I”ve had a cold the past week. I know, you wives out there are
saying there”s nothing more annoying than a husband hanging
around the house nursing a cold. At least we know why we get
colds. These cold viruses are sneaky things that come in such a
variety of forms that it”s hard to build up immunity to enough of
them to make a difference. In recent years, we learned that hand
shaking and such contact is a great way to spread the little
buggers. We also hear repeatedly that antibiotics have no effect
on viruses and that taking them for a cold or flu just speeds the
development of those really nasty antibiotic-resistant viruses.
These transient diseases like cold and flu are reasonably well
understood and, at least for the flu, vaccines are available that do
a pretty good job of preventing the disease. But what about the
ravaging chronic diseases such as Alzheimer”s, schizophrenia,
multiple sclerosis (MS) and the like? Here the story is much less
clear and the causes of these chronic diseases are the subjects of
a great deal of research and ongoing debate.
There is one chronic affliction for which the cause has been
discovered – ulcers. When I grew up, ulcers were something I
had no personal contact with but everyone knew that if you got
them you were stuck with this bland diet for the rest of your life.
No spicy foods, no tart juices (the acids forbidden), etc. Twelve
years ago, I found myself in the intensive care unit of our local
hospital suffering from loss of half my blood due to some sort of
ulcer-like condition never really pinned down. After five pints of
blood and the consumption of much beef (raising my cholesterol
to 312!), my blood count returned to normal. What surprised me
was that my doctor said that my diet, aside from some limitations
on coffee and alcohol, could be perfectly normal. Spicy foods
and orange juice? Fine! After all, he said, the stomach uses
acids to digest the food and the orange juice is less acid than your
stomach. As a chemist, I wondered why hadn”t I thought of that
myself?
By that time, word had spread among the medical community of
the work of an unknown young gastroenterologist in Australia.
This guy, Barry Marshall, had found in 1981 that there was this
funny bacterium, now known as helicobacter pylori, hanging
around in the stomachs of his patients. Over the next few years,
he concluded that h. pylori could actually cause ulcers. At first,
his work was either derided or just ignored by the medical types.
Today, standard treatment for most ulcers is a regime of
antibiotic treatment to kill the h. pylori. This pathogen has now
been implicated as causing not only ulcers but also certain gastric
cancers. Marshall”s work became a landmark in the search for
the causes of chronic diseases.
The problem today is well stated by the title of an article by Carl
Zimmer in the September 14th issue of Science. The title is “Do
Chronic Diseases Have an Infectious Root?”. At about the same
time as Marshall”s work, others showed that viruses could trigger
both liver cancer and cervical cancer. Unfortunately, the
situation for other chronic diseases is not so clear. Take MS. It
was generally believed that chronic diseases such as MS had a
genetic cause and that the disease might be triggered by a
defective immune system.
This belief should have been questioned after what happened in
the remote Faeroe Islands in the North Atlantic back in the
1940s. There had been no cases of MS on these islands when
suddenly an outbreak of MS occurred. The outbreak coincided
with the appearance of British troops during World War II. It
certainly wasn”t the first time that the arrival of outsiders in a
locale has spurred an outbreak of some dread disease. The only
problem is that MS wasn”t supposed to be caused by a germ! But
that was three decades before Marshall”s work.
What is MS? Sadly, some 300,000 people in the U.S. share this
disease, in which the victims suffer loss of muscle coordination,
speech control and eyesight. We know a number of people with
MS, including a nephew who has suffered all of these insults. In
healthy individuals, the nerves in our central nervous system (the
brain, spinal cord and optic nerves) are surrounded by a myelin
sheath. This myelin sheath is like the rubber or plastic insulation
covering the wires in our lamp cords. Without the insulation,
sparks would fly and you”d blow your circuit breaker. Similarly,
the myelin sheath functions as an insulator to keep your nerves
from “shorting out”. The myelin also serves other important
functions. MS occurs when immune system cells attack the
myelin. The result is bare spots and damaged areas that result in
slowing down or halting of nerve impulses and, the equivalent of
shorting circuiting, cross-talk between nerves. This breakdown
in the nervous system causes the symptoms of the disease.
How come our immune system doesn”t know any better than to
attack our own body like this? Those favoring an infectious root
of MS believe a pathogen that either contains or makes proteins
that resemble myelin could do the job. When the pathogen first
appears on the scene the immune system gets primed to repel the
invader when it shows up again. The only problem is that now
the immune cells might not be able to tell the difference between
the invader proteins and the similar myelin proteins. As a result,
the immune cells might gobble up the myelin as well. Just a few
months ago, in the July 2001 issue of Science, workers at
Northwestern University Medical School in Chicago published a
study supporting this possibility. They injected mice with a
specially modified virus containing a gene from a bacterium that
makes a protein resembling myelin. Indeed, two weeks later, the
mice”s myelin sheaths were under attack by the mice”s” immune
systems.
What pathogens might do the same thing in us humans? One
possibility is a bacterium known as Chlamydia pneumoniae.
Let”s call it Clammy for short. As you might expect from its real
name, Clammy invades the lungs and can cause respiratory
diseases. There”s also some evidence that Clammy is involved in
heart disease and atherosclerosois. It seems that Clammy makes
a protein that”s similar to the protein in heart muscle. The
conjecture, of course, is that when the immune cells go after
Clammy they also attack the heart muscle. This is believed to
cause inflammation leading to atherosclerosis. Clammy is great
at causing inflammation.
In 1998, a worker named Sriram at Vanderbilt University found
Clammy bacteria in the cerebrospinal fluid of almost all (97%) of
a group of MS patients but in only 18% of the controls. Sriram
suspects that Clammy attacks myelin just as it does heart muscle.
The only problem is that workers in three other labs were unable
to duplicate his findings. His response was that the sensitivity of
the their detection techniques were not sufficient to detect
Clammy.
In an unusually cooperative attempt to resolve such a dispute, the
conflicting workers agreed to a blind test involving patients with
and without MS. The result was that Sriram found Clammy in
73% of the MS patients and 23% of those without MS. The
other three labs found no evidence of Clammy in any of them!
Advantage Sriram! However, even assuming he”s right, there”s
still the problem of the chicken or the egg. Does Clammy cause
the MS or does it just arrive on the scene and help aggravate the
disease? To try to begin to answer these questions, Sriram is
starting a trial using antibiotics to kill Clammy in MS patients to
see if they improve.
Another possible culprit that”s been proposed is a virus, the
human herpesvirus 6 (HHV-6) discovered in 1986. HHV-6
usually infects humans within a few months after birth and is
responsible for many of the fevers in babies. The HHV-6 may
hide out in the body and never be seen again. On the other hand,
it may spring to life, causing diseases like mononucleosis or give
rise to complications when the immune system is compromised,
as in those receiving organ transplants. The story of HHV-6 and
MS is much the same as with Clammy. Some workers find
HHV-6 in MS patients – others don”t. One clinical trial involving
treatment of MS patients with an antiviral medication found no
improvement in the patients” symptoms. It seems to me that
Clammy is the more likely culprit from what I read.
The situation with regard to Alzheimer”s disease is similar. It”s
believed that inflammation plays a key role in the clumping of
proteins and entanglement of nerves in the brains of Alzheimer”s
victims. Could Clammy be involved? Sure enough, in 1998
workers at Wayne State found Clammy in the brains of
Alzheimer”s victims but not in most of the healthy people. Of
course, other workers couldn”t repeat the results. However, the
most recent work from Finland is in agreement with the 1998
work. Stay tuned.
All this work is complicated by the fact that Clammy and HHV-6
are everywhere and chances are we”ve all encountered them
somewhere along the way. If they do play a role in MS or other
diseases, we may have been infected with them as a young child.
These microterrorists share with today”s macroterrorists that trait
of inserting themselves into our bodies or our society and then
lying in wait for the time to do their dirty work. Let”s hope we
make progress in understanding and controlling both.
Allen F. Bortrum
