Since I am soon to finish my course of chemo with taxol (only two more infusions to go!), I thought I would find out a little more about this drug before saying goodbye to it. I knew it was derived from the Pacific yew tree, but that's all I knew. That was enough to intrigue me, though. It's a great story.
A Pacific yew tree.
World War II. Penicillin is widely and successfully used. Postwar, other antibiotics are developed. Infectious diseases are on the run. Folks become convinced that all diseases can be vanquished through chemistry. Heady times!
Again World War II. Research into gas warfare leads folks to believe that chemical agents could be used to destroy or control the growth of cancer cells. At first nitrogen mustards were tested to treat leukemia, and soon an all-out search for possible other cancer drugs was underway. A well-funded national screening program is established under the auspices of NIH to test drugs submitted by companies and institutions.
In 1960, the program began testing natural compounds from plant and animal sources--anything and everything (recall that penicillin was derived from bread mold). While there was a lot of traditional wisdom about the healing properties of plants, very little scientific testing had been done, and virtually none looking specifically for anti-cancer effects.
Now that changed. In 1960 NIH's cancer screening center entered into a formal agreement with the US Department of Agriculture: USDA botanists, already deployed out in the field all over the country, would collect plants from throughout the US, aiming for as broad a variety of samples as possible. Some 35,000 plant samples were tested.
So it happened that Arthur S. Barclay, a young USDA botanist, spent four months in the summer of 1962 collecting samples and sending them in. On August 21, after spending most of the summer in the southwest, he was winding up his collection tour in the state of Washington, in the Gifford Pinchot National Forest, about 10 miles from the town of Packwood near the foot of Mt St Helens.
Note Packwood in the upper right.
For no particular reason--just because it was there, and the goal was to collect as many different plant samples as possible--Barclay took samples from a Pacific yew tree, a somewhat shrubby understory tree native to and growing only in the Pacific northwest. His sample included needles, twigs, and bark.
When the yew samples were tested, the results were exciting. Something in the bark had a strong anticancer effect. The chemists requested more yew bark for more testing.
Pacific yew bark.
And there the problem began to become clear. It took an enormous amount of bark to yield a single gram of the active compound to test. Harvesting that much bark meant, essentially, killing the tree.
The active compound was isolated and named taxol (after taxus brevifolia, the scientific name for the Pacific yew), and continued to show exciting medical possibilities. But producing one dose of taxol required the bark of one entire 40 foot Pacific yew, and a yew tree took about 200 years to grow to 40 feet. Clearly, this was not sustainable. Pretty soon all the yew trees would be logged out. And all that logging was taking place within pristine old growth forests. Old growth forests that were the habitat of the northern spotted owl, an endangered species.
Those of you Of A Certain Age may remember the uproar around saving the spotted owl. It was environmentalists vs. people with cancer (and those who loved them). Taxol proved highly effective against ovarian, breast, pancreatic, and a certain kind of lung cancer, among others. And it had a unique way of attacking cancer cells, which meant it worked for people whose cancer had become resistant to other treatments. But to get it might destroy an entire unique ecosystem: Pacific northwest old growth forest.
Gifford Pinchot National Forest, near where Barclay collected his yew samples,
with Mt St Helens in the background.
Enter the chemists. They were confident they could synthesize taxol and all would be well. But after 20 years of trying, that goal proved to be elusive. The closest they could come was to synthesize it from a precursor molecule from yew trees that was more abundant than the taxol molecule itself.
The story has a happy ending, though. Some researchers in France discovered that the precursor molecule could be extracted from yew needles, which, unlike bark, were a renewable resource, and that it could be found in the needles of the English yew as well as the Pacific yew. Some US researchers, building on the French work, developed a significantly more efficient method for producing taxol from the precursor molecule, also using English yew needles as the precursor source. The Pacific yew trees, spotted owls and all, could be left in peace.
English yew is a plant you know well, whether you realize it or not: those ubiquitous taxus bushes that everybody seems to plant around their house foundations. If you stop pruning them, they grow into trees.
I kind of love it that the taxol molecule can't be synthesized from scratch, that they have to start with the yew needles: plants and people working together. I like that sense of being embedded in the larger reality of creation. And I also love it that my chemo comes ultimately from a tree. I've always had a thing for trees.
UPDATE: Ten down, two to go. Last chemo infusion scheduled for the day after Christmas. My blood counts continue to be very good, hemoglobin just a hair below normal (iron frying pan!) and everything else within the normal range. The steroid-induced insomnia finally became overwhelming this week, and despite my deep dislike of sleeping pills I asked for and got a script. Took one last night and got a lovely night's rest, yay! I plan to take one the night of an infusion and maybe 1-2 nights after, but that's all. Once the steroid high is over, I really don't need that kind of help.
My view as I sit in my recliner at the cancer center being infused.
The enhanced version of my view. Michael has been a wonderful support.
