LETTER FROM INTERNATIONAL TAX ATTORNEY




Dirk:

I enjoyed reading your "Biotechnology is Murder" while on a business and pleasure trip to the Cayman Islands. And while laying over a few days in Orlando, what did I see on cable TV but a story on cancer compounds from sponges! Was science repeating fiction or vice versa?

When I got back home to the S.F. Bay Area, I did an Internet search (www.alltheweb.com) and here's what I found: Harbor Branch (Oceanographic Institution) to study cancer fighter. "Ross Longley is leading the study funded by a three year grant of 1.1 million. Involves compound, Discodermolide, extracted from deep-sea sponge & used to fight cancer. Co-researchers are Sarath P. Gunasekera, co-discoverer (with Longley) and David Myles, UCLA.

Tell me: Is this where you got your idea for your story about turning sponge compounds into drugs?

V.E. Rosswell
International Tax Attorney
and author of Into the Deep





Dear V.E.:

Thanks for bringing me up to date on happenings in my own back yard (Florida). Yes, your finding is right on target. No, it was not exactly what I had in mind when I wrote "Biotechnology is Murder." My starting point was a Japanese article on an anti-cancer compound from sponges. And I actually mentioned that article in the novel. But for my fictional Dr. Tehong Moon's discovery, I invented an anti-cancer compound that worked by "inhibiting protein kinase C." Longley's Discodermolide seems to work on the "cytoskeleton." Your finding was on target, but not a dead ringer.

Here's what I found from a PubMed search using the leads you gave me: The search on Discodermolide yielded 12 articles, the oldest published in 1991. The studies describe the compound as an "anti-microtubule agent" or a "microtubule stabilizer." It binds to the same site as Taxol (paclitaxel). The target microtubules serve as an internal skeleton for the cell, and their rearrangement is an important step in cell division. Without going into a lot of detail, it would appear that Discodermolide inhibits tumor cell growth by interfering with the rearrangement of their microtubules so that they cannot undergo cell division.

Longley and collaborators publishes first account of pharmaceutical action as an immunosuppressant: "Discodermolide--a new, marine-derived immunosuppressive compound." They correctly concluded, "Discodermolide's in vivo immunosuppressive action appears not to be that of a generalized immunosuppressive agent and that its specific in vivo mechanism of action warrants further preclinical evaluation."

This is how the drug activities of many natural products are discovered. The first drug effects of a compound are found for one physiological target (immune system), then a much better drug effect is found in a different test system (tumors). How can one "drug" have two activities? Well, my Ben Candidi talks about this in the opening pages of the second novel: "writhing, copulating molecules."

Also in the novel, Ben asks chief scientist Cheryl North if there would be a sufficient supply of the sponge compounds. There was a similar question with Taxol. The most recent paper on Discodermolide comes from Cambridge University group which reports the chemical synthesis of the compound.

Yes, fact and fiction cross paths sometimes.

Thanks for the nudge that got me up to date.

Dirk





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