Biomedical Engineering Reference
In-Depth Information
inactivated or partially inactivated vaccines, but cases of
paralytic polio unfortunately occurred following vaccina-
tion in human clinical trials (
Horstmann, 1985
).
Nevertheless, nonhuman primates played an important
role in helping to put polio research back on track. In 1931,
throat washings from patients were inoculated into
monkeys and resulted in infection (
Paul and Trask, 1932
).
Later work showed that poliomyelitis was an enteric
infection. The discovery by
Enders et al. (1949)
that
poliovirus could be grown in human tissue culture was
a major scientific advance for which the Nobel prize was
awarded in 1954. Any possibility that this might reduce the
need for nonhuman primates in the development and testing
of a vaccine for polio was never realized. Vastly expanded
research and testing programs immediately followed that
were heavily dependent on using nonhuman primates for
many years to come.
Jonas Salk's report of formalin-inactivated polio
vaccine grown in monkey kidney cell culture paved the way
for extensive and successful field trials (
Salk et al., 1953
).
This dramatic achievement was overshadowed shortly after
use of the vaccine began when an improperly inactivated lot
of commercial vaccine resulted in a number of cases of
polio in 1955 (
Horstmann, 1985
). This incident led the US
Food and Drug Administration (FDA) to adopt the much
more vigorous vaccine testing program that constituted
a major use of macaques for many years afterwards.
At about the same time, Sabin was working on the
development of a polio vaccine from another direction.
Depending greatly on the use of monkeys and chimpanzees,
he searched for attenuated strains of naturally occurring
poliovirus. His painstaking work reportedly used 9000
monkeys and 150 chimpanzees (
Sabin, 1985
). The result
was the development of an oral polio vaccine that remained
in wide use for many years. Interestingly, Sabin's vaccine
was widely tested in the Soviet Union. Because the IEPT in
Sukhumi was initially the only nonhuman primate based
research institution there, it tested candidate vaccines for
both safety and efficacy and, during the period from 1946 to
1955, carried out basic research on the etiology, patho-
genesis, clinical features, and pathomorphology of polio-
myelitis (B. A. Lapin, personal communication, 2010).
While relatively modest in the early years, the use of
monkeys increased dramatically following Salk's discovery
of an effective vaccine. The high point of this usage was in
1957 and 1958 when about 200 000 monkeys were
imported annually into the USA (
Lecornu and Rowan,
1979
). According to Lecornu and Rowan, the greatest
single use of the more than 1.2 million rhesus monkeys that
were imported into the USA during the 20 years that
followed Salk's discovery was for producing and testing
polio vaccine.
The legacy of the 1955 polio vaccine incident continued
for many years. The more rigorous testing program that was
adopted after the incident accounted for 20
25% of all
nonhuman primates used in research and testing (
Marten,
1981
). However, the number of monkeys required for
producing and testing polio vaccine declined through the
years as the result of refined testing procedures and the
adoption of preferable models. Two events have been of
particular importance in this respect. The first was the
decision by FDA in 1998 to replace the use of oral polio
vaccine with inactivated vaccine, which dramatically
reduced the need for monkeys. The second was a recom-
mendation by the World Health Organization (WHO) at
about the same time, which has been widely adopted
internationally, to replace neurovirulence testing in
monkeys with a newly developed transgenic mouse test.
There was no longer a need to use monkeys for the routine
production and testing of polio vaccine.
e
Kuru
Carlton Gajdusek won the Nobel Prize in Medicine in 1976
for showing that the neurodegenerative disease Kuru,
which was associated with the cannibalistic rituals of a tribe
of New Guinea natives, was caused by a transmissible agent
that produced a noninflammatory encephalopathy atypical
of that seen in viral infections. Although he attempted to
demonstrate the transmissibility of the disease in a number
of species, it was not until he inoculated the brain tissue of
Kuru victims into chimpanzees that he began to see the
delayed progression of neurological and behavioral clinical
signs typical of the disease (
Gajdusek et al., 1967
).
Gajdusek was an eclectic and accomplished researcher with
well-established credentials in social anthropology as well
as in infectious disease and cancer research, where he used
a variety of nonhuman primates in his studies. As noted
later (see the section “Retroviral disease and simian
immunodeficiency virus (SIV)” below), Gajdusek's
continued work with nonhuman primates touched tangen-
tially on the discovery of SIV. His research helped set the
stage for the later work of Stanley Prusiner, who was
awarded the Nobel Prize for Medicine in 1997 for his
discovery of prions. That discovery not only defined the
nonviral etiology of Kuru but also a host of similar diseases
like scrapie in sheep, Creutzfeldt
Jacob disease, and
e
bovine spongiform encepalopathy.
Virus (Herpes B Virus or Macacine
Herpesvirus 1)
Until 1934, the only biohazards people thought about when
working with nonhuman primates were bites and physical
injuries. Tuberculosis was recognized fairly early as
a relatively common disease, but it was more devastating to
nonhuman primates than it was to humans. However, in that
year, a fatal human case of encephalitis occurred in
a laboratory worker after he was bitten by a monkey
