From: rms@acsu.buffalo.edu (Robert M. Straubinger)
Newsgroups: talk.politics.animals
Subject: Re: Animal Research (About Polio [long])
Date: 28 Sep 92 04:50:42 GMT
Organization: SUNY/Buffalo Pharmaceutics


  *In article <15SEP92.08553949@wums.wustl.edu> w95_cook@wums.wustl.edu writes:
  *[...]
  *the polio vaccine (perhaps the finest example of the need for animal research

In article <1992Sep16.210301.28015@clpd.kodak.com> black@che.serum.kodak.com (Ro
bert Black (x37236)) writes:
>
>Is this really true? I assume here that you're referring to the Salk
>vaccine (1956) and Sabin vaccine (1962), which used kidney tissue from
>monkeys.
>
>But did they need to use monkeys? Was it wise to use monkeys, who harbor
>more than 60 viruses, some of which are dangerous to humans?

   Polio virus has a stringent host-restriction that makes the virus
highly unlikely to be able to infect any cell other than primate cells.
In developing a (killed) polio vaccine, some method was needed to determine
whether the vaccine would actually confer immunity to polio and prevent the
disease. Thus subjects were needed that would be given a test vaccine
and then 'challenged' with live, virulent polio. A non-animal alternative
that could have been used would be to innoculate groups of humans with
various candidate vaccine preparations, and just wait, using epidemiology
and statistics to determine whether an effective vaccine had been developed.
Although I do not know why this latter approach was not taken as the main
one, I suspect the tens of thousands of deaths and paralyses resulting from
polio put something of an air of urgency to the matter.
   In the case of developing the subsequent 'live' (attenuated) polio
vaccine, researchers were concerned that the weakened virus would revert
to greater virulence after passing through several individuals. Although
the benefits of the 'live' versus 'killed' vaccine are debated today,
the live vaccine was favored as a way to spread the vaccine strains of
polio through a population without direct vaccination of each individual.
So primates and (incompetent) humans were used to investigate whether
repeated passage of the vaccine strains of polio through new individuals
would result in virulent polio. In this case, humans might have been used
solely, but an important part of the vaccine testing was to sacrifice
the primates some time after vaccination and challenge with virulent
polio, in order to examine (histologically) the dorsal root ganglia and
other nerve tracts for microscopic signs of polio. The humans were only
observed for signs of infection or paralytic disease.

>As a result of this use of monkeys, several hundred thousand people have
>unintentionally received live SV-40 virus and other possible
>cancer-causing viruses from the these polio vaccines.
    To date, SV40 has not been implicated in the cause or promotion
of human cancer (to my knowledge). I have my fingers crossed, having been
from that generation

>   Also there is
>recently the (admittedly unproven yet) theory that AIDS gained a
>foothold through the polio vaccination program.
   (see below; one story has it that 'the event' happened in tissue culture)
>
>Yet Enders, Weller, and Robbins had shown in 1949 that all three main
>types of polio virus could be grown in human tissue culture (L.
>Hayflick, Laboratory Practice, 58-62, volume 19, 1970).  If animal
>research had been halted in 1950, scientists would have used the safer
>human tissue to produce a safer vaccine and human lives would have been
>saved.
     I suspect the problem is that (1) as above, the vaccine had
to be developed and tested.  (2) demonstrating a virus can be
propagated in tissue culture is a different thing from being able to produce
the quantities of virus necessary to vaccinate hundreds of millions of
people. Remember that the '50s were like prehistory, compared to the
scale of cell culture that is practiced in the pharmaceutical industry
today. Note also that no *normal* cell grows immortally in tissue
culture; in the '50s, the immortal tissue culture cells were [all, I believe]
derived from human cancers. One of the most popular of the lines was HeLa,
which is now known to have carried a number of adventitious viruses.
I believe that was not known at the time. Thus tissue culture sources
of polio vaccine would not necessarily be safe(r). To elaborate the story that
primate tissue used in vaccine production was the unwitting step that
introduced AIDS into humans, there is a variant of the story that says that
virus-contaminated human cells used in vaccine production allowed recombination
(genetic mixing) of (several) viruses, producing HIV. Extremely speculative,
that version. But with time we are likely to know the answer; until then,
it's difficult to say whether vaccine production would have been
safer in human cell culture or in monkey kidney cell culture.

>
>Did the rate of polio occurrence peak just before the vaccine's
>introduction and die down afterward as a result? This would lend proof
>to its effectiveness in human populations under real world situations.
>
>Finally what was the incidence of polio in areas not covered so
>extensively by the vaccination program, say the Rocky Mountain states or
>Europe, during this same period?
>
   I don't understand exactly what you're getting at -- that the vaccine could
have been developed in tissue culture, but then maybe a vaccine wasn't
necessary after all?  I surmise you're hinting polio incidence was
already falling and the vaccine was just an unrelated coincidence --
ie changes in sanitation, etc. already were wiping out the virus
without vaccination? Assuming that's the case, the following is
from _Science_ v257 (11 Sept 92) p1467:

  "The success of an intensive vaccine campaign that has left the Americas
polio-free for the past year is fueling the drive to remove the disease
from the rest of the world - but some tough hurdles remain.
  "Paralytic polio strikes 120,000 ... every year ... But the Pan American
Health Organization ... [has] eliminated the disease with a 7-year-old
program that relies primarily on ... [intensive vaccination]. ... These
mass immunization campaigns are bolstered by an agressive surveillance
program that also chases down each new case ..., confirms [it] was caused
by wild poliovirus, then saturates the local community with vaccine ...
   "... The last case of polio [in the Western Hemisphere] surfaced in
Peru on 23 August 1991.
    [The article goes on to say that the World Health Organization is trying
to promote similar campaigns elsewhere, realizing that it may be possible to
eliminate polio worldwide (as was done with smallpox) but that in China
and other countries] "there's not enough vaccine to go around".

   While the article quoted above is not a 'primary citation' dealing
with the specific questions you asked, it deals with the issue I believe
you are raising. 

Bob Straubinger
Dept of Pharmaceutics
SUNY/Buffalo          "Above are my opinions, not those of SUNY"
rms@acsu.buffalo.edu
Newsgroups: talk.politics.animals