On Sat, 26 May 2007 21:52:21 -0400, J <nexsw@nvalid,anon> wrote:
>Matti Narkia wrote:
>
>> On Sat, 26 May 2007 05:41:45 -0700, John Corliss
>> <jcorliss@fake.invalid> wrote:
>>
>> >I was surfing a few years back and found a website which claimed that a
>> >famous researcher, back in the late 19th century or early 20th, had
>> >found out that if he intentionally gave a certain disease to a person
>> >suffering from cancer and then was able to cure that disease (apparently
>> >he wasn't always successful in this endeavor), the patient would be both
>> >cured from the cancer they had AND from what the researcher could see,
>> >would be immune to cancer for the rest of their life.
>> >
>> >IIRC, the disease was something truly horrible like necrotizing
>> >fasciitis (flesh eating bacteria infection) or the like.
>> >
>> >Shortly after reading this and when I tried to go back to the site, no
>> >amount of Googling would find it. And I have literally spent hours
>> >looking for the site.
>> >
>> >Can anybody help me out here?
>> >
>> >TIA
>>
>> Are you possibly referring to Dr. William B. Coley (1862-1936),
>> currently regarded as a father of cancer immunotherapy? If so, see
>> Hobohm U.
>> Fever and cancer in perspective.
>> Cancer Immunol Immunother. 2001 Oct;50(8):391-6. Review.
>> PMID: 11726133 [PubMed - indexed for MEDLINE]
>> <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlu s&list_uids=11726133>
>> Despite initial hopes, the efficacy of tumour necrosis factor in treating cancer patients has been
>> disappointing. But a more careful selection of patients, and more appropriate treatment, might be fruitful.
>
J, the main active substance in Coley's toxins is Lipopolysaccharide
(LPS), not tumor necrosis factor (TNF), although LPS stimulates also
TNF production, but for those tumors against which it works, Coley's
toxins and LPS are much more effective than TNF. Murray J. Shear, a
biochemist at National Cancer Institute (of USA) found this out in
1943. Stephen S. Hall writes about this in his book "A Commotion in
the Blood", which I have in my bookshelf. The article
GlycoScience: State of the Science Review
By Bill H McAnalley, PhD and Eileen Vennum, RAC
<http://www.glycoscience.org/glycoscience/document_viewer.wm?FILENAME=D007>
also reports about William B. Coley, Murray J. Shear and
lipopolysaccharide (LPS):
"Cancer has long been linked with glycoconjugates. Beginning
in the 1700's, doctors noticed that some cancer patients
experienced remissions after contracting bacterial
infections. A hundred years later, Dr. William B. Coley
initiated a large-scale effort to use this phenomenon to
benefit his patients. In fact, he was successful in treating
some of his patients (particularly those with soft-tissue
sarcomas) by infecting them with live bacteria. Because of
the dangers inherent with such a procedure, Dr. Coley then
developed vaccines of killed bacteria. These vaccines, which
had essentially the same effect without causing an actual
infection, became known as "Coley's toxins".19 In 1943, Dr.
Murray J. Shear identified and purified the specific
component of the bacteria associated with the cancer
remission. This component was a lipopolysaccharide (LPS).
LPS, found in the cell walls of certain types of bacteria, is
composed primarily of fat (lipo) and sugar (polysaccharide).
In 1973, Dr. Lloyd Old and his colleagues learned that the
effect of LPS on the tumors was not a direct one. Instead,
LPS stimulated the production of a substance in the body,
which caused tumors to necrose, turn black, and dry up. Dr.
Old termed this substance tumor necrosis factor (TNF).20
With the advent of radiation and chemotherapy, treatments
that are intended to treat a wide-variety of cancers, the use
of Coley's toxin (best suited to patients with sarcomas)
diminished. This is unfortunate, because radiation and
chemotherapy typically don't achieve long-term control of
such cancers and, once patients have received such
conventional treatments, they are then less able to respond
to Coley's toxin treatment.19 Nevertheless, for the purposes
of this review, it is noteworthy that the molecules
triggering the remission response that Coley observed were
lipid/carbohydrate combinations found on the cell walls of
certain bacteria.
In vitro studies showed that the addition of either fucose,
mannose, glucose or galactose to culture medium inhibited the
growth of malignant mammary cells in a dose-dependent
manner.21 Fucose and mannose provided the most significant
inhibition. Rats with chemically induced transplantable
mammary tumors showed significantly suppressed tumor growth
following fucose injections. No toxic effects were found to
be associated with fucose treatments.22 ,23 ,24
Successful clinical trials have also been conducted in cancer
patients using infusions of D-galactose, a simple sugar.
Eighty patients with stomach adenocarcinoma25 and 76 with
colon adenocarcinoma26 were enrolled into controlled,
randomized clinical studies. Both studies demonstrated a
significant reduction in hepatic metastases and improved
overall survival of patients treated with D-galactose."
LPS is also mentioned in my 1996 write-up
Coley's Toxins a.k.a. Mixed Bacterial Vaccine (MBV)
<http://cancerguide.org/coley.html>
which I originally wrote in 19996 in CANCER-L mailing list as a part
of a discussion about fever and cancer and related therapies. Steve
Dunn happened to like it and asked my permission for including it in
his CancerGuide he was working on. Coley's toxins are what we now call
nonspecific immunotherapy. IL-2, which cured Steve's "incurable"
widely metastasized stage IV kidney cancer also belongs to the
nonspecific immunotherapies.
BTW, Coley's daughter, Helen Coley Nauts
(<http://www.cancerresearch.org/nautsob.html>), who has tabulated and
organized his father's work after his death, once called me to thank
me for my write-up about his father's discovery. Helen Nauts died on
the January 2, 2001. She was 93.
Wikipedias's article
Coley's Toxins - Wikipedia, the free encyclopedia
<http://en.wikipedia.org/wiki/Coley_Vaccine_therapy>
also mentions my little write-up among its references:
"References
* Hoption Cann S, van Netten J, van Netten C (2003). "Dr
William Coley and tumour regression: a place in history
or in the future". Postgrad Med J 79 (938): 672-80.
PMID 14707241. link
* Zacharski L, Sukhatme V (2005). "Coley's toxin
revisited: immunotherapy or plasminogen activator
therapy of cancer?". J Thromb Haemost 3 (3): 424-7.
PMID 15748226.
* Wayne Martin. Coley's Toxin at second-opinions.co.uk
* Wayne Martin. How to Make and Use Coley's Toxins at
second-opinions.co.uk
* Matti Narkia. Coley's Toxins also known as Mixed
Bacterial Vaccine (MBV) at cancerguide.org
* Thuo hypothesis at second-opinions.co.uk
* Coley Toxins Detailed Scientific Review at mdanderson.org
Further reading
* Hall, Steven S. (1997) A Commotion in the Blood. New
York, New York: Henry Holt and Company. ISBN
0-8050-5841-9
External links
* MBVax Bioscience Inc produces Coley's toxins
* Coley's fluid clinical trial
See also
* Coley Fluid"
The link for the above mentioned "Coley Toxins Detailed Scientific
Review at mdanderson.org" is
Biologic/Organic/Pharmacologic Therapies:
Coley Toxins Detailed Scientific Review
Overview
<http://www.mdanderson.org/departments/cimer/display.cfm?id=35F66009-F06A-11D4-810200508B603A14&method=displayFull&pn=6EB86A59-EBD9-11D4-810100508B603A14>
(<http://tinyurl.com/3a6gfg>)
It describes the current situation with Coley's toxins as follows:
"Current Situation
Charles Starnes at AMGEN in California15 and Dr. Lloyd J.
Old, retired from Sloan-Kettering Institute18, have used the
toxins experimentally within the laboratory4. The Coley
Pharmaceutical Group, a private biotechnology company, is
conducting research with specific genetic sequences that may
have contributed to the therapeutic effects of Coley
toxins19.
The Waisbren Clinic in Milwaukee, Wisconsin, treats patients
with cancer with a mixed bacterial vaccine consisting of
modified Coley toxins plus 10 strains of the heat killed
streptococcus bacteria which causes burn infections, plus
BCG, transfer factor donated by relatives of patients, and a
strain of lymphoblastoid lymphocytes combined with Epstein-
Barr virus 20. An uncontrolled clinical series study by that
center is reviewed within the Summary of Research and
Annotated Bibliographic sections of this therapy review.
Further information concerning the treatment at that clinic
is available at that web site21.
The toxins are reportedly being used outside the U. S. in
Mexico22, Guatemala23, Germany24 and the People’s Republic of
China (Beijing Children’s Hospital and Shanghai5).
According to the American Cancer Society’s Guide to
Complementary Alternative Cancer Methods, "Scientific
evidence suggests Coley toxins or the mixed bacterial vaccine
(MBV) may have a therapeutic role in the treatment of cancer
in a combined treatment approach." However, they also comment
that much has been learned about the science of immunology
and practice of immunotherapy since Coley’s time and that
modern immunotherapy is likely to be of greater value25.
Coley toxins therapy has also been reviewed by Wiemann and
Starnes in the Department of Pharmacology of Amgen, Inc.15
More information on the science and research in Coley toxin
therapy is provided in the Summary of Research."
Links for the other parts of the M.D.Anderson article:
Summary of Research
<http://www.mdanderson.org/departments/cimer/display.cfm?id=8640749B-13EE-11D5-811000508B603A14&method=displayFull&pn=6EB86A59-EBD9-11D4-810100508B603A14>
(<http://tinyurl.com/2tjtzy>)
Annotated Bibliography
<
http://www.mdanderson.org/department...0100508B603A14
Reference List
<http://www.mdanderson.org/departments/cimer/display.cfm?id=864074F5-13EE-11D5-811000508B603A14&method=displayFull&pn=6EB86A59-EBD9-11D4-810100508B603A14>
My write-up would need some updating. I haven't followed the topic for
many years, so I don't know whether for example any of the contact
information provided is still valid. And in 1996 I wasn't aware that
the first doctor to try the "Coley's" bacteria (Streptococcus
pyrogenes) on a cancer patient was a German physician W. Busch in
1868, and that in 1883 Friedrich Fehleisen, a German surgeon, had
successfully identified S. pyrogenes as the cause of erysipelas, and
begun treating cancer patients with the living cultures of the
bacteria. IMHO the honor about the discovery about these bacterial
toxins should be shared between Coley, Busch and Fehleisen. If I ever
get to update my write-up, I probably mention these two German
physicians as well. More about them and Coley in the text of the
following U.S. patent:
Agents and methods for treatment of disease by oligosaccharide
targeting agents
United States Patent 20050026866
<http://www.freepatentsonline.com/20050026866.html>
"[0009] Perhaps the first cancer patient to be purposefully
infected with bacteria was treated by German physician W.
Busch (1). Busch, in 1868, induced a bacterial infection in a
woman with inoperable sarcoma by cauterizing the tumor and
placing her into bedding previously occupied by a patient
with `erysipelas` (Streptococcus pyrogenes). Busch reported
that within a week the primary tumor had shrunk by half and
that lymph nodes in the neck had also shrunk in size,
however, the patient collapsed and died nine days after the
infection had begun (1). Almost 30 years later, William B.
Coley, a young surgeon at New York Hospital, encountered a
cancer patient who seemed to be cured by a severe infection
with erysipelas (2-3). Coley wrote, "I had found one case of
very malignant round-celled sarcoma of the neck, four times
recurrent, in which an attack of erysipelas had accidentally
occurred shortly after the last operation by Dr. Bull. At
this time the tumor so extensively involved the deeper
tissues of the neck that no attempt was made to remove it. A
few days after the first attack of erysipelas had subsided, a
second attack followed, lasting for a week. During these
attacks of erysipelas, the tumor of the neck entirely
disappeared and the patient left the hospital in good health.
After great effort I finally succeeded in tracking the after-
history of this patient and found him alive and well in 1891,
seven years later." This observation led Coley to begin
deliberate infection of cancer patients with live S.
pyrogenes. Unbeknownst to Coley, similar studies had already
been launched in Europe, where, in 1883, Friedrich Fehleisen,
a German surgeon, had not only successfully identified S.
pyrogenes as the cause of erysipelas, but had at once begun
treating cancer patients with the living cultures of the
bacteria (4).
[0010] Both Coley and Fehleisen reported success in eliciting
tumor regression, and Coley was so convinced by his results
that he devoted much of his life's work to exploring the use
of bacteria in cancer treatment. Coley soon abandoned the use
of live bacteria in favor of isolated preparations of
bacterial toxins. A record of his work was carefully
assembled by his daughter, Helen Coley Nauts, which also
summarized case reports over 200 years wherein neoplasms
regressed following acute infection (5-6). It seemed that
when neither the cancer nor the infection was too far-
advanced, yet the infection was of sufficient severity or
duration, some tumors completely disappeared and the patients
remained free from recurrence. However, these studies were
controversial, because they were anecdotal and difficult to
repeat, and would not live up to current standards for such
clinical trials. Nonetheless, subsequent evidence in mouse
tumor models indicated that at least some of the anti-cancer
effects of bacterial infections might have indeed reduced
tumor size, and, in part, the effects seemed to have been
mediated through stimulation of the host immune system.
Carswell et al. (7) first reported that endotoxin
(lipopolysaccharide, LPS) from gram-negative bacteria
triggers release of tumor necrosis factor alpha (TNF.alpha.),
by cells of the immune system, initiating a cascade of
cytokine-mediated reactions, culminating in the destruction
of tumor cells (8). Subseqently, bacterial adjuvants were
shown to be immuno-enhancing in cancer patients (e.g. 9-11).
Today, these and numerous related studies have culminated in
the large and diverse field of cancer immunotherapy, of which
William Coley is generally recognized as the founder (1). In
addition, the use of bacterial toxins in cancer therapy
remains a topic of considerable current interest (12)."
At least one of the Coley's original publications, published in 1893,
was republished in 1991 and its reference information is in Medline:
Coley WB.
The treatment of malignant tumors by repeated inoculations of
erysipelas. With a report of ten original cases. 1893.
Clin Orthop Relat Res. 1991 Jan;(262):3-11. No abstract available.
PMID: 1984929 [PubMed - indexed for MEDLINE]
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlu s&list_uids=1984929>
Unfortunately eeven the abstract is not available online.
>many common chemotherapeutic agents are bacterial toxins ---Doxorubicin, Bleomycin and Mitomycin C are the
>toxins of various strains of streptococci
>Difference being they're produced in tightly controlled conditions and used by oncologists, who know their
>applications.
>J
J, you are comparing apples and oranges. The drugs you mention are
cytotoxic chemotherapeutic agents. Coley's toxins are not directly
cytotoxic and their effect is not based on cytotoxicity, but instead
on the extremely powerful nonspecific stimulation of immune system,
i.e. with similar mechanism that IL-2 and interferon cause their
effect. Coley's toxins raise very high fever for one day. I was
treated with Coley's toxins about 7-8 times around 1992-93, and every
time my temperature went over 40 degrees Celsius (over 104 degrees
Fahrenheit).
Some reading about cancer immunotherapies, Coley is also mentioned, in
the chapter "3.0 THE ORIGINS OF IMMUNOTHERAPY":
Cancer and Immune System: The Vital Connection
Oki K. Dzivenu, D.Phil., and Jill O’Donnell-Tormey, Ph.D.
Copyright © Cancer Research Institute 2003
<http://www.cancerresearch.org/immunology/immuneindex.html>
Coley's toxins are an important part of the history of cancer
treatments. They could possibly in some form belong also to the
arsenal of modern cancer treatments for certain spefic cancers and
purposes, if they weren't so old invention. I don't know if Coley or
anyone else ever patented them, and even if they did, the patent would
have expired ages ago. And I think that it's no longer possible to
patent an invention, which has been know so long and been in general
use, although someone seems to have patented something similar as show
in the link I provided earlier in this message. And if there is no
patent, there will be no investment money coming for research needed
for the acceptance.
Coley's toxins are not an easy cure though. High fever with nausea and
vomiting are very hard for the patient, especially when for the best
results the treatments would probably have to be repeated 2-3 times a
weeks for a few months. Although Coley's toxins are less harmful for
the body than say chemoradiation, and is not likely to cause permanent
damage, when appropriately administered by a physician, in my
experience chemoradiation is much easier to tolerate. Coley's toxins
are a pure torture on the treatment day, but the next day you feel
fine and healthy - until the next treatment day comes ;-).
--
Matti Narkia
Please help me find a website. 
