From: fulk@cs.rochester.edu (Mark Fulk)
Newsgroups: sci.med
Subject: Re: On pre-scientific traditions of medicine (was: Use of term allopath)
Date: 18 Aug 92 22:27:27 GMT
Distribution: sci
Organization: Computer Science Department University of Rochester

In article <1992Aug17.212548.24748@alw.nih.gov> des@helix.nih.gov (David E. Scheim) writes:
>I recommend the book "The Cancer Industry" by Ralph Moss for some
>counterexamples to this ideal.  Both radiation and chemotherapy were
>initially looked upon as quack remedies for cancer, with surgery the only
>accepted treatment.

Looked on by whom?  I'd bet surgeons' opinions differed from those
of internists.

A much better counterexample to the equivalence "established = tested"
is the psychosurgery fad of 1937-1960.  Antonio Egas Moniz even received
the 1949 Nobel Prize in Physiology or Medicine for this travesty of good
medical practice.

> He also points out that Fleming's published discovery
>of penicillin (1928) was not put into clinical practice until 12 years
>later, and then with lots of concern by drug companies on how to make money
>from an intrinsically unpatentable substance.  (Indeed, what could be more
>ridiculous than the thought that something made from bread mold could cure
>disease?)

Penicillin lay unused because Fleming did not have the personality or
resources to push its use.  In fact, the first antibiotic to be put
into widespread use was gramicidin, developed by Rene Dubos at
Rockefeller University.  I used to eat picnic lunches by the flower
gardens where Dubos got his cultures of fungus.

The effective use of penicillin required a massive effort involving
thousands of people; probably only a few governments had the resources
at the time.  You should read the history of penicillin; Howard Florey,
the Army, corn steep liquor, and a canteloupe from Peoria.  Penicillin
stands with radar, Ultra, the Norden bombsight, and the atomic bomb as
a major contributor to the Allied war effort in World War II.

Eli Lilly seems not to have suffered very much from the non-patentability
of penicillin.  In practice, production methods and preparations were
enough protection.

>Various forms of therapy involving promoting an immune response and dietary
>factors, components of which today are accepted as valid, were dismissed as
>close to quackery for years even though careful patient records and trials
>demonstrated success in some cases.

This is so vague I can't evaluate it.  Could you supply some more details?

>Rous's claim that a germ so small it
>passed through any filter could cause cancer was dismissed as fantasy --
>his discovery of the Rous Sarcoma is now hailed as a breakthrough.

Actually, viruses were well known by the discovery of RSV.  As I recall,
the general opinion was that the RSV was not particularly important, and
that viruses were not likely to be major causes of cancer.  Rous had to
wait something like 60 years for recognition.

Oddly enough, that particular conventional wisdom seems to have been
correct (sort of).  It is now generally accepted that RSV was a sort
of laboratory accident.  It was important in that it gave us access
to the first oncogene, and deliberate repetitions of the circumstances
leading to RSV gave us access to about 40 more, thus leading to the
current ascendance of the (mostly somatic) mutation theory of cancer.

On the other hand, the enthusiasms of the cancer virologists were fed by
RSV and the connection between Epstein-Barr virus and Burkitt's lymphoma.
This led to that caricature of a government research program, the
Nixonian War on Cancer.

>In cancer research, to some degree, the Watson molecular biology model of
>carcinogenisis v. the Warburg respiration/membrane dynamic model has
>determined what has been deemed "scientific" v. "alternative."

I believe that the work of the last 13 years has utterly demolished the
Warburg model.  If you know of any reliable data predicted by the Warburg
model, and not already incorporated into the mutation model, please let
me know.

I have been a follower of the oncogene story since I worked at Rock. U.
in 78-79.  At that time, the molecular biologists believed it and would
talk about it over lunch; all of the oncologists I knew about pooh-poohed
the idea.  The RSV oncogene (v-src) was discovered around 1980; it was
followed by a rash of other viral oncogenes.  I think it was around 1982 that
the cellular oncogenes were discovered.  Immediately there was a huge
amount of activity as people published the discovery of yet more oncogenes.
The function of c-src was discovered somewhere in there (vinculin kinase; it
breaks down cell adhesion plates), and this led to the ill-fated dosage
hypothesis.  At this point the story gets too complicated and long to
tell in a posting.  What I noticed at the time, however, was the fierce
opposition of those in traditional oncology to the new ideas.  Nature
could have run a second letters column entitled ``But what about...?''

It was amazing how quickly those questions were answered.  Often they
led to important discoveries.  For example, it takes more than one mutation
in one cell to get a metastatic cancer.  It takes fewer mutations to get
leukemia than to get a carcinoma.  Some oncogenes are recessive:
retinoblastoma/Wilms tumor for example.  Lots of things cause or encourage
mutations, for example, many chemicals, viruses, repeated injury, and
radiation.  Benzopyrene from tobacco binds to DNA, then an enzyme mistakes
the complex for an injury to the DNA, and misrepairs it, thus causing a
mutation and perhaps lung cancer in the smoker.  Certain mutations are only
meaningful in particular cells, for example, c-sis in glial and connective-
tissue cells.  Cancer seems to arise frequently enough that there is a
defense mechanism against it, including the ``natural killer'' T-cells.
The activity of these T-cells is somewhat suppressed in depressed or
otherwise unhealthy patients, perhaps leading to the observed higher
incidence of cancer in these patients.

By the way, Perry is probably more responsible for the mutation theory
than Watson.  His classic study of xeroderma pigmentosum provided the
first really good evidence.
-- 
Mark A. Fulk			University of Rochester
Computer Science Department	fulk@cs.rochester.edu