Jim: > Rather than Israeli Acute Paralysis Virus, "IAPV", we can call
it: "Ian Lipkin's Pet Virus", "ILPV" And where did Ian go, anyway? He
certainly found the exit quickly once the Evans/Chen data hit the fan.


Excerpts from "Pathogen Discovery" (April 2008, by W. Ian Lipkin):

''What has become clear to you since we last met?'' -- Benjamin Franklin

The rate of discovery of new microbes, and of new associations of
microbes with health and disease, has accelerated over the past two
decades. Many factors are implicated. New pathogens have truly emerged
with the globalization of travel and trade, changes in demographics
and land use, susceptibility to opportunistic organisms associated
with immunosuppression, and climate change.

Proof of Causation

Finding an organism is only one step in establishing a causal
relationship or understanding how it causes disease. Many have
wrestled with the challenge of codifying the process of proving
causation. Based on the germ theory of disease of Pasteur, Koch and
Loeffler proposed criteria that define a causative relationship
between agent and disease: the agent is present in every case of a
disease; it is specific for that disease; and it can be propagated in
culture and inoculated into a naive host to cause the same disease.

Pathways to Pathogenesis

Implication of an agent is easiest if it is present in high
concentration at the site of disease when the disease is manifest.
Examples include poliomyelitis, where death of infected motor neurons
results in paralysis, or infectious diarrheas where the causative
agent (bacterium, virus, or parasite) is found in the gastrointestinal
tract. More complex examples of intoxication occur in botulism or
tetanus, where replication in the subcutaneous tissues or the
gastrointestinal tract results in release of toxins that have remote
effects on the nervous system.

Strategies for Pathogen Discovery

Over the past two decades, subtractive cloning, expression cloning,
consensus PCR, and high throughput pyrosequencing resulted in
identification of novel agents associated with both acute and chronic
diseases, including Borna disease virus, hepatitis C virus, Sin Nombre
virus, HHV-6, HHV-8, Bartonella henselae, Tropheryma whippelii, Nipah
virus, SARS coronavirus, and Israel Acute Paralysis virus.

* * *

Comments:

Science has not gotten simpler with more knowledge and understanding.
Combined with the effects of globalization, greater knowledge has
often led to lesser understanding. Or, perhaps what we thought we knew
and understood has simply been overturned. Cause and effect are almost
never as clear as in the movies. If you watch the gunman shoot the bad
guy, you see the gun in his hand and then the bullet hit the bad guy.
You forget it's all staged and the two images could have been filmed
in different locations on different days. So, what looks at first
glance to be linked, with a little further knowledge may turn out not
to be. And vice versa. As Lipkin says, "replication in
gastrointestinal tract results in release of toxins that have remote
effects on the nervous system."

Many of us still remember the first Shuttle disaster in 1986. Although
they were able to pinpoint the exact moment when the mission went bad,
it was found that there were dozens or hundreds of mission critical
flaws in the system, which had been passed over in the effort to get
the ship into the air. "The unrelenting pressure to meet the demands
of an accelerating flight schedule might have been adequately handled
by NASA if it had insisted upon the exactingly thorough procedures
that were its hallmark during the Apollo program. Arnold Aldrich, the
Space Shuttle program manager, described five different communication
or organization failures that affected the launch decision on January
28, 1986.  Four of those failures relate directly to faults within the
safety program."

The point is, cause and effect are often unclear and in fact there may
be multiple, interlinked factors that simply cannot be addressed
individually. One problem with the human mind is it tends to proceed
in a trouble shooting mode. Fix this or that and get back up and
running. Like my first car, it could get me there most of the time --
but I had to pump the brakes, finesse the gas pedal and clutch, and
fuss with the point gap all the time. It was never what I would now
call "a good car". Health is not the absence of disease, or something
that can be assembled from parts. It is the ideal state of the
organism, and a honey bee colony has an optimal condition too.

* * *

Ian writes: "The most advanced technology will fail if samples are
degraded, and data will be uninterpretable without accurate
information on clinical course and sample provenance; thus, emphasis
should be placed on engaging clinicians as equal partners."

This means that the field work is every bit as important as the lab
work, and the results can be made completely useless the moment a
sample is taken. Oh, and the equal partners thing goes both ways.

pb

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