmly linked to its genes or genetic changes.

Dr. Montagnier, the French researcher, speculates that the virus may have gone unrecognized in the past when it had more of an affinity for the brain or some other organ and that is has come to dramatic attention now when it somehow changed to affect the T-4 cells of the blood that play such an important role in the immune system.

Dr. Anne C. Bayley, a professor of surgery at University Teaching Hospital in Lusaka where she has been a leader in research on Kaposi's sarcoma, one of the manifestations of AIDS, says scientists seemed to have refrained from discussing the possibility that the virus had resulted from a laboratory accident involving genetic engineering.

Still others wonder whether the virus could have mutated in some unknown way as a reaction to the widespread use of antibiotics.

If scientists do trace the geographic origin of AIDS to a remote village in Africa, the question of how it got there might still remain.

One possible explanation could be that the AIDS virus belongs to a group of diseases known as zoonoses that involve animals primarily and infect humans accidentally and secondarily. However, most zoonoses, rabies for example, are not spread from human-to-human except under unusual circumstances. Proving that AIDS is a zoonosis would only raise another question. Scientists Focusing On Primates When viruses cross species, such as from animals to humans, many become more dangerous to the human. For instance, monkey B virus, which apparently does not harm monkeys, is usually fatal when it strikes humans. Many members of the retrovirus family infect animals in either of two ways: endogenous, causing no apparent harm, and exogenous causing disease.

Since retroviruses are found in a wide variety of animals, any could theoretically be the original source of the AIDS virus.

However, scientists have focused on primates as a potential source of AIDS largely because a similar immune system disorder has been found among simians. The disease, called SAIDS, was found in these monkeys at primate centers in the United States at about the same time as AIDS was first recognized in humans. A virus that bears some resemblance to the human AIDS virus has been been found in these monkeys.

Moreover, viruses similar to the AIDS virus have also been found in monkeys that do not have SAIDS.

Dr. Max Essex of the Harvard School of Public Health is one of several researchers exploring the hints offered by these findings.

He has presumed that the African green monkey was the natural carrier of the Marburg virus, or the natural reservoir, as it is also known. From intuitive guesswork based on the epidemiology of AIDS, he compared maps of Africa showing outbreaks of AIDS with those of the distribution of primates, and found that African green monkeys stood out.

Dr. Essex and other researchers in the United States, France and West Germany have searched for viruses in the blood of healthy appearing monkeys exported from Africa or caught in the wild there. He reported last week in the American journal Science that he had isolated a virus from tissues of seven healthy, recently captured African green monkeys, and that he has grown it in human cells in the laboratory. The virus, he found through immunological tests, closely resembled the human AIDS virus.

Recently developed molecular biology techniques allow scientists to compare the genetic structure and other aspects of molecular biology of monkey and human viruses. But the early results have produced considerable debate over how closely the human and animal viruses actually are related.

Several scientists who are intrigued with the theory of a monkey origin of AIDS have been critical of colleagues who were making what some regard as too big or too quick a leap in linking the monkey and the AIDS viruses.

"It is too early to conclude anything about the primate origin of AIDS," said Dr. Luc Montagnier, a French AIDS expert.

Dr. James Else says blood tests done in London of more than 350 primates from the Institute of Primate Research that he directs in Nairobi had shown no evidence of the human AIDS virus. Dr. Else also has noted that tests of African green monkeys in the Caribbean that had come from Africa more than a century ago had shown no evidence of the AIDS virus or a related one.

If research ultimately shows a link between an animal virus and the human AIDS virus, still more major questions must be resolved.

What happened in recent years to animals to make them so dangerous to humans, if indeed, they are ultimately proved to be?

Dr. Essex of Harvard says said he presumes that, if the monkey virus is linked to AIDS, it will be found to have been transmitted when humans ate monkey meat or were bitten by monkeys. But humans have eaten monkey meat and have been bitten by them for centuries without apparent harm.

And did the virus pass from monkey to man? Or from man to monkey?

In the last six weeks, Lawrence K. Altman has interviewed more than 50 medical scientists and public health officials to report on the international search for the origin, cause and cure of AIDS.

Discovering the origin is regarded by many in the medical field as vitally important to the quest for the cure of this fatal and thus far incurable disease. Such a finding might also help health officials prevent future epidemics.

In his first report from Africa, on Nov. 8, Dr. Altman said the disease there, unlike the patterns elsewhere in the world, appears to be spreading by conventional sexual intercourse among heterosexuals and is striking women and men in nearly equal numbers. He said, too, that the incidence among children was radically higher that elsewhere.

But he also found scientists in another battle: fighting suppression of information crucial to needed medical research into the many unanswered questions: Did the disease originate in monkeys? Was it a mutated virus?

This is his second report; others will follow.

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