Richters HerbLetter

Date: 95/06/12
1. A Drug ‘Only a Tree Would Make’ Raises Big Questions
By Jay Ingram

TORONTO, Toronto Star, June 11 -- Mark Plotkin is an ethnobotanist, a combination of explorer, botanist and crusader. His years in the rain forests of South America have convinced him that plants have great potential as medicines. But as the forests are encroached upon by farming and mining, both the plants and the specialized knowledge about their medicinal properties possessed by shamans are being lost.

Plotkin was in Toronto recently to talk about his book, "Tales of a Shaman’s Apprentice," and to arouse public concern about this situation. He points to the impressive statistic that one-quarter of all prescription drugs have active ingredients derived from plants. But to me the very idea that chemicals from plants could be useful in treating human disease raises some profound scientific questions.

Take the anti-cancer drug taxol as an example. It comes from the yew tree, and while some yew species do grow in the rain forests, many others are common in North America. I have yews growing in my backyard but the species that first produced taxol was the Pacific yew. Taxol is found mostly in the bark, and for a while environmentalists were worried that the tree might be killed off by bark strippers. Estimates were that 27 kilograms of bark might be needed for a full treatment for each cancer patient. That worry has disappeared now that taxol has been made from scratch in the laboratory. Taxol has shown great promise in the treatment of ovarian and breast cancer. Why? Does the yew tree have to protect itself against tumors? Not likely.

Cancer drugs work by targetting rapidly dividing cells, whatever and wherever they are. Tumor cells divide quickly and are susceptible but so do some normal cells. It’s the death by "friendly fire" of these normal cells that underlies the severe side-effects of some cancer drugs.

Taxol interferes with the mechanics of cell division (something rapidly multiplying cells are doing much of the time) and so qualifies as an anti-cancer drug. When a cell divides, it first produces a duplicate set of its chromosomes, then builds an internal scaffolding to guide the separation of these two sets, one to each daughter cell. The parent cell must quickly snap together cellular building blocks called microtubules to form the scaffold, then be able to break it down again once the chromosomes have moved so that the two daughter cells can separate. Taxol prevents the breakdown of the microtubule skeleton, so a cell on the verge of division gets stuck, waiting for the scaffold to be removed so that it can finish dividing. With taxol present, it never happens. Other cancer drugs (such as vincristine and vinblastine, also from a plant) prevent the formation of the scaffold. Taxol prevents its removal.

If the yew invented taxol, what a route it must have taken! The taxol molecule is incredibly complicated, something that (as one scientist put it) "only a tree would make." Presumably it was the trial-and-error of natural selection that produced it, but as far as I know the history of taxol is unknown.

One curious discovery might shed some light on this. A pair of American researchers discovered a taxol-producing fungus nestled in the bark of a single yew in Montana. It is not inconceivable that there has been some exchange of taxol-producing genes between the tree and the fungus. But in what direction? Was the fungus first? Or (as most assume) did the tree inadvertently donate some genes to the fungus?

Now the key question: Why would yews have developed this fiendishly clever way of interrupting cell division? Most botanists suspect it was to protect the tree from insects, fungi or other dangerous creatures. Hardly anything grows faster (or has more rapidly dividing cells) than a voracious caterpillar. Ingesting a little taxol would change that in a hurry.

It does make sense that a tree wanting to defend itself would produce a chemical that disrupts cell division (providing it doesn’t affect the tree itself). But what about plants in the tropical rain forest that are reported to lower blood sugar in diabetics, or are apparently effective against HIV? They sure aren’t producing these chemicals for our benefit. Why are they producing them at all? That’s the fascinating science of the rain-forest pharmacopeia.

[Jay Ingram hosts the TV program on the Discovery Channel.]

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