Hunting for the Hidden Killers
They could not afford to jump to conclusions—any conclusions. Their
only hope was to be grindingly, interminably thorough. Otherwise, they
could pursue a course of investigation for hours or days, only to find
it ended nowhere.
—The Andromeda Strain by Michael Crichton
The enemy is always time—an agonizing reminder of the suffering that
can result from staying one step behind an elusive killer. At the
outset of each new inquiry, they may not even know the description of
their quarry, but its power is often all too evident. Along with
old-fashioned legwork and intuitive insights, the specialists use the
latest in scientific technology to compile and compare clues about
nature’s threatening puzzles. Such is the work, such is the mission,
such are the stakes for America’s disease detectives, whose special
calling it is to track invisible killers, to identify mysterious
illnesses that erupt from nowhere to menace life and health. Today an
elite cadre of these experts—pathologists and epidemiologists,
assisted by a larger army of lab technicians and doctors—are
coordinating their skills in an effort to conquer a new threat:
Acquired Immune Deficiency Syndrome, the confounding killer known as
AIDS.
As of last week, there were 1,641 victims of AIDS, including 644 deaths,
since it was first identified as a disease in the U.S. two years ago.
Each month an average of 165 new cases is reported. The largest
concentration of victims is in New York City .
San Francisco has the next largest outbreak ,
followed by Los Angeles . AIDS is spreading,
albeit slowly, to other nations; 122 cases have been reported in 17
countries.
AIDS attacks its victims by knocking out the immune system, thus leaving
them defenseless against a host of “opportunistic” infections. A rare
form of cancer or pneumonia becomes a deadly invader, but so does a
fungus or a common virus. Thus far, there is no cure for AIDS and its
source remains unknown. “We’ve looked at a lot of suspects,” says Dr.
Anthony Fauci of the National Institutes of Health , “but we have
not come up with enough grounds for an indictment.”
Asking questions. Hunting for clues.
Testing theories. Hitting blind alleys. Asking more questions. The
assault on the mystery of AIDS is a prime example of how disease
detection works. The foundation has been laid by epidemiologists who
have carefully analyzed the spread of the disease. So far, 75.9% of the
victims in the U.S. have been active homosexual men, 16% intravenous
drug users, 5% immigrants from Haiti, and 1% hemophiliacs. Only 96
victims so far are not known to be members of one of these risk groups.
More than 90% of the victims are males between the ages of 20 and 49;
young people account for just 1.3%. One cause for concern is that the
incubation period of AIDS may be anywhere from six months to three
years, and many people may have the disease without knowing it.
The outbreak of an epidemic* can provoke a primal panic by raising the
specter of a rampant “Andromeda strain.” Indeed, perhaps the most
severe side effect of AIDS has been the largely unwarranted hysteria
that has accompanied the syndrome . In order to
allay fears that AIDS is widely contagious, Secretary of Health and
Human Services Margaret Heckler last week visited the Warren Magnuson
Clinical Center in Bethesda, Md., where she shook hands with AIDS
victims and sat at their bedsides. Said Heckler: “What’s just as bad as
the disease is the fear of the disease. The fear has become
irrational.” Explains Dr. James Curran, head of the AIDS task force at
Atlanta’s Centers for Disease Control : “For a person not in a
known risk group, the risk is not only minimal but likely to remain
minimal. It apparently is not spread through routine contact or through
respiration, like the flu.” Indeed, none of the hundreds of health-care
workers who have treated patients have been infected by AIDS.
Nevertheless, Heckler stressed to the patients that “AIDS is our No. 1
health concern and the epidemic is our No. 1 priority.” Her department,
which includes CDC and NIH, is spending $14 million on AIDS research
this year and requesting $12 million more. Some gay activists have
charged that the Reagan Administration is neglecting AIDS because it
primarily affects homosexuals. Heckler’s
department also publishes a biweekly bulletin reporting the findings of
researchers; next week it will start operating a toll-free hotline
to answer questions about the syndrome.
American health officials once dreamed of eliminating infectious
diseases, at least in the U.S. That Faustian ambition has been foiled
by the mobility of American society, the influx of tourists and
immigrants , changes in technology that
create new, inviting environments for organisms and, most notably, by
casual intimacies encouraged by the sexual revolution. As many as 20
million Americans may now suffer from genital herpes, an incurable but
nonfatal disease. In addition, an estimated 1 million new cases of
gonorrhea and 100,000 of syphillis are reported each year. “What may be
different these days is the number of persons who can be exposed in a
short period,” says Dr. William Foege, 47, director of the CDC. “The
average AIDS victim has had 60 different sexual partners in the past
twelve months.”
The struggle to conquer such epidemics, and the fear they spread, is
the work of a special breed. They are spiritual descendants of Dr. John
Snow , who tracked the incidence of cholera during the London
epidemic of 1831 and stemmed further devastation by shutting down one
of the city’s water pumps. In the past few decades, his followers have
significantly improved the quality of life. In much of the world they
have virtually eliminated the threat of such onetime plagues as polio,
smallpox, cholera and diphtheria.
Those medical-mystery solvers include general practitioners and
specialists who become involved in a particular case because it affects
their patients. Others can be found among the nation’s state and local
public health officers. Researchers at the NIH supply scientific
support. Coordinating this network, and indeed serving as the FBI of
disease detection and the Interpol for medical sleuths around the
globe, are the 4,030 workers at the CDC. The vanguard of this
organization is the center’s Epidemic Intelligence Service , which
sends out its corps of 120 young, bright and determined investigators
around the U.S. and the world. “We see the CDC people as our sort of
big brother,” says Nevada Health Official Dr. Otto Ravenholt.
The CDC complex near Atlanta belies its importance. Its headquarters are
located in a squat suburban brick building, graced in front by a bust
of Hygeia, the Greek goddess of health. Some sections are housed in
wooden barracks around a former Army hospital. The agency, then known
as Malaria Control in War Areas , was created in 1942 to find
ways to protect U.S. soldiers against malaria. The organization has
since taken part in the successful campaign against polio , and lessened the threat of
rabies . The CDC also conducted
nationwide childhood immunization programs for measles, mumps and
rubella. Says Director Foege: “Today 5,000 children are running around
who would be in their graves if it weren’t for these programs.”
For all its successes, the CDC has had to fight for funds—including
money to set up EIS in 1951—by stressing the national security
benefits of the center. In 1981, the White House considered cutting the
CDC budget by 23%; Richard Schweiker, who was then HHS Secretary,
successfully fought to protect its funds. With the current concern
about AIDS, the CDC seems secure for the present; its 1983 budget is
$261 million, less than 1% of the amount spent for Medicare and
Medicaid.
Each year the CDC accepts 60 or so people involved in health care for a
two-year tour of duty with the EIS. “We look for the bright, somewhat
aggressive independent thinker,” says Dr. Lyle Conrad, head of the
division’s field service officers. About half are based in Atlanta; the
rest are assigned to public health departments around the country, with
which the CDC works closely. All are on call 24 hours a day, ready to go
wherever a disease breaks out, be it food poisoning or a case of
primary pneumonic plague that appeared in 1980 in California . After completing their two years, EIS
graduates are given a prized emblem of their craft: a key chain with a
tiny metal keg of Watney’s Red Barrel Beer, served at the John Snow Pub
on the site of the infamous water pump in London.
With a malady of unknown cause, the first step is to decide how to
define it. “We wanted the definition to be broad enough to include most
cases, but not so broad that it would include everybody with a cold,”
Tsai recalls. Six EIS agents fanned out across the state, questioning
other suspected victims. Where did they eat and drink? Were the windows
open in their hotel rooms? What events did they attend? A more detailed
survey went out to all 4,400 Legionnaires who had attended the
convention, and 3,500 were returned within three days. Other agents
followed up stray leads, like a call from a magician who admitted
lighting a sparkler at the hotel. Back in Atlanta, clinicians noticed
the high white blood cell counts in specimens from the victims, and
began to search for bacteria under their microscopes.
At first CDC experts suspected an attack of swine flu, which health
officials had been fearing that year. But the evidence did not support
that hypothesis. Some who had merely walked past the hotel contracted
the disease. Yet it was noncontagious: no one caught it from the
original 182 victims, 29 of whom died. Nor were any bacteria found.
“The picture slowly evolved that we didn’t know what we were dealing
with,” Tsai remembers.
The outbreak vanished as quickly as it began, but researchers at CDC,
including Microbiologist Joseph McCade, 43, continued to examine the
specimens taken from the victims. Five months after the convention, he
took another look at some red sausage-shaped bacteria and concluded
that they were the culprits. They had festered in the water of the
hotel’s cooling tower and had been carried through the air as the water
evaporated. The antibiotic Erythromycin proved effective in treating
the disease, and many similar cooling towers across the country are now
chlorinated to guard against another outbreak.
Another famed mystery was solved primarily by the epidemiologists rather
than the lab scientists. In January 1980, doctors in Wisconsin and
Minnesota noticed that an unusual number of young women were suddenly
developing high temperatures and low blood pressure, with potentially
fatal results; out of the 55 patients in the CDC’s initial study, seven
had died by the end of May. Dr. Kathryn Shands of EIS led the CDC
investigation, developing a clear definition for what soon became known
as toxic shock syndrome and recording in detail all the cases.
A staphylococcus bacterium was clearly the cause of the outbreak, but
the medical question was “Why?” Through further epidemiological
studies, the medical sleuths found that most of the new cases under
investigation involved menstruating women who had been using tampons. A
majority had used Procter & Gamble’s Rely tampons, a new
superabsorbent brand, which may have provided an environment that
encouraged bacterial growth. After the product was removed from the
market, the number of reported toxic shock cases dropped sharply.
Nothing in the history of disease detection compares in size or
intensity with the chase now under way to solve the mystery of AIDS. It
began in early 1981, when Dr. Michael Gottlieb of U.C.L.A. told Los
Angeles health officials that he had five patients, all of them active
homosexuals, who were suffering from an unusual and deadly form of
pneumonia, pneumocystis carinii. More alarming still, their immune
systems seemed to have broken down. Gottlieb and an EIS agent based in
Los Angeles reported the grim news in CDC’s weekly publication. Almost
simultaneously, Dr. Alvin Friedman-Kien of New York University noted
that several of his homosexual patients had the same weakened immune
systems and were suffering from Kaposi’s sarcoma, a rare cancer of the
skin usually seen only in older men. Later that summer Dr. Harold Jaffe
of CDC, while attending a conference in California, was told of an
additional case of a young homosexual suffering from Kaposi’s.
“We were struck by how strange this was,” recalls Jaffe. A group of
medical detectives at the CDC was organized into an AIDS task force
under the direction of Dr. Curran, a venereal disease specialist. They
quickly uncovered 50 cases around the country that fit the definition
of what the CDC officially dubbed AIDS. Initially it seemed that the
culprit might be amyl nitrate or butyl nitrate, often known as “Rush”
or “poppers,” which are inhalants that provide a short-lasting high.
But a study comparing homosexuals with AIDS to disease-free gays showed
little correlation with use of the drug. The 20-page questionnaire
disclosed, however, that AIDS victims tended to be sexually
promiscuous. In addition, some were the passive partners in anal
intercourse.
Then came another clue: reports of drug abusers, most of them
heterosexual, coming down with AIDS. This added credence to the theory
that a virus or some other infectious agent, transmitted by dirty
needles as well as by sexual contact, might be the cause. This
conjecture was supported by evidence that sexual partners of drug
users, and even a few children of those with the disease, had
contracted what seemed to be AIDS. So had a few hemophiliacs and
blood-transfusion recipients. One baby in San Francisco with symptoms
of AIDS, it was discovered, had been given blood from a donor who
turned out to have the disease.
The strongest evidence that an infectious agent was on the loose came
from what has been called the Los Angeles cluster. Interviewing
victims, investigators began compiling the names of their sex partners.
Three different men, none of whom knew each other, each mentioned the
same man in New York City; he turned out to be an AIDS victim. Since
then, 40 cases in ten cities have been linked to one another by sexual
relationships.
The next clue was confusing. Immigrants from Haiti turned up with AIDS.
Not only was this puzzling—many claimed they were neither homosexuals
nor drug users—but the discovery raised special problems for the
epidemiologists. Homosexuality is scorned in Haiti, and the victims
were reluctant to talk about their sexual habits. The language barrier
also played a role; it was hard for investigators to describe in
Creole—the everyday patois of Haiti—the homosexual acts in question,
particularly since the same word applies to both homosexuality and
transvestism. Many of the immigrants were in the U.S. illegally, and
thus understandably reluctant to talk to Government agents about
anything.
The Haitian connection is still puzzling. The disease apparently broke
out on the impoverished Caribbean isle in 1981, at about the same time
as it did in the U.S. Some experts suspect that AIDS is caused by a
newly introduced viral agent from Africa, where Kaposi’s is common, and
may have been transmitted by Haitians who once worked in Zaïre.
Port-au-Prince has many popular gay bars, and the disease could have
been brought back to the U.S. by visiting Americans—or taken to Haiti
by Americans in the first place. Recent investigations suggest that the
disease is probably transmitted in Haiti, much as it is in the U.S., by
homosexual activity or by dirty needles, and that Haitians have no more
propensity for the disease than victims in the U.S.
As the search and speculation went on, researchers in U.S. labs added
their own clues: the blood of AIDS victims has an imbalance among the
cells that help govern the production of antibodies. A normal immune
system has twice as many helper Tcells, which stimulate the making of
antibodies, as it does suppressor Tcells, which keep antibody
production under control. In an AIDS victim, the ratio may be reversed.
Often there are fewer cells of both types.
Based on what is known so far, two theories have emerged. One is that
AIDS is caused by a specific agent, most probably a virus. “The
infectious-agent hypothesis is much stronger than it was months ago,”
says Curran, reflecting the prevailing opinion at CDC. NIH Researcher
Fauci, who staunchly believes that the culprit is a virus, has been
collecting helper T-cells from AIDS victims to look for bits of viruses
within their genetic codes. So far, however, this and other complex
methods of detecting viruses have yielded nothing conclusive. Suspicion
focuses on two viruses: one is a member of the herpes family called
CMV; the other, called human T-cell leukemia virus, or HTLV, is linked
to leukemia and lymphoma.
The other theory is that the immune system of AIDS victims is simply
overpowered by the assault of a variety of infections. Both drug users
and active homosexuals are continually bombarded by a gallery of
illnesses. Repeated exposure to the herpes virus, or to sperm entering
the blood after anal intercourse, can lead to elevated levels of
suppressor Tcells. The immune system eventually is so badly altered
that, as one researcher puts it, “the whole thing explodes.” Other
experts combine the two theories, speculating that a new virus may
indeed be involved, but that it only takes hold when a combination of
factors affects the potential victim, such as an imbalanced immune
system or certain genetic characteristics.
Whatever theory may prove to be correct, the research has provided
inspiration for fresh studies by epidemiologists. The levels of
Tcells, the presence of HTLV and CMV viruses, and the swelling of
lymph glands are regarded as possible “markers” that indicate the early
stages of AIDS. At the New York Blood Center, Dr. Cladd Stevens and
Friedman-Kien are examining the blood of homosexuals who do not have
AIDS to see what factor might be unique to those who do develop the
syndrome. By chance they have thousands of samples of blood, 1,500 of
them from homosexuals now being studied, which were collected in 1979
for an unrelated hepatitis-B project. To date, 18 men in the survey
have developed AIDS.
No cure is in sight. But the research already has benefited some
patients. New knowledge about the immune system has inspired doctors to
be more careful when treating Kaposi’s to use therapies that do not
lead to further suppression of the immune system. Fauci of NIH has
conducted a bone marrow transplant that bolsters a patient’s immune
system. Along with many other researchers, he is testing the effects on
AIDS patients of new forms of interferon, a component of the human
immune system that can now be reproduced by genetic engineering.
Despite the concern about the death and suffering of its victims, and
despite the lack of any solution so far, health officials are
optimistic that science will eventually conquer AIDS. “We’ve beaten
other diseases, and we’re determined to beat this one too,” says HHS
Secretary Heckler.
Heckler’s opinion, which is shared by many medical detectives, is rooted
in a century of victories over diseases whose ravages once shaped the
course of history. Only a few decades ago, fear of a polio outbreak
could empty schools; victims in iron lungs would be put on exhibit in
small towns to raise money for the March of Dimes. All that is history
now.
Optimism about AIDS is bolstered by new weapons being added to the
medical arsenal. Interferon holds the promise of retarding the growth
of cancerous cells. Potentially as powerful is a process that creates
new cells called hybridomas. Cells that build antibodies against
specific diseases are fused with tumor cells to make hybrids, which
have the durability of tumors and the power to create antibodies. These
cells may eventually be used to develop vaccines that will protect
humans against new diseases and can help the body fight certain
cancers.
Nevertheless, optimism is tempered by knowledge that the struggle
against disease never ends. Of the deadly African Ebola virus, Foege
says: “What keeps it from spreading here? I don’t know.” Thus research
work on Ebola at Atlanta’s Maximum Containment Lab goes on. Another
potential threat is a subviral particle that combines with the
hepatitis-B virus to cause more severe infections and liver cancer.
Discovered in 1977, this so-called Delta agent is starting to show up
in high-risk groups, including some of the same ones who develop AIDS.
Even the victory over smallpox permits no complacency. In its place, a
disease called monkeypox has erupted in Africa. “It’s probably a
disease that’s been around a long time but has been masked by
smallpox,” Foege says. “Once you get rid of one disease, a new one
becomes visible.”
Then there are the scourges that have always been with us, the
Legionnaire’s bacteria that suddenly find an environment in which to
flourish anew momentarily, or the influenza virus that undergoes minor
mutations to spring forth with renewed vigor. Indeed, of all the
potential disease agents looming on the horizon, it is the familiar flu
virus that worries Foege the most. “I fully anticipate that possibly in
our lifetime we will see another flu strain that is as deadly as 1918.
We have not figured out good ways to counter that.” The same holds for
the most common of bacteria and viruses, like the staphylococcus, which
are adept at evolving into new forms.
“Just a few years ago, in an excess of hubris, I predicted we were
nearly finished with the problem of infection,” Dr.
Lewis Thomas, noted biologist and prize-winning author , observed recently. “I take it back.” Through the
heroic struggle of medical sleuths, most diseases faced today can be
controlled, as some day AIDS will be. But microbes, which have
existed on this planet far longer than man, show no signs of being
unconditionally conquered. Amid the billions that exist harmoniously
around us, there will always be some that become unexpectedly
disruptive, mysteriously virulent. Said Thomas: “There is a lot
more research to be done, not just about AIDS but into infectious
diseases in general. We have not run out of adversaries, nor is it
likely we will do so for a long time to come.” Thus the disease
detectives must keep pounding the pavement, peering through
microscopes, asking their questions.
—By Walter Isaacson.
Reported by Joseph N. Boyce/Atlanta and Peter Stoler/Washington, with other
bureaus
* The classic definition of an epidemic is an outbreak of
disease affecting 1% of the population. But most doctors now agree on a
newer criterion and declare an epidemic whenever the incidence of a
disease rises above its normal “background level,” or rate of natural
occurrence.
Joseph N. Boyce, Peter Stoler
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