HAVE YOU BEEN CHOOSEN TO DIE YOUNG
Dr. Rakesh Kumar Shrivastava
The terse litany of a medical report could never
capture the drama of a patient’s illness and death. Although all physicians have tricks for
maintaining enough emotional distance from their patients’ ordeals to avoid risk of becoming
emotionally paralyzed and unable to practice medicine. It has been shattering to witness, with
uncharacteristic impotence, the patient’s entire body fail, one organ after another, seemingly
overwhelmed by waves of infection in Acquired Immuno- Deficiency Syndrome (AIDS).
A frail man of thirty three presented with an unusual
respiratory disease; pale almost ashen, extremely thin bordering on classical anorexia, a month full
of white “cottage cheese” indicative of fungal infection; coughing uncontrollably, and evincing
severe lung pain, looked like pneumonia. It was in the end of 1980, when this case was brought to
the notice of Dr. Michael Gottlieb of Los Angeles Medical Centre in California USA. The young
man’s lungs were filled with Pneumocystitis carinii, a parasitic protozoa, almost exclusively seen
among newborn infants in intensive care, terminally ill cancer victims or elderly individuals living in
nursing homes. While nearly everyone has some Pneumocytitis in his or her body the organism is
usually considered harmless because it is effectively kept in check by the immune system. And
pneumocytitis does not spread sexually. .Mystery was deepened after blood tests. The young
man’s antibody producing capacity seemed intact, but his T-cell response was virtually nil. T-or
thymus derived cells perform a range of crucial functions in response to infection, including
identifying an invader, and signaling the rest of the immune system to take defensive action against
the microbe. Without an intact T- cell system, no human being can hope to halt the advance of
even something as normally benign as pneumocytitis. That was the beginning of a voyage to
explore the mystery of a disease that was threatening the very existence of human civilization on
earth.
Initially it was termed as Gay Related Immune
Deficiency Disease (GRID) directly correlated with promiscuity. The study found that in some of the
men a special class of T- cells, called CD4 or T-helper cells, were virtually absent. These cells
normally drew the body defensive apparatus to the site of an infection and marshaled responses to
rid the blood stream of invading organisms. Without CD 4 cells the immune system would be hard
pressed to fend off any microbes. The most promiscuous men in the study had the lowest CD4
counts, while the monogamous participants in the study had normal numbers of the T-helper cells
i.e., CD4. That means that continued promiscuity could be lethal.
Two leading symptoms marked the GRID
syndrome. Kaposi’s sarcoma; disfiguring, yet painless, purple tumors of skin and Pneumocytitis
carinii pneumonia. Other odd ailments were also seen, oral thrush, caused by candida fungal
infections, pronounced herpes simplex II throughout the body, blood contamination of active
cytomegalovirus with unknown effect; mononucleosis due to Epstein Barr virus; marked lymph
node swelling; radical infections of the stomach and gastrointestinal tract with entamoeba
histolytica, diarrhea and gastric problems caused by the cryptosporidium parasite; similar
symptoms caused by, of all things Mycobacterium avium, a tuberculosis bacteria usually found in
chickens; galloping infections in many organs of cryctococcus fungus; out of control bacterial
infections with common organisms, such as staphylococcus aureus, Echerichia coli, and Klebsiella.
Autopsies revealed severe organ damage with vast expanses of necrotic tissues. Microbes of all
types; bacterial, fungal, and viral had invaded and it seemed every organ showed signs of having
been colonized and damaged. Much of the worst damage was caused by microbes that were
usually utterly harmless to humans. And the only possible explanation was that the collapse of
immune system. Discovery of fluorescence activated cell sorter or FACS by Dr Lean Herzenberg,
at Stanford University Medical Centre, explored the opportunity to understand the extraordinary
complexity of T-cellular immune response. Different types of T-cells which are white blood cells
have various proteins protruding from their surfaces that served to identity their function and form
other components of the body. Every single cell, from those that comprised a heart muscle to the
brain’s neurons, have such protein markers on their surfaces, allowing cells to “see” and
“recognize” one another. Without such “sight” and “recognition” a collection of billions of cells could
not organize itself into the complex entity that is a cat, a leopard or a human being. The elegant
complexity of immune system is necessary to recognize an incoming microbe, macrophages latch
on to the foe in order to draw the attention of the other components of immune system, single
secondary and tertiary lines of defense, and eventually consume and destroy the invader. Once the
enemy is defeated, other immune system cells have to call off the attack, and dampen the
response, lest the entire system overreact and destroy human cells. Most of the job marshalling
immune system forces for microbial attack falls to T- helper cells that bear markers designated
CD4. The job of calling off the attack and calming the agitated T- helper cells falls to so- called Tsuppressor cells, which bear CD8 markers. It was found in GRID patients that the CD8 to CD4
ratios were off. Most of the patients had too many CD8 cells and too few CD4 cells. Furthermore, it
seemed the slow diminution in CD4 cells paralleled the patient’s decline. The question of
insurmountable importance with GRID was how could immune system dysfunction be contagious?
However it was definite that a sexually transmitted infectious agent or exposure to a common
environment has a critical role in the pathologies of the immune -deficient state.
Don Francis, in Phoenix, thought, as early as June 1981 that the ailment
was caused by a virus, though he had no idea what microbe might be blamed. However there was
compelling proof that GRID was a sexually transmitted infectious disease, that rapidly progressed
from infection to symptoms, and death. It would later be clear that the disease’s latency period may
be averaged over ten years, and healthy, middle class men in particular almost never developed
symptoms as serious as Kaposi’s sarcoma or pneumocystitis carinii pneumonia within seven to
fourteen months of infection. The problem arose when three siblings suffering with a genetic blood
clotting disease known as hemophilia developed GRID, after receiving many injections of factor VIII
blood coagulant concentrate without any history of aberrant sexual escapade. Factor VIII is made
from the pooled plasma of thousands of donors. In August1981, the CDC quietly dropped the term
GRID, changing the name to Acquired Immune Deficiency Syndrome (AIDS) to effect the
recognition that it wasn’t just a disease of gay men. By December all three of the original
hemophilia/ AIDS patients were dead. “Transmission of an AIDS agent from mother to child, either
in utero or shortly after birth, could account for the early onset of immunodeficiency in infants”
wrote CDC scientists. By the end of 1982 the CDC had nailed down every basic aspect of
epidemiology of AIDS save one; identifying the causative microbe.
In addition to T –cell abnormalities, patients with AIDS had
severe problems in their B-cell systems: though they had lots of B-cells of the highly activated antibody producing type, other classes of B-cell were deficient, even entirely absent. It was concluded
that the B- cell system recognized. It was challenged by microbe, but, due to massive disruption of
the T-cell system, was unable to respond with the control and precision customary when both arms
of the immune system functioned properly. In 1982 the French scientist Jacques Liebowitch put
forward the hypothesis the AIDS was a viral disease of African origin “completely burning out the
immune system”. On January 3, 1983 Willy Rozenbaum of Pitie – Saltpetriere, France, removed an
enlarged lymph node from neck of an AIDS patient and discovered the evidence of reversetranscriptase activity in the cell with the help of colleagues on January 25.Only one entity on the
planet was known to use the reverse transcriptase enzyme, retrovirus. The tiny RNA viruses used
the enzyme to make mirror-image copies of their RNA genetic material, creating a DNA version of
themselves that could be incorporated into the genes of the animal cells that they infected. Two
human retroviruses were known to exist at that time- HTLV (Human T- Lymphotropic Leukemia
Virus) I and HTL VII, and initially it was assumed that the reverse- transcriptase activity indicated
that AIDS was caused by one of these two agents.
Could the leukemia causing virus be a variant of the
immunosuppressive virus? And if it is, it is a very subtle variant with a minor antigenic difference.
Levy postulated that “ the virus has mutated itself to such a close imitator of the immune systemof same component of the immune system- that when the system tries to attack the virus, it ends
up attacking itself”. The result was a profound autoimmunity, or immune system self destruction, in
which the mighty forces of B-and T cell system mistakenly attacked the body’ s defenses.
John Maddox, editor of Nature wrote in his editorial “There is
now a serious danger about the disease physician call Acquired Immune Deficiency Syndrome will
get out of hand. For the characteristics of the previously unrecognized and perhaps non-existent
condition are so alarming that the temptation to portray it as disease invited by a decadent
civilization, a kind of later day version of the fate of Sodom and Gomorrah is almost irresistible
pathetic promiscuity of homosexuals the most obvious threat to public health mercifully, the
disease whatever its causation is neither especially infectious nor certain in its effects.” In Europe,
thoroughly respectable, usually conservative scientists were openly comparing AIDS to the plague.
Even the reverend Billy Graham cried at full throttle. “AIDS is a judgment of God.” By February
1985, it was found and agreed upon that AIDS virus was a close cousin to well known lentiviruses
which produced slow- killing veterinary disease, such as visna in sheep and equine infectious
anemia in horses. Dr Floossie Wong Stahl further discovered that under natural circumstances of
infection the AIDS virus mutated rapidly, and it was impossible in nature to find two different
viruses a continent apart that varied genetically by less than one per cent. It was not “natural virus”,
in that, as time would tell, its key outer envelope sites bore only a partial resemblance to wild virus.
Subsequently, HTLV-VIII, LAV and ARV discovered at different centers by different groups of
scientist would all be renamed the Human Immuno -Deficiency Virus (HIV).
Some times in early 1983, a handsome Ugandan trader had
come through selling cloth for women’s Kangas patterned with the name Juliana on the Ugandan
border. A village girl with no money traded the stranger with sex for a Kanga, as did several other
women who coveted the beautiful Juliana cloth. Around February or March 1984, it was noticed
that several patients had genital ulcer disease that wouldn’t respond to normal treatment. The
disease was named Juliana disease, and the people of Ugandan border village Lukunya decided
that the Ugandan was a witch, and that Juliana’s cloth had evil powers. However, 97 per cent of
the patients diagnosed as AIDS cases had antibodies against HIV. More troubling; so did many of
the controls, which indicated that there was an asymptomatic stage of the disease and that
infection was far more prevalent than it had initially seemed. The vital question was, if a virus
related to HIV has been present in the United States, Africa or elsewhere for several decades, its
failure to spread in an epidemic fashion earlier may reflect either a recent genetic change in the
virus or socio-cultural factors involving sexual practices or numbers of sexual partners. For if AIDS
could emerge so successfully worldwide in the age of genetic, microbes might in the future exploit
similar conditions? If humanity hoped to prevent its next great plague, it was vital to understand the
origin of this one.
Sometime in the early 1970s a biological event occurred that
resulted in the sudden and explosive divergence of what had been a virtually linear evolutionary
path for HIV, because the virus had existed since the beginning of the tome. The period 1970-75
was marked by guerrilla warfare, civil war, tribal conflicts, mass refugee migrations, and striking
dictatorial atrocities in some parts of central and southern Africa. In protracted low- intensity
warfare the deeds of war could not be carried out anonymously. The enemy had faces. Soldiers
seized villages and imposed their rule on civilians. Brutality and rape easily became companion to
more legitimate forms of combat. The net result were several human activities that were
advantageous for sexually transmitted microbes increased multiple partner sexual behavior
(whether voluntary or not), famine or malnutrition that stressed immune systems, large scale
migration of people from remote areas to central zone of food supplies, or safety, increase
prostitution and diminution or devastation of health care services. In many ways urban centre may
be considered an ecosystem that can amplify infectious diseases. This appears to have happened
with HIV in various African cities. But it has spread not simply because the virus was present, a
change in the interaction between the agent, the host, the environment is usually required for an
epidemic to develop. In this context, (we believe that) social change including the effects of
urbanization and population movements, merits consideration in our attempt to understand the
changing patterns of disease. Though it had been the focus of attention of some of the greatest
minds in contemporary biomedical science, nobody had yet pinpointed a time , place or key event
responsible for the emergence of HIV. But the human factors responsible for amplification of that
event for the rapid expansion of an isolated infection to an outbreak cluster and later epidemic,
were very well understood. The World Health Organization was able to delineate those factors in
pamphlets and the UN General Assembly adopt resolutions that cited factors for societal
emergence of HIV. Yet the virus would continually find vulnerable homo-sapiens all over the world,
for human factors responsible for spread of the virus would resist change.
For further querries/ comments/ critique:
Contact : Dr. Rakesh Kumar Shrivastava MD(AIIMS), FACP(USA), FICA(Boston), FCCP(USA)
At drrakeshshrivastava@Hotmail.com or call 91-0755- 4254542, 4249973, 4249982 or
+919893054254