NEWS

What Ever Happened To . . .?: A 10-year Retrospective

Nancy J. Nelson

One way to measure the progress of cancer research is to begin at some past point in time and see if things have changed. 1988 is the year that the News section of Journal of the National Cancer Institute began. What has happened in the 10 intervening years to the stories first reported back then?

Some issues don't seem to go away. In May 1988, the News reported that the U.S. Surgeon General C. Everett Koop, M.D., after releasing a U.S. Public Health Service report on American nutritional habits, encouraged Americans to reduce their consumption of cholesterol, fat, and alcohol, and to increase the amount of fiber in their diets.



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Dr. C. Everett Koop

 
Likewise, in this year's Oct. 1 issue of Cancer, Susan M. Krebs-Smith, Ph.D., of the National Cancer Institute's Cancer Surveillance Research Program in Bethesda, Md., reporting on trends in American dietary habits from 1971 through 1995, found American dietary habits wanting. For example, data from the most recent survey showed that the 16 grams of dietary fiber that adults consumed each day remain well below the recommended 20 to 30 grams per day. Equally discouraging was a study reporting that 50% of the energy in children and adolescents diets came from fat and added sugars.

Another 1988 News item had a familiar ring: A forum of oncologists met to discuss low participation in clinical trials at the annual meeting of the American Society of Clinical Oncology in May. The News section wrote, "This low participation rate of 2.5% hampers the development of new cancer therapies according to several oncologists at the meeting." Today, the rate is about 3.0%.

Prevention Trials

Another "same-old, same-old" story discussing the feasibility of prevention trials appeared as a commentary in the Nov. 16, 1988, issue of the Journal. The author, M. Zelen, Ph.D., from Harvard's School of Public Health, in Boston, was opposed to conducting prevention trials unless intermediate end points could be found. He argued that the size and length of these trials will be very expensive. "Using incidence as a primary end point will require much larger numbers of participants than therapy trials and will need long-term follow-up," said the author.

Similarly, at a recent American Association of Cancer Research meeting, Frank L. Meyskens, M.D., director of the University of California Irvine Clinical Cancer Center, reported that "the major limitation in the development of micronutrients [vitamins and minerals] as chemoprevention agents has been the unavailability of intermediate biomarkers of cancer, making phase III trials very long and expensive."

"So far a validated marker predictive for subsequent cancer development is not available for any cancer," said Meyskens.

Knowledge has been advanced, however, in several areas. Studies to look for a link between silicone gel implants and breast cancer were just getting under way in 1988. Now with the completion of nine studies, Louise A. Brinton, Ph.D., of NCI's Division of Cancer Epidemiology and Genetics in a review article in the Sept. 17, 1997, issue of the Journal, commented that the accumulated epidemiological evidence suggests that breast cancer risk might actually be reduced among women with implants.



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Dr. Louise A. Brinton

 
Although she cautioned that the data will become clearer when several ongoing follow-up studies, including one being conducted by NCI, are complete, she concluded that "there is currently little evidence to support the notion that breast implants increase the risk of subsequent breast cancer."

Gene Therapy

And the answers are now in for two more cancer treatments. In 1988, the National Institutes of Health's Recombinant DNA Advisory Committee approved the first gene therapy protocol for transferring genetic material into humans. Researchers were trying to correct a single gene defect in a gene, adenosine deaminase (ADA), in two girls, by adding copies of a normal gene to the patients' T cells. However, time has shown that neither of the patients could make enough of the normal enzyme with the gene therapy alone.

Similar results have been found in the 100 U.S. gene therapy trials launched since then involving therapeutic approaches to cancer. These results led a blue-ribbon panel of scientists to conclude (in a 1996 report to assess NIH's investment in gene therapy research) that the most common approach for delivering genes to cells, viral vectors, cannot yield high enough levels of protein expression for therapeutic benefit and there is no flexibility to change the level of expression once the gene is in the target cell.

In July 1988, NCI's National Cancer Advisory Board approved funding for the completion of phase III trials for another type of cancer treatment, high energy neutron therapy — that is, instead of treating tumors with x-ray radiation, researchers were treating them with high energy nuclear particles, such as neutrons or protons. Frank J. Mahoney, Ph.D., acting chief of NCI's Radiotherapy Development Branch, said the results are interesting, but "nothing spectacular. . . . It seems to work for a small number of rare tumors. For example, for some reason neutrons are better than anything else for salivary gland tumors. There's also some controversy over whether they're better for prostate cancer at certain stages."

He said that there are now three places to receive treatment with neutrons; the University of Washington in Seattle, the Fermi Laboratory outside Chicago, and the Gershen Radiation Oncology Center at Harper Hospital in Detroit.

Also, the News in July 1988 announced the launching of an intense anti-smoking intervention trial known as COMMIT (Community Intervention Trial for Smoking Cessation). The findings, reported in the February 1995 issue of the American Journal of Public Health, showed that the intervention — using the media, community events, worksite programs and smoking cessation resources — helped light-moderate smokers stop smoking, but were unable to help heavier smokers end their addiction. Currently, NCI's anti-smoking programs are directed more toward policy changes on a state-wide level; creating smoke-free facilities, restricting youth access, and advertising.

In spite of the success of the COMMIT program, the current smoking trends in the U.S. do not augur well. Donald Shopland, from NCI's Smoking and Tobacco Control Program noted that the smoking rate for adults had been declining for over 20 years until 1991. "But since 1991 smoking prevalence among adults has not changed, and among kids it has been going up."

Shopland said that the adult prevalence has been pretty steady at 25% during the 1990s and among high school age children, the rates are as high as 20%. "A lot of things are not too encouraging," he mused.

Sequencing Genes

Finally, the News reported in November 1998 that after 3 years of extensive debate, the NIH established the Office of Human Genome Research. At a cost of $200 million per year for 15 years, the Genome Project announced it would sequence the entire human genome and make the data freely available to everyone.

Looking back over those 10 years, Elke Jordan, Ph.D., deputy director of the now National Human Genome Research Institute seemed very pleased with how well things have worked out.

The sequencing is still within budget and is expected to be finished 2 years ahead of schedule.

"At the same time that it's gone well, it's more complicated than we expected," said Jordan. "The rapid growing interest of industry in carrying out mapping and sequencing for their own purposes has been a surprise. They are soaking up skilled people and, not suprisingly, in many cases, want to patent and protect the information in proprietary ways."

However, one of the most gratifying innovations, Jordan said, was the genius of Nobel laureate James D. Watson, Ph.D., the first associate director of the Office of Human Genome Research, in announcing even before the program began, that 3% of the project would be spent in addressing the ethical, legal, and social implications of the research. Because of that program, known as ELSI, the Working Group on the Ethical, Legal and Social Implications of Human Genome Research, the issues have become clearer and the debate better informed.

"Initially the public was concerned that we were going to clone people or create monsters, which at the time seemed unreal," said Jordan. "Now the public realizes that the real issues are more practical ones — issues of privacy, confidentiality, protection from discrimination, how the information will be used in a clinical setting, and educating professionals and the public who will use the information. Because of the ELSI program, we have all matured in our thinking about these problems."



             
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