Q: The other thing which has been voiced by your critics in the pages of JAMA
is they say you used the wrong neurological tests for your hypothesis. The
wrong tests for OPIDN
A: Yes. Some critics have suggested that the neurological tests we used were
not the ones that they would prefer for this Organophosphate Induced Delayed
Neuropathy. Unfortunately that comment comes from misunderstanding of the
spectrum of the Organophosphate Induced Syndromes. The assumed is that the
only type of illness you get from organophosphates is a severe neuro --
peripheral neuropathy. That is dysfunction or malfunction of the nerves
in the arms and the legs. In fact, the truth about OPIDN, or organophosphate
induced delayed neuropathy, is there's a spectrum from, if you take a very big
dose of poisoning of one of these compounds, all at once in one dose, typically
about 10 days later you get paralysis of the -- tingling or paralysis in the
arms and legs, but over a year or so that tends to go away, leaving, in its
place, severe dysfunction, or mild dysfunction of the spinal chord and the
lower bone stem. So, critics say, Well you should have done studies of the
peripheral neuropathy. Well, see, we were studying this 3 and 4 years later.
After which you would have expected the peripheral neuropathy to have resolved
and gone away leaving only the bone stem and the spinal chord. So why did we
do studies of the peripheral neuropathy when in fact all we would
predict that only the brain stem damage would be left. So see it reflects just
a misunderstanding of the progression of this illness.
Q: But I thought that there was no evidence of large doses, acute symptoms in
the field, or any of these typical --
A: I didn't make myself clear. If you're exposed only to small doses, for
example a pesticide sprayer gets exposed, they don't have peripheral
neuropathies. And our critics were saying, You should have tested for
peripheral neuropathies. People who were exposed to small doses over periods
of time and in combinations, they only get central problems. In fact they are
often mistaken for psychiatric disorders, depression, schizophrenia, and so
forth. So, Why did you test for peripheral neuropathy, when small doses should
produce central problems. Central nervous system problems? The criticism
doesn't make any sense based on what we know about the disease and what we
expect occurred in the Gulf. Low doses, combinations, perhaps over a period of
time, only cognitive, possibly psychiatric type changes in the brain, and very
few symptoms related to neuropathy, why did we want to test for neuropathy and
not test for central nervous system findings?
Q: I think that's a confusion. The hypothesis you're testing for is
organophosphate induced delayed polyneuropathy, right?
A: Right, and organophosphate induced delayed polyneuropathy has a spectrum of
symptoms. With a one time large dose you expect peripheral neuropathy. With
repetitive small doses and combinations of things you expect central nervous
things to -- abnormalities to predominate. We proposed that it was small doses
over a short -- over a period of time and perhaps in combinations that would
produce central neuropathic findings, the symptoms that the veterans have are
of the central nervous system nature and we did tests, neurological tests to
brain stem and central nervous system and spinal chord disorders. Our critics
have said, You should have tested for peripheral nerve disorders. But that
only occurs when you have severe one-time exposures, and even gets well after a
year or two, and this was three or four years later, so it doesn't make any
sense at all to test only for peripheral neuropathy and to avoid testing for
central neuropathy as our critics have suggested. What we did was exactly what
you would want to do.
Q: The other thing the critics say is that you have these 23 patients, which
are then divided between three.
A: Right, the syndromes, right.
Q: Fairly small numbers, and then you run a lot of tests on them and therefore
you run into the what is sometimes called the Texas Sharpshooter Problem, or
the multiple comparison problem. How do you answer that? Don't you, in these
things, have to be really specific up front about your hypothesis? Otherwise
you're bound to find some sort of match.
A: Right. The Texas sharpshooter problem is a very good criticism. We
anticipated it and in the articles we answered that criticism. We did an
analysis of the number of tests that we performed on the 23 cases and 23
controls. We analyzed all of the total numbers of tests we did, how many
showed that the ones with the syndromes may have merely been the controls.
And, vice versa, how many of the tests came out the other way. The controls
more sick than the cases. And then we did a statistical test on that to see if
that difference of that pattern could have occurred by chance. And you know
what the probability of that could have occurred be the sharpshooter effect?
Less than one in 10,000.
Q: What do you say to the argument of the scientific panels that stress is a
likely exacerbating factor for the symptoms--much more likely in fact than low
levels of chemicals.
A: Right. Some of the critics have said that the Gulf War veterans' physical
symptoms that they're having are due to stress. Now what does that argument
really entail? The only illness we know of in the list of medical diseases
and psychiatric diseases, that's caused by stress, is post traumatic stress
Listen, I've been in stressful conditions for three and a half years doing
study and I don't have post traumatic stress disorder, and I don't have
physiological affects. -- Business executives are all the time under stress.
People who are forced to be on welfare or on -- have terrible stress. And
no-one's ever connected these types of stresses to the types of symptoms these
Gulf War veterans are having. That's just completely specious.
Q: People have fund the notion of chemical weapons terribly exciting. Much
more exciting that DEET or other pesticides, right? But you are saying, am I
getting you right? Your theory doesn't need chemical weapons?
A: Our findings show that our first syndrome, syndrome one, is associated with
what appears to be pesticide exposure. Syndrome three is associated very
strongly with DEET and pyridigstigmine bromide exposure, and probably a
synergistic effect of the two. Our syndrome two, which is the most severe,
most of the veterans who have it, unemployable very very handicapped with these
neurological, very severe neurological deficits. This was most strongly
associated with risk factors that strongly suggest low level chemical nerve
agent exposure and toxicity from peritostigmine and a synergistic effect
between the two. Does our theory need chemical weapon exposure to explain it?
I don't think theories need anything. I think the problem is, that's what the
risk factors suggest.
Others will, hopefully, duplicate this study and see that they find the same
effect. We're going to do the same study in a large representative sample of
veterans, and maybe we won't find the same thing the next time. That's
certainly possible. Then we would have to adjust to that and our
theories would have to change. But right now, on the table, that's one of the
risk factors that -- and there's no counter evidence in veterans, epidemiologic
evidence, that would suggest that's not right. It's just there's no other
evidence. No-one else has done a study.
Q: I want to come back to the exposure question. For chemical agents to explain
Gulf War illnesses, there has to be exposure that gets to masses of US troops
all over the Gulf. Even if the doses are very very small, there still has to be
a way to distribute it very widely. I mean the chemicals have got to come from
somewhere. Now one popular theory is aerial bombings. But UNSCOM (the UN
special commission on chemical and biological weapons who have been to all of
Sadam's bunkers to find and destroy the weapons) told me that in their view
allied bombings destroyed hardly any of Sadam's chemical weapons duing the war.
And I pressed them on this, I said, "do you mean that Saddam, ended the war
with about the same amount of chemical weapons than he started" -- they said,
"Yes. A very small fraction was destroyed".
Now, I have problem from just the point of view of basic physics of how you
get this stuff to so many troops if not much of it was blown up. Isn't that a
problem that has to be addressed...you can't just say, Oh the epidemiology says
A: I'm just an epidemiologist. I'm not qualified to talk about aerial bombing
and intelligence information and so forth. That's so far out of my area I just
couldn't comment on it.
Q: So-- it doesn't follow that there was any widespread chemical exposure from
what you've found, from chemical weapons?
A: Our evidence pretty strongly suggests that chemical weapon, the perception
of chemical weapon exposure and interaction, synergistic interaction with
pyridigstigmine bromide is a serious risk factor that needs to be explored.
Whether there were actual exposures on the battlefield, the evaluation of all
the evidence, the political evidence and the intelligence evidence is just so
far beyond my expertise I really just couldn't comment on it.
Q: But isn't that the point. There's a difference between perception of a
toxic exposure and the toxic exposure?
A: We have a very high relative risk, which is a number indicating how strong
the association is, with the perception of chemical exposure, synergistic
effect with pyridigstigmine bromide which is a very dramatic finding
epidemiologically. How that squares with intelligence information is somebody
Q: But perception of a toxic exposure is not the same as actual toxic exposure.
A: That's correct. Yes. But what you do have to worry is the plausibility of
an eye witness testimony versus the plausibility of intelligence information,
and again, that's just out of my area of expertise.
Q: To establish the ideas we've been talking about, you have to convince your
scientific colleagues, it's not a question of being popular with veterans or
with politicians. You have to establish in the scientific community. Is that
going to be a hard job?
A: No. Very easy. That's the easiest part of the job. Where they,
scientists, become convinced is, they read scientific papers and they go to
scientific meetings and hear scientific presentations given on those data. And
that's it. And then they form their opinions, or they don't.
Note: Dr. Haley's 1997 articles in Journal of the American Medical
Association can be accessed at JAMA's web site.
Haley's articles elicited many letters in JAMA criticizing his studies. For
example, read Dr. Philip J. Landrigan's editorial "Illness in Gulf War
Veterans" Access this by going to JAMA's web site
. Type in Landrigan's name and title of his editorial on the search page.