THE ORIGIN OF AIDS A Startling New Theory Attempts to Answer the Question 'Was It An Act o
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
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 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.
....
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.
* * * * *
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.
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 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."
....
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 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 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 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 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
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 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 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 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 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 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."
....
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."
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.
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."
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.
....
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 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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