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Dr. Ehrlich's Magic Bullet

Posted by Frederick Wasti
May 12 2012

When is chemotherapy maybe not really chemotherapy? Well, the quick answer might be "when it works like a 'magic bullet' instead of like a sledgehammer". Let me try to explain what I mean by that in this entry.

I just read an article in ScienceNow (from 2006) entitled "Chemo on the Brain" (which is a report on an original research paper in the Journal of Biology). I have heard references before to "chemobrain" (that's the common nickname) on the CLL mailing lists that I follow as well as on the web. Chemobrain unfortunately is one of the long-term side effects of chemotherapy. As the article points out, chemobrain "may leave as many as 80% of all cancer patients with memory loss, confusion, and an inability to concentrate". Therefore, chemobrain is one of the things I'd like to avoid when receiving the various drugs given to me to fight against my leukemia. (And, I'm sure we'd all agree that I don't need anything that would lower my intellect further below where it has already slipped to by now - <g>.)

From the article:

"Scientists at the University of Rochester in New York examined the neural impact of three chemotherapeutic drugs: cisplatin, often used to treat breast, lung, and colon cancer; carmustine, used to treat brain tumors; and cytarabine, a treatment for leukemia and some lymphomas. The drugs caused widespread brain cell death in human cancer cell cultures and in live mice, even when administered at low levels, the researchers found."

The next quote from the article ~really~ brought me to attention:

"In cell cultures, the dosage needed to kill 40% to 80% of the cancer cells also killed 70% to 100% of healthy brain cells."

Wow !!! That is indeed a sobering finding - the dosage needed to kill 1/2 or 3/4 of the cancer cells also killed 3/4 to ALL of the brain cells.

Furthermore, the researchers found that:

"Particularly vulnerable were neurons in the hippocampus, an important memory center, and oligodendrocytes - cells that make a compound called myelin, which insulates neurons to allow electrical impulses to travel quickly across the brain."

~Not~ good news. Continuing:

"A particularly surprising find was the drugs' killing effect on mature, nondividing cells, which contradicts the long-held belief that chemotherapy targeted only rapidly dividing cells."

OK, so what can science/medicine do to minimize using such toxic chemotherapy drugs? In other words, what can be used to fight against a disease that doesn't do too much "collateral damage"?

What's needed are more "magic bullets" and fewer "sledgehammers"...

Many of the drugs used for chemotherapy against cancers work by interfering with DNA structure and function in cells, especially in rapidly dividing cells (which, by definition, cancer cells are, of course). One problem with this strategy is that many other cells in the body that are also dividing rapidly (e.g., hair follicle cells, bone marrow cells, cells lining the digestive tract, etc.) are generally also affected by these drugs (as evidenced, for example, by the number of chemotherapy patients who go bald during treatment).

Part of the significance of the study referred to in the above article is that it emphasized the effect of three commonly used chemotherapy drugs on cells of the central nervous system, which are ~not~ rapidly dividing cells. Therefore, the outward sign of chemotherapy-induced baldness may be more obvious, but the damage going on deep below the scalp, in the brain of a chemotherapy-treated patient, may be much more significant and long-lasting.

The concept of a "magic bullet", i.e., a drug that would target a particular disease and do no damage to the rest of the body, goes back to the late 19th Century, when some scientists found that they could selectively stain certain types of bacteria differently from other bacteria, leading to the thought that perhaps medicines could be developed that would work against just certain bacteria.

In the early 20th Century, the German scientist Paul Ehrlich was working to develop a more specific drug for the treatment of syphilis than the commonly used "sledgehammers" of the time, various toxic mercury compounds. He is most famous for developing "Compound 606", which was not only less toxic than the mercury-based drugs being employed against syphilis at the time, it was also the first drug to be chemically ~created~ (since, up to that time, medicines in common use were ~discovered~ by simply testing common substances on patients, rather than being intentionally chemically ~synthesized~ in laboratories), and was the first chemical compound ever shown to cure a specific human disease.

Compound 606 (also known as Salvarsan and as Arsphenamine) was commonly used to treat syphilis until the mid-20th Century, when it was supplanted by penicillin. Paul Ehrlich's work towards developing more specific treatments for diseases, for which he received the Nobel Prize in Physiology and Medicine in 1908, was the subject of a 1940 film biography, starring Edward G. Robinson, that was titled, appropriately enough, "Dr. Ehrlich's Magic Bullet".

I'll have more to say about chemotherapy drugs and "magic bullet" drugs for treating CLL in an upcoming entry - please stay tuned...

 

(...for now...)

Categories: Leukemia