Saturday, January 2, 2016

Part 1 ~ Immunotherapy....The Original Super Heroes and Ratties!!!!

You needn't have looked at this blog very long to recognize my penchant for Super Heroes and Ratties. (According to the Les Lexicon:  Rattie - noun; humans who participate in often demeaning and difficult clinical trials out of desperation and named mostly because of my love of The Rats of N.I.M.H., by Robert O'Brien.) There was this...after all:  The Melanoma Avengers

But now, with thanks to NPR and Rebecca well as the research of Dr. David Levine, director of archives at the Hospital for Special Surgery in New York, we have the details of the real Super Heroes and Ratties who brought us the first inkling of the power of immunotherapy.  (My synopsis follows...) Cutting edge cancer treatment has its roots in 19th century medicine

In 1890, Dr. William Coley examined a new patient, 17 year old "Bessie" Elizabeth Dashiell, whose complaint was a small painful lump to her hand.  Despite thinking it was nothing more than a simple infection, Coley took a biopsy.  He found malignant sarcoma.  In those days, before radiation or chemo, Coley did all he could.  He amputated Bessie's right arm below the elbow.  Within a month tumors had spread to Bessie's vital organs and all over her body.  She died a painful death January 23, 1891...just months after her first visit with Dr. Coley.

The rapid decline and loss of his young, healthy patient made a huge impression on Coley.  He started searching through hospital records - looking for some clue that could provide greater understanding - while thinking back on his early lessons from the work of Charles Darwin.  "Pay attention when there is biological exception." Coley found that exception.  A German immigrant, Fred Stein, had been a patient 8 years prior with a persistent neck tumor that doctors had attempted to remove repeatedly with no success.  He was expected to die of his disease.  However, after his last surgery, he was stricken with a skin infection due to strep.  It appeared that this would certainly be his end.

It wasn't.  Not only did he survive his life threatening infection - his tumor disappeared!!

In 1891, Coley began a search of the Lower East Side of Manhattan.  Could Fred still be alive?  After weeks of searching, Coley found Fred Stein - alive and cancer free - with a distinctive scar to his neck.

What had happened? Coley postulated that the strep infection had somehow reversed Stein's cancer.  Coley tried purposefully giving infections to an Italian immigrant, Zola, who had sarcoma like Bessie, but was so advanced that there were tumors in his throat....such that he could hardly breathe or swallow...and death was imminent.  For months Coley attempted to give Zola an infection by rubbing superficial cuts with bacteria.  There would be minor effects in his tumors, but nothing impressive.  Coley attained a more virulent bacterial sample.  He succeeded in making Zola violently ill.  While the infection itself could have killed him, in 24 hours Zola's "orange sized tumor began to liquefy and disintegrate".  He went on to a full recovery...from both his sepsis and cancer!

Coley continued his work, experiencing much success, but the American medical establishment remained skeptical.  No one knew how "Coley's Toxins" worked - why they worked sometimes and not others - not even Coley.

The immune system, with its T-cells, checks and balances, obscure pathways....was much more of a mystery then than now.  With the advent of radiation therapy in the early 1900's, Coley's Toxins were pushed into the shadows and upon his death were no longer pursued at all.

Had his daughter, Helen Coley Nauts, not looked through his papers after her father's death, finding 1,000 files of patients her father had treated with toxins, his brilliant, intuitive work may have died with him.  She sought experts to study her father's work.  Finding none, she decided to do it herself.  After years of analyzing the cases, she knew her dad had been on to something.  In 1953 she started the Cancer Research Institute.

In the 125 years since Coley first met Bessie, the study of the immune system has unlocked many mysteries related to infection, allergy, immune related disease, and cancer.  Treatments like ipi and anti-PD1 actually harness the power of our own immune systems to fight cancers as disparate as that of the stomach, lung, kidney, leukemia and melanoma.

There is still much that we do not understand, but without Super Heroes Coley, his daughter and his Ratties - it is hard to imagine that I would still be here today.  More to come.  Stay tuned. - c

1 comment: