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Taken from KeelyNet BBS (214) 324-3501
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June 27, 1992
POLIOHIV.ASC
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THE ORIGIN OF AIDS
A Startling New Theory Attempts to Answer the Question
'Was It An Act of God or an Act of Man?'
By Tom Curtis
from Rolling Stone Magazine, March 19th, 1992
It was almost thirty years ago, but I clearly remember one
event on that hot and humid day early in August 1962. Like
communicants in some universal mass, my two brothers, my parents and
I slowly moved to the head of a very long, snaking line composed of
thousands of people -- a significant part of the population of
Galveston, Texas. All were awaiting admittance into the central
hallway of Ball High School so we could approach a simple wooden
table -- a kind of altar of science --where a volunteer nurse handed
each individual a tiny paper cup containing a sugar cube. I gazed
intently at mine. One side had a faint yellow tinge and dark specks
where the helf-cubic-centimeter of so drop of liquid vaccine had
landed. Though I was surprised that my cube was so dirty looking, I
popped it in my mouth, chewed and swallowed. The rest of my family
followed suit.
Over the next two years, the same ritual was played out in
towns and cities across America. These other patient believers,
like me and my family, were seeking not life eternal but science's
more secular but no less miraculous promise: everlasting immunity
from the most dreaded scourge of the Forties and Fifties --
paralytic poliomyelitis. Before the polio vaccines were introduced
in the Fifties, the disease had struck about 22,000 people a year in
the United States alone -- often young children. The new, vibrant
medium of television showed kids like us shackled by leg braces and
crutches or imprisoned in iron lungs -- huge cylinders covering all
but their heads. I had an even more terrifying image of the ravages
of polio: A close friend of my parents, a vital young physician
named Martin Schneider, had contracted the disease in 1948 and would
Page 1
spend the last two decades of his life paralyzed from the waist down
and confined to a wheelchair.
In one of the greatest triumphs of twentieth-century medicine,
the promise to deliver us from that crippling contagion was kept.
The one-two punch of the "polio shots" developed by Dr. Jonas Salk
and the oral vaccine developed later by Dr. Alfred Sabin effectively
eradicated polio in developed countries and later in much of the
Third World. But there was a shadow over the conquest of polio.
It's estimated that early on, at least, the polio vaccines
administered to many millions of people in the U.S. and around the
world were inadvertently contaminated. "We took all the precautions
we knew of at the time," Salk says today. "Sometimes you find out
things after the fact."
What Salk and the other pioneers of the polio vaccine found out
was that accidents did happen. In the preparation of massive
amounts of various polio vaccines -- either weakened or killed virus
that causes recipients to form protective antibodies -- things
occasionally went horribly wrong. Hundreds of people actually
contracted polio by the very means they sought to protect themselves
-- and some died. Researchers who cultured the virus using tissues
of animals were stricken and sometimes killed by other viruses
infecting the animals. And finally, the medium that scientists used
to produce the vaccine -- the kidneys of monkeys caught in the wild
-- was found to be sometimes contaminated by simian viruses that
were later passed on to millions of unsuspecting people.
There is the prospect that we may find out something else after
the fact: that another polio vaccine may have inadvertently
infected its recipients with an even more fearsome and insidious
virus, the one that causes acquired immune deficiency syndrome --
AIDS.
In August 1991, Blaine Elswood, and articulate AIDS-treatment
activist and diligent sleuth of medical literature who works at the
University of California at San Francisco, mailed me a terse note
paper-clipped to several xeroxed items from medical and scientific
journals raising the issue. "Here's a bombshell story just waiting
for an investigative reporter," he'd said.
We'd had a casual, two-year telephone-and-mail acquaintance
ever since Elswood had been recommended to me as a source by a West
Coast dermatology professor working on new treatments for AIDS.
Clearly a maverick, Elswood was proudest of having co-founded
"guerilla clinics," which research and provide alternative drugs for
those with AIDS, in San Francisco and elsewhere. Elswood is neither
a physician nor a Ph.D., and he has one clear bias: He does not
think American doctors will easily acknowledge that medical science
itself may have played an unintentional role in introducing AIDS to
the human population.
As I soon find out, Elswood is right. When I broach the idea
to Salk, who is once again working to develop a vaccine, this time
for AIDS, he flatly refuses to discuss the subject. "I don't think
I can be helpful to you," he says, "other than to try to dissuade
you from pursuing that kind of hypothesis, because what value is it?
What value is it to anyone to try to imply such a cause-and-effect
relationship?" He also makes it clear that he strongly subscribes
Page 2
to another plausible theory: that the AIDS virus has lingered for
eons in African jungle tribes and erupted to cause epidemics in
recent decades only when those rural peoples migrated to the cities.
African Genesis
AIDS first appeared in equatorial Africa, many scientists now
believe. The earliest evidence of its presence on the African
continent dates from a plasma sample drawn in 1959 in what was then
Leopoldville, the Belgian Congo, and is now Kinshasa, Zaire. Dr.
Mirko D. Grmek's definitive book _History of AIDS_, published in
1990 by Princeton University Press, describes the primary African
epidemic's radiating outward from a region located in Zaire and
Rawanda. There's also a tantalizing connection with monkeys and
other primates: Several African species carry a virus related to
the human immunodeficiency virus (HIV), which causes AIDS in human
beings. Although HIV has yet to be found in monkeys, a "missing
link" simian virus much closer to the human virus has been
identified in two wild chimpanzees from Gabon. This has led to
speculation that a chimp or a monkey with an AIDS virus identical to
the human virus will eventually turn up.
Scientists have proposed a grab bag of ideas to explain how the
disease may have leapt the vast chasm from monkey to man. There is,
for instance, the kinky-African-sex theory. It involves a bizarre
sexual practice in which, to heighten sexual arousal, male and
female members of tribes bordering the large lakes of Central Africa
introduce monkey blood into their public regions, thighs and backs.
Then there's the cut-hunter theory, recently described to me by the
premier American AIDS researcher, Dr. Robert Gallo. Gallo suggests
that since monkeys in Africa are killed for food, a hunter might
have nicked himself while skinning an infected monkey and thus might
have mixed virus-laden monkey blood with his own; repeated such
incidents over time, he argues, could have infected enough people to
spark an epidemic. Last Thanksgiving, an Oxford clinician writing
in the prestigious British scientific magazine _Nature_ presented
another startling hypothesis: that the disease may have sprung from
scientific experiments that lasted into the Fifties in which
chimpanzee and monkey blood was directly injected into human beings
to see if people could carry the form of the malaria parasite that
infests those primates.
There are problems with each theory, The first couple are
basically speculations that can't easily be confirmed or tested
scientifically. Anyhow, those African sexual and hunting practices
presumably have been going on for thousands of years; the AIDS
epidemic is new. The idea involving the malaria experiments is
extremely provocative. It may prove to be more than that if
material from the original experiments still exists and can be
scientifically checked. But the number of people involved in the
tests was tiny: As discussed in _Nature_, a total of about seventy
people received primate blood or primate-tainted human blood during
the entire range of the malaria experiments, which ran from 1922 to
1955. Still, AIDS had to start somewhere, so like the other
theories, this one has to be considered.
* * * * *
Page 3
Sprinkled through the medical literature of the last thirty-
five years are facts that buttress the unnerving prospect that HIV,
the AIDS virus, may have crossed the species barrier as an
unintended byproduct of a live-polio-virus vaccine. There was, in
fact, an almost forgotten mass-vaccination campaign in which an oral
polio vaccine was administered to at least 325,000 people, and
perhaps more than half a million people, in equatorial Africa from
1957 to 1960. One of the two vaccines used in that experimental
effort was subsequently reported to have been contaminated with an
unknown monkey virus.
The timing seems right. A process called genetic sequencing,
which tracks the evolution of a virus by measuring genetic changes,
can read the molecular history of a disease. According to Gerald
Myers, the federal government's chief expert in genetic sequencing,
HIV dates from about 1960, assuming it arose from a single, common
ancestor.
There are natural obstacles preventing a virus from crossing
the barrier to become established and thrive in a new species. But
it happens. And when it does, the virus frequently becomes much
deadlier in the new species than it was in the original species.
In recent decades, some scientists believe, live-virus vaccines
may have actually helped transfer viruses across species lines.
Perhaps the classic example is canine parovirus, or CPV, which
abruptly appeared in dogs in 1977 and within months had become a
widespread animal epidemic -- or epizootic -- on virtually every
continent, causing entirely new dog diseases of the intestines and
heart muscle. CPV is intriguingly similar in its genetic structure
to a cat disease called feline panleukopenia virus (FPLV), but it's
even more similar to to the vaccine for this disease. This has lead
several virologists to suggest that by accident or design, the cat
virus most likely was introduced into dog cells in the laboratory,
where the strain adapted itself to the new host.
A 1989 article in the _Journal of the Royal Society of
Medicine_ noted that case and a number of other cross-species
transfers of viruses in the context of AIDS. "It would appear," the
piece said, "that the AIDS epidemic may be just one of the latest of
several mammalian cross-species viral transfers triggered by the
techniques of virology developed in the 20th Century, which
subsequently spread out of control in the new host species."
To grasp how this possibility relates to a polio vaccine used
in Africa, it helps to know how polio came to be suppressed in most
of the world.
"It's Not Good to Know Too Much"
Jonas Salk, backed by a private philanthropy popularly known as
the March of Dimes, introduced the first widely used polio vaccine
in 1954. His vaccine was a virulent form of the polio virus that
had been killed by formaldehyde. This dead, or "inactivated," virus
was injected into people to provoke the body's immune system to
manufacture disease-fighting antibodies that would repel the wild,
paralyzing types of polio. But medical science ultimately rejected
Salk's shots in favor of a weakened but still-living virus
administered by mouth -- Albert Sabin's sugar cube. Unlike the Salk
Page 4
shots, which were believed to require periodic booster vaccinations,
the oral vaccine conferred lifetime immunity. It could be taken by
mouth and required no injections; and the live vaccine silently
spread the weakened, non-paralyzing virus even to those who failed
to take the oral vaccine. These "susceptibles" would simply catch
the weakened virus and get the infection without noticeable
symptoms. They also would become immune to paralytic polio.
Polio vaccines are produced by selecting weakened strains of
polio virus and then placing them in tissue cultures -- live cells
from primates. (Either monkey or human cells will work, but
researchers selected monkeys because their tisue was more available
and there were fears that human cell lines might spread cancer. The
unrecognized danger, though, was this: Because monkeys are
genetically similar to human beings, some simian viruses can leap
the species barrier with devastating effect.) The virus then enters
the cell and reproduces itself. All the polio viruses grown to
produce the mass vaccines in the Fifties were fed one particularly
nourishing medium: fresh monkey kidneys. And throughout the
Fifties -- a period that was barely beyond the dawn of scientific
knowledge regarding tissue culture -- some of those monkey kidneys
were infected with numerous monkey viruses. Scientists knew about
some of these viruses and developed tests to identify and then
eliminate the tissues that contained them.
One of the earliest and deadliest was the so-called monkey B
virus -- a herpes virus first identified and isolated in 1932 by
Sabin after it killed a medical colleague at New York's Bellevue
Hospital. The unfortunate polio researcher had been bitten by a
monkey. "He had developed paralysis after the monkey bite," Sabin
recalls almost sixty years later as I interview him in the office of
his Washington, D.C., apartment. "He died after a short time."
Sabin, who with his full white beard and hair looks like Robert E.
Lee, continues: "At the autopsy I collected specimens and isolated
a virus. Because I was too green behind my ears in virology, I
would not accept [it] as being an ordinary herpes virus with which
human beings are infected -- which a professor at Columbia
University, who knew much more than I, did." Chuckling at the
memory, he adds, "Sometimes it's not good to know _too_ much."
While working at the Lister Institute, in England, in 1934,
Sabin was able to prove that what he found was a distinct virus.
And in 1949, when he was working in Cincinnati, Ohio, he again
isolated the virus after another physician researcher was killed by
it. "Then, as thousands of monkeys began to be used for the
preparation of the Salk vaccine in the early Fifties," Sabin says,
ten or so caretakers working with the monkey kidneys or who were
bitten while handling the monkeys also developed the same illness
and died.
"In monkeys, it's a disease which is as mild as ordinary fever
blisters are in human beings," Sabin says, but in humans it
paralyzes and kills. "As a result of that, all the [research]
monkeys had to be tested." Special precautions were instituted.
"But often precautions were not used," Sabin says. Deaths from
monkey B virus, though infrequent, have continued, the latest a
veterinarian at a south Texas primate facility who died of monkey B
virus last fall.
Page 5
The Fortieth Monkey Virus
So monkey B was kept out of the polio vaccines. But thee was
another monkey virus that polio researchers missed. Between 1954
and 1963, an estimated 10 to 30 million Americans and scores of
millions of people around the world were exposed to a virus that
infected the kidneys of Asian rhesus monkeys imported mainly from
India. The virus survived the formaldehyde that Salk used to kill
his polio viruses. Since 1961 researchers have tested monkeys for
SV40 -- so called because it was the fortieth such simian virus
identified -- before using their kidneys for vaccine production.
SV40 was delivered straight into people's bloodstreams along
with their Salk shots and via sugar cubes in field trials of the
weakened living virus developed by Sabin. Though it was later shown
to cause cancer in hamsters and to "immortalize" human cells in test
tubes -- thus predisposing these cells to cancer -- SV40 has not
been proven to generate illness in human beings. Nevertheless,
researchers at Johns Hopkins recently discovered that when they
injected cells treated with SV40 into "nude" mice, which lack an
immune system, the mice developed Kaposi's Sarcoma-like tumors,
similar to those afflicting many AIDS victims. Remarkably,
considering the large numbers of people who received the SV40-
contaminated polio vaccines, no one ever conducted a major
epidemiological study in the U.S. to discover whether there is any
pattern of illnesses caused by the virus.
Still, there are some troubling statistical associations. In
1968 a scientist in Australia described a correlation between polio
immunization and cancers in children past one year of age. Much
later, German scientists found evidence of SV40 in 30 out of 110
brain tumors, and later reports indicated a jump in the frequency of
brain tumors among those who had received vaccine contaminated with
SV40. And SV40 has been associated with other human cancers as
well.
After news broke about the monkey virus SV40 contaminating some
lots of Salk's and Sabin's polio vaccines, congressional hearings
were called to examine the explosive issue. On April 14th, 1961, a
rival polio researcher of Salk's and Sabin's sent a letter to the
House Health and Saftey Subcommittee taking issue with growing live-
polio-virus vaccine in monkey kidneys.
Sounding like someone who had come to his understanding through
hard experience, the researcher -- Dr. Hilary Koprowski of
Philadelphia's Wistar Institute -- suggested that human cells be
used instead. "As monkey kidney culture is host to innumerable
simian viruses, the number found varying in relation to the amount
of work expended to find them, the problem presented to the
manufacturer is considerable, if not insuperable," Koprowski wrote
to the committee. "As our technical methods improve we may find
fewer and fewer lots of vaccine which can be called free from simian
virus."
But when Koprowski, Salk and Sabin were doing their initial
vaccine development in the Fifties, little was known about the
simian viruses, and there were no federal regulations stipulating
that the viruses be grown in a specific type of tissue culture. No
one knew then about retroviruses like HIV that might take years to
Page 6
develop, and so it was assumed that if no viruses had shown up in
preparations after a couple of weeks, then those vaccines were
clean.
In 1988, when researchers in Washington, D.C., area reexamined
an earlier study run between 1959 and 1965 on nearly 59,000 pregnant
women, they found a startling connection: The incidence of brain
tumors in children of mothers who'd been injected with the Salk
vaccine was thirteen times greater than that of offspring of mothers
who hadn't had those polio shots. Stored blood serum from those
mothers still existed, and it was retested. The tests seemed to
exclude SV40 as the cause. But if not SV40, what about the Salk
vaccine might explain the increased risk of brain tumors in
offspring of vaccinated women? The researchers asserted that some
other infection was probably the culprit. After all, they noted,
the Salk vaccine was known to have been contaminated _numerous_
monkey viruses.
The Marburg Monkey Virus
In mid-August 1967, six years after the SV40 problem came to
light, a mysterious, dangerous, infectious disease broke out
simultaneously in German and Yugoslavian research institutes.
Thirty-one people, including the technicians making polio vaccines,
suddenly became ill -- and seven died. All those infected had
direct contact with monkeys or their blood, organs or tissue
cultures. Other people later got the disease, too, including
hospital personnel who had contact with these patients. In one
case, a woman contracted the disease from the semen of her husband,
who had been infected three months earlier. Though millions of
monkeys had been used as experimental animals and as raw material to
provide kidneys to make vaccines, no such disease had ever been seen
before. Eventually the "Marburg Virus" was isolated, and its source
was traced to monkeys shipped from Uganda.
But if HIV were one of those numerous anonymous monkey viruses
contaminating the early Salk and Sabin vaccines, presumably there
would have been an explosion of AIDS in the U.S. outside of the
currently defined high-risk groups: male homosexuals, intravenous-
drug users, hemopheliacs and the sexual partners of those people.
Of course, that sort of eruption hasn't happened in the U.S. But it
did happen someplace else: in equatorial Africa.
The Congo Vaccine
As it happens, equatorial Africa was the site of the world's
first mass trials of an oral polio vaccine -- a vaccine cultured in
monkey kidneys but different in at least one important respect from
the Sabin vaccine ultimately adopted worldwide. This footnote in
medical history took place from 1957 to 1960 right in the middle of
what was then the Belgian Congo, Rwanda and Burundi -- the epicenter
of the future African AIDS epidemic. It was developed by a
naturalized American polio researcher named Hilary Koprowski -- the
same Dr. Koprowski who four years later would warn congressmen of
the dangers of an almost infinite number of monkey viruses
contaminating polio vaccines.
Hilary Koprowski, the developer of the vaccines used in the
Congo, is a charming, deep-voiced man of seventy-five. Born and
Page 7
educated in Poland, where he studied to be a concert pianist while
going to medical school, Koprowski began work for Lederle
Laboratories in 1946. Like Salk and Sabin he took up the cause of
saving the world from polio. He tested weakened strains of the
virus in monkeys and chimps and in March 1951 surprised a meeting of
polio researchers sponsored by the March of Dimes in Hershey,
Pennsylvania. There he revealed that he had become the first
physician in history to administer a polio vaccine to humans. The
"volunteer" research subjects for Koprowski's live, weakened polio
vaccine included twenty children he later described as "mentally
deficient" who lived in Letchworth Village, a facility operated by
the New York State Department of Mental Health. Later he vaccinated
other groups of children, among them the newborn babies of
institutionalized women in New Jersey. But a larger test of the
vaccine, planned for children of Belfast, Northern Ireland, in 1956,
was scrapped amid reports that some of his tamed oral vaccine had
reverted to its wild, paralytic form. While no one was paralyzed
and Koprowski insists that one one ever would have been, authorities
in Belfast feared that such a "reversion to neurovirulence," to use
the medical jargon, might spark a new polio epidemic.
* * * * *
After the Belfast debacle, Koprowski, who was racing Sabin for
the distinction of producing the oral polio vaccine of choice, left
Lederle Laboratories to direct Philadelphia's Wistar Institute, then
a modest research organization best known for developing a unique
laboratory rat. But he held tightly to his goal of producing the
winning polio vaccine.
Almost immediately, Koprowski arranged to have his weakened
polio viruses tested in a colony of 150 chimpanzees in Camp Lindi at
Stanleyville, in the Belgian Congo (now Kisangu, Zaire). To protect
the animals' caretakers, these humans, too, were fed the weakened
virus. The successful immunization of the keepers then became the
justification for the mass vaccination trials in the Congo itself --
the first mass trials in the history of an oral polio vaccine.
Called by drums, rural Africans traveled to village assembly
points. There they lined up and had a liquid vaccine squirted into
their mouths. Using this spray method, nearly a quarter million
Africans were innoculated in six weeks. Later another 75,000 or so
children in Leopoldville, now Kinshasa, got the vaccine, too --
though European children living there apparently received their
vaccine in capsure form, possibly a significant variation.
From the beginning, Koprowski's campaign was marked by
controversy. _Trial by Fury_, Aaron Klein's 1972 account of the
development of the polio vaccines, reports that Koprowski apparently
claimed he had the backing of the World Health Organization, but the
WHO denied sanctioning the claim. Koprowski says today that
although he was challenged by WHO, he needed only the approval of
the Belgian authorities -- and there's no doubt he had that. Other
preparations of Koprowski's polio vaccines were later used in
Poland, Yugoslavia and Switzerland, among other places.
Herald Cox, Koprowski's superior at Lederle, had begun growing
the polio virus in developing embryos in chicken eggs. Early on,
Koprowski also used the brains of cotton rats to select his weakened
Page 8
strains and nurture the virus. But by 1956 and 1957, when he was
readying his vaccine for use in the Congo, Koprowski had long since
switched to minced-up monkey kidneys.
Monkey kidneys contained innumerable monkey viruses. Might
the one that causes AIDS be one of them? And if it were, would
Koprowski's method of delivery -- shooting liquid into people's
mouths -- be capable of transferring the virus from monkeys to
humans?
"You can't hang Koprowski with that," Albert Sabin growls at
me. He's sitting at the desk in his study; the walls are covered
with testimonial plaques, certificates of commendation and
achievement, photos of him with several presidents. Sabin insists
that the AIDS virus won't survive swallowing. He's certain of it.
But whether it does or doesn't survive is really not so clear-
cut, Dr. Robert Gallo and other retrovirus researchers acknowledged
to me; no one knows for sure. Moreover, Gallo's colleague, Dr.
William Haseltine of Harvard and also of the Dana-Farber Cancer
Institute, in Boston, and others have reported that the AIDS virus
infects mucous cells -- which of course occur in the mouth as well
as the genetalia.
And Dr. Robert Bohannon of Baylor College of Medicine, in
Houston -- who in November 1991 reported finding a monkey retrovirus
in the tumor of an AIDS patient with no known contact with monkeys -
- pointed out to me that the process of squirting the polio vaccine
in people's mouths would tend to send tiny drops into the air. It
might go directly to the lungs or nose and thence to the blood cells
it is known to infect.
Later I pose the same question -- Could squirting an HIV-laden
polio vaccine into people's minds cause AIDS? -- to Dr. Tom Folks,
the chief retrovirologist at the Centers for Disease Control in
Atlanta. "Sure it could," he says. "Any time a person has a lesion
in his mouth, then there could be transmission if you put enough" of
the virus in.
Monkey AIDS
But was there anything to transmit? The answer to that
question hinges on the kind of monkeys used to make Koprowski's
vaccine.
In 1957, when the Congo trials began, most researchers were
using rhesus macaques from India. It would be another four years
before scientists fully appreciated the danger that macaques, the
natural hosts for SV40, were passing along the virus to humans.
Once that troubling discovery was made, in 1961, vaccine producers
shifted to kidneys from African green monkeys, which in the wild
were free of SV40.
Unfortunately, green monkeys were infected with something else.
More than two decades later, in 1982 and 1983, veterinarians at the
California Primate Research Center and at Harvard's New England
Primate Center observed that large numbers of their macaques were
dying periodically of AIDS-like illnesses. These disorders had been
killing animals since 1969, but suddenly, the researchers were
Page 9
struck by the similarity to the new disease afflicting American
homosexual men. The monkeys' illnesses, the researchers discovered,
were triggered by a previously unrecognized retrovirus called simian
immunodeficiency virus (SIV).
Among the natural hosts for this virus were none other than
African green monkeys, but in that species, typically, SIV didn't
cause serious disease. SIV turned out to be related to HIV, though
it was only about forty percent similar in genetic structure to the
chief AIDS-causing human retrovirus, known as HIV-1. Robert Gallo
says some versions of this monkey virus are virtually
indistinguishable from some human variants of HIV-2, the second
virus that causes AIDS in human beings and mainly afflicts western
Africa.
No one who was involved with Koprowski's Congo project and is
alive today remembers what kind of monkey kidneys were used in 1957-
60. Koprowski is still vigorous and remains at the Wistar
Institute, in Philadelphia -- now as an institute professor and
until 1991 as the director of the facility, which is housed in a
stolid Victorian structure on the campus of the University of
Pennsylvania.
Koprowski insists that his associates used kidneys from African
green monkeys to make the Congo vaccines. When I express surprise
and mention that Salk and Sabin were using rhesus monkeys at that
point, he agrees to check. When we speak next, he admits he can't
find a single paper describing which species was used to make his
vaccine. "But I have a suspicion the virus was grown in the rhesus
monkey at the original beginning," he tells me in his thick Polish
accent. "Now when we switched to green monkeys, I have no idea."
Thomas Norton, his associate who grew the virus for the vaccine, is
now dead, Koprowski says -- as are those who worked with Norton to
prepare the vaccine. Significantly, the large lots of the vaccine
used in the Congo apparently were prepared at the laboratories of
the Wistar Institute, he says. Wyeth Laboratories made subsequent
preparations, including those used in Poland.
Contamination
The question of which monkeys were used to make the Congo
vaccine may not be crucial. The virus that causes monkey AIDS
occurs in several species, though the original hosts -- African
greens and others --remain healthy even when infected. Monkeys
frequently were gang-caged in those days, facilitating the spread of
the viruses. If a green monkey turned out to have a virus quite
similar to HIV-1, it could have infected the other monkeys.
Although most American researchers in this period apparently
did use rhesus macaque monkeys from Asia, for a while around the
time Koprowski was working with his vaccine, the monkey supply was
interrupted. The Indian government -- responding to popular alarm
among its people about the widespread slaughter of Indian macaques
for vaccine production and other research -- barred export of rhesus
monkeys to the U.S. For a time at least, that ban must have made
suppliers scramble to find different markets and alternate monkey
species, probably including African monkeys. Moreover, Koprowski
says the kidneys used at Wistar were bought already removed from
their hosts, meaning that researchers might not have been sure what
Page 10
kind of monkeys they came from, much less what viruses came with
them.
According to no less an authority than Albert Sabin himself, at
least one other virus did contaminate Koprowski's vaccine used in
the Congo. In 1959, Sabin reported in the _British Medical Journal_
that a special test he had devised revealed the presence of an
"unidentified" cell-killing virus in "Koprowski's Type 1 'Chat'
vaccine used in the Belgian Congo trials." More than three decades
later, Sabin says he never figured out exactly what the virus was.
Koprowski insists -- as he did at the time in the _British
Medical Journal_ -- that two other labs examined his vaccine and
found nothing except the weakened polio virus. But one eminent
polio researcher, Dr. Joseph Melnick, former chairman of the
Department of Virology at Baylor College of Medicine in Houston, who
himself developed an oral polio vaccine while working at Yale
Medical School, says Sabin probably was right. "Sabin was a very
careful worker in the laboratory," says Melnick, a tall, formal,
distinguished-looking man. "And I have not known him ever to say
that he has found a virus in some preparation that did not exist in
that preparation."
In any even, Melnick says, "Monkeys have a very high prevalence
of lentiviruses," one of the subfamilies of retroviruses. "You can
isolate it from their tissues, particularly from their kidneys.
That is one reason why we stopped using monkeys from the wild and
just used home-grown monkeys." Melnick pauses. "It's of interest,"
he says, "that HIV is a lentivirus." So are simian immunodeficiency
virus and the so-called foamy virus, both of which widely infect
monkeys, Melnick says. "In the early days of the vaccines, we
didn't know much about monkey viruses." As for Koprowski's
contention that others looked and didn't find the virus in his Congo
vaccine that Sabin had noted, Melnick has a simple explanation, "It
may not be in one batch and may be in another batch."
A Tale of Two Maps
Writing in the _British Medical Journal_ on July 26th, 1958,
Koprowski and his colleagues offered a preliminary report on their
mass vaccination campaign. They included in the paper a detailed
map showing where nearly a quarter million inoculations had taken
place in the northeastern part of the Belgian Congo. The area
outlined corresponds roughly to another map in a report published
thirty years later in the _Reviews of Infectious Diseases_ -- this
one identifying the regions of highest HIV infection in equatorial
Africa.
Still another paper that appeared in the _British Medical
Journal_ in 1985 reviewed HIV infection in the Kivu District, a
remote, rural population in eastern Zaire. There, somewhat
puzzlingly, the researchers discovered "a high prevalence of
antibodies" to the AIDS virus without symptoms of the disease. The
Kivu District happens to be where Koprowski's colleagues vaccinated
the lion's share of their reported sample --215,504 children and
adults. And there may have been many more vaccinations than
initially reported. "Could have been 200,000 more, I really don't
know," Koprowski says, because the subsequent mass trials were
interrupted by tribal chaos and the civil war the followed
Page 11
independence. No one really knows how those individuals fared over
time. No long-term follow-up was possible, Koprowski says.
The researchers who studied the Kivu District in 1985 offered
several possible explanations for why the people they found with
antibodies for the AIDS virus might not have the disease. The fact
that there were more children than adults with antibodies to the
virus suggested that the adults could have been exposed in
childhood, and some of them might have died or departed from the
area. Perhaps, the researchers ventured, if members of a rural
population that was biologically adapted to the virus moved into an
urban area, exposing a pool of more susceptible adults, this would
create "new opportunities for the virus to cause illness in urban
adults and the epidemic appearance of the disease in Africa."
Moreover, the researchers pointed out that they were looking at a
region of "high mortality in childhood, particularly from infectious
diseases." Cases of AIDS in children a generation ago simply might
have gone unrecognized.
Of course, many of the viruses contaminating the monkey kidneys
went unrecognized in the Fifties and early Sixties. Koprowski and
his colleagues in the mass-vaccine campaigns found some monkey
viruses and eliminated them from their preparations. But many
others weren't known, and no test to identify their presence had
been developed. "That's the problem," Koprowski says. "The viruses
which you know, there's a test -- there's no problem; the viruses
which lurk, for which there is no test, obviously you can't do
anything about."
So, might Koprowski's Congo vaccine have been the vector that
unwittingly first unleashed the AIDS virus among people in Africa? I
ask the question and Koprowski dismisses the idea with a deep laugh:
"Ho, ho, ho, ho, ho."
I'm asking the question, I say. He laughs again, this time
longer and deeper. "By then you would have had plenty of
opportunity to see AIDS in the vaccine," Koprowski says. "You have
started in 1960; now it's thirty years. The latency period of AIDS
is nine years."
But according to Dr. Gallo, I point out, some retroviruses may
take up to forty years to express themselves.
"There is no indication from any part of the world that any
other virus occurring there [in the various polio vaccines] causes
any problem," Koprowski says.
There are reasons, however, why AIDS in the former Belgian
Congo may have been invisible to medical science. In remote, rural
eastern Zaire, where most of Koprowski's vaccine was administered,
or even in Kinshasa, the disease simply may have passed unnoticed or
may not have been identified. "In the tropics, the wealth of lethal
infectious pathology is matched by the poverty of diagnostic
facilities, rendering undetectable sporadic appearances of AIDS,"
notes Dr. Mirko D. Grmek, a medical historian, in his recent book
_History of AIDS_. "It is entirely possible that localized or even
moderately large epidemics have passed unnoticed."
On the other hand, AIDS may have been slow to express itself
Page 12
when it was confined to rural areas where people had fewer sexual
partners. A laboratory experiment with monkeys also showed how AIDS
may have taken a bit longer to emerge as an epidemic in its present
nasty form. When a researcher took a simian AIDS virus from a
healthy mangabey, a monkey species in which it typically causes no
symptoms, and injected it into a group of macaques, the disease
became progressively more virulent each time it passed through the
body of another macaque. Finally, this isolated virus even sickened
a mangabey, although that species has natural resistance to the
original virus. A similar process may have made African AIDS in
humans increasingly deadly over time: It's easy to envision a
progression in which an original carrier infected by, let's say, a
Congo vaccine would have to infect several others before the disease
became virulent. Such a process would take time and might explain
the lull before the African epidemic appeared (just about the same
time the epidemic surfaced in the United States and in western
Europe).
The Zaire Connection
In 1987, Belgian researchers writing for a Scandinavian medical
journal identified seven AIDS cases originating in Zaire and in
nearby Burundi between 1962 and 1976 -- well before the African
epidemic exploded. Three of these were retrospectively identified
as AIDS; the other four were cases in which patients had antibodies
for the AIDS virus. Taken together, the authors said, the evidence
indicated "that AIDS had already occurred in Central Africa several
years prior to its emergence in the United States."
There is yet another curious Zaire connection: its relation to
the secondary AIDS hot spot, Haiti. No one knows for sure whether
AIDS migrated from Africa to Haiti or from the U.S. to Haiti. But
according to Grmek, in the early Sixties, after independence came to
the former Belgian Congo, many Haitians worked in Zaire, especially
in Kinshasa. The Haitians -- who were French speaking, black and
had no ties to Belgium -- filled the void previously occupied by
Belgian colonialists. Their arrival, of course, came only a couple
of years after Koprowski's vaccine had been tested in Kinshasa and
in remote eastern Zaire.
As for the idea that the Congo vaccine started the African
epidemic, Koprowski is skeptical. "Why do you choose Africa?" he
asks. "Why don't you compare the enormous number of other countries
where exactly the same [vaccine] material was used? Why didn't it
start an HIV epidemic there?"
This answer seems to beg the question. Specific lots of a
particular vaccine -- not all polio vaccines everywhere -- might
have unintentionally spawned AIDS. For instance, specific batches
of Salk's killed-poliovirus vaccine prepared by Cutter Laboratories
turned out to be insufficiently inactivated by formaldehyde, and
those batches paralyzed 150 of the people who received them and
killed 11. Later, specific lots of Salk's and Sabin's vaccines were
found to have been contaminated by the monkey virus SV40, with as-
yet undetermined long-term consequences in people. Why is it
unreasonable to ask whether a specific batch of Koprowski's
preparation -- say, the unique lots prepared at the Wistar Institute
solely for use in the Congo mass trials -- likewise might have been
Page 13
made from monkey kidneys unknowingly contaminated, in this case by a
retrovirus that causes AIDS?
"You're beating a dead horse," Koprowski says. "My opinion is
that this is a highly theoretical situation, which ... does not make
sense."
Testing Seed Stock?
Koprowski told me that he maintains the seed stocks -- samples
of the original vaccines -- from the Congo mass trials in freezers
at the Wistar Institute. I venture that it would be easy enough to
answer the question just by testing those stocks.
"Yes," Koprowski begins uncertainly. "But I don't really know
how much HIV is really present in monkey kidney .... I have great
doubt it would find its way to epithelial cells such as kidney. You
are postulating that in the highly processed monkey kidney, you'll
get these viruses. I doubt that they are present there."
Later, Koprowski describes for me how the kidneys used in
tissue culture were minced up using "scissors or something like
that." He is quite correct that HIV and its monkey counterpart,
SIV, do not appear to grown in kidney cells. Instead, as he points
out, these viruses are known to grow in lymphocytes and macrophages
-- cell froms found in the blood. But this doesn't mean that under
the right conditions a polio vaccine grown in monkey kidney cultures
might not harbor an AIDS virus.
I raise this issue with Tom Folks, chief of the retrovirus
laboratory at the Centers for Disease Control in Atlanta. "You see,
the problem with the kidney," says Folks, is that "there's blood and
there are lymphocytes that would be contaminating the tissue. So,
no matter how hard you try to mince it up -- and I've made monkey
kidney tissue cultures many a time -- you haven't gotten rid of
contaminating lymphocytes. So, if the monkey that it's derived from
has a pretty fulminant SIV infection, and then they were placing
polio [virus] on top of the monkey kidney, but there were
contaminated lymphocytes, that is going to be part of the stock.
Yeah, it would be there.
"That wouldn't be surprising at all," Folks continues. "And
the fact that it's a live vaccine would indicate that they had not
gone through any inactivation procedures to denature the AIDS virus,
because it would probably denature the polio virus. So, the polio
virus is kept alive, and the SIV virus would just travel with it.
The theory, the possibility is real. And I don't think anyone would
deny it."
The ultimate way to test the idea, Folks agrees, would be to
return to the original seed stocks of the vaccine and actually
isolate the retrovirus, if any, from the polio vaccine.
Does Folks think there is value in figuring out where AIDS came
from? "I think any time we can learn more about natural history, it
helps us understand the pathogenesis [how the disease process
works], and it helps us understand the transmission." Nonetheless,
he says: "It's a delicate issue. You're going to put some people
on the spot -- the person who has the stocks."
Page 14
Some others in the AIDS establishment -- like Dr. David
Heymann, who heads the office of research for the World Health
Organization's Global Programme on AIDS, and Harvard pathology
professor William Haseltine -- are so hostile to the possibility
that a vaccine could have introduced AIDS that they refuse to
discuss it. "The origin of the AIDS virus is of no importance to
science today," Heymann says in a phone interview from Geneva. "Any
speculation on how it arose is of no importance."
Haseltine is even more adamant. "It's distracting, it's
nonproductive, it's confusing to the public, and I think it's
grossly misleading in terms of getting to the solution of the
problem," he says. "It's over, it's done with, it's very, very,
very unlikely it happened that way, and it's another nonsense
article. It's the worst kind of reporting as far as I'm concerned."
But you haven't even heard anything about it, I say. "I know
what the theory is," Haseltine snaps. You don't think the origin of
AIDS is a significant question? "It's not relevant," Haseltine
insists. "Who cares what the origin was? Who really cares? If you
want to do something good, write about problems people experience.
Who cares where it came from? It's an unanswerable question."
It may or may not be unanswerable, I say. "I'm not interested
in discussing it," he says again, and we end the conversation.
Monkey Virus == Human Virus
In AIDS research, and in any inquiry about it, all roads lead
to Dr. Robert Gallo, the federal government's preeminent AIDS
researcher. Gallo, the embattled chief of the National Cancer
Institute's Laboratory of Tumor Cell Biology in Bethesda, Maryland,
was more open-minded than Haseltine and Heymann.
Among the reasons Gallo cites supporting what he considers the
settled question of the origin of AIDS in Africa was "the greater
divergence in people of the virus." "The more divergent a microbe
is in a population, the more time it's had to diverge, all things
being equal," Gallo says. "The divergence in Zaire is far greater
than the divergence in the United States or Europe or anywhere
else."
But how did the virus come to infect Africans? Thanks to
recent research by Gallo's protege, Beatrice Hahn of the University
of Alabama, Gallo notes, we now know that there are genetic
sequences of SIV that are extremely similar to HIV-2, the second
identified AIDS virus that afflicts people and is found mostly in
western Africa. "In other words," Gallo explains, "the monkey virus
_is_ the human virus -- there are monkey viruses as close to
isolates of HIV-2 as HIV-2 isolates are to each other."
The same is true of HTLV-1, the human T-cell leukemia virus, a
retrovirus he discovered that causes a form of leukemia in people.
Genoveffa Franchini in Gallo's lab has found some monkey viruses,
specifically simian T-cell leukemia viruses know as STLV-1, which
are, Gallo says, as close to most of the human HTLV-1 viruses
isolated from the Caribbean islands, southern United States,
southern Japan and equatorial Africa as some STLV-1s are to one
another.
Page 15
What does this mean? Logically, it seems to suggest that there
may well be a monkey with a virus that exactly matches the one that
causes AIDS in humans. So far, however, nobody's found it. The
closer counterpart -- the so-called missing link -- has been found
in two chimps from Gabon. But Gallo says that it is nowhere near as
close as the two other monkey viruses he described are to HIV-2 and
HTLV-1.. "Close enough to argue that it might have been a source of
entry some decades ago," he says. "But it's not close enough to be
called equivalent."
I ask if Gallo thinks a monkey with a virus resembling HIV-1
will ever be found. "I wouldn't be shocked if there was another
species where [the virus] was even closer [to HIV than the variant
found in the two chimps]," he says. "Nobody would be shocked. It
would be interesting and in a sense exciting, but you wouldn't say,
'I can't believe it.'"
So I raise the question of whether Koprowski's polio vaccine,
if contaminated with a simian AIDS virus, could have passed it on to
man. At first Gallo dismisses the idea. "Chimps have a virus like
ours," he says. "The African green monkey doesn't. So start with
the basics, okay? You make an assumption that it's got to leapfrog
and change dramatically. Well, that's ridiculous. ... SIV from
African green monkeys is not real close to HIV-1. So, stop right
there. It ends your theory. Period."
But, I ask, if we know some monkeys have a virtual twin of HIV-
2, and if some monkeys have a virtual twin of the human T-cell
leukemia virus, why wouldn't some group of monkeys somewhere have a
twin for HIV-1? Might this monkey virus exist somewhere?
"Your point is well taken," Gallo says. "In support of your
contention is the fact that HTLV-1 is a far more ancient virus in
man. A _very_ ancient virus in man. You can say that conclusively.
There are Melanesians who were never exposed to Europeans until the
last fifty years who are widely infected with HTLV-1 .... Yet, yet,
there are HTLV-1s that are virtually identical to some monkey STLV-
1s, even though it's had much longer to evolve [in man]. Similarly,
HIV-2 is probably an older infection in man than HIV-1. Yet there
are HIV-2s and SIVs that are almost identical -- that are as
identical as many HIV-2s are to each other.
"Therefore, you would suppose that in a newer infection of man,
you would be far more likely to find an identical virus in a species
of monkeys," says Gallo. "That's the support of your notion. Very
much so. Against it is that a great number of species have been
looked at without finding anything.
"Maybe I'll just say I would have expected somebody would have
found it by now," Gallo says. "But maybe we just haven't looked at
anywhere near enough monkeys. Because I guess you could argue that
even a monkey species where we think we know the virus [exists],
that it could have a second virus [equivalent to HIV]. And that not
all monkeys are infected with that second virus, and that we haven't
hit the monkey that is."
After pausing for thought, Gallo adds, "I don't think that we
can easily come upon that data, though, because there's not a lot of
experiments being done on monkeys in the wild in Africa."
Page 16
A Theoretical Possibility
But even assuming that a monkey version of human
immunodeficiency virus exists, Gallo, like Koprowski, initially
questions whether it would grow in monkey kidney cells and whether
enough virus would be in the preparation to infect people -- perhaps
through lesions in their mouths, through mucous membranes in the
mouths or, since the vaccine was sprayed into people's mouths and
some of it may have become airborne, through the lungs into the
bloodstream. After hearing how the polio vaccines were prepared in
the Fifties, Gallo concedes that in some fashion this way of
transmitting AIDS is "a theoretical possibility." One important
issue is whether the virus can be absorbed through mucous membranes.
Gallo has his doubts, but Haseltine and others think it can.
Earlier in our talk, before I broached the polio-vaccine
theory, Gallo discussed the case of a Norwegian seaman who visited
an east African coastal city in the mid-Sixties, became sick with an
AIDS-like illness in 1966 and died in 1976 at age thirty after
infecting his wife and a daughter, who died shortly thereafter. The
family's blood-serum specimens were tested in the mid-Eighties and
were positive for HIV.
Gallo reminds me of the Norwegian sailor's case. "That sort of
thing goes against" the theory, he says, noting that the sailor was
only known to have been in east Africa, some 700 miles away from the
Kivu.
The virus "sure traveled," says Gallo sarcastically. He
pauses, considering the large numbers of people inoculated with the
oral polio vaccine. "It _might_ travel," he says, "but if those are
rural people, I wouldn't expect it to travel to east African
prostitutes that fast."
It Could Happen
But the vaccine wasn't administered only in rural areas. It
was given to at least 75,000 people in Leopoldville, a port city on
the Congo River that was on a major trade route and that was visited
at the time by around a million people a year, according to a paper
by Koprowski and his colleagues.
After hearing these facts, Gallo pauses and then says: "It
could happen."
Well, I ask, based on the circumstantial case alone, wouldn't
it be wise to check Koprowski's seed stocks?
"Sure, why not?" Gallo says. "Certainly it's not a hard thing
to do. How can I argue against checking the seed stocks? I think
clearly that would be interesting. You have to say what they
[Koprowski and his colleagues] were doing was a good thing, trying
to help people."
Absolutely, I agreed. If this happened, it would be as
unintended an effect as -- Gallo cut me off. "It happens sometimes,
in medicine."
Epilog: Avoiding Future Catastrophes
At my suggestion, Dr. Robert Bohannon of Baylor College of
Page 17
Medicine has already written to Koprowski in Philadelphia requesting
samples of his Congo vaccine so that the material can be tested for
the presence of extraneous viruses including HIV. Koprowski hasn't
yet responded, but the pressure on him to do so may be building.
The original source for this story, Blaine Elswood, has submitted a
paper to a European medical journal, which has sent Elswood's paper
to Koprowski for comment.
Bohannon has also written to the U.S. Food and Drug
Administration requesting access to early seed stocks of the Salk
and Sabin vaccines. The FDA has agreed to supply seed stocks from
1976 on. But Bohannon won't be getting any earlier samples -- there
isn't enough of this material left. Dr. Gerald Quinnan, acting
director of the agency's Center for Biologics Evaluation and
Research, tells me that Sabin's original seed stocks from the early
Sixties were not tested even by the World Health Organization in the
middle Eighties when concern about simian AIDS was high. That was
because there are "only a small number of vials" of the preparation,
Quinnan says, and tests "might use it all up."
In his 1991 book _Virus Hunting_, Robert Gallo suggests that
probing for the origins of AIDS and especially seeking to find out
whether a monkey carries the virus that causes AIDS in people is an
important quest. "We may never know for certain the answers to
these questions," he writes, "but they are of more than academic
interest because answering them may help avoid future zoonotic
catastrophes -- that is, transmission of disease from lower animals
to humans."
Current methods of growing the Sabin poliovirus vaccine
"eliminate most of the blood and lymphocytes" known to be
susceptible to the AIDS viruses, Quinnan tells me. Preparations are
monitored, and that "provides assurance that there is freedom from
most agents," he says. As for being sure the stuff is free from all
agents, like some new retrovirus we don't yet know about, Quinnan
says: "No, you can never prove something absolutely. However, as
far as we know, the system we use doesn't result in any extraneous
viruses."
Like Salk and Sabin, Koprowski had the best intentions: He
wanted to eradicate a debilitating and deadly scourge. But with
what we know now, it's clear there was a certain hubris involved in
the rough-and-ready campaigns to conquer polio. There is evidence
that all three pioneers used vaccines inadvertently contaminated
with viruses from a species dangerously close to our own. If the
Congo vaccine turns out not to be the way AIDS got started in
people, it will be because medicine was lucky, not because it was
infallible.
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