TIME: Almanac 1993/TIME Almanac 1993.iso/time/040191/0401350.000

Text File | 1992-08-28 | 9.7 KB | 214 lines

                ∩                                                                  MEDICINE, Page 64

Forging a Shield Against AIDS


Vaccines are in the works, but how should they be tested and who
should pay?

By ANDREW PURVIS


    What might have been a methodical, scientific quest has
turned into a wild crapshoot. In more than 60 laboratories
around the world, researchers are working with at least 40
different concoctions in pursuit of one of medicine's most
urgent goals: the development of an AIDS vaccine. Any team that
succeeds will reap fame, fortune and the satisfaction of
possibly wiping out a disease that ranks among the deadliest
scourges ever to afflict humanity.

    But first it will be necessary to bring some order to the
bewildering array of options. While there are still some doubts
that an ideal vaccine can actually be created, some researchers
believe that enough good candidates now exist to warrant
drastically narrowing the search and selecting the best and the
most effective experimental vaccines for major trials in
humans. Last month at a meeting of the Institute of Medicine
in Washington, scientists and health officials began to lay the
groundwork for trials in the U.S. and other nations. In April
researchers from the World Health Organization (WHO) will begin
visiting countries in Africa, Asia and Latin America to locate
groups in which such studies might be conducted.

    But even early planning for such experiments has raised
thorny economic, political and ethical questions that some
researchers fear could interfere with the introduction of a
lifesaving vaccine. "If one of these trials goes badly, we
would lose not only time, but we could lose the opportunity to
test an AIDS vaccine altogether," said Dr. Jonathan Mann,
professor of epidemiology and international health at Harvard.
"It's very important that they be done right."

    The basic principle behind such human tests has changed
little since the 19th century. Several thousand people at high
risk for the disease will be inoculated with the experimental
agent, most likely an altered version of the AIDS virus (HIV)
or some portion of it. The vaccine should not be dangerous
enough to cause the disease, but enough like HIV to confer
immunity by triggering the production of antibodies and other
virus-fighting components of the immune system. The subjects in
the trial will be carefully monitored to see if they have a
better record of avoiding infection than groups who were not
vaccinated.

    The theory seems simple enough, but the peculiar
epidemiology of AIDS has already raised disturbing issues about
how these trials will be conducted. In particular, the
populations at greatest risk for the disease -- including drug
abusers, prisoners and prostitutes in the U.S., as well as
truck drivers and military recruits in some African countries
-- are not ideal candidates for a structured scientific trial.
Drug abusers and prostitutes may be transients who are not easy
to monitor, and inadequate transportation and communications in
many African countries will hurt efforts to keep track of
volunteers.

    Scientists, moreover, cannot guarantee that these trials
will be risk free. If a vaccine is made from a whole AIDS
virus, for example, there will be a slight danger that some of
those vaccinated will get the disease. In 1955, during early
testing of the polio vaccine, 80 children in California got the
illness from improperly prepared shots. Even if the
immunization works and produces large amounts of antibodies to
HIV, participants will have to cope with the social stigma of
being HIV positive. The antibodies generated by a vaccine are
the same ones that doctors look for when they test for AIDS.
Thus researchers are concerned that participants in the studies
could suffer the same discrimination -- in getting health
insurance or a job, for example -- that plagues people with
AIDS around the world.

    One uniquely troubling aspect of these trials is that many
of the subjects in Africa, and elsewhere in the Third World,
are unfamiliar with the ways of Western medicine and may not
fully comprehend the risks of participating. Explains Dr. David
Heymann, chief of the research office at the WHO Global Program
on AIDS: "It is vital that African volunteers understand that
they are getting an experimental product that might not work."
Without such "informed consent," doctors cannot in good
conscience carry out their research, and may face charges that
they are using people as guinea pigs. "The problem," concluded
a report from last month's meeting at the Institute of
Medicine, "will be to avoid what has been called `safari
research' or `medical im perialism' while gathering the
necessary data."

    The delicacy of these human tests greatly increases the need
for cooperation between the drug companies that ordinarily foot
much of the bill for vaccine research and various government
and intergovernment agencies that are trying to ensure that the
product gets to the people who need it most. Yet so far such
cooperation has been sporadic at best. A report issued this
month by the National Academy of Sciences notes that there is
currently no way of telling which of the scores of candidate
vaccines are the most promising, since relatively few have been
tested against each other in head-to-head comparisons. Unless
investigators financed by different companies and by the
National Institutes of Health are willing to work together, the
report concludes, discovery of a useful vaccine could be
dangerously delayed. Dr. Wayne Koff, head of AIDS-vaccine
research at the NIH, worries that researchers will be too
inclined to stick with their own projects rather than pool
their resources.

    In addition, some health officials are concerned that
drug-company investigators may be ignoring a particular kind
of vaccine -- those using a whole virus -- not because they are
less promising scientifically, but because they carry a
slightly greater risk of infection and, in turn, a greater
potential for liability suits. In fact, some scientists contend
that the threat of such suits has kept many major drug companies
out of vaccine research altogether. To combat this chilling
effect, the NAS report urges Congress to provide drug companies
with liability protection.

    Perhaps the most difficult ethical question is the cost of
the vaccine. A successful shot that sells for an exorbitant
price will be of little use to most Africans, who have no more
than a few dollars a year to spend on health care. Nine years
have passed since the discovery of a vaccine for hepatitis B,
a viral disease that, like AIDS, is spread by sexual contact
and the sharing of hypodermic needles. But the product has yet
to reach many people in poor U.S. neighborhoods and Third World
countries largely because it costs more than $120 a shot. It
would be a gross injustice, says Harvard's Mann, if Africans
helped develop an AIDS vaccine by taking part in trials only to
see it priced out of the reach of their countrymen. To prevent
such a situation, Mann recently proposed that Congress offer
drug companies an extension on exclusive marketing rights for
other lucrative drugs in exchange for keeping the price of an
AIDS vaccine down. Says he: "This is the time to make a deal,
not after the vaccine is on the market."

    Many researchers are hopeful that regulators, vaccine
manufacturers and individual investigators will put aside their
differences when the best candidate emerges from the
laboratories. If they do not, one of the greatest medical feats
of this century may be remembered not just for the lives it
saved but also for the victims it failed to reach.


____________________________________________________________
WAYS TO TRIGGER IMMUNITY


    Many different types of vaccines are being tested to see if
they provoke the body into mounting an immune response that
blocks the AIDS virus (HIV). Researchers stress that none have
yet protected humans from infection and that significant
obstacles remain. Any successful vaccine must stop the virus
before it can infect a single cell, no matter where or under
what conditions the invasion occurs. In addition, since the
virus is extremely variable, a vaccine that works in Uganda,
for instance, may not work in the U.S., or even in another
African country. Four different kinds of vaccines:


    WHOLE KILLED VIRUS

    Description: HIV is killed and then injected into the body
in an effort to trigger antibody production without causing
AIDS.

    Results: In monkey tests, the vaccine blocked infection from
SIV, the simian form of HIV, at least under ideal conditions.

    DISABLED LIVE VIRUS

    Description: HIV is altered by genetic engineering just
enough to make it incapable of causing AIDS. But the virus still
reproduces and stimulates the body's defense system.

    Results: In preliminary human trials, the product appeared
to slow the onset of the illness in patients already infected
with HIV. Bust safety concerns make this method the least
likely to be used.

    SUBUNIT VACCINES

    Description: These vaccines consist of one or more
genetically engineered proteins that resemble those found in
HIV.

    Results: Chimps given one of these vaccines gained
protection against HIV infection.

    ALTERED VACCINIA VIRUS

    Description: Vaccinia, the virus used as a vaccine against
smallpox, is subtly changed to resemble HIV. Other candidates
for this technique include the vaccine used for tuberculosis.

    Results: Early studies in healthy humans showed the vaccine
is safe and can spur some antibody production, but that does
not prove that it confers immunity to HIV.