Wandering The Woods For A Breast Cancer Treatment

The following is an excerpt from Radical: The Science, Culture, and History of Breast Cancer in America, by Kate Pickert.

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Radical: The Science, Culture, and History of Breast Cancer in America

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The first chemotherapy drugs were products of war. During World War I and World War II, some American service members were exposed to chemical weapons, including mustard gas. Doctors who performed autopsies on the men who died noticed something odd—the soldiers’ bone marrow had been particularly devastated by the gas. Their white blood cells, which are made in the marrow, had been nearly wiped out. The mustard gas acted with such precision that scientists later found it could be used to treat leukemia and lymphoma, both cancers of the white blood cells.

By the 1950s, six chemotherapy agents were approved in the United States to treat cancer. All were synthesized by scientists in laboratories. For the first time, the drugs allowed doctors to fight cancer systemically, sending treatment all over the body through the bloodstream. Surgery, radiation, and chemotherapy constituted a new trifecta that offered a fresh promise of cure for people with some of the most virulent forms of the disease. The new chemotherapy drugs were effective against some cancers, especially leukemia and lymphoma, but for many cancer patients, including those with breast cancer, existing chemotherapy drugs fell short. Hoping to spur development of new agents, in 1955 the National Cancer Institute launched the Cancer Chemotherapy National Service Center. Five years later, the NCI started an ambitious program to look outside the lab, in the natural world, for anticancer compounds. (A juniper bush and a flowering periwinkle already looked like they might be useful in developing medicines to fight cancer.) The NCI hired botanists to collect plants from across the United States and outside the country. Samples were bagged and sent back to labs that tested the specimens to see if they affected cancer cells. Scientists suspected that the natural world contained cancer-fighting compounds, but they had few leads, so the NCI botanists collected samples randomly, hoping to get a hit. Some 30,000 plant samples were screened between 1960 and 1981. One looked particularly promising. It was collected by a Harvard-trained botanist named Arthur Barclay.

Barclay worked for the U.S. Department of Agriculture, which was collaborating with the NCI on the project to search for anticancer compounds in nature. He traipsed through forests, collecting specimens for the USDA in South Africa, Mexico, and the Western United States, gathering seeds, clipping leaves, and scraping bark from trees.

In August 1962, Barclay was on the last leg of a collection trip, walking through Washington State’s Gifford Pinchot National Forest with some students, when he spotted a 25 foot Pacific yew growing at about 1,500 feet above sea level. The tree had a reddish bark, glossy needles and small, salmon-colored berries. Barclay peeled some bark from the tree, grabbed some of the tree’s needles, put his loot in a bag, and sent it to a lab working with the NCI. Scientists there tested the bark and found that it was toxic to living cells. In 1964, the NCI asked Barclay to return to the site of his initial collection and retrieve a second, larger sample. It would take years to determine if the bark toxin would work as an anticancer drug. By 1970, scientists had figured out the bark compound’s complex molecular structure. The next year, President Richard Nixon declared in his State of the Union address that the federal government was launching a “War on Cancer.” Congress passed and Nixon signed the National Cancer Act, which sent millions more dollars flowing into federal cancer research.

In the late 1970s, a molecular pharmacologist at the Albert Einstein College of Medicine in New York City figured out precisely how the compound, which was named Taxol, worked to destroy cells. (A team of NCI scientists had also determined the chemical’s mechanism of action.) Most chemotherapy drugs developed in the lab induced cancer cells’ death by damaging DNA or inhibiting specific enzymes essential to cell division. Anticancer drugs derived from plants, however, killed cancer cells by hampering their ability to create internal structures made of tiny filaments called microtubules. Taxol did the opposite—it prompted cells to create microtubules, but in a way that stopped a cell from constricting and changing shape during cell division. The discovery was a major breakthrough. Lab and mouse experiments seemed to show that Taxol was particularly effective against metastatic breast and ovarian cancer, and scientists had finally figured out how to distill Pacific yew bark toxin into a soluble form that could be delivered intravenously. To know for sure, they had to administer the drug to patients. The NCI launched phase 1 clinical trials of Taxol in 1984.

But there were some obstacles to overcome. First, there was the tree itself, which was small in stature; it could take as many as six Pacific yew trees to make enough medicine for a single patient. Stripping a Pacific yew’s bark is deadly for the tree, which takes about a hundred years to reach maturity, so quickly producing more bark would be impossible. Plus, Pacific yews were not grown in nurseries or neat rows. They were scattered all over federal lands, hidden among other types of trees. No one knew exactly how many Pacific yews existed in the forests. Finding, cutting and stripping the trees one by one would never yield enough bark to produce all the Taxol that doctors predicted they would need every year for women diagnosed with ovarian and breast cancer. One alternative was to clear-cut the forests, hacking down all trees in a given area and sorting the Pacific yews from the rest. This was unpalatable for environmentalists newly committed to protecting the centuries-old forests of the Pacific Northwest, home to the threatened spotted owl among other species.

“I thought it was such a unique opportunity—being a bridge between forestry and medicine.”

But the NCI couldn’t give up. By the 1980s, several chemotherapy regimens had been shown to work against breast cancer, but many women still saw their disease return and become resistant to existing treatments. Plus, the chemotherapy cocktails in use were highly toxic and sometimes caused heart damage. The idea that Taxol might work better than these other drugs and have fewer side effects was too appealing to ignore. By the late 1980s, NCI-contracted tree harvesters had managed to collect enough Pacific yew bark to supply the first round of human clinical trials. A small study at Johns Hopkins University showed that one-third of ovarian cancer patients whose tumors had not responded to other types of chemotherapy had major responses to Taxol. At M. D. Anderson Cancer Center, a small trial of women with metastatic breast cancer found that half the patients saw their tumors shrink considerably. A few women saw their masses disappear entirely. Other trials were already under way, but the doctors guiding them quickly ran short on Taxol, which slowed down the research.

In 1989, when Nancy Lankford was reassigned to the Pacific yew harvest, there was no time to lose. “The message was that the women in those trials were women who did not respond to any other chemical treatment,” said Lankford. “I thought it was such a unique opportunity—being a bridge between forestry and medicine.” Lankford’s first job was to count. She helped compile a Pacific yew tree inventory in Mount Hood National Forest, mapping the known trees and measuring their heights and diameters. Locals in Oregon who had permits to cut trees in the national forest—for timber, boughs for Christmas decorations, or other uses—were recruited en masse and hired to cut the trees and strip their bark. Protesters showed up at some of the harvests, charging the federal government with environmental destruction and irresponsible land management. The criticism stung Lankford, who had devoted her life to the Pacific Northwest’s forests.

Pharmaceutical giant Bristol-Myers Squibb entered into a cooperative agreement with government laboratories to harvest and synthesize Pacific yew bark from federal lands, removing nearly five million pounds of raw material from the forests over several years. To ensure the process was environmentally responsible and not wasteful, Congress passed the Pacific Yew Tree Act in 1992, which, among other provisions, banned the trees from being burned in slash piles. The harvests Lankford helped coordinate produced enough Taxol to keep the clinical trials in business. The studies proved definitively that the drug worked for breast and ovarian cancer that had not responded to standard chemotherapy. The Food and Drug Administration approved Taxol for these patients in 1992 and for metastatic breast cancer patients in 1994. But the race was on to find an alternative raw material, one that wouldn’t draw the ire and protests of environmental groups and, crucially, would be sustainable. Doctors were eager to see if Taxol might work for women with early-stage breast cancer as well. For this use, they would need far larger supplies of the drug. Two months after Taxol gained its first FDA approval, Bristol-Myers Squibb announced the Pacific Northwest yew harvest would wind down. The company had discovered that a faster-growing yew species, found in Europe and Asia, could be used to produce a drug very similar to Taxol. European and American scientists, meanwhile, figured out how to create semisynthetic versions of the drug in the lab.

In the fall of 2011, Lankford was diagnosed with estrogenreceptor-positive breast cancer. “I actually found the lump myself,” she told me. She was treated with docetaxel, the drug developed from the bark of the European yew tree. Lankford finished her treatment in mid-2012, a few years before she became a grandmother.

Arthur Barclay’s trek through the woods of Washington in 1962 was a long shot that has saved countless lives. The discovery of Taxol also eventually established a new treatment paradigm for breast cancer, demonstrating that less-toxic therapy, which Taxol was when compared with previously existing chemo drugs, could work as well as harsher treatments. But that kind of thinking came later. Right around the time the FDA approved the Taxol chemotherapy treatment for breast cancer, another trend was taking hold. Oncologists thought they had found a way to beat back even the most dire cases of breast cancer without any new drugs at all.

Excerpted from Radical. Copyright © 2019 by Kate Pickert. Used with permission of Little, Brown and Company, New York. All rights reserved.