Polio vaccines and the origin of AIDS
in the subsection on W D Hamilton's rejected submission to Science.
It is located on the website on suppression of dissent.
The headline "Rolling Stone rolls over for Koprowski" (Random
Samples, 26 November) is right for the "clarification" that Rolling
Stone published but your piece that follows oversimplifies. A reader
might gather (as also from your earlier column on the Wistar
Institute committee's report {30 October 1992, p738}), that the idea
that the pioneer polio vaccination campaign in Central Africa in the
late 50s could have started the AIDS pandemic is now thoroughly
dismissed.
This is far from being the case. The "clarification" that Rolling
Stone published on 9 December 1993 hardly says more than was obvious
to most readers already -- no objective to defame. The original
article was good science journalism. It was well researched and was
attentive to alternatives: I was astonished that Koprowski sued.
After a re-reading I still cannot see what, apart from a very slight
geographical error which concerns only the two sides of one valley,
plus a retracted report (1) that Curtis might have noticed, Koprowski
considers unfactual, unreasonable, or unduly ad hominem in the
matters described. Tom Curtis, the author, was airing a scientific
theory and had as much evidence as is usual initially. The theory he
wrote about admittedly has snags, but so does any. It is easy to make
a longer list of plain errors from Koprowski's ("As a scientist ...")
brief rebuttal (2). {SEE APPENDIX-NOT for publication}.
Regarding snags to the Curtis theory, let us admit first, for
example, that the evidence is for a precursor SIV from chimpanzees:
how would that have arrived in an attenuated polio virus vaccine
raised in cercopithecine tissues? Second, if reaching such cultures,
how could the SIV multiply in a monolayer kidney cell medium that did
not include the virus's preferred cells, CD4 lymphocytes? Third, even
if the culture could have been based by error upon tissue of a
chimpanzee harbouring an SIV, must not absence of the favoured cell
type still exclude the virus?* Fourth, why is the geographic fit of
AIDS in Africa to the polio campaign of the region not matched by a
corresponding fit in Poland where a parallel early campaign was
applied and no early AIDS appeared (2)? Fifth, how explain a
Manchester seaman dying of AIDS too soon to have been infected from
the vaccine (3)? And so on.
Similar snags, however, can be produced to all the other theories.
Yet clearly the AIDS virus came to Homo from some other species and
did so via unusual events just as does any parasite moving to a new
host. All the above snags can be answered in ways that, while not yet
dismissing them, at the very least suggest further work. Thus SlVs
are known to exist as deeply divergent genotypes within single wild
primate populations (4) and this implies that SlVs much more similar
to HIV-1 may yet be found in the monkey species [but which
exactly? -- no one seems to know (2, 5)] that were used for the
vaccines. Neither this idea expressed by Curtis in his article nor
that of an unusually rapid evolution as the virus begins cycling in a
new species, is at all unreasonable. Assisting pathogen "passage" several or many times through a new host in which it is to be
cultured, is standard and is nothing more than the experimenter
inducing rapid evolution, a rapidity potentially greater in
retroviruses through their diploidy and recombination. Turning to the
second snag, contamination of tissue cultures with retroviruses is
common even in the best endowed institutions (6) and Koprowski's team
was regularly dissecting chimpanzees in the conditions of a remote
Congo laboratory (7,8) for purposes connected with polio. Third,
lymphocytes are not completely absent from kidney tissue cultures
(9,10) and there are many other cell types which HIV-1 and its simian
cousins can infect with or without contaminant viruses aiding their
entry. The paper (9) on which the Wistar Committee relied in stating
HIV-1 could not survive in the cultures did not consider the issue of
co-infection and was weak in several regards. Even its main
conclusion was unclear as the SIV may at the end have been
increasing. If HIV-1 can be grown at least with co-viral assistance
in non-immune-system tissues cultured from organisms as distant as
mink and mouse, as has been done (11), why should a simian precursor
of HIV not gain entry and multiplication in pre-infected,
non-lymphocyte tissues of an unusual host primate, or be pseudotyped
onward with help of the same or other co-infecting virus into the
tissues of yet another host, Homo? Indeed might it not increase
virulence to become more HIV-like during such a passage, as has also
been shown (12). Fourth, the Polish polio campaign was on a very
small scale (one hundredth) compared to the Congo trials, did not use
intra-oral spray, and unlike the African trial (13) excluded neonates
as subjects for inoculation (14), all points which severely weaken
the comparison. Fifth, it is not true as Koprowski has stated that he
could not be a secondary case arising from a contact from Africa. He
had visited Africa and the dates although unlikely to mesh are not
impossible.
It is not my object here to say that these ways around the snags I
have mentioned amount to any great joint likelihood, still less to
say that the theory Curtis reported is the most likely. My object is
simply to emphasise that every theory has snags and ways round them,
and that the proper course of Science is to allow all theories
to be discussed so that their critical points can be focused and
tested. It is certainly not the way to use lawsuits to terrorise
individuals and journals that try to promote discussion. Being burned
alive as a heretic is admittedly worse than facing financial ruin as
a heretic, but except for the threat being different we have seen
this mode before and have also seen, last year, its belated and
shame-faced finale in the Vatican's apology to Bruno and Galileo. Are
we starting this all over again with a Medical Establishment now in
the robes of the universal Roman Church? Apart from shame in the
method, the overcrowding of present humanity plus its fluid mixing
means that in respect of future human epidemics, failure to
heed lessons before launching new public health campaigns has a
potential to result in hundreds of millions of deaths. Nor is it just
potential if the AlDS-polio contention turns out to be right and the
above rough figure is certainly no overestimate. Mistakes in this
field are much more directly dangerous for all of us, and dangerous
even within our lifetimes, than was the failure to face up to the
heliocentric theory of the universe.
A circumstantial case that the precursor virus of HIV-1 (not HIV-2)
might have transferred to humans during the polio vaccination
campaign in the Congo seems to have stirred action in a half dozen or
so scattered people. Others followed them, Curtis, for example,
writing for Rolling Stone in support of originator Elswood.
Concerning an earlier, independent, more detailed, yet still closely
parallel version due to Louis Pascal (8), the editor of the Journal
of Medical Ethics wrote recently that it was "important and
thoroughly argued" and deserved to be "taken seriously by workers in
the AIDS field" (15). Before I read the Rolling Stone article I
already had been strongly persuaded by Pascal's account that there
was a serious case to investigate. I was shocked by his evidence of
outright and never explained resistance to his idea from medical
scientists and journals. Koprowski is clearly far from alone in
feeling the idea should not to be aired. Yet in Pascal's account as
in Curtis's I detected nothing that seemed exaggerated towards
defaming Koprowski, instead only a wish to outline a possible huge
tragedy that might have arisen from a noble venture, a great good and
a great bad tangled together. Above all he had delineated a tragedy
which, if real, should at all costs be allowed to imprint its lesson
on future policy. Proponents of the idea mentioned so far are none of
them scientists. Two who yet again published it independently,
Lecatsas and Alexander, are professors of virology and microbiology
respectively (16). An idea occurring to scattered, diverse,
well-informed people, that many others subsequently have acknowledged
to be worthy of study, and that has been noticed in Research in
Virology (17), cannot be considered frivolous or devoid of
evidence. It did not deserve a lawsuit.
A strange feature of the case is that a step towards a refutation of
the idea is readily available. A sample of a vaccine stated as
possibly relevant to the Congo campaign have been located at the
Wistar Institute and yet so far no test has been reported nor any
sample released for testing (10). If provenly untampered samples of
the questionable batch of vaccine are tested and convincingly found
free of SlV/HIV-type viruses, this would go far towards dismissing
the theory. Testing for and even sequencing a retrovirus if present
is relatively easy but contriving an acceptable setting and protocol
may be less so and perhaps that is the difficulty. Nevertheless that
almost two years after the original Curtis and Pascal articles came
out, and twenty months after discovery of the stored samples, nothing
should be even in motion towards testing them seems
extraordinary.
After six months of deliberation a panel convened by the Wistar
Institute to examine the AlDS-Polio theory produced a strongly
dismissive report. This ended, however, with the oddly contrasted
recommendation that current methods of raising vaccine viruses in
non-human primate tissues should be superseded as soon as possible.
Several items in the report seemed weak, some being answerable on the
lines I have touched on above. Oddest of all the report gave only
lukewarm support for testing just one of the many vaccine or seed
samples related to polio that are at the Wistar Institute. These
could even, one would think, have been tested within the six months
of the committee's term. Curtis has summarised the outcome as like a
jury bringing a verdict of not guilty when an obvious key witness is
still waiting in the courtroom to be heard.
The Wistar panel's final suggestion that the technique of raising
attenuated viruses for vaccines needed to be changed appeared to
admit overstatement elsewhere. Similarly thirty years ago, four years
after the Congo campaign began, Hilary Koprowski, then as now (2)
believing that the techniques he had used were danger free, became a
pioneer spokesman for an identical view on the undesirability of
non-human primate tissue culture for virus vaccines.
To conclude, cercopithecine tissue culture is still being used and at
the same time other techniques that might also facilitate species
jumps by pathogens such as organ transplants from non-human primates
into humans are increasing fast. These various medical techniques may
be very dangerous for human future, indeed they could conceivably
deny humans having a future. Scientists should listen to and
investigate with due care common-sense suggestions and warnings
arriving from outside their ranks; they should not endeavour to
suppress them (18). In the face of overbearing professional mystique,
disregard, and now even litigation, the public is justified in its
growing disillusion with science and also in some of its deepest
fears.
1911 words
W. D. Hamilton
Royal Society Research Professor
Department of Zoology
Oxford University
South Parks Road Oxford OX1 3PS
England
* Not for publication: I am aware of the recent exchange in
Lancet about negative testing of some more vaccines and the issue of
trypsinization. However (a) the new findings were not available at
the time of the Koprowski lawsuit, (b) they were challenged, and (c)
the spirit of the exchange shows that some in medical circles
are taking the Curtis theory seriously, in keeping with my letter's
theme that seriousness is deserved.
1. R. Biggar Lancet 1985 ii 808 (1985).
2. H. Koprowski, H. Science 257, 1026 (1992).
3. G. A. Corbitt et al., Lancet 1959 ii, 51
(1959).
4. Gao, F et al. Nature 358, 495-499 (1992); Li, Y. et
al., J. Virol. 63, 1800 (1989); Johnson PR et al.,
J. Virol. 64, 1086 (1990).
5. H. Koprowski, J. Am. Med. Assoc. 178, 1151 (1961); T.
Curtis, Rolling Stone, no. 626 (19 March 1992).
6. C. Mulder, Nature 331, 562, (1988); S. Wain-Hobson
and G. Myers Nature, 1990. 347, 18 (1990); B. Culliton
Nature 351, 267 (1991).
7. G. Courtois, et al., Brit. Med. J. ii, 187
(1958).
8. L. Pascal, Univ. of Wollongong Sci. Techn. Anal. Res. Prog.,
Working Papers 9, 5 (1991).
9. Y. Ohta et al., AIDS, 1989. 3, 183
(1989).
10. C. C. Basilico et al., Report from the AlDS/Poliovirus
Advisory Committee, Wistar Institute of Anatomy and Biology
(1992).
11. B. Chesebro, et al., J. Virol. 1991. 65,
5782(1991); P. Lusso, et al., Science 247, 848
(1990).
12. N. Rothwell Understanding Genetics New York: Wiley-Liss
(1993).
13. A. Lebrun et al. Bull WHO 22, 203 (1960).
14. F. Przesmycki et al. Bull WHO 26, 733 (1962).
15. R. Gillon J. Med. Ethics 18, 3 (1992).
16. G. Lecatsas and J.J. Alexander South Afr. med. J.,
76, 451 (1989).
17. B. Elswood and R. Stricker Res. Virol.144, 175
(1993).
18. B. Martin BioScience 43, 624 (1993).
Errors in ref. (2):
1. The Ruzizi river is the boundary between the region of Burundi
where the Koprowski team conducted its first large scale vaccination
campaign, and the Kivu District of what is now Zaire. Curtis may have
been slightly inaccurate but it is only a matter of the two sides of
a river and it is certainly unfair to call him "completely wrong". On
the scale of a map of Africa or even of Zaire and in a comparison of
the map of the polio campaigns with the map of the distribution of
AIDS the distinction makes little difference.
2. The first AIDS case listed in the source Koprowski cites was in
Kinshasa where a campaign using the suspect CHAT vaccine had been
applied (13). The two following were in Burundi where the first
campaign was mounted (2). All three cases must be described as close
to where vaccine was applied, contrary to Koprowski's
implication.
3. No possible two points relevant to the discussion in Zaire plus
Ruanda/Burundi are "thousands of kilometres" apart (i.e. all are
<2000, while the absolute greatest distance attainable in the
three countries together, about 2300 NW to SE, involves points
completely irrelevant). Koprowski's claims on distances are wrong and
careless.
4. The Manchester sailor's truly AlDS-like symptoms were not present
"throughout 1958" but began in December 1958 (3). A quarter of a
million Africans had been vaccinated by April 1958. It is therefore
an error to say that the sailor had symptoms of AIDS before the polio
campaign began unless Koprowski claims gingivitis and eczema confirm
AIDS. It is more likely on anyone's theory these had been
predisposing factors to infection. The sailor had visited Tangier.
The time is short and he would have to have been a rapidly developing
case, but he is not an impossible secondary case to follow
from the African campaigns, as Koprowski implies.
5. Rhesus monkeys occur in India but not in the Philippines. If
Koprowski knows of a naturalised or even captive population in the
Philippines whence Rhesus were "captured" he should give details.
6. Koprowski's statements about the sources of his monkey's have
varied (2,5) His paper in ref. (5) (J. Am. Med. Assoc. 178, 1151
(1961) gives both India and the Philippines as source and hence does
not support (2).
7. Koprowski might have a basis for saying SlV-infected monkeys have
few SIV infected cells in their kidneys but there is no basis
from either of his given references for saying that they have none
(see critique in ref. 8, Appendix).
8. Koprowski claims that the contaminating virus that Sabin claimed
to find twice in Koprowski's material was in a seed lot for
vaccine; but Sabin himself says he found it in vaccine that was
used in the Belgian Congo (BMJ, 14 March 1959, 663-80) and in
Poland (First International Conference on Live Poliovirus
Vaccines, 577), and these claims were never contested on grounds of
Sabin's mention of vaccine by Koprowski. Perhaps there are
distinctions here that I do not understand but as they stand the
statements conflict.
9. Curtis's claim was circumstantial evidence pointing to just one
batch of vaccine as the possible source of AIDS. This batch was only
given to about 3000 children in Poland and not to nationals of any of
the other countries mentioned. Koprowski's large numbers of
recipients with apparently no ill effects in Poland, Switzerland and
Croatia are therefore irrelevant to Curtis's argument as he should be
the first to know.
10. Koprowski's statement that "Again there was no doubt about the
safety of the vaccine (given to 76,000 children in Leopoldville)
because there were no untoward reactions that could be attribute to
an extraneous agent" may be treated with some sympathy but is again
irrelevant when the extraneous agent under discussion is expected to
manifest on the time scale of the AIDS virus.
11. There was very careless editing and/or proof reading affecting
almost the entire referencing of the paper. (This was however
corrected three issues of Science later.)
12. Other matters are touched on in my letter. On one other yet, the
adverse 'low' frequencies of AIDS Koprowski claims in the primary
vaccination areas compared to higher frequencies in towns is too
complex to take up in detail here and it must suffice to say that
Koprowski appears to misunderstand that (a) the rates he mentions are
not low by any standards in the world other than those of certain
African towns, (b) Curtis did not suggest any but a very few,
probably specially susceptible, recipients of the questioned vaccine
were catching the precursor SIV, and (c) his thesis in no way denies
probability that after the start, the well known pattern for venereal
disease with prominent roles for prostitutes, travellers and towns,
will emerge.