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Dr. John Martin Lecture Stealth Virus Encephalopathy
March 9, 1997
3rd Speaker
Dr. John Martin
General Comments
I must say I have been working on Chronic Fatigue Syndrome or viruses that can cause or
infect not only chronic fatigue but a whole series of neuropsychiatric illnesses from autism in
children, Attention Deficit, manic depression, schizophrenia and so forth and this work
proceeds slowly and all of a sudden I had a call from Donovan to say that hes had an
outbreak up here, would I be interested in looking at some of the samples to see if, in fact, we
could see a similar virus to the virus that we have been studying called the Stealth virus, and
he sent the samples and Im thrilled to say that yes we do have some positive cultures and I
really think we do have now an opportunity for a major advance in understanding this illness,
not only to the benefit to the local people here, but hopefully to the benefit of large numbers
of people throughout this country and perhaps throughout the world who are neurologically
impaired, dysfunctional brain syndrome, being shunted from psychiatrists to neurologists,
often finishing up in institutions and very much being dropped by the medical system. It was
on the idea of sharing this work that I established or founded a center for complex infectious
diseases to emphasize the complexity of these illnesses and the need for hard, solid research to
understand what is going on, hopefully to lead to a cure.
Dr. Anderson was kind enough to visit us in the laboratory. It occupies half of the top floor.
We have really excellent space. One of the laboratories of the offices is occupied by a Dr.
Zacky Salahuden (spelling questionable - CV) who is the inventor or the first person to
describe a major human virus called Human Herpes Virus 6. We have facilities for electron
microscopy, chemistry, tissue culture and so forth. So we have the location and we have the
equipment to proceed to study a class of viruses, the diseases that are associated with these
viruses and hopefully we can extend this to therapeutic endeavors. And again, I really want to
emphasize the opportunity that this epidemic that Dr. Anderson has described in terms of
making substantial progress is really here and now and I am thrilled to be here and hope there
will be additional visits and certainly additional samples to look at and perhaps to work
through Dr. Anderson in terms of evaluating some of the potential therapies.
As with any research we have to start from the beginning. I want to describe the viruses, then
the diseases and then something about the therapies. The viruses were termed Stealth viruses
essentially because of this line.
(Slide 1)
By nature they evoke very little inflammation or
cellular information in the body. So, theyre not so virulent in the sense that they dont grow
so aggressively in the test tube, but they have this enormous advantage that theyre not seen
by our immune system. Theyve deleted those components that our immune system would
ordinarily engage the virus. So something like the stealth bomber avoiding radar, these viruses
have adapted themselves to avoid the cellular inflammatory reaction. Theyre cytopathic in
that they can damage cells and we can see that both in the test tube, in vitro, and also in
patients, in vivo. There is a very broad range of cell permissiveness and whats important as
far as epidemics are concerned is that they grow equally well in animal cells and in animals, in
fact, as they do in humans. So this is an exception to the usual barriers that exist between
viruses jumping species that these viruses can, in fact, grow in animals and are potentially
transferable from humans to animals and back into humans.
One important piece of science thats evolving is an understanding of how these viruses have
learned to adapt to avoid the immune system. And the basic premise is that rather than having
a completely intact, fully formed genome, they exist in a fragmented, unstable form. And the
fragments have essentially deleted away from themselves those parts that the immune system
might recognize. So thats an important concept because it goes against the conventional
wisdom that viruses are complete entities and if you had a fragment it couldnt grow and
produce damage. There were a number of these viruses being molecularly heterogeneous and
the other point which Ill focus on a lot today is we know that some of these viruses
undoubtedly have come from African green monkey cytomegaloviruses. And the relevance of
that will appear later since we use African green monkeys, still use them, and certainly have
used them in the past, to make polio vaccines at a time when it was considered appropriate to
use fresh animal tissues to make vaccines, a practice that nobody would ever initiate again
today. So, those are the generalizations and the general comments I wanted to make about
these viruses.
Viruses
Essentially these viruses are defined by the fact that if we put them in tissue culture in a test
tube with indicator cells, they will damage the cells. This shows kind of an essentially near
normal cell culture but you can see appearing in this cell culture these few abnormal cells
picked up by that differential staining. So one can see what a culture essentially looks like
without those cells in normal or if exposed to blood cells from a normal person. If we take
that same culture and watch it over time from a patient that has one of these neuropsychiatric
illnesses, we can see this absolutely spectacular formation of foamy vacuolated cells
that fuse together and you can see this bizarre looking cell. This type of virus is very damaging to these
cells providing we make the effort to allow it to grow in culture with these cells. So the
viruses, even though they are not seen by the immune system, under the appropriate
conditions, can be very damaging to the cells that they infect.
Ill mention that weve been working on this for a long time. Back in 1991, we had such a
culture from a patient who still has Chronic Fatigue Syndrome. So this was a lady that was in
Los Angeles, worked as a health care worker and basically became sick with a typical chronic
fatigue like illness. Her virus was fortunate in a sense that it was more intact than many of the
viruses you do see and by using an electron microscope and looking at the infected cells from
cultures, we could begin to see particles that were indicative of a virus. This is a larger
magnification. These are pretty typical viruses that generally look like the herpes virus, that
would include cytomegaloviruses, Herpes Virus 6, Herpes Simplex Virus. These other larger
units are the types of viral materials that viruses use to assemble themselves. So here we had a
culture from a patient and it looked as if it might be a herpes virus, yet when we did all the
various tests for that, it did not show to be a normal human herpes virus. Rather we found it
was something different. We proceeded to do molecular studies on that virus and essentially
this
(Slide 2)
summarizes some of the studies on it as well as results of the molecular studies.
It produced, as I said, vacuolated cytopathic effects in humans and as I indicated earlier, even
in animal cell linescat cells, even some insect cell lines. It looked like herpesvirus-like
particles. This polymerase chain reaction is a very sensitive molecular technique that was used
and that gave us portions of the virus genome and when we sequenced one portion it showed some
relatedness to human cytomegalovirus, partial--50%--similar but not really human
cytomegalovirus. And when we extended that study and the sequence analysis and had
sequence analysis available for African green monkey Simian cytomegalovirus it was apparent
that we had 90 - 95% relatedness of parts of that virus to this African green monkey derived
cytomegalovirus. And for those people who can appreciate the numbers, this
(Slide 3)
is a kind of quantitative analysis that shows a measure, either by FASTA score or BLASTN score,
a measure of the relative relatedness of this virus to human cytomegalovirus. The FASTA
score was 348. More closely related to the cytomegalovirus from Rhesus monkeys, a score of
1000. But the highest of all with African green monkey viruses, referring to the simian
cytomegalovirus. The BLASTN score shows powers to the tenfold, and 10 to the 245 is an
unbelievably high number. Without any equivocation then, we can say that this virus came from
African green monkeys, simian cytomegalovirus. It was not the same because it had changed,
but essentially, that is where it came from. And I was able to publish this in this article
definitively stating the African green monkey origin of the stealth virus isolated from this
patient was the Chronic Fatigue Syndrome. It was on this basis that I could make the
understatement, if you want, that concern should be given to the fact that we have been using
African green monkeys to make polio vaccines and that should be looked into as a potential
source of these viruses in the community.
The whole issue of using monkeys relates to the issue of the prevention, which has been
effective, of polio. As you can all recall in your lifetime, the polio vaccine program began
around 1954. Dr. Jonas Salk devised a protocol for developing an inactivated polio vaccine.
He used Rhesus monkeys at the time and his vaccine was inactivated. Competing with Dr.
Salk was Dr. Albert Sabin and his approach was to use live attenuated or modified polio virus
that was grown as live virus whereas Dr. Salk was using formaldehyde to inactivate his virus
and required large amounts. It had to be injected and took some time to work. Dr. Sabin had
the advantage of using live virus required only to be taken on a sugar cube, worked very fast
and was clearly a preferable vaccination protocol from the point of view of inducing anti-polio
immunity. About 1960 it was realized that the choice of Rhesus monkeys had a major
problem. They were commonly infected with a virus called Simian Vacuolating Virus, SV-40
or Simian Virus 40, a type of small DNA virus. Realizing this, a major switch was made very
abruptly to move from Rhesus monkeys to African green monkeys. At the same time the
switch was being made to go from an activated vaccine to a live vaccine whereas in the initial
choice of Rhesus monkeys--the initial evaluation of vaccines--there was a major concern of
potential contaminants and so forth. That concern was not addressed as aggressively because
people do not want to interrupt the vaccination program, yet throughout the 1960s there
were repeated reports to raise concerns that the use of fresh animal monkey kidney cells and no
inactivation process at all was going to potentially lead to problems. And Ive taken three
quotations from eminent people here, one with Dr. Hilary Kroprowsky and to quote him "As
monkey kidney tissue is host to innumerable simian viruses, the number found varying in
relation to the amount of work expanded to find them, the problem presented to the
manufacturer is considerable if not insuperable. As our technical methods improve we may
find fewer and fewer lots of vaccines that can be called free of simian virus." This was dated in
1961 and it was the concern at that time that there could be atypical viruses. This concern was
discarded in some regard because the vaccines were in production, the children were receiving
it, there was a push into this program. It continued, however, as a concern and a
memo
in 1968 specifically was addressed at that time by Lederle which has now become American
Cyanamid or now American Home Products. The person representing the vaccine
manufacturer was referring to a discussion with Dr. Roderick Murray who was then the head
of the Food and Drug Administration Regulatory Affairs that there were some concerns at
Lederle about a possible requirement barring the use African green monkey kidneys as a
substrate for the growth of attenuated polio viruses. Dr. Murray had stated that the
adventitious agents that Dr. Kendall Smith is presumably detecting by his technique was of
little consequence for an oral preparation in that such a large experience exists with the use of
oral polio vaccine without any evidence of trouble relating to these agents. So politically, the
process at that time was essentially to say, look weve been using these vaccines, people could
raise concerns that there might be contaminants but clearly nobody is getting acutely sick as a
result of these vaccines, so lets not trouble the system, lets not pursue it. That attitude was
in 1968 still persisted. People like Dr. Kendall Smith were identifying agents, other people
were identifying viruses in these vaccines and it came to an issue in 1972 when 11 monkeys
were put aside, not to make polio vaccine, but to see what might grow out from the kidneys
that might otherwise be used for polio vaccine, and in this study which was part of a
contingency plan in response to the results, it was shown that the Lederle Bureau of Biologics
which is FDA cooperative CMV study has been completed. All 11 monkeys studied
demonstrated the presence of CMV like agents. These monkeys all originated from Kenya
over a short period of time and 7 of those monkeys would have passed their existing test
standards. In other words, only 4 of those CMV viral isolates would be detected using their
standard detection system. So, it was clear that they had a finding and most of the rest of this
contingency plan dealt with what response Lederle would take if in fact the FDA were to
disclose this information and require some change in the use of African green monkeys.
Unfortunately, there was no response at all from FDA, but more pertinent to the issue, there
was no disclosure of this to the scientific community. Again, for various reasons which I dont
need to go into, but it was still a persistent issue because one year later in 1973
correspondence from American Cyanamid, being concerned that the bureau was taking longer
with their vaccine approval and perhaps were going to give preference to an alternative
vaccine made in the human cell lines, the argument was, if the bureau wanted to restrict us
they should bring up the subject of cytomegalovirus in our substrate (i.e. African green
monkey kidney tissue) which they have not done even though they have told us the monkeys
in the collaborative study performed in 1972 were all positive for this agent. So we have,
unfortunately, this clear demonstration of something going wrong in the public health system.
Primarily what went wrong was an unwillingness in the regulatory system to bring this
information to the scientific community. If society as a whole had endorsed the continued use
of monkeys even though they had cytomegaloviruses in them, one would expect that, that
societys perspective and can suffer the consequence. Its when this information is withheld
and not disclosed that one has reason to be concerned and one can now look back with some
real concern at what has occurred over the last 30 years or more using this kind of vaccine
with this information not being openly discussed.
Its not that easy, I can tell you that if it were just a straight forward virus perhaps one could
detect it. There are differences between the stealth viruses and regular viruses. Ive had
continued discussions with people at FDA, American Cyanamid, recent communications with
people doing the testing in American Cyanamid. To quote them specifically, they still not
infrequently detect cytomegaloviruses, but they certainly take concerns now to avoid
cytomegaloviral contamination but it may be a little bit too late. The horse is already out of
the barn. The viruses are in the community. There are other concerns about the issues that we
have raised about fragmented genomes. The representative from FDA even a few weeks ago
was saying that, no they still do not want to test the vaccines for cytomegalovirus because if
they find a fragment, they wont know how to interpret it and they prefer to do nothing. There
is a basic difficulty with these viruses. To show it here, if this is our friend, Human Herpes
Virus 6, we can see in this cell relatively intact viral particles that develop before the cell
undergoes a major cytopathic or damaging effect. When we look at a typical stealth viral
infected cell we often see this appearance which is very degenerate,
foamy vacuolated cell.
Theres a lot of material that is virus like but it hasnt formed itself into an intact complete
virus. And you get rather these incomplete viral forms. Still enough to cause cytopathic effects
and one would have thought that this would certainly be of cause or concern and to be told
that one does not want to look at vaccines because one might see only a fragment of a virus is
not particularly satisfying. There have been public health approaches to this problem, primarily
to recommend a switch from live polio vaccine to split protocols, inactivated followed by live,
to increase the production of inactivated, then bringing the inactivated one in totally, but this
is a very slow non-response to what could be considered a much more urgent public health
problem in terms of vaccines or even a much larger problem in terms of the nations blood
supplies, individuals who can get infected from other individuals and so forth.
Diseases
What Id like to do in the second phase is emphasize to you some of the diseases that can be
associated with these viruses.
Slide 6
Now Ive purposely chosen some of the more severe cases. I
can certainly talk to you about the young children we see that have Attention Deficit, Turret
Syndrome, failing in school, who have signs of a modest encephalopathy. We dont get the
occasion with those individuals to look at the brain tissue and so forth, and also, since Ive
presented these cases to CDC and FDA I want to put you in the same situation as theyve
been put in to see cases that I think anyone of them is so compelling that they ought to evoke
a major public health response and, yet, each of these cases has been discarded as something
fitting into a wastebasket. They are unusual cases, but why bother.
The first case in this area is a lady from Palm Springs, a school teacher and I use this word
dysphasia, difficulty in speaking, but that underestimates her initial problem and her later
problem. So she worked in the school in Palm Springs and, I guess, in early 1989 she made
spelling mistakes in sending a note home with her pupils and this led to the school
administration getting on to her case. She was under a lot of stress. She saw therapists and
basically had to switch schools, became a part time kindergarten teacher, later still had
difficulties and was somewhat relieved when she finally went to a neurologist and the
neurologist, though not finding any major signs, found that she lost her sense of smell and
went ahead and did some other tests. At that stage though, she started to really deteriorate in
her ability to speak, identify things, and she also lost her ability to draw clearly and this was
her attempt as a person who, I think she was in her thirties at the time, all of a sudden found
herself unable to draw a clock, a house and so forth. She was then subjected to neurologic
examination. This technique called magnetic resonance imagingyou can see the heightened
white area around that ventricular part of her brain. It was clearly abnormal. Another way of
looking at the brain, you can see the same white areas around the ventrical regions. So she
was referred to USC to try to understand what was the process occurring in this poor lady.
They went ahead and did a biopsy of that area. This shows where a very fine needle, and there
is a small black area which is some small air entrapment and for those in the front you may see
a very small rounded black area also, a small piece of brain tissue was removed and referred to
us to look to see if there was a leukemic process, if there was some kind of conventional viral
infection, what was going on. This was tissue that came to the lab and the first comment to
make, even at this level, is that is that it doesnt show the typical inflammatory reaction of
lymphocytes, which if it did, itd be essentially a blue looking tissue because lymphocyte stains
blue. On higher magnification there was essentially nothing very much to pick out by light
microscopyno cancer, no inflammation, would be perhaps discarded as essentially normal.
But using that molecular technique I referred to, polymerase chain reaction, we had evidence,
that there was some kind of virus in this ladys brain, and when we spent a lot of time doing
electron microscopy, we could see, and this is a glial cell, glial fibers, on the top there you can
see those vacuoles of lipid filled vacuoles as in the bottom, a lot of lipofuscin type material,
which is degenerate material from an aging cell and a few viral particles that we could see in
other parts of the section. So it was very clear that this lady did, in fact, have a viral infection,
but it was not a typical, conventional virus. This lady became ill in 1989. She has steadily
deteriorated over the last several years and for the last 2 years has been in a nursing home in
Palm Springs. This is now her MRI and her brain is markedly atrophied, degenerated and
shes quadriplegic, essentially requiring feeding, assisted ventilation. Only her husband has
stayed by her and when comments are made, the neurologist doesnt like to visit the nursing home.
One can see how these patients, from being so prominently worked up to have brain biopsies
in a major medical center finish up falling through the cracks to lay abandoned in nursing
homes.
If there was only one patient one could say, yes, well things happen, we dont know about it.
But there were many. I have presented 12 cases to FDA. Another one, once again from this
area, was a 30-year-old dentist who worked in Bakersville, sheI guess I could date it back
to mid-1995she changed in her whole personality, from a vibrant young person to
somebody suffering personality disorder, had severe headaches, tried to do so many things to
revitalize herself: joining clubs, lost her job at one position where she was working, got
another job at a dental practice but failed to turn up for work, and only towards the nine
months or so into her illness did she finally call her mother for help. Her mother had her go to
various physicians and as with so many of these people when theres alteration in the level of
consciousness and theres this abnormal behavior, the first diagnosis is a psychiatric illness and
theyre admitted to a psychiatric hospital. She deteriorated further there and it was clear that
she had organic brain disease. She actually went ahead and had a brain biopsy and it showed
again this lack of any inflammatory reaction. By regular microscopy though we could see
these markedly vacuolated cells with degenerate nuclei, so we again had clear evidence of
some pathology and the electron micrograph again showed these very characteristic
vacuolated degenerate cells. Now this lady became so comatose that she was unresponsive to
pain stimulation. I would see her, she would spend only moments trying to engage who I was,
what I might be doing. Im happy to tell you that she has shown quite remarkable recovery
from that. I can discuss with her things, though she still has many of the features that we
associate with Chronic Fatigue Syndrome, particularly poor memory, its very unlikely that
she will ever go back to work and again, nobody can fully evaluate who she was before to
where she is now.
I could go through more and more of these cases but I wanted to present this one. This ones
again another gentleman who came into to Los Angeles County hospital with a two week
acute illness with behavioral changes. He was reluctant to come in. Again in the emergency
room they decided that he probably had a psychiatric illness. They sent him to a medical ward,
there were abnormalities in his MRI at the time. He did go through the process of slow
recovery, rehabilitation convalescent hospital, told to come back for rehabilitation. When he
came back he was told he was still too sick, stay at home. He basically would have a number
of episodes--just to recount two of them--he came back to the emergency room complaining
of pain, they asked when hed last gone to a bathroom and since it was a few days was given
an enema for constipation, another time he would drive his car and get totally lost and finally
45 minutes beyond his expected exit he crashed the car. He just gave up. Admitted up to a
hospital they would suture his lacerations, but nobody would ask why this 30-year-old person
was in such a state. How could he have ever been there and why wasnt somebody caring for
him? He finally had an exacerbation, became comatose, was taken to the hospital, again had a
brain biopsy and died. His brain biopsy showed the same characteristic cells and what was
interesting in this person as an additional complication, around the blood vessels there were
damaged blood vessels and he had evasculitis in addition, and then this gentleman died. And
again, I dont want to be overly critical but his death certificate read heart failure because they
thought they might have missed something in terms of neurologic exam and the people that
are most concerned were the nursing staff on the ward because they realized that medicine
didnt have anything to offer this individual and that this poor individual slipped through the
cracks, having died from what is essentially an unexplained illness that every indication is that
he had a viral infection.
Theres only one other patient whom I have this in vitro culture showing viral particles and
this is a lady who I think when she was 19 came into County Hospital. They saw her and
admitted her because they thought she was schizophrenic. She showed some response. They
changed the diagnosis to manic depression. Four years later she became acutely comatose.
Into County Hospital primarily because of cerebral spinal fluid, the fluid surrounding the brain
and the spine did not show any evidence of inflammation. They ascribed her illness not to a
viral infection, but obviously to a drug overdose. This woman became comatose and has never
recovered from her coma. And if one needs any justification for doing the work were trying
to do, its to go and see these people who have been essentially been year after year in a
comatose stage with every indication of having a viral infection and yet not meeting current
criteria and not fitting into established existing diagnoses.
Now all of these papers have been subject to publications. There is this top one, the Genetic
Instability, the Fragmentation of the Viral Genome. Theres this person who diedfatal case.
The other ones where these, actually three patients but having a severe stealth virus
encephalopathy following a chronic fatigue like illness. And this last lady with a bipolar
psychosis. So they've been presented out there.These cases along with several others, one
would have thought would have been sufficiently compelling to evoke a major public health
concern, particularly since in two of them we have very clear evidence that the virus is African
green monkey cytomegalovirus and therefore can be linked directly to the use of vaccines. But
unfortunately were still having an uphill battle, which, again, as I started this talk is the real
encouragement I have that Dr. Anderson has, in fact, identified another group of patients who
will come through with some of this illness.
I think for those who may be having this illness or having friends with it, Id like to provide a
couple of explanations that will give you a sense of the broad basis of this dysfunctional brain
syndrome and why I see Chronic Fatigue Syndrome as just part of a very broad
spectrum. Essentially the hypothesis were working on is that stealth viruses can be implicated as
contributing factors to a wide range of neuropsychiatric illnesses, Autism, Attention Deficit,
Occupational Defiance, Turrets Syndrome in children, Chronic Fatigue Syndrome,
fibromyalgia, Multiple Sclerosis where it can initiate the illness and thee complicated by
autoimmune responses and so forth. The reason that this would make sense is because the
brain, unlike other organs in the body has a very selective localization of its functions and the
brains function is essentially to respond to different stimuli.
Slide 8
And if we take a normal brain, we get appropriate responses. In an abnormal brain we can have
inappropriate response, for example, with a lot of brain illnesses, it can trigger a sense of fatigue.
If thats a predominant symptom, people will be classified as Chronic Fatigue Syndrome.
Fibromyalgic patients have a lower threshold for pain and so theyll feel pain in their back and
their jaw and muscles and joints, so theyll be the predominant symptoms in what we call our
affectour mood. If we become depressed, then it will become depression. If we dont think
clearly and we can no longer make rational thought processes, then having cognitive deficits,
then people will use labels, like schizophrenia, and if we have parts of our body normally
regulated by the brain and now being dysregulated, for example, bowel function, we can have
things like Irritable Bowel Syndrome. What is clear as I get a chance to see these various
patients is that very few patients fit into a single category and many of these patients, if you
look at them, have a range of these symptoms and often they vary with time and it depends
on who they see. If they see a psychiatrist, theyll be called one thing, a neurologist something
else and its clear that this type of illness process in the brain, clinical neuropsychiatry has a
long way to go to understand that in many of these patients, viruses may be involved and
particularly concerned for those people who are given a psychiatric diagnosis because
unfortunately nobody ever recovers from a diagnosis of schizophrenia. So if I go on a little
bit more about this disease process, obviously were trying to learn a lot about it and useful insights
were gained working with Dr. Tom Glass up in Oklahoma. I mentioned these viruses can grow
in animals. We dont see any obvious personality changes in a mouse or a rat, but we do see it
if we take cats. We chose cats because a number of the Chronic Fatigue Syndrome patients
reported that their household pets were showing behavioral changes, with neurological illness
or other changes that were confusing to the veterinarian and they wondered if the disease
may have passed between them. So we actually took the virus that we had grown from our
chronic fatigue patient and put the virus into the cats and wondered what would happen
and I can tell you from friendly, frisky, happy-go-lucky animals they became reclusive,
irritable, shied away from bright lights, rubbed their backs and necks against the cage
making their area quite hairless, were very difficult to handle and so forth. We looked in the
brain and again we find the subtle changes but not obvious inflammation in the brain.
If we looked at it by electron microscopy we can see viral particles causing this brain illness.
And the benefit from the cat model was that we could see what else was going on in the
animal. And this gave a clear indication that the illness was not confined to the brain. If
we looked at the animals, many of them would have this gingivitis and its an unfortunate
point of our Chronic Fatigue Syndrome patients. Many of them do in fact have their teeth
excised, they get a gingivitis. Weve seen people with large salivary glands where the virus
can be resident. It comes out and seems to find a little nidus in the soltace between the
gum and the tooth. We see this being very important in terms of transmission. Weve even
given patients toothbrushes and then taken the toothbrush and cultured viruses from it.
Again, you get the sense that I see this as a very severe potential
spreading disease that Im not really surprised at all that Dr. Anderson has come up with
evidence of direct transmission when you see this kind of occasion in animals.
If we look at the various organs and this is a liver of the cat, we know that there is infection in
the liver and in the bowel. We know that the liver is not dysfunctional in the sense that theres
not a lot of cellular destruction. They dont become jaundiced but wed also realized that the
ability of the liver to detoxifythe normal toxins that would come from the bowelwere
being impaired, that the bowel would have leaky bowel syndrome, that we could aggravate
the brain damage as a result of added toxins coming though the bowel not being fully
detoxified. So we have a good understanding of this disease process in the animals.
Epidemiology
Now with all that I want to talk a little bit about the spread of infection
Slide 9
and then a little bit
about the therapy. As I mentioned Dr. Anderson now has examples of people that over the
last five or six years, unfortunately have come across the same type of situation without being
able to molecularly define the virus. We had a family in Florida where the wife has Chronic
Fatigue Syndrome and she attends various groups. She knows, but her husband doesnt admit,
the fact that he has Chronic Fatigue Syndrome also. Their mother, the grandparent, has
Parkinsons disease and their son is called shizophrenic. They know as a family they have the
same pervasive illness. When I talked to the neurologist he will be apologetic about the
diagnosis of Parkinsons, its just a label. He knows that. I did not get an apology, though,
from the psychiatrist and it was basically the argument, well the person benefits from being
called schizophrenic but the other one is that medicine demands that we categorize people
with disease related groups and there is no reimbursement if we start saying we do not know
whats going on. Very sad. Fortunately, this child has pulled out from schizophrenia and I got
a card from him that he got married, probably a year ago. There is illness in household pets
and Im not sure if fits the dog of anybody here, but I have a dog at home called Sassy and we
had a dog from Sassy also from which a sample that Dr. Anderson arranged for us to have.
This idea of diverse clinical manifestations is confusing to the typical clinician who would
expect the same symptoms in husband and wife as opposed to appreciating the fact that brains
are different, locations in brains that can be infected can be different. This whole issue of why
some people get infected and others dont, I think we can relate to the presence of antibodies
that cover a much broader range of antigens in the cellular immune system. And Im keen on
observing and trying to prevent the spread of infection if its already in an infection in a family
by seeing who else in the family have antibodies that could neutralize the virus and those who
dont have it, I think that something should be done to protect those individuals. We know
from animals as well from human studies that it can be passed orally, sexually and
transplacentally. Were looking at the moment at two twins in Tarzana Hospital who were
born premature with brain damage for whom viruses can grow and finally the virus itself is a
nasty virus in that its so downsized its not dependent upon a lot of genes and its relatively
stable that we can take a tube and dry it out and still reconstitute live virus from it.
Therapy
I come to this one
Slide 10
and again I think Ive emphasized to you the sense theres a big problem
here. Theres a problem in its recognition, its acceptance and so forth. Its not very pleasant to
be told that there are problems, that people made mistakes and so forth. Im optimistic and
hopeful that the unconventional nature of these viruses holds them open to therapeutic
endeavors that conventional viruses may have resisted. So, I do therefore have a real interest
working with Dr. Anderson and others to evaluate different therapies. If I list the approaches
here they certainly begin with antiviral therapies. And theres a lady I was going to visit this
morning but perhaps later in Palm Springs who is on gangcyclovir. Some of the sick patients
have had foscarnet. So were trying to evaluate how useful these compounds are. And we also
have in the test tube an inhibitor which I gave the name Epione. If I have to say that we do not
have yet an antiviral agent and what can people do, its clear that sensory input can aggravate
certain symptoms and they should be avoided. Other sensory input can ameliorate some of the
symptoms and patients soon work out what they can take and what they cant take, whats
useful and not useful. Even this placebo benefit to some patients is quite useful to at least try
to boost themselves beyond what medicine can do. Reducing exposure to toxic factors and
food adjustments is clearly important and people soon realize this. The number of patients
with this illness who will move away from alcohol and so forth is very clear. The
detoxification pathways, if theyre not working, the liver is impaired, I think one can help
reduce the added burden of these toxic agents and finally though I havent emphasized it too
much as a systemic illness there are other organs that can be damaged, oftentimes altering
immune responses against the thyroid, the pancreas, other organs and they need to be looked
into by a clinician. Its very hard to find the appropriate clinician who can address all of these
problems for these patients and oftentimes its the patients who can learn more about this
illness than any one particular physician. I did want to go through these because one reason
for being here is to say,
"What kind of response can be made to Dr. Andersons description and finding of this
situation?"
I think its clearly very important that we extend beyond the
four patients that we have so far and culture many more people. Those whom we have
cultured wed like to reculture. Wed like to see how many people have no symptoms and
those who do have symptoms, to understand this whole process so that we can understand
how somebody might be infected without symptoms and so forth.
We need, because so far I can tell you that a cytopathic infected culture is very convincing but
it doesn't have the hard currency that sequencing of a virus has. A major challenge for us it to
take the viruses that we have cultured and clone out a portion of that virus and sequence it. I
mention that we have the facility, we dont have resources yet but thats a very high priority
because once we can establish where the virus with this outbreak has occurred, what its
portions of genetic sequences are, we can than have a molecular probe that we can do a much
wider survey then we can just through cultures.
I mentioned the idea of testing family members. Again, I am very sensitive having seen this
illness. I think that many of you should be tested to know where you stand in relationship to
this kind of an epidemic. I think we should go back, though again, they are expensive,
difficult, painful for the animals and for the animal caretakers, I think its important to look at
this particular virus and see what it does do in animals and have the animal model available for
evaluating antiviral therapies and finally, since there were so many patients that Dr. Anderson
has seen, I think its appropriate to create the treatment groups so that we could have two
people in the one family and have one person take one type of therapy and see what happens
to the other person by comparison. I think this in an important opportunity to make some real
headway with this kind of an illness.
I want to acknowledge Dr. Anderson. It was very gratifying for me when first he identified the
outbreak and then made contact and secondly when he came to the lab and saw the need
to make a move in this direction. I think we have the instincts and the ability to do it though
we certainly, absolutely need your help if we can benefit, not only this community, but truly
a much larger community out there. We do need a lot of help with this kind of an illness.
Donations
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Dr. Martin's Web Site: http://www.ccid.org
Transcripts of the John Martin video tape lecture were prepared by
Carolyn Viviani
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