Bacteria – Friend or Foe?

Many years ago, when we were working in the Middle East, we had a friend of ours who would lug a case of bottled water on his trips to Kerala for holidays. We would pull his legs about this with great mirth telling him how fickle his gut had become and he would counter with a grand argument that the flora and fauna in his NRI stomach could no longer handle the Indian toxins, unhealthy water and the heavy oily food etc and so as an added insurance he was taking these bottles along. Well, we continued to make fun of him and we still remark about this even today. Imagine, a guy who would eat from the roadside eating places with gusto, suddenly becoming sensitive, but then he was quite right, for one does lose the resistance and as you move, start cultivating different families of microbes in your body. Anyway that was the first time somebody brought focus to the flora & fauna in one’s innards.


The next time bacteria came to focus was when I read a fascinating (I think it was in Fortune) account of the miserable way the medical community and the drug industry treated the great Australian doctor Barry Marshall for some 20 years. He kept saying that H Pylori was the main cause for peptic ulcer while the learned medical fraternity and as it appears, the antacid lobby went against him and prevented his rise to fame for a full two decades, before everybody finally accepted his views. Well, that by itself is an interesting story which I will not get into (I had briefly covered it earlier in another blog), as it has been widely covered in press since then. When he first came to speak in US about his ideas, the doctors or their spouses were heard remarking "They were talking about this terrible person that they imported from Australia to speak- How could they put such rubbish in the conference?" Eventually he went on to win the Nobel Prize and he can be seen in PA these days. Marshall, along with his colleague and fellow Nobel winner Robin Warren, proved that up to 90 percent of peptic ulcers are caused by a bacterium called Helicobacter pylori. At a point of time, he had to swallow the bacterial concoction himself to prove the point.

But back to the point, did you know that there are some 300-1600 species of friendly bacteria in ones stomach? Have you thought about where they live actually? In the acid lining, in folds here & there? Or some other place? Or that they are needed to break the food down and keep you healthy? Or that, they help you keep your immune system healthy? But then, what exactly do they do living in your gut? Did you ever consider that when you take antibiotics unnecessarily or even eat antibiotic fed meat or poultry, you end up killing even the friendly bacteria and create even more problems in your own body?

To answer all these questions, let me first take you to the world of home aquariums. Most of them today have an aeration section where the water falls on a bio-wheel spinning it in pleasing fashion. As the Bio-Wheel rotates, beneficial bacteria grow and thrive on its surface. Nourished by oxygen, the bacteria eliminate more ammonia and nitrite with every turn. In addition, when you change the water or clean the gravel and get rid of all the healthy bacteria in there, the stored bacteria in the bio-wheel helps out create new colonies to break down all the waste..

Well, we humans have a similar mechanism, not that it was meant to be that, but over eons it evolved that way, for you will read here, if you don’t know it already, it is the useless appendage called appendix which is the store for large colonies of bacteria. An AP story in msnbc states - The function of the appendix seems related to the massive amount of bacteria populating the human digestive system, according to the study in the Journal of Theoretical Biology. There are more bacteria than human cells in the typical body. Most of it is good and helps digest food. But sometimes the flora of bacteria in the intestines die or are purged. Diseases such as cholera or amoebic dysentery (in old times) would clear the gut of useful bacteria. The appendix’s job is to reboot the digestive system in that case. The appendix “acts as a good safe house for bacteria,” said Duke Surgery professor Bill Parker, a study co-author. The location of the appendix - just below the normal one-way flow of food and germs in the large intestine in a sort of gut cul-de-sac - helps support the theory, he said. Also, the worm-shaped organ outgrowth acts like a bacteria factory, cultivating the good germs, Parker said.

The gut bacteria life story is another of those interesting mysteries that was cleared up recently, for the gut has an effective immune mechanism against unfriendly bacteria, but at the same time tolerates friendly bacteria. The controller gene in this fight is what is known as the ‘pims’ gene. And thus the 100 trillion microbes in our body live happily…They help in many ways by promoting production of various antibodies, hormones, acids, peroxides, nutrients like vitamins B12 and K, food digestion. And interestingly infants acquire their basic colonies from their mothers.

Now that you have a slightly better idea about these bacteria and what they do to you, I have to take you to a radically different word of a particular type of unfriendly bacteria and a brilliant and fascinating individual who worked with them for a cure, fighting fire with fire so to say, using toxins against toxins. Strangely not much of this story can be found in mainstream media and in many ways was a complete surprise to me, as it was discovered over 100 years ago and quickly vanished from limelight. Not much is written about this doctor or his techniques though I found them fascinating to say the least. Let me now go on to tell you a bit about this very interesting gentleman.


Parmenides Greek physician (about 540-480 BC) said: “Give me the power to induce fever, and I cure all diseases.”

William Bradley Coley


And Dr Coley took notice…but not from his perusal of literature

Sometime around 1888 Dr Coley began his career as a bone surgeon at New York Cancer Hospital (which later became part of the Memorial Sloan-Kettering Cancer Center) but became more interested in cancer treatment. Elizabeth Dasheill, a patient was admitted with malignant bone cancer, but even after a forearm amputation, she died, affecting Dr Coley deeply. The girl happened to be a childhood friend of John D Rockefeller who decided to fund in a small way further cancer research by Dr Coley. Coley set to studying old cases and one concerning a patient named Fred Stein, whose tumor disappeared following a high fever from an erysipelas infection (Streptococcus pyogenes) grabbed his attention. Coley searched for the patient trudging through New York and found him finally, living cancer free. This sparked Coley’s interest. Coley thus developed the theory that it was the infections which had helped patients in the past to recover from their cancer. So he began to treat patients by injecting a brew of Streptococcus directly into inoperable tumors. Coley’s first intentional erysipelas infection was performed on a patient named Mr. Zola on May 3, 1891, who had tonsils and throat cancer. Mr. Zola came down with erysipelas and his condition improved tremendously. Mr. Zola lived for another eight and a half years. Coley was convinced that he could effectively use bacteria to treat cancer and created a mixture of killed bacterial infusions called Coley's Toxins. The infusion was administered by injection in increasing doses to induce a fever. Once stimulated, he observed, the immune system could be capable of tackling cancerous cells along with the infection. Coley declared, “Nature often gives us hints to her profoundest secrets and it is possible that she has given us a hint which, if we will but follow, may lead us on to the solution of this difficult problem.”

Parke-Davis, the pharmaceutical company, produced the toxins commercially for many years, but they heated the formula, which reduced its effectiveness. Despite that, even this weakened form of toxins, Parke-Davis formula #IX, showed 37 percent cure rate for inoperable patients. Some 270 people had their cancers cured from a lot of roughly 1000 patients passing through Coley’s toxin care.

But as life goes, the treatment with toxins soon became unfashionable, and Coley’s regimen was too strict for others to emulate. Best results were always evidenced when Dr. Coley or his colleague supervised the production of toxins. There were other problems like frequent fevers being quite trying on the patient. The preparations were of differing potency. This led to much confusion and disappointment for other doctors who ordered them. Some doctors, initially enthusiastic about the treatment, naturally became disillusioned when they used less effective preparations. In many cases, other doctors did not use the toxins aggressively enough. There were some 13 types of mixtures and post treatment follow-up, administration and documentation was never done properly. So new doctors found reasons to criticize the various undocumented methods and unable to replicate Coley’s success took to ridiculing him a charlatan and a quack, even though he was still respected and held big & respectable positions in various institutions until late in his life. By 1894 the JAMA officially criticized the toxin potion and declared it a failure in the face of successes in radiation and chemotherapy which were coming into vogue. On top of all that Dr Ewing a big supporter of radiation, was Coley’s director and boss and his biggest critic. Soon Ewing banned the use of the Coley toxins in the Memorial hospital, thereby denying a place for Coley to practice his development and also ensured that Coley had stiff resistance at the Bone Sarcoma registry.

On April 15, 1936, William B. Coley suffered a recurrent attack of diverticulitis, was operated on by Dr. Eugene H. Pool under local anesthesia, and died the next day.

After his death, the use of Coley's toxins began to decline further. By 1952 Parke Davis stopped manufacturing the toxins and by 1962 the Food and Drug Agency declared that Coley's toxins were ineffective in the treatment of cancer even with the positive statistics. As a result of the FDA's decision it became illegal to use and produce the vaccine in America since then. By the 1940s researchers discovered that a chemical warfare agent, nitrogen mustard, suppressed cancer and then chemotherapy with nitrogen mustard and other agents, along with radiation therapy and surgery, began to supplant Coley’s toxins.

But then, life is life, Coley lived and faced a hostile world during all of his career while enduring to find answers to reduce human suffering and is today considered the father of immunotherapy and even in certain forms of hernia surgeries. As is stated in his eulogy, English literature was his greatest hobby; to him the great masterpieces of the world, apart from their solace and charm, were the master instruments of a solid education.

The subsequent history of Coley's toxins is rather sad. His son, Bradley Coley, MD, continued to use the vaccine at Memorial Sloan-Kettering into the 1950s, but in an increasingly hostile environment. Coley's daughter, Helen Coley Nauts, founded the Cancer Research Institute of New York to save and promote his work. But although she got her father removed from the American Cancer Society "quack list" in the mid-1970s, she was never able to get his treatment used widely.

In 1975, a protein responsible for the immunity boost was identified and called tumor necrosis factor alpha (TNF-alpha). Eventually the cytokine family and TNF were isolated and are finally in use today in the fight against cancer. That was the beginning of immunology and for that reason Coley is considered the father of immunology, though scientists are still working on his theories and creating what is known as MBV’s (mixed bacterial vaccines).

Why did Coley’s toxin fail in the market? Despite outstanding successes, they were opposed by the medical establishment. The (then) new technology of X-Rays and Radium was superior for hierarchical control and profits from cancer patients than the low-tech produced Coley's Toxins. Individuals with Radium mining interests made large donations in return for the promotion of radium in the treatment of cancer….

Have we heard all these arguments before? Somewhat like the antacid story, right??

Notes:

1. The role of bacteria as anticancer agents was recognized almost a hundred years back. The German physicians W.Busch and F. Fehleisen separately observed that certain types of cancers regressed following accidental erysipelas (Streptococcus pyogenes) infections that occurred whilst patients were hospitalized. Fehleisen, in 1882, identified Streptococcus as the pathogen leading to erysipelas, and he achieved three remissions by injecting cultured living bacteria into seven cancer patients. William Coley (1862-1936) was not the inventor of the treatment of cancer using bacterial infections. However, he was the first to do it systematically on a large number of patients.

2. With the current widespread use of antibiotics to treat infections and antipyretics to ‘‘manage’’ symptoms of an infection, the critical part played by fever in the human body is often overlooked. Fever is frequently suppressed as a matter of routine. Historically, fevers were not only considered beneficial, but were actively encouraged. For example, Native Americans were known to treat acute febrile diseases with sweat baths

3. Both radiotherapy and chemotherapy have an immune-suppressing side-effect. Since both treatments kill the rapidly dividing cells of the immune system along with the rapidly dividing cancer cells, both can be used together if care is taken. On the other hand immune-stimulating Coley’s Toxins work entirely differently, and their effect would be cancelled out if used at the same time as high-dose immunosuppressant chemo- or radiotherapy. It became an either/or situation– and in the end, the fashionable new treatments won out over Coley’s fiddly reworking of an ancient ‘natural’ remedy.

References

Bacteria in cancer therapy: a novel experimental Strategy -S Patyar1, R Joshi1, DS Prasad Byrav, A Prakash, B Medhiand BK Das

A Medical Application of Matzinger’s Danger Model-Coley’s Cancer Vaccine -Gar Hildenbrand

The toxins of Edward Coley – Edward Mc Carthy

Dr William Coley and tumour regression: a place in history or in the future - S A Hoption Cann, J P van Netten, C van Netten

William Bradley Euology – Carl G Burdick

Time article

The Body Can Beat Terminal Cancer - Sometimes - Jeanne Lenzer (Discover magazine)

Comments

Happy Kitten said…
And interestingly infants acquire their basic colonies from their mothers.
--------
Loved the analogy...but then they dwell in colonies right?

as for cancer treatment, it is sad that this treatment was discarded for the present which I hear is not good on the patient. Hopefully it shall be revived and this dreaded disease meets it's end too.
harimohan said…
Dear Maddy
intersting
commensals are bacteria living in us serving useful function like in digestion etc
some drugs like antibiotics do wipe them out occasionaly but they do get replaced and one needs antibotics too right at times ?
but the bigger problem is in immunocomprised situations like in cancer patients ,HIV patients post transplant patients etc when such commensals became aggresive and produce resistant infections and sepsis !
now coming to our orhto sugreon hats off to his pioneering sense ,strangely TNF
( tumour necrosis Factor ) is a cytokine used in oncomedicne today but alas is not the panacea to the disease .
if only oncology and its managemnt has been so simple to get a magic pill which would be the answer it would have been nice.
today we need all weapons possible the immunosupresing chemotherapy and radiotherapy the resecting surgery and immnuostimulating immunotherapy too !
good thins is science is more regulated than in yesteryears no one can get away with a concotion of his own and call it a cure
evidence based medicne demands double bling trials under reputed scholars and to pass under the scrutiny of strict panels before acceptance and international guidelines dictate tratemnt protocols all over the world
bacteria are used to create antibiotics and many are used in cancer like adriamycin etc .
the five yr survical of cancer today is more than 50 % from amere 10 % in the sixties but still miles to go
chemo and radiotherapy are harmful to other tissues and are immunosuppresive but they are fine tuned to be least toxic day by day and they have proved thier efficacy
emerging technologies have improved managemnt strategies gentic research have openegd great vistas in cancer treament and hopefully we may have that eluding magic pill in the fauture God willing
Bernard said…
Thanks to Maddy for this attempt.


We have not yet fully understood the extent of gene wealth and diversity in the bacterial kingdom, just because of the fact that only ~1% of them could be studied in laboratory, under standard lab-culture protocols. Majority is falling into a state known as VBNCs,Viable, but non Culturables. As Nalappat exclaimed about Universe, let us exclaim about bacterial kingdom.

Thanks to bold new attempts like Meta-genomics and all. We are trying to walk through the dark kingdom of Bacteria.

Antibiotic-resistance in bacteria is in itself a great topic for a discussion, but a promising new solution may be 'phae therapy'.
Maddy said…
hi HK..
There were just two underlying themes in the whole subject as I saw it, one being the fact that there are many non conventional possibilities and secondly that some of these ideas always get drowned in corporate greed and the desire to quickly denounce anything that does not fit the norms of a time.
Maddy said…
Thanks hari..
you know more than any of us about these things and you are right.

yes, you are correct about the replenishing of the good bacteria, but the point was that there is a hypothesis today that the appendix is the store for such bacteria.

But there were some pioneers who did things a little differently..like our man Dr Coley!!
Maddy said…
Thanks Bernard..
yup this journey started while trying to understand a bit more about Coley and his ideas when i came across him. Now i will leave the micro world of bacteria for a macro one with people, good and devious!!!
December chills said…
Dear Maddy,

Very good post.Especially story of Dr Coley.

Regards,

D.C
MY VERSION said…
When I was in school, we were taught that the appendix in the human body is a vestigial structure with no real use or work of its own. When we had to learn to spell “vestigial “, I really used to think, what a waste of time trying to learn so much about so little and useless an appendix. We were led to believe that losing it in an operation would not impair you in any way. In fact when we had an extra hard exam coming up, we would pray for either a tonsil (more attractive -since we were told, they feed you ice cream after the operation) or an appendicitis operation.
Now I know that , the scientists have discovered that it is the "good bacteria" breeding factory. lucky i did not hastily go for an operation.
That fish tank analogy was superb.
Rohini
Maddy said…
Thanks Rohini..

I was also quite surprised to read that the appendix was perhaps a repository for good bacteria..the human body is indeed an amazing thing!!
Maddy said…
Thanks DC..
yes, when I read about Dr Coley, I was quite amazed...

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