NEWS

What Ever Happened To . . . ? Looking Back 10 Years

Christine Theisen

This is part of an occasional series that recalls some of the stories reported 10 years ago in the News section of the Journal.

The News reported in its Aug. 7, 1991, issue that the National Cancer Institute had signed agreements with private companies, research institutions, and the U.S. Food and Drug Administration to test foods for cancer prevention. The agreements brought resources together to support the NCI’s Designer Foods Program, which was started under toxicologist Herbert Pierson, Ph.D.

The Designer Foods Program aimed to "create food products fortified with natural phytochemicals found in fruits, vegetables, and other plants." The idea was to identify and isolate possible cancer-preventing agents in foods such as citrus fruits, soybeans, and garlic, and then develop those agents separately to be included in processed foods such as baked goods or salad dressings.

Ten years later, the Designer Foods Program no longer exists. However, scientists are still looking for what are now called the bioactive components of different foods. This means that scientists are not designing new foods. Instead, they are focused on naturally occurring constituents of foods that already exist.

"Pierson deserves enormous credit for showcasing the area and getting people to think about what I would call minor food components and their importance in health," said John Milner, Ph.D., chief of the Nutrition Science Research Group in NCI’s Division of Cancer Prevention. "Almost single handedly, he moved this area into a whole new dimension."

Researchers are now looking at foods’ bioactive components, as well as at how genes are involved in the processing of these components. Current research shows that there is considerable variety in the response that occurs in different people exposed to the same bioactive food components. In the near future, NCI will fund studies to look at how nutrients modify the genes involved in the cancer process. The plan is to have teams of investigators determine which nutrients and which genes are most important for study.

Mark Messina, Ph.D., who was director of the Designer Foods Program after Pierson, now researches soy and its possible benefits for anticancer activity and activity related to heart disease, osteoporosis, and renal function. The phytochemicals of most interest in soy are isoflavones.

"Soy is a unique dietary source of isoflavones, and I believe most of the hypothesized benefits of soy are due to the isoflavones," said Messina.

Milner believes that future research will allow for a move from observation to a more individual approach. "We are trying to unravel that mystery of what nutrients do and under what circumstance. We cannot assume that what is good for one person is necessarily good for another."

Paclitaxel (Taxol)

In the July 3, 1991, issue of the Journal, the News reported that scientists were probing Taxol’s mechanism of action in an effort to help develop a synthetic formulation of the drug. Taxol, known generically as paclitaxel, was under investigation at the time as a treatment for ovarian cancer. Earlier studies had shown it effective in stopping the growth of tumor cells.

The problem was that the paclitaxel molecule was derived from the bark of the Pacific yew. The Pacific yew, which grows primarily in the western United States, is a slow-growing tree. Because the Pacific yew had largely been ignored before its cancer fighting properties were identified, there were too few naturally occurring and easily harvestable trees available to produce the amount of Taxol that would be required to treat patients once the drug was approved.



View larger version (145K):
[in this window]
[in a new window]
 
The paclitaxel molecule is derived from the bark of the Pacific yew tree, which grows primarily in the western United States.

 
Developers also encountered challenges from environmental activists worried that harvesting the yew trees would disturb the habitat of the northern spotted owl, which is on the endangered species list. Eventually, guidelines restricted the number of trees that could be harvested for paclitaxel production.

Since 1991, great advances have been made in both the synthesis and the use of paclitaxel. Early on, scientists recognized a need to develop a synthetic or semisynthetic form of paclitaxel using a method that would not require harvesting thousands of trees to create just 25 kilograms of the drug.

"The total synthesis of Taxol was a tour de force," said David Newman, Ph.D., a chemist in the NCI’s Natural Products Branch. The previous method of harvesting the bark of the Pacific yew tree and then isolating Taxol "never would have been a sustainable method for the production of large quantities of the drug," Newman said.



View larger version (145K):
[in this window]
[in a new window]
 
Dr. David Newman

 
Under an NCI grant, a researcher developed an efficient way to produce the semisynthetic form of paclitaxel that is in use today by adding a side chain to the nucleus of the paclitaxel molecule. Basically, the nucleus of the paclitaxel molecule (compounds called baccatins) occurs about three times as often in the leaves or needles of the European yew and other yew species as does the whole molecule. Converting the baccatins, isolated from the leaves or needles, to paclitaxel by adding the side chain to the nucleus allowed sufficient amounts of paclitaxel to be produced.

"You no longer kill the tree by removal of the bark, and you can grow very large quantities of yew bushes for sustainable harvesting of the leaves," said Newman. This method is so effective that researchers no longer plan to pursue development of a completely synthetic form of paclitaxel.

In 1992, the FDA approved the use of Taxol as a treatment for women with advanced ovarian cancer. Since then, it has also been approved for use in the United States to treat advanced breast cancer, lymph node-positive breast cancer, non-small-cell lung cancer, and AIDS-related Kaposi’s sarcoma.

Smoking Rates and Smoke in the Air

On Feb. 6, 1991, the News reported on the possibility of the United States becoming a smoke-free society by early in the 21st century. This was the outlook of Donald R. Shopland, then coordinator of the National Cancer Institute’s Smoking and Tobacco Control Program. A few decades earlier, more than 60% of men were regular smokers, but by 1991, U.S. adult smoking prevalence was approaching 25%. The Environmental Protection Agency was soon expected to identify environmental tobacco smoke as a known human carcinogen.

Some of what was expected in 1991 has come about, but none of it without challenges.

Adult smoking rates are only slightly reduced. The Centers for Disease Control and Prevention reported in 2000-2001 Profile Of The Nation’s Health, that the U.S. adult smoking prevalence is 24%—not the decrease that was hoped for. Researchers are not certain why.

"We do know that tobacco industry has increased its marketing of products," said Scott J. Leischow, Ph.D., chief of the Tobacco Control Branch at NCI. The stagnation of rates "may be related to a hardening of the target; one possibility is that we’re getting to a population of harder core, more dependent smokers. Another possibility is that the treatments we have available may not work as well in the real world as the clinical trials show that they do," Leischow added.



View larger version (136K):
[in this window]
[in a new window]
 
Dr. Scott J. Leischow

 
In 1992, the EPA classified environmental tobacco smoke as a known human carcinogen, but the report that the classification was based upon was partially vacated by a 1998 North Carolina District Court decision. The EPA reports that none of the findings concerning the serious respiratory health effects of secondhand smoke in children were challenged. In 1998, the Clinton Administration filed an appeal of the North Carolina District Court’s decision. The appeal is still pending.

Looking back 10 years shows minimal progress in reducing the adult smoking rates. What will the next 10 years bring? Healthy People 2010, a statement of national objectives for preventing threats to health, lists goals for smoking reduction among both adults and adolescents. For adolescents the goal is to reduce smoking rates from 35% to 16%. For adults over age 18 the goal is to reduce smoking rates by half, from 24% to 12%.

"My hope is that we redouble our efforts to encourage people to quit who are current smokers, improve access [to smoking cessation programs], and encourage treatments," Leischow said. "We know what treatments can work; the challenge is getting it implemented into healthcare systems and the communities. That’s a high priority for us."



             
Copyright © 2001 Oxford University Press (unless otherwise stated)
Oxford University Press Privacy Policy and Legal Statement