A MONKEY virus that contaminated millions of doses of polio vaccine has been
directly implicated in triggering cancer. The virus, SV40, which scientists have
found in several types of tumour, destroys a key defence mechanism by switching
off a protein that protects cells against cancerous changes.
In 1961, SV40 was discovered in the kidney cells of macaques used to culture
the polio virus for vaccines. By that time, more than 90 million people in the
US and more in the former Soviet Union had been vaccinated against polio in the
aftermath of the great epidemic of the 1940s and 1950s. Epidemiologists have
estimated that between 10 million and 30 million people in the US received live
SV40, and an unknown number elsewhere. Since 1961, monkey cells used to make
vaccine have been screened for SV40.
The first hints that the virus might cause disease in humans came two years
ago, in a study by Michele Carbone at the National Institutes of Health in
Bethesda, near Washington DC, and others. The team discovered genes and proteins
identical to those in SV40 in tissues from people with mesothelioma, a cancer
found mainly in people exposed to asbestos (This Week, 21 May 1994, p 4). Then
last autumn, researchers at Baylor College of Medicine in Houston, Texas, found
the whole live virus, rather than just its genes and proteins, in a human brain
tumour. This cleared up any doubts that the virus found in human tissues was the
same as the one found in monkeys.
Carbone and his colleagues knew from earlier work that if SV40 is injected
into hamsters, it causes mesothelioma and brain and bone tumours. Because of
these findings, they speculated that SV40 might cause mesothelioma in humans,
too, either on its own or with another carcinogen such as asbestos. But they
knew that simply finding SV40 in human tumours still did not prove that the
virus caused them—it might have been just an innocent bystander.
Advertisement
Now the same researchers have discovered a mechanism that directly implicates
SV40 as a carcinogen. Carbone, who now works at Loyola University in Chicago,
announced his findings to researchers at a meeting on mesothelioma at the
Academy of Medicine in Turin, Italy, this summer.
He and his colleagues had wondered why mesothelioma tissues contain large
amounts of a protein called p53, which normally protects against cancerous
change. The protein, known as a tumour suppressor, prevents cells from dividing
uncontrollably. In many tumour types, p53 is damaged or absent because of
mutations in the gene that encodes it, allowing cells to divide unchecked. So
how, the researchers wondered, could mesothelioma be such an aggressive cancer
when its tissues contained plenty of the normal healthy protein?
To answer this, they examined human mesothelioma tissues in laboratory
cultures. They found that more than half the samples contained high levels of
the normal p53 protein, and that these tissues also contained SV40 proteins.
Carbone’s team discovered from these human tissues what other researchers had
already shown in experiments: that one of the proteins in the SV40
virus—known as T antigen—can bind to p53 and deactivate it. They
also discovered that other proteins, made only if p53 is active, were missing
from the cells, indicating that the tumour suppressor had been somehow switched
off. The results, Carbone told his colleagues in Turin, suggest that the virus
“contributes to malignancy”. They also explain why the healthy p53 in the
tissues is powerless to prevent the tumour’s growth.
Janet Butel, who works at Baylor and has studied SV40 since the 1970s, says:
“The findings strengthen the evidence that SV40 is carcinogenic in humans. This
shows that what seems to be happening in the human tumour parallels what we know
happens in experiments.”
Mesothelioma is expected to kill 80 000 people in the US alone
before the year 2015. Up to 80 per cent of those who develop it have been
exposed to asbestos, and no one doubts that this is the main cause.
However, if Carbone and his colleagues are right, people infected with SV40
are likely to be even more vulnerable to the fibres’ carcinogenic effects than
uninfected people. SV40 might also be causing mesothelioma independently. This
might help to explain how people who have not been exposed to asbestos develop
it.
Butel says that while there is no doubt that SV40 contaminated polio
vaccines, it is impossible to prove that people infected with SV40 today got the
virus from the vaccine. There could have been some other unknown source.
