From: fulk@cs.rochester.edu (Mark Fulk)
Subject: Re: On pre-scientific traditions of medicine (was: Use of term allopath)
Organization: Computer Science Department University of Rochester
Distribution: sci
Date: Wed, 19 Aug 1992 16:39:40 GMT

In article <des.10@helix.nih.gov> des@helix.nih.gov (David E. Scheim) writes:
>There were many factors that delayed its commercial production and 
>widespread clinical application, but one was the general skeptism at that 
>time that any chemical compound could have sharp antibacterial effects and 
>still be chemically safe -- such diseases had been intractable up through 
>then.  During the thirties, some other chemical agents were discovered and 
>proven effective, which lead investigators to look seriously for more such 
>compounds and then back to Flemings discovery.  Some British investigators 
>actually found Flemings work by performing a literature search (undoubtedly 
>without the benefit of MEDLINE).

One problem with the conventional/alternative debate is the unstated
assumption that there is always a single conventional position.  On many
issues, there are or have been a wide variety of respectable opinions,
especially when evidence is scant.  Although there may have been a lot
of skepticism about antibiotics in some groups, clearly some very
important groups disagreed.  Among those groups was Oswald Avery's,
where Dubos worked.  Avery ran the largest research effort on
pneumonia in the U.S. at the time.

>>This is so vague I can't evaluate it.  Could you supply some more details?
>
>The earliest and simplist was "Coley's Toxins," which were tried late in the 
>19th century by a Harvard-trained physician, William Coley.  Upon hearing of 
>a case in which advanced cancer disappeared following a bout of the 
>disease  "erysipelas," he tried inducing this condition in some of his 
>patients using cultured germs.  He got several other such spectacular 
>remissions, but the treatment method clearly had its limitations given the 
>dangerous condition this disease produced (including very high fevers) and 
>its contagious nature.  Today, both hyperthermia and immunotherapy are 
>recognized as valid experimental approaches to cancer treatment, and "Coley'
>s Toxins" were in 1975 quietly dropped from the American Cancer Society's 
>list of "uproven methods" for cancer treatment, but he was scorned and 
>ostracized for years.

I thought it was Cooley's toxins.  I believe this is a case where the
therapeutic effect was unreliable and infrequent.  Experiments that
don't work reliably have a hard time getting accepted into the canon;
witness the treatment of Avery/MacLeod/Macarty's paper on DNA and
the transforming factor of pneumonia.

>>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.
>
>That was my original point -- that there have been fads of thought governing 
>medical treatments, and that occassionally they influence what is accepted 
>or rejected as standard treatments.

And I don't disagree.

>I don't think anyone, including Warburg himself, believed that he had a well-
>developed expanation for carcinogenis.

[Explanation of Warburg model deleted: essentially that cell membrane
defects promote mitosis, thereby perpetuating the defects; mutations
being a consequence of the repeated mitosis]

Were this model correct for carcinogenesis, one would not expect to find
consistent patterns of mutations in cancer cells.  In fact, we find that
all of the cells from a single cancer exhibit the same mutations in
the 40 or so oncogenes that we have identified.  Typically, in benign
tumors, one to three oncogenes are found mutated; in lymphomas, about
four, in advanced metastatic carcinomas and sarcomas, about six.

Although all the cells in a given cancer have the same oncogene mutations
(as well as other mutations, mostly chomosome breaks), different cancers,
even of the same type, often have different mutations (either different
oncogenes, or, if of the same type, different mutations of the oncogenes).
One of the most striking bits of data involves sarcomas and gliomas,
especially astrocytomas.   These tumors typically carry a mutation
in the oncogene c-sis, which, it turns out, codes for platelet-derived
growth factor (PDGF) (I'm proud of this, as some programs I wrote at
Rock. U. had something to do with the discovery.)  Interestingly, and
very very hopefully, it turns out that even very advanced cancers
retain their need for PDGF to drive growth; the mutation means that
they make their own.  Monoclonal antibodies against PDGF have proved
very effective in the treatment of artifical brain tumors in rats,
up to and including glioblastoma multiforme.  I believe that the
Warburg hypothesis is very hard to hold in the face of this evidence.

>By the way, I went to the University of Rochester as an undergraduate and 
>also have a Math/Computer background.  -- David Scheim

You are a nice advertisement for the program.
-- 
Mark A. Fulk			University of Rochester
Computer Science Department	fulk@cs.rochester.edu