Tag Archives: HIV/AIDS

Hilary Koprowski’s Oral Polio Vaccine: The Bizarre Claim that it was the Source of HIV in Humans

Jonas Salk and Albert Sabin are justly celebrated for developing their respective polio vaccines which, together, have nearly eradicated polio worldwide. However, it was Hilary Koprowski (1916-2013) who actually developed the world’s first safe and effective polio vaccine, doing so several years before Salk and Sabin brought out their more famous vaccines (1). In fact, Koprowski’s oral polio vaccine was used throughout the world between 1957 and 1960. But, it was never licensed in the United States, where the U.S. Surgeon General rejected it in favor of Sabin’s more highly attenuated oral vaccine. [By the way, Sabin developed his vaccine from a sample of attenuated poliovirus that he received from Koprowski.] In any case, Koprowski was the first to demonstrate the practicality of an oral polio vaccine.

An earlier posting told how Koprowski’s reputation was sullied when, in 1950, he tested his live polio vaccine in 20 patients at Letchworth Village; a facility for mentally disabled children in Rockland County, NY (2). Another posting told of Koprowski’s harrowing escape from Poland on the eve of World War II, and of his serendipitous introduction to virology in Brazil, where he sought refuge from the Nazis (3). Here we relate another episode in Koprowski’s tumultuous life; the 1990s assertion that his oral polio vaccine was responsible for the onset of the HIV/AIDS epidemic, when it was administered, between 1957 and 1960, to nearly a quarter million people in the former Belgian Congo. But first, some background.

On June 5, 1981, the Morbidity and Mortality Weekly Report (a publication of the U.S. Centers for Disease Control) told of five sexually active gay men who were suffering from a lung disease caused by the protozoan Pneumocystis carinii. Importantly, those men also presented with “profoundly depressed numbers of thymus-dependent lymphocytes.” That CDC report was singularly notable since it brought to light the onset of a strange and deadly new disease, which soon would be named the acquired immunodeficiency disease or AIDS. Within two years, a “new” virus, which was later termed the human immunodeficiency virus (HIV), was isolated and shown to be the cause of AIDS (4).

The general public, as well as the biomedical community, wanted to know the origin of HIV, and how and where it entered the human population. Research would show that HIV likely crossed into humans from particular subspecies of chimpanzees, unknowingly and on multiple occasions during the 20th century. However, two 1990s publications—a 1992 Rolling Stone article by writer Tom Curtis (5) and The River, A Journey to the Source of HIV and AIDS, a 1999 book by British journalist Edward Hooper (6)—proposed a rather different hypothesis; that Koprowski’s oral polio vaccine gave rise to the HIV/AIDS epidemic.

At the heart of the accusation was, first, the claim that some of Koprowski’s vaccine lots were propagated in primary monkey or chimpanzee tissue that harbored the related simian immunodeficiency virus (SIV). Second, they alleged that SIV was transmitted to the Congolese via the contaminated vaccine and, third, that SIV evolved into HIV in humans.

In the Rolling Stone article, Curtis rightly noted that Koprowski indeed grew his vaccine in monkey cells, and Curtis stated so again in a 1992 letter to Science (7). Curtis also asserted that 87% of the 39 confirmed cases of HIV-positive blood samples that were collected in Africa before 1981 came from towns within 100 miles of sites where the Koprowski’s vaccine was administered (5, 7).

Koprowski responded to Curtis’ charges in his own letter to Science (8). First, he addressed the claim that the vaccine harbored SIV: “After the original batch of the type II polio vaccine was produced in cotton rat brain, all other batches were produced in kidney tissue obtained from rhesus monkeys (Macaca mulatta) captured either in India or the Philippines… Curtis’ speculation that we could have used in our production kidney tissue from other species of monkeys that might have harbored a simian immunodeficiency virus (SIV) or an HIV virus has no basis in fact.”

Next, Koprowski addressed the claim that the outbreak of HIV correlated geographically to the regions where the vaccine was administered: “Curtis has theorized that the ‘African epidemic was spawned by a contaminated polio vaccine administered from 1957 to 1960 to at least 325,000 people in Rwanda, Burundi and the former Belgian Congo.’ He has stated that the area of vaccination of children in Ruzizi Valley in 1958 corresponds to ‘roughly to another map . . . the one identifying the regions of highest HIV [human immunodeficiency virus] infection in equatorial Africa.’ This is completely wrong. Ruzizi Valley, where 215,504 subjects were vaccinated in 1958, is located in the northwestern part of the Republic of Burundi, not in the Kivu district of Zaire, an area where Curtis placed ‘the lion’s share of their [Koprowski and his associates] samples (8).’” See Aside 1.

[Aside 1: Koprowski justified taking his dispute with Curtis to Science as follows: “As a scientist, I did not intend to debate Tom Curtis when he presented his hypothesis about the origin of AIDS in Rolling Stone. The publication of his letter in Science (29 May, p. 1260), however, transferred the debate from the lay press to a highly respected scientific journal. I would now like to state my views, based on facts, in order to counter and thereby repudiate Curtis’ hypothesis about the origin of AIDS (8).]

Curtis received considerable pushback from the biomedical community. Yet his Rolling Stone article seems to have been an earnest and sober attempt to put forward a credible premise for how HIV might have crossed into humans. Before Curtis wrote the piece, he first interviewed several top retrovirologists and polio researchers, including Robert Gallo, William Haseltine, Joseph Melnick, Albert Sabin, and Jonas Salk, as well as Koprowski; asking each probing questions concerning the plausibility of his premise. ‘“You can’t hang Koprowski with that,’ Albert Sabin growls at me… Sabin insists that the AIDS virus won’t survive swallowing…Dr. Robert Gallo and other retrovirus researchers acknowledged to me; no one knows for sure… Salk… flatly refused to discuss the subject (5).”

Curtis defended his Rolling Stone article in his 1992 letter to Science, writing: “…I think any fair-minded reader will recognize that I took great pains not to demonize medical science in general or any individual research scientist.”  To that point, Curtis acknowledged in the Rolling Stone: “Like Salk and Sabin, Koprowski had the best intentions: He wanted to eradicate a debilitating and deadly scourge.” Nonetheless, in Science, Curtis added: “As for the assertion that there is not a ‘picogram of evidence” supporting the theory, that is flat-out wrong. There is a strong, if circumstantial case.”

Turning now to The River, bear in mind that it was published seven years after Curtis published his Rolling Stone article. During that interim, significant evidence had accumulated, and had been reported in scientific journals, repudiating the charge that Koprowski’s vaccine was responsible for the HIV outbreak. What’s more, the CDC had issued an official statement that the “weight of scientific evidence does not support the idea.”

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Nonetheless, Hooper’s assertions in The River were more immoderate than those made earlier by Curtis. Hooper’s argument began with the fact that before the mass trial of the Koprowski vaccine in the Congo, the vaccine was tested first in a colony of chimpanzees living near Stanleyville (now Kisangani) —the headquarters of the vaccine campaign. [The animals’ caretakers were vaccinated concurrently. In fact, the successful immunization of those workers provided the justification for the ensuing first ever mass trial of an oral polio vaccine in humans.]

Hooper then noted that the Stanleyville chimpanzee colony was maintained by Philadelphia’s Wistar Institute (where Koprowski developed the vaccine). Hooper next alleged that Wistar scientists took kidneys from those chimpanzees back to Philadelphia, where they used them to produce the cell cultures in which they grew more of the vaccine. Hooper’s argument continues with the assertion that the chimpanzees carried SIV, which thus contaminated the vaccine, and that the SIV evolved into HIV after being introduced into humans via the vaccine.

In response to Hooper’s claims, the Wistar Institute engaged three independent laboratories to test 40-year-old leftover vaccine lots for the presence of HIV and SIV, and also for chimpanzee mitochondrial DNA. The combined results of those studies, which were reported at a 2000 meeting of the Royal Society of London, failed to support the claims put forward by Hooper, nor did they support the earlier clams advanced by Curtis. The vaccine lots did not contain either HIV or SIV, nor was there any evidence that any of the lots were grown in chimpanzee cells. See Aside 2.

[Aside 2: Stanley Plotkin (1932, currently an adviser at the vaccine firm Sanofi Pasteur) was a Wistar scientist who, in the 1950s, collaborated with Koprowski on the polio vaccine project. In a 2001 paper, Plotkin disputed Hooper’s charge that Wistar scientists were oblivious to the threat of extraneous agents in their primary cell cultures (9). Plotkin added: “This is the strangest paper I have ever given, belonging perhaps more to the world of literary exegesis than to the world of science. However, it is time that the true history be told… to correct the misrepresentations that have been widely disseminated by The River (Hooper 1999) and subsequently by articles written about the book…The river has been praised for its precise detail and wealth of footnotes, but one can be precise without being accurate (9).”]

Hooper was not to be dissuaded by the reproach of the science community. Instead, he fought back. He dismissed the fact that tests of 40-year-old leftover vaccine lots did not find any evidence of SIV, HIV, or chimpanzee DNA, claiming that the particular vaccine lots that were produced in chimpanzee cells were no longer in existence and, thus, were not tested.

Even if Hooper were correct on that particular point, his allegations against the Koprowski vaccine were discredited by several other lines of evidence. For instance, the SIV strain in the Stanleyville chimpanzees was phylogenetically distinct from all strains of HIV (10). Thus, even if the SIV carried by those chimpanzees had somehow contaminated the Koprowski vaccine, it could not have been the progenitor of HIV in humans. To that point, other studies showed that the chimpanzee virus that is the precursor of HIV actually originated in west-central Africa; not in the Congo.

Moreover, a comparison of HIV samples taken over time leads to the estimate that the crossover of SIV into humans occurred sometime during the1920s and 1930s, and perhaps even before that; at any rate, decades before Koprowski’s African vaccine program. [That analysis assumes that the rate of change of HIV has been constant over time.]

Earlier, in 1993, Koprowski filed a defamation suit against Curtis and Rolling Stone. Just before Koprowski was scheduled to give a deposition, his lawyers reached a settlement, in which Koprowski was awarded $1 in damages. However, in addition to that symbolic award, the magazine agreed to publish a “retraction” of sorts, which (in December 1993) stated in part: “The editors of Rolling Stone wish to clarify that they never intended to suggest in the article that there is any scientific proof, nor do they know of any scientific proof, that Dr. Koprowski, an illustrious scientist, was in fact responsible for introducing AIDS to the human population or that he is the father of AIDS…”

Hooper, on the other hand, has stood by his assertion that the Koprowski oral polio vaccine (OPV) program in the Congo was responsible for the emergence of HIV. He maintains a current web site—AIDS Origins: Edward Hooper’s Site on the Origins of AIDS—which, in a December 2015 update, stated: “Though members of the “bushmeat school” would have you believe otherwise, the arguments for the OPV/AIDS hypothesis grow consistently stronger as more information becomes available.” [The bushmeat or hunter theory holds that the HIV precursor was transmitted to humans when a human hunter was bitten or cut while hunting or butchering a monkey or ape for food. It is considered the simplest and most plausible explanation for the cross-species transmission of HIV to humans.] Elsewhere on the site, Hooper states: “In the years since 1992, I and many others (including the great evolutionary biologist, Bill Hamilton) have examined further evidence from many different sources, and found that OPV is in fact a far more compelling theory of origin than bushmeat.”

Hooper has gone so far as to suggest that the biomedical community is engaged in an organized cover-up of the OPV-HIV connection: “Because of the enormous implications of the hypothesis that AIDS may be an unintended iatrogenic (physician-caused) disease, it is almost inevitable that this theory will engender heated opposition from many of those in the scientific establishment, and those with vested interests (11).” See Aside 3.

[Aside 3: Conspiracy theories about the origin of AIDS—particularly that HIV was man-made and deliberately introduced into humans—first appeared in the late 1980s and abounded in the 1990s. They gained especial traction in the African American Community. Some may recall Reverend Jeremiah Wright, President Barak Obama’s former pastor, whose comments on several subjects raised a storm in the media (causing Obama to ultimately disassociate himself from Wright). One of those comments was that “the U.S. government invented AIDS to destroy people of color.”]

Although Hooper’s claims have been discredited by rigorous scientific testing, The River was well-received in the popular press. Consequently, and sadly, the book’s anti-vaccine sentiments gained credibility in the public; stirring a distrust of vaccines that set back global efforts to eradicate polio, while also discouraging many Americans from having their children vaccinated against polio and other diseases as well. To that point, Koprowski concluded his 1992 letter to Science as follows: “Tremendous efforts were made by scientists to save children from paralytic polio. The current anxiety among parents of children who have been or are going to be vaccinated against polio followed dissemination by the lay press of unproved theories of the origin of AIDS. This was unnecessary and harmful, particularly since the vaccine was tested thoroughly before any vaccination was done; the vaccine was and continues to be safe (8).”

Yet the story does not end on so simple a moral lesson. As asserted by noted retrovirologist Robin Weiss: “Yet one lesson to be learned from considering OPV as a source of HIV is how plausibly it might have happened and how cautious we need to be over introducing medical treatments derived from animal tissues, such as live, attenuated vaccines… (12).”

To Weiss’ point, recall that early lots of both the Salk and Sabin polio vaccines were unknowingly contaminated with simian virus 40 (SV40) (13). What’s more, the contaminated vaccines were administered to hundreds of millions of people world-wide, before SV40 was even discovered! In fact, SV40 was discovered as a contaminant of those vaccines. The early polio vaccine lots were contaminated with SV40 because that virus was unknowingly present in the rhesus monkey kidney cell cultures in which the vaccines were grown. Afterwards, it was discovered that SV40 causes tumors in newborn hamsters. We owe it to good fortune that SV40 was not a serious threat to humans.

Curtis was well aware of the SV40 story when he wrote the Rolling Stone article. “There is evidence that all three pioneers (Koprowski, Salk, and Sabin) 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 (5).”

References

  1. Jonas Salk and Albert Sabin: One of the Great Rivalries of Medical Science, Posed on the blog March 27, 2014.
  2. Vaccine Research Using Children, Posted on the blog July 7, 2016.
  3. Hilary Koprowski: Genesis of a Virologist, Posted on the blog August 26, 2016.
  4. Who discovered HIV? Posted on the blog January 23, 2014.
  5. T Curtis, The origin of AIDS, Rolling Stone, no. 626 (19 March 1992)
  6. E Hooper, The River, A Journey to the Source of HIV and AIDS, Little Brown & Co, 1999.
  7. T Curtis, 1992. Possible origins of AIDS. Science 256: 1260-1261.
  8. H Koprowski, 1992. AIDS and the polio vaccine. Science 257:1026-1027.
  9. SA Plotkin, 2001. Untruths and consequences: the false hypothesis linking CHAT type1 polio vaccination to the origin of human immunodeficiency virus. Philosophical Transaction of the Royal Society of London. Series B, Biological Sciences 356:815-823.
  10. Worobey M, Santiago ML, Keele BF, et al., 2004. Origin of AIDS: contaminated polio vaccine theory refuted. Nature 6985:820.
  11. E Hooper, 2001. Experimental oral polio vaccines and acquired immune deficiency syndrome. Philosophical Transaction of the Royal Society of London. Series B, Biological Sciences 356:803-814.
  12. RA Weiss, 2001. Natural and iatrogenic factors in human immunodeficiency virus transmission. Philosophical Transaction of the Royal Society of London. Series B, Biological Sciences 356:947-953.
  13. SV40-Contaminated Polio Vaccines and Human Cancer, Posted on the blog July 24, 2014.

 

Zika Virus, Part 3: Update on the Science, Some History, a Little Politics, and an Appearance by Pope Francis

Much has happened since our lasting posting on the Brazilian Zika outbreak (1). In particular, the major topic of our last posting was the uncertainty regarding whether Zika virus causes congenital birth defects. Recent findings may be settling the issue.

One reason for the earlier uncertainty was that although Zika virus has spread to more than a dozen countries since its discovery in Uganda more than 50 years ago, Brazil remained the world’s only country in which the virus was associated with microcephaly. However, in February 2016, Brazil’s neighbor, Colombia, now the world’s second-most Zika-affected country, reported its first cases of birth defects linked to Zika.

More direct and compelling evidence for Zika as an agent of microcephaly was reported early this March in the New England Journal of Medicine (2). Ultrasound examination of Zika-infected pregnant woman revealed that 29 percent of them carried fetuses suffering “grave outcomes, including fetal death, placental insufficiency, fetal growth restriction, and CNS injury.” Zika infection of the mothers was confirmed by reverse-transcriptase–polymerase-chain-reaction assays of blood and urine specimens. “To date, 8 of the 42 women in whom fetal ultrasonography was performed have delivered their babies, and the ultrasonographic findings have been confirmed.”

Although the above study examined only 88 women, all at one clinic in Rio de Janeiro, an article in the New York Times (March 5, 2016) quotes Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases as saying, “Now there’s almost no doubt that Zika is the cause.”

Another notable report described a case of a pregnant woman who, while living in Brazil, came down with a Zika-like feverish illness at the end of the first trimester of her pregnancy (3). The mother opted to abort her 29-week-old fetus after it showed signs (by ultrasonography) of microcephaly—subsequently confirmed by autopsy of the fetus. Importantly, a flavivirus was visualized in the fetal brain by electron microscopy, and the entire Zika genome (unambiguously identified by reverse-transcriptase–polymerase-chain-reaction assay) was recovered from it.

Next, we consider a new finding that Zika can be present in breast milk. Whereas Zika is an arthropod-borne virus that is transmitted primarily by its mosquito vector, our first posting on the Brazilian Zika outbreak noted at least one instance in which Zika was transmitted via a blood transfusion (4). In addition, there were reports of Zika being sexually transmitted (5). Now there is a report of Zika virus in the breast milk of a mother in New Caledonia (6).

The woman was feverish in July 2015 when she arrived at the hospital to give birth. Nevertheless, she breast fed her apparently healthy baby immediately after delivering it. Samples of the mother’s serum and breast milk then tested positive for Zika virus by reverse-transcriptase–polymerase-chain-reaction assay, while a test of a serum sample from the 3-day–old baby was ambiguous. The mother’s fever, now accompanied by a characteristic Zika rash, persisted for the next several days. Nonetheless, she and her baby were each healthy when they left the hospital.

This report would appear to raise considerable concern that a Zika-infected mother might transmit the virus to her baby via her breast milk.  All the same, the US Centers for Disease Control and Prevention (CDC) maintains that the benefits of breastfeeding outweigh the theoretical risks of Zika virus infection via breast milk, and recommends that infected women should breastfeed.

Next, we consider some recent history. On February 1, 2016 the WHO declared that Brazil’s Zika outbreak is as an international public-health emergency. But, uncharacteristically, the WHO put forth this pronouncement despite the fact that the scientific community was still not sure of the threat that Zika poses to humans. In point of fact, this was the first instance in which the WHO proclaimed its highest level of alarm for an agent of uncertain danger. [The CDC likewise elevated its Zika virus surveillance program to its highest priority level.]

Why did the WHO make its frightening declaration when the threat posed by Zika was still not clear? Obviously, a failure to take immediate action might allow the Zika outbreak to get well out of hand, with possibly devastating consequences.

In contrast to the hurried response by the WHO to the Zika outbreak, that agency responded more leisurely to the 2013/2014 West African Ebola outbreak, which did get out of control, and which persists even to this day. So, perhaps the more urgent response of the WHO to the Zika outbreak reflects a lesson learned from the Ebola affair.

But, why did the WHO wait longer before responding to the West African Ebola outbreak? One reason is because it was strongly criticized for “overreacting” to the risk posed by the 2009 H1N1 influenza epidemic—which turned out to be far less threatening than originally feared.

While the WHO may have learned a lesson from its somewhat unhurried response to the Ebola outbreak, its more urgent February 1, 2016 Zika declaration did not go far enough for some observers, since it stopped short of advising pregnant women not to travel to Zika-affected regions. For that reason, the WHO has been accused of taking political considerations into account, to the detriment of good public health policy. Any travel ban—even one aimed only at pregnant women—would be embarrassing and costly to Brazil, which has been moving ahead with its plans to host the Olympic Games this summer. Still, hundreds of thousands of people from around the world, including female spectators and participants, some of whom may be pregnant, are expected to attend.

Lastly, we note that the Zika outbreak has been stirring up a fierce religious debate in Latin America; a debate that is actually challenging the very authority of the Catholic Church in the hemisphere. But first, an earlier posting on the blog recounted how in 2002 Colin Powell, at the time Secretary of State in the George W. Bush administration, advocated that sexually active young people should use condoms to protect themselves against HIV/AIDS (7). Powell’s advocacy of condom usage was contrary to the Bush administration’s strongly held abstinence-only approach for preventing sexual transmission of HIV. Moreover, then as now, Powell’s stance was contrary to the official position of the Catholic Church on artificial contraceptives. Nevertheless, Powell asserted, “I certainly respect the position of the Holy Father and the Catholic Church. In my own judgment, condoms are a way to prevent infection. Therefore, I not only support their use, I encourage their use among people who are sexually active and need to protect themselves.”

Now, presumably in response to reports that Zika virus might be transmitted sexually, Pope Francis declared on February 18, 2016—during a mid-air news conference on his flight from Mexico back to Rome—that contraceptives could be used to block the spread of Zika virus. That same day, the WHO advised the sexual partners of pregnant women to use condoms, or to abstain from sex, if they live in a Zika-affected area, or if they are returning from one of those areas. Also, several Latin American governments asked their female citizens to delay getting pregnant.

Pope Francis after deplaning in Ciudad Juarez, Mexico, on February 17, 2016
Pope Francis after deplaning in Ciudad Juarez, Mexico, on February 17, 2016

Those suggestions, whether from Latin American governments, or from the WHO, offended many Latin American women, in part because of the strict anti-abortion laws, and laws that restrict access to contraceptives in some of those countries. Moreover, the situation is compounded in some regions of the hemisphere by rampant sexual violence against women. In any event, the Pope’s pronouncement intensified an angry debate over contraception, and abortion as well, that was already underway in Latin America.

Pope Francis did not condone abortion, which he referred to as an “absolute evil.” But, he did make a point of justifying his statement condoning contraception by citing as a precedent a 1960 judgment by Pope Paul VI, which permitted nuns in the Belgian Congo, who were in danger of being raped, to use contraceptives.

Pope Francis’ remarks, such as “avoiding pregnancy is not an absolute evil,” has encouraged Latin American opponents of the church’s longstanding ban on the use of artificial contraceptives to campaign harder against those policies. In any case, the Pope’s pronouncement, and the heated response it is provoking, shows that the Zika outbreak is now impacting religious institutions. And, as noted by Ana Ayala, the director of the Global Health Law Program at Georgetown University, “The pope’s positioning on this subject can significantly shift how governments see access to contraception.” See Aside 1.

[Aside 1: Ayala’s comment can be found in a February 18, 2016 article in the New York Times, entitled “Francis Says Contraception Can Be Used to Slow Zika”, by Simon Romero and Jim Yardley. This piece offers an extensive account of the response in Latin America, and elsewhere, to the Pope’s comments. “While international researchers are still trying to prove definitely a link between Zika and microcephaly, the pope’s comments on contraception seemed to catch up to the reality in parts of the hemisphere where many Catholics pay little heed to the church’s teachings on birth control.”]

References:

  1. Zika Virus, Part 2: The Link to Birth Defects, Is It Real?, Posted on the blog February 23, 2016.
  2. Brasil, P., Pereira, J.P., Gabaglia, C.J., et al., Zika Virus Infection in Pregnant Women in Rio de Janeiro — Preliminary Report, N. Engl. J. Med., March 4, 2016DOI: 10.1056/NEJMoa1602412
  3.  Mlakar, J., Korva, M., Tul, M., et al., Zika Virus Associated with Microcephaly, N. Engl. J. Med. 2016; 374:951-958 March 10, 2016 DOI:10.1056/NEJMoa1600651
  4. Zika Virus: Background, Politics, and Prospects, Posted on the blog February 4, 2016.
  5. Foy, B.D., K. C. Kobylinski, J.L. Foy, et al., 2011. Probable Non–Vector-borne Transmission of Zika Virus, Colorado, USA, Emerg Infect Dis. 17: 880–882.6.
  6. Myrielle Dupont-Rouzeyrol, M., Biron, A., O’Connor, O., Huguon, E., and Descloux, E., Infectious Zika viral particles in breastmilk, The Lancet 387:1056, March 2016. doi:10.1016/S0140-6736(16)00624-3
  7. Colin Powell on HIV and Condoms, Posted on the blog July 30, 2014.