by Donald H. MacAdam
Dr. William Coley (1862–1936) was an American bone surgeon and cancer researcher, pioneer of cancer immunotherapy. He developed a treatment based on provoking an immune response to bacteria. In 1968 a protein perhaps related to his work was identified and called tumor necrosis factor alpha
Chapter Two
Coley
In 1999, a group of researchers compared cancer patients
treated by William Coley with contemporary cancer
patients and reached the following conclusion: "Given the
tremendous advances in surgical techniques and medicine
in general, any cohort of modern patients should be
expected to fare better than patients treated 50 or more
years ago. Yet no such statistical advantage for the
modern group was observed in this study." 1
In 1891, Dr. William Coley plunged a syringe into the
neck of a young Italian man and carefully injected a
solution of infectious bacteria. This particular type of
bacteria was known to cause a skin disease called
erysipelas. At the time, long before the discovery of
antibiotics, erysipelas was often fatal even in a healthy
person. But the young Italian man was not healthy. He was
terminally ill with cancer. Coley’s intention was to
produce erysipelas in the hope the patient, while
recovering from the skin disease, would also recover from
cancer. It was an experiment. But, as is often the case
in medical research, there was an unforeseen problem. The
first injection, then the second, then the third, failed
to produce an infection. But Coley persisted, time after
time injecting the young man with bacteria but repeatedly
failing to infect him. Finally, after four months without
success, an injection of a particularly virulent strain
did the trick. Within an hour, the typical symptoms of a
severe attack of erysipelas appeared. There was pain,
nausea, a chill lasting forty minutes, and a fever that
rose as high as 105°. The attack of erysipelas lasted for
more than one week. By the time it subsided, the tumors
had begun to break down, and within weeks the tumors had
disappeared. 2 The young man returned to his home in Italy
where, ten years later, he died of unknown causes. 3
The young Italian man was only the second cancer patient
treated by Coley. He had treated his first patient less
than a year before. Bessie, a teenager from a prominent
family, had bone cancer in her right hand. The year was
1890. Radiation had not been discovered, chemotherapy had
not been dreamt of, and the only medical treatment for
cancer was surgery. Coley did everything that could be
done when he amputated Bessie’s arm beneath the elbow
but, as is so often the case with cancer, everything that
could be done was not enough. The following month, lumps
appeared in her breasts and lymph nodes, and Bessie was
in constant, debilitating pain that could only be managed
with increasingly larger doses of morphine. In her next
and final month, more nodules developed, more lymph nodes
hardened, Bessie’s enlarged liver turned her skin yellow
from jaundice, and the cancer filled her abdominal cavity
and covered her skin from head to foot. Unable to
tolerate solid food, her condition steadily declined.
With the young doctor at her bedside, death finally
brought relief. 4
Coley was painfully aware that surgery was rarely
effective except when the cancer could be completely
removed and the patient was in good physical condition,
but this was exactly such a case. Bessie was healthy and
her cancer was confined to the extremity of a limb. Her
death had a profound impact on Coley. If the fact that
his surgical skills had proven useless in this one case
was troubling, the knowledge he was not equipped to face
the next case was even more so.
The medical schools of the late nineteenth century, even
the great ones like Harvard from which Coley graduated in
1888, taught much about anatomy, bone-setting, surgery
and diagnosis, but very little about the treatment of
disease. By today’s standards, diseases usually went
untreated. Other than morphine to dull pain, there were
very few available medications. Ailments were either
self-limiting or incurable. To the nineteenth century
physician, his or her role was to perform practical
doctoring and, when there was nothing practical to be
done, to diagnose disease and to explain its probable
course, positive or negative. It was all that could be
expected. But Coley wanted to do more. In a personal
campaign to find something that might help the next
Bessie, Coley researched about 100 similar cases treated
at the New York Hospital during the previous 15 years. 5 He
found nothing out of the ordinary except for a peculiar
incident involving a German immigrant named Stein that
had occurred seven years previously.
In 1884, the 31-year-old Mr. Stein had undergone an
operation to remove a cancerous growth from his neck. It
had been his fifth operation in three years and, for the
fifth time, it proved impossible to remove the entire
tumor. And there was more bad news to come. After two
weeks confined to his hospital bed recuperating from the
ineffective surgery, Mr. Stein contracted a dangerous
skin disease called erysipelas. He experienced high
fever, chills, nausea and pain, then, as the skin disease
began to subside there was a second attack. Once more Mr.
Stein was racked with fever, chills, nausea and pain,
until finally, the second attack of erysipelas gradually
came to an end. It was at this point that the attending
physician, Dr. Bull, witnessed an extraordinary event.
During the resolution of the skin disease, the wound from
the operation healed along with all visible traces of the
tumor. Shortly thereafter, Mr. Stein was discharged from
the hospital.6
After this remarkable incident, there was no further
mention of Mr. Stein in the records of the hospital, not
even a follow up examination. After five surgeries in
three years, the most reasonable explanation for the
extended absence was that he had died, but no one knew
for sure. Coley set out to discover what happened to Mr.
Stein. Even today, it is difficult to reconstruct a
patient’s history seven years after the fact, but in 1891
it must have seemed an impossible task. Nonetheless,
Coley searched New York’s immigrant neighborhoods for
someone with knowledge of Mr. Stein’s ultimate fate.
Then, in his own words, "After great effort I finally
succeeded in tracing the after-history of this patient
and found him alive and well." Coley persuaded Mr. Stein
to accompany him back to the New York Hospital where he
was examined by Coley and Dr. Bull. No trace of the
cancer remained.7
The only clinical factor that distinguished Mr. Stein’s
case from the others was the erysipelas infection. To
Coley, it seemed obvious that the accidental infection
must have somehow cured the cancer. If so, Coley
reasoned, then an intentional infection might also have
curative effects. Coley decided to act on his intuition.
He resolved to purposely induce an attack of erysipelas
in his next appropriate cancer patient. It would be
something like fighting fire with fire and, in
researching the bacterial cause for this new kind of
fire, Coley found there were others who had come to the
same conclusion before him.
In 1867, a German professor named Busch wrote what is
likely the first account of an attempt to cure cancer by
intentionally infecting a patient with erysipelas.8
Busch applied the used bandages of an erysipelas patient
to the neck of a 19-year-old female patient with a
child-head-sized tumor. The young woman contracted
erysipelas, her temperature rose to 104°F, and the huge
tumor shrank to the size of a small apple within two
weeks. After the erysipelas infection was cured, the
tumor grew back and the woman left the clinic to an
unknown fate.9
In 1882, a German scientist named Fehleisen was the
first to identify, isolate and culture the bacteria
responsible for erysipelas. 10 Fehleisen injected the live
cultured bacteria into seven cancer patients and achieved
remissions in three of them.11
As mentioned earlier, remission has a different meaning
than regression. Tumors in a cancer that is in remission
have stopped growing, and tumors in a cancer that is in
regression are becoming smaller either in number or size.
In total, Coley found more than 20 published accounts
before 1890 linking infections of erysipelas to
remissions or regressions of cancer.12
In May 1891, Coley conducted his first erysipelas
experiment with the young Italian man described at the
beginning of this chapter as his patient. By the
following year, he had treated a total of ten "inoperable
and quite hopeless" cancer patients, but continued to
find it difficult to produce an erysipelas infection.
After his initial success with the Italian man, Coley was
able to induce an attack of erysipelas in only two out of
his next nine cancer patients. In these two successfully
infected patients, the cancerous tumors entirely
disappeared in one and reduced in size and number in the
other.13
These results were very encouraging because every
patient who contracted erysipelas showed remarkable
improvement. However, most patients did not contract the
disease and there could be no therapy without the
disease. Coley needed a more efficient method of
infecting patients, and perhaps he found one because the
next two consecutive patients were successfully infected.
But then there was a setback. Both patients died, but not
from cancer. They died from erysipelas.
The consecutive fatalities forced Coley to rethink his
strategy. He needed an alternative method to deliver the
beneficial effects of erysipelas without the necessity of
producing the disease itself. Coley suspected the
anticancer activity of his treatment was not the result
of the skin disease erysipelas, but rather due to an
unknown component of the bacteria that was "toxic" to the
cancer. If so, it might be possible to treat patients
with killed bacteria. That way the patient would receive
the benefit of the anticancer toxin without the necessity
of contracting an often-fatal skin disease. These
thoughts, more intuitive than scientific, led Coley to
abandon the use of live bacteria and begin treating
patients with killed bacteria.
In the first version of "Coley Toxins," which despite the
name are not poisonous, the bacteria responsible for
erysipelas were heat sterilized and passed through a
porcelain filter. This version was used in four cases of
inoperable cancer but failed to generate the intense
symptoms such as chills and high fevers that had been
observed in all successful treatments. As an experiment,
a revised version of Coley Toxins was prepared that
included a second type of killed bacteria known to
generate intense reactions in rabbits. Coley hoped the
mixture of the two types of bacteria would generate a
more intense and therefore more beneficial reaction. 14
The first patient to receive the mixed version of Coley
Toxins was a sixteen-year-old boy who was bedridden with
an abdominal tumor measuring six by five inches in width
and about five inches in thickness. An exploratory
surgery revealed the tumor to be inoperable because it
involved the entire thickness of the abdominal wall and
was attached to the underlying bones. A sample of the
tumor was microscopically examined and found to be
cancerous. Over a period of four months, every few days
Coley injected his new mixed toxin directly into the
tumor mass. On each injection, there was dramatic rise in
body temperature and extreme chills and trembling. The
tumor gradually diminished in size. At discharge from the
hospital in May 1893 after four months of intensive
treatment, the tumor was a fifth its original size. Two
weeks later, a small mass could be felt but it was no
longer visible. By August the remains of the growth were
barely perceptible. The boy returned to his regular work
and received no further anticancer treatment. He remained
in very good health until he died suddenly of a heart
attack 26 years later.15
Between 1891 and 1896, Coley published 16 papers
describing his method but his reports did not generate
widespread excitement. At the time, most physicians
practiced surgery and firmly believed there could be no
cure for cancer other than surgery. Since it was
impossible for Coley’s treatment to be successful,
surviving patients must not have had cancer in the first
place. As one 1893 observer succinctly put it, "A cure by
means other than surgical is … sufficient proof of a
mistaken diagnosis."16
To most members of the medical community, non-surgical
approaches to the treatment of cancer were simply of
little interest. The medical journals in which Coley
published, however, had a wide readership. While most
readers ignored Coley’s articles, a number of
independently minded doctors began to make use of the new
cancer treatment. Before the turn of the twentieth
century, at least 42 physicians from Europe and North
America had reported cases of cancer that had been
successfully treated with Coley Toxins.17
Cancer therapies have improved since Coley’s day, but
improvements in treatment have resulted for the most part
in prolonging the disease rather than curing it. For
example, when an appeal for donations on behalf of the
American Cancer Society claims, "Today, far more than
half of all cancers are curable,"18
it is referring to the fact that about 60% of patients
diagnosed with cancer during the period 1989-96 survived
for at least five years.19
According to the National Cancer Institute, the
five-year survival rate includes "persons who survive
five years after diagnosis, whether in remission,
disease-free, or under treatment".20
This concept is far different than Webster’s definition
of cure as something that "heals or permanently
alleviates a harmful or troublesome situation."21
According to the National Cancer Institute, about 60% of
cancer patients survive at least five years after initial
diagnosis compared to only 35% in 1950.22
The principal difficulty with this kind of comparison is
that the process of cancer diagnosis has improved over
the years. Many patients seem to be surviving longer
simply because their cancers are diagnosed sooner.
Instead of dying in four years in the 1950s, an
equivalent group of cancer patients in the 2000s might be
dying in six years. In these cases, the improvement in
survival is the result of better diagnosis, not better
treatment. For example, in white females resident in the
United States, the five-year survival of breast cancer
patients during the period 1988-1997 was about 82%
compared to only 64% in the period 1975- 1987. That
appears to be a considerable improvement. However, during
1988-1997 about 63% of breast cancers were initially
detected when the disease was confined to a primary tumor
compared to only 51% in the period 1975-1987.23
The 28% increase in five-year survivability must be
tempered by the fact that 24% more breast cancers were
diagnosed before they began to spread.
Earlier diagnosis is the most important contributing
factor in the observed increase in five-year survival
rates. Only that portion of the improvement in survival
rates that is independent of time of diagnosis can be
rightfully credited to modern cancer therapies. The
improvement in survival due to modern cancer treatments
is small but we are grateful for it. However, this
improvement, encouraging as it might be, masks a
fundamental problem. Modern therapies have added some
years to the life of the average cancer patient, but
modern therapies have not reduced the patient’s chances
of dying from the disease. In fact, a resident of the
United States is more likely to die of cancer today
(202.8 per 100,000) than in 1950 (195.4 per 100,000).24
The greatest value of Coley Toxins is evident through
the experience of patients who received the therapy.
Rather than surviving additional years with cancer, many
of these patients lived the rest of their lives without
cancer. For example, in December 1895 a woman was
diagnosed with inoperable cancer. She had a tumor the
size of an orange in her upper left breast that extended
to a region under the clavicle and surrounded major blood
vessels. The woman was in a rapidly declining state of
health and had lost 24 pounds in the previous six weeks.
Her Connecticut surgeons administered 76 injections of
Coley Toxins over a period of three months and, as the
tumor shrank in size, on nine occasions incisions were
made into it to facilitate the drainage of dead tissue.
By the end of three months of therapy, the tumor had
entirely disappeared and the woman soon regained her
weight and her health. She lived a normal life and died
of pneumonia in her 89th year, more than 47 years after
diagnosis.25
Progress against cancer is calculated in terms of
five-year survival after diagnosis. Five years is an
arbitrary, but practical, unit of measure. It might be
more meaningful to measure longer-term survival, but it
would be impractical in terms of patient-tracking and
reporting delays. Doctors and patients want to know the
expected performance of current therapies, not the
performance of historical therapies. In any case, the
infrastructure that would be needed to follow the
long-term medical histories of cancer patients does not
exist. We must be content with an imperfect reporting
system that makes no distinction between patients who
survive five years and patients who enjoy the remainder
of their lives without cancer.
Most patients with inoperable cancer do not survive even
five years. However, even before the turn of the
twentieth century some patients with inoperable cancer
went on to live normal lives. In 1893, a 29-year-old
woman noticed a small swelling on the left side of her
abdomen that rapidly increased in size. An exploratory
operation found an inoperable tumor involving much of the
abdominal wall. Microscopic examination of a tumor sample
returned a diagnosis of cancer of the connective tissue.
Toxin therapy was begun the following month. Injections
directly into the tumor were given daily for six weeks
and then, after a month of rest to allow the inflammation
caused by the repeated injections to subside, the therapy
was continued for an additional month. Over the treatment
period the tumor steadily decreased in size to the point
it was no longer detectable. There was no trace of
malignancy at the time of her death from heart failure in
1918, 25 years after diagnosis.26
After the death of her father in 1936, Helen Coley Nauts
inherited her father’s papers including his diaries,
medical reports, case files and a correspondence
numbering many thousands of letters. Her original
intention was to write her father’s biography but, after
a meticulous reading of the archive, she found her true
vocation. For more than fifty years, the daughter labored
to "rehabilitate her father’s reputation and revive use
of the toxins in modern medicine."27
Thanks to the relentless detective work of Helen Coley
Nauts, we now know that many of Coley’s patients were
long term survivors who went on to live normal lives.
For example, even with the best modern treatment, widely
spread cervical cancer is a virtual death sentence with
only 13% of women surviving five years after diagnosis.28
Yet, more than 100 years ago a 43-year-old woman with
widely spread cervical cancer recovered from the disease
and went on to live a normal life. In her case, an
exploratory surgery revealed two growths, one on each
side of the abdomen, attached to the small and large
intestines. No attempt was made to remove the tumors.
Microscopic examination confirmed a diagnosis of
inoperable widely spread cervical cancer. The woman’s son
was a doctor and he treated his mother at home. Coley
Toxins were injected deeply into the cancerous masses
twice a week for six months, then once a week for a year.
Each injection resulted in a full reaction including high
fever and the tumors slowly reduced in size. By the
completion of the first eighteen months of therapy, the
woman was able to resume her normal activities. After a
period of rest, the treatments were resumed for an
additional eighteen months as a precaution against
reoccurrence. An extended therapeutic regimen is
difficult both for the patient and the physician, but in
the end it proved to be worth the effort. The woman died
of pneumonia in her 79th year, 36 years after diagnosis.
29
We owe this account to a son and a daughter. Without the
son’s dedication to provide his mother with long-term
therapy there would be no happy ending. Without Helen
Coley Naut’s painstaking research into the ultimate fate
of her father’s patients, the happy ending would be
unknown. Sons and daughters, mothers and fathers; unlike
dispassionate medical statistics, cancer is very much a
family affair and the most tragic cases, and also the
most heartwarming, are those involving children. There is
the case of a nine-year-old girl, bedridden in a
Connecticut hospital, and unable to close her mouth. The
marble- sized tumor that distended her jaws could not be
surgically removed. The only possible treatment was toxin
therapy. Injections were given twice weekly and on each
occasion the girl experienced high fever and violent
chills. After two months, the tumor had completely
regressed and the patient was allowed to go home where
she continued to receive injections for an additional
five months. The little girl grew up and remained in
excellent health. She was free from recurrence when last
traced in 1953, more than 46 years after diagnosis. 30
Coley Toxins therapy was usually administered in the
patient’s own home. Even one hundred years ago, it was
considered too expensive to tie up a hospital bed for
many months at a time. The Mayo Clinic, for example,
would begin toxin therapy and then discharge the patient
into the care of a local doctor. In most cases, however,
cancer patients were never hospitalized at all. These
patients relied entirely on their family doctor. One such
physician, Dr. Calkins of Watertown, New York, routinely
treated his cancer patients for a full year. He would
give daily injections of Coley Toxins for six months and
then twice weekly for another six months. Using this
technique, Calkins achieved an 80% five-year survival
over a 32-year period. 31
Another family physician, Dr. Arthur Burns of Kentville,
Nova Scotia, knew he had a difficult case when a young
woman’s health unexplainably began to rapidly
deteriorate. He referred her to a large Halifax hospital
where an exploratory surgery revealed a huge mass of
tumor attached to and growing outwards from her kidney.
When microscopic examination returned a diagnosis of
widely spread kidney cancer, her condition was considered
hopeless. She was discharged from the hospital and
returned to her hometown on a stretcher. Dr. Burns
administered injections of Coley Toxins for six weeks and
on each occasion her temperature rose to about 105°F. Her
condition gradually improved and she began to gain back
weight. Four months after therapy began, she returned to
a normal, healthy life. When the woman was last traced in
1952, she was entirely healthy 40 years after diagnosis
of widely spread kidney cancer.32
There are many more examples of desperately sick cancer
patients who received a new lease on life after receiving
toxin therapy. An extremely sick woman with widely spread
ovarian cancer received fifteen months of toxin therapy
beginning in 1916, and completely regained her health
until she died suddenly of a cerebral hemorrhage 20 years
later. 33
A patient with recurrent melanoma received injections of
Coley Toxins in 1902 and remained well without further
recurrence for 41 years. 34
A patient who had become paralyzed due to a massive
tumor involving the spine received injections for three
months in 1902, completely recovered, and lived a normal
life without further recurrence for 42 years. 35
A patient with egg-sized tumors in the neck and jaw,
received six months of toxin therapy in 1906 during which
the tumors entirely disappeared without further
recurrence for 46 years. 36
A patient with inoperable bone cancer received six
months of toxin therapy in 1909 and went on to live a
normal life without recurrence for 42 years. 37
During his career, Coley treated about one thousand
cancer patients with comparable or better results than
the best treatments available today. However, Coley did
not understand how his therapy worked and therefore had
no scientific model to guide its proper implementation.
He made changes in treatment protocol based solely on
personal observations. He learned it was necessary for
patients to experience a strong reaction including a high
fever and chills in order to benefit from the therapy. He
also learned through experience that different patients
required different amounts of toxin, so he began with
small doses, then gradually built up the strength until
he observed the desired reaction. Some of this
dose-variable effect was due to the various preparations
of Coley Toxins available over the years. Each contained
the same mixture of two killed bacteria, but varied
greatly in potency. In particular, the commercially
available Coley Toxins made by Parke Davis & Company
between 1899 and 1951 were often of poor quality.38
Finally, after hundreds of patients and years of follow
up, Coley learned that the therapy must be continued for
some months after apparent recovery or else there was an
increased risk the cancer would return.
These observations, perfectly sensible in hindsight, came
slowly after years of experience. By the time Coley
appreciated the importance of quality control in the
manufacture of the toxins and exactly how they should be
administered, he was nearing the end of his career. There
were few physicians willing to revisit an old therapy
without a satisfactory medical explanation, let alone one
that required months of treatment and constant
surveillance, when radiation therapy was well understood
and straightforward to administer. After Coley’s death in
1936, the use of the toxins gradually dwindled until by
the end of the 1950s, when chemotherapy was considered
the anticancer treatment of the future, Coley Toxins were
almost, but not quite, forgotten. In the United States,
perhaps the last recorded use of Coley Toxins as a
primary cancer treatment occurred in the 1960s. In this
case, a 69-year-old man with colon cancer that had spread
to his liver and lungs was in such a hopeless condition
he was expected to survive less than one week. As a last
resort, a doctor in Oklahoma City administered eight
daily doses of Coley Toxins and each time the patient
experienced the healing bouts of high fever and chills.
This period of treatment is far short of the amount of
time usually required to assure a long-lasting response.
Nevertheless, one week after completion of the toxin
therapy, the man returned home, his weight and strength
increased, and complete regression occurred. The man was
free of disease when last traced eight years after
receiving the toxin therapy.39
Perhaps the last recorded use of Coley Toxins as a
primary cancer treatment anywhere in the world occurred
in China during the 1980s. An adult male had terminal
liver cancer involving large tumors in both lobes of the
liver. The man received 68 injections of Coley Toxins in
34 weeks. By the end of this course of treatment, all of
the tumors had completely regressed.40
The examples that have been described are but a small
sample of the Coley Toxins cases documented in the
medical literature.41
These accounts are so compelling that readers can be
easily seduced into unwarranted conclusions about the
efficacy of a forgotten therapy more than one hundred
years old. By themselves, Coley Toxins are not the cure
for cancer. To keep a reasonable perspective, it is
useful to remember that about half the time toxin therapy
did not work. It can be argued that many of these
failures were due to weak versions of the toxins or
improper administration, but a similar argument can be
made for the shortcomings of any cancer treatment. For
whatever reason, Coley Toxins failed about fifty percent
of the time. In that respect, this historical therapy is
no better than its modern replacements. On the other
hand, when Coley Toxins did work, more patients went on
to live a normal life or enjoyed longer periods of
disease-free survival.
For example, of 896 patients treated with Coley Toxins in
one retrospective study, 33 had breast cancer. Of these
patients, 13 had operable cancer that had not widely
spread and all 13 survived at least five years. The
remaining 20 patients had inoperable, widely spread
disease. Of these, 65% survived at least five years.42
In comparison, five-year survival of women with widely
spread breast cancer at Yale-New Haven Hospital was about
7% in the 1920s and improved to about 15% in the 1950s.
43
More recently, according to the American Cancer Society,
20% of women diagnosed with widely spread breast cancer
in 1989-1996 survived five years.44
As we have seen, Coley Toxins were a highly effective
anticancer treatment. As we shall see, Coley Toxins work
by stimulating a powerful immune response. By itself, a
powerful immune response is sufficient to cure some
cancers in some patients but cannot cure all cancers in
all patients. A powerfully stimulated immune system is
only part of the answer because cancer cells are
frequently able to hide from the immune system. The
immune system cannot kill what it cannot see. The
remaining part of the answer, training the immune system
to recognize hidden cancer cells, is the subject of
ongoing research that is beginning to yield tangible
results. However, before we discuss the end of cancer, we
must start with its beginnings.
FOOTNOTES
1
Richardson MA, Ramirez T, Russell NC, Moye LA. Coley
toxins immunotherapy: a retrospective review. Alt Ther
Health Med 1999; 5:42; comparison of 128 Coley cases with
1,675 controls from the official registry of the National
Cancer Institute.
2
Coley WB. The treatment of malignant tumors by repeated
inoculations of Erysipelas, with a report of ten original
cases. Am J Med Sci 1893; 105:487-511.
3
Nauts HC. Bacteria and cancer -- antagonisms and
benefits. Cancer Surv 1989; 8(4):713-23.
4
Hall, Stephen S. A Commotion in the Blood. London:
Little, Brown and Company, 1997. An excellent and
readable account of Coley’s life.
5
Nauts HC. Bacteria and cancer -- antagonisms and
benefits. Cancer Surv 1989; 8(4):718; Coley WB. The
treatment of malignant tumors by repeated inoculations of
Erysipelas, with a report of ten original cases. Am J Med
Sci 1893; 105:487.
6
Coley WB. The treatment of malignant tumors by repeated
inoculations of Erysipelas, with a report of ten original
cases. Am J Med Sci 1893; 105:487-8.
7
Coley WB. Late results of the treatment of inoperable
sarcoma by the mixed toxins of erysipelas and Bacillus
prodigiosus. Am J Med Sci 1906; 131:375.
8
Busch W. Aus der sitzung der medicinischen section vom
13 November 1867. Berl Klin Wochenschr 1868; 5:137.
9
Hobohm U. Fever and cancer in perspective. Cancer
Immunol Immunother 2001; 50(8):391-6.
10
Fehleisen F. Über die Züchtung der Erysipelkokken auf
künstlichem Nährboden und die Übertragbarkeit auf den
Menschen. Dtsch Med Wochenschau 1882; 8:553.
11
Hobohm U. Fever and cancer in perspective. Cancer
Immunol Immunother 2001; 50(8):391-6.
12
Coley WB. The treatment of malignant tumors by
repeated inoculations of Erysipelas, with a report of ten
original cases. Am J Med Sci 1893; 105:487-511.
13
Coley WB. Late results of the treatment of inoperable
sarcoma by the mixed toxins of erysipelas and Bacillus
prodigiosus. Am J Med Sci 1906; 131:375-430.
14
Ibid., p 378-9.
15
Coley WB. Late results of the treatment of inoperable
sarcoma by the mixed toxins of erysipelas and Bacillus
prodigiosus. Am J Med Sci 1906; 131:393-4; Nauts HC,
Fowler GA, Bogatko FH. A review of the influence of
bacterial infection and of bacterial products (Coley’s
toxins) on malignant tumors in man. Acta Med Scand Suppl
1953; 276:21-2.
16
Nauts HC, McLaren JR. Coley toxins -- the first
century. Adv Exp Med Biol 1990; 267:483-500.
17
Table of Successful Cases Treated by Other Surgeons:
Coley WB. Late results of the treatment of inoperable
sarcoma by the mixed toxins of erysipelas and Bacillus
prodigiosus. Am J Med Sci 1906; 131:422-8.
18
American Cancer Society appeal for funding. Website of
the Illinois State and University Employees Combined
Appeal, http://www.secaillinois.org/acs.hlm accessed
December 17, 2002.
19
Greenlee RT, Hill-Harmon MB, Murray T, Thun M. Cancer
Statistics, 2001. CA Cancer J Clin 2001; 51:15-36.
20
Understanding prognosis and cancer statistics.
National Cancer Institute web site,
http://cis.nci.gov/fact/8_2.htm accessed December 17,
2002.
21
Webster’s Ninth New Collegiate Dictionary. Markham,
Ontario: Thomas Allen & Son, 1989, p 316.
22
Table I-3, SEER Cancer Statistics Review 1973-1999.
National Cancer Institute website www.seer.cancer.gov.
Accessed April 2, 2003.
23
Clegg LX, Li, FP, Hankey BF, et al. Cancer survival
among US whites and minorities. Arch Intern Med 2002;
162:1985-93.
24
Table I-2, SEER Cancer Statistics Review 1973-1999.
National Cancer Institute website www.seer.cancer.gov.
Accessed April 2, 2003. These statistics, by the way,
have been age-adjusted to make today’s numbers comparable
with those of 1950; otherwise the increased chance of
dying from cancer would be even greater
25
Nauts HC, Fowler GA, Bogatko FH. A review of the
influence of bacterial infection and of bacterial
products (Coley’s toxins) on malignant tumors in man.
Acta Med Scand Suppl 1953; 276:27-8; Coley WB. Late
results of the treatment of inoperable sarcoma by the
mixed toxins of erysipelas and Bacillus prodigiosus. Am J
Med Sci 1906; 131:398-9.
26
Nauts HC, Fowler GA, Bogatko FH. A review of the
influence of bacterial infection and of bacterial
products (Coley’s toxins) on malignant tumors in man.
Acta Med Scand Suppl 1953; 276:22-5.
27
Quote from: Hall, Stephen S. A Commotion in the Blood.
London: Little, Brown and Company, 1998, p 118. An
excellent account of Coley’s life.
28
5-year survival in metastatic cervical cancer is 15%
for white women and 7% for black women. Greenlee RT,
Hill-Harmon MB, Murray T, Thun M. Cancer Statistics,
2001. CA Cancer J Clin 2001; 51:34.
29
Nauts HC, Fowler GA, Bogatko FH. A review of the
influence of bacterial infection and of bacterial
products (Coley’s toxins) on malignant tumors in man.
Acta Med Scand Suppl 1953; 276:28-30.
30
Ibid., p 39-40.
31
Nauts HC, McLaren JR. Coley toxins -- the first
century. Adv Exp Med Biol 1990; 267:486.
32
Nauts HC, Fowler GA, Bogatko FH. A review of the
influence of bacterial infection and of bacterial
products (Coley’s toxins) on malignant tumors in man.
Acta Med Scand Suppl 1953; 276:59-61.
33
Ibid., p 75-7.
34
Nauts HC, McLaren JR. Coley toxins -- the first
century. Adv Exp Med Biol 1990; 267:488.
35
Nauts HC, Fowler GA, Bogatko FH. A review of the
influence of bacterial infection and of bacterial
products (Coley’s toxins) on malignant tumors in man.
Acta Med Scand Suppl 1953; 276:30-2.
36
Ibid., p 40-2.
37
Ibid., p 51-3.
38
Ibid., p 93-6.
39
Nauts HC. Bacteria and cancer -- antagonisms and
benefits. Cancer Surv 1989; 8(4):718-9.
40
Ibid., p 720.
41
A critical analysis of 30 inoperable cases treated
with Coley Toxins: Nauts HC, Fowler GA, Bogatko FH. A
review of the influence of bacterial infection and of
bacterial products (Coley’s toxins) on malignant tumors
in man. Acta Med Scand Suppl 1953; 276:1-103; also see
extensive list of references in: Wiemann B, Starnes CO.
Coley’s toxins, tumor necrosis factor and cancer
research: a historical perspective. Pharmacol Ther 1994;
64(3):529-64.
42
Nauts HC. Bacterial pyrogens: beneficial effects on
cancer patients. Biomedical Thermology 1982; 690.
43
Todd M, Shoag M, Cadman E. Survival of women with
metastatic breast cancer at Yale from 1920 to 1980. J
Clin Oncology 1983; 1(6):406-8.
44
By race, 22% of white and 15% of black women with
metastatic breast cancer survived five years. Greenlee
RT, Hill-Harmon MB, Murray T, Thun M. Cancer Statistics,
2001. CA Cancer J Clin 2001;
51:15-34.
No comments:
Post a Comment