The Greatest service which can be rendered any country
is to add [a] useful plant to its culture . . .
Thomas Jefferson
American President/Author (1743-1826)
With the number of latex allergies jumping from a single case report in 1979 to 6.5% of Americans in 1994, it would seem that latex is dropping from the sky. A report in the January 1995 issue of the Journal of Allergy and Clinical Immunology and a followup article in the March 1996 issue of Chest find that urban air does contain latex particles, shed into the environment by normal tire wear.
Along a four-lane road in Denver, Colorado, a team from the Allergy Respiratory Institute of Colorado led by immunologist Brock Williams collected particulate air pollution. Their samples included black fragments containing latex proteins, which were recognized in tests by human antibodies to latex. More than half (58%) of the airborne debris was small enough to be inhaled into the lungs. Airborne latex could partially explain the rise in latex sensitization. "Until we know more about it," says Williams, "it's difficult to weigh the importance of airborne latex to the overall problem. But it's probably in every city in the world with cars."
Proteins in the sap of the Brazilian rubber tree (Hevea brasiliensis)--used to produce latex--trigger latex allergies ranging from annoying skin rashes to anaphylactic shock. The surge in latex allergies coincided with increased global demand for latex gloves in the late 1980s to prevent the spread of HIV and hepatitis. Manufacturing shortcuts, such as skipping washing steps that remove latex proteins, contributed to the epidemic that first struck medical personnel exposed to latex-containing supplies. Recent studies find that latex allergies affect up to 14% of healthcare workers.
Because 57 latex proteins are known allergens, removing them is impractical. So is avoiding rubber, which is found in 40,000 items, including 300 medical products. To circumvent latex allergies, USDA researchers at the Western Regional Research Center in Albany, California, have developed hypoallergenic rubber from guayule (Parthenium argentatum), a shrub native to the southwestern United States. In clinical trials to be published in the Journal of Allergy and Immunology, people allergic to Hevea latex do not react to guayule.
Latex in our lives. A combination of exposures to proteins found in latex products and certain foods may be the cause of a rise in latex allergies.
The USDA team, headed by plant physiologist Katrina Cornish, created processing methods to extract guayule and manufacture rubber products with superior resilience, strength, and elasticity. The USDA granted an exclusive license for the patented technology to American Medical Products in Burlingame, California. The first guayule products will be medical supplies for latex-sensitive patients and medical workers. Cornish is continuing genetic studies to improve latex yields and adapt guayule for growth in diverse climates.
Up to half of latex-sensitive patients also show allergic reactions to certain fruits including avocados, bananas, kiwifruits, papayas, and peaches, according to a study published in the October 1994 issue of the Annals of Allergy. "These plants contain the same proteins that are allergens in latex," says Dennis Ownby, director of pediatric allergy research at Henry Ford Hospital in Detroit, Michigan. People with fruit allergies should warn physicians before undergoing procedures, he says, because anaphylactic reactions from contact with physicians' latex gloves have occurred in those with mild fruit allergies.
Williams, now director of research at IBT Reference Laboratory in Lenexa, Kansas, theorizes that this fruit/latex cross-reactivity is worsened by ethylene, a gas used to hasten commercial ripening. In nature, plants produce low levels of the hormone ethylene, which regulates germination, flowering, and ripening. But when forced to ripen quickly under high ethylene concentrations, plants produce allergenic wound-repair proteins, which are similar to wound-repair proteins made during the tapping of rubber trees. Sensitive individuals who ingest the fruit "get a higher dose and worse reaction," suggests Williams. Some people may even first become sensitized to latex through fruit, Williams suggests, although this hypothesis remains to be proven.
Women's Health Initiative
Attempting to make up for the historic exclusion of women from clinical research, Bernadine Healy, then head of the National Institutes of Health, launched the Women's Health Initiative (WHI) in 1991. The WHI is an ambitious effort to evaluate several strategies aimed at preventing heart disease, breast and colorectal cancer, and osteoporosis in postmenopausal women.
The initiative is divided into three parts. The first part encompasses three clinical trials evaluating the benefits of a low-fat diet, hormone replacement therapy, and calcium and vitamin D supplementation, respectively.
The second part of the initiative, an observational study, runs simultaneously with the clinical trials. Participants are followed for 8 to 12 years while investigators track a wide range of factors to determine the relationship of these variables to disease outcome. Participants regularly fill out questionnaires on items such as diet, environmental exposures, exercise, and smoking. In addition, clinics store participants' blood samples for later evaluation. Both the clinical and observational studies began recruiting volunteers in 1993.
The third part of the study, a collaborative venture with the Centers for Disease Control and Prevention (CDC), funds a variety of disease prevention programs at several university-based centers nationwide. With the particular goal of including women of diverse races and lower socioeconomic status, these projects focus on such issues as improving delivery of diabetes care, reducing cardiovascular risk among black women, and measuring physical activity in women. This arm of the initiative began in 1995 and will run on a five-year funding period.
To date, approximately 65,000 women have enrolled in the observational and clinical trials at 40 centers around the country. The director of the initiative, Loretta Finnegan, says the investigators aim to have 164,500 participants by 1998. The study will be completed in 2005, at which point researchers will analyze data. They expect to provide results by 2007.
This is the largest study of women ever undertaken and the numbers involved can become overwhelming. To manage the project on all levels, the NIH established one central coordinating center in Seattle, Washington. Staff at the center manage all data from that location, aided by a computer network. "All of our sites are connected all the time by a network," explains Garnet Anderson, a project director for data coordination at the center. Thus, Anderson can freely access data from all 40 clinical centers.
Source: National Institutes of Health
Because the initiative extends over such a long period, the scientists must continually reevaluate the research protocol and integrate new data as they become available. Judith Ashley, a study investigator and assistant professor in the Department of Medicine at University of California at Los Angeles, is impressed with the adaptability built into the study. As an example, when recent research results indicated that women who have not had a hysterectomy should not take estrogen without progesterone because of increased incidence of cervical dysplasia, the investigators responded quickly and changed the study design.
The WHI is approximately one-third of the way through its projected life span. So far, outside organizations are optimistic about the project. "We are pleased that NIH is taking on a comprehensive study of women's health," said Lisa Cox, program director for the National Women's Health Network, a public interest group devoted to giving women a stronger voice in the nation's healthcare system. "We hope the study will finally provide answers to questions that have been posed for a very long time--questions such as the relationship between hormone replacement therapy and breast cancer."
According to Luella Klein, director of women's health issues for the American College of Obstetrics and Gynecology, the initiative has already provided benefits by calling attention to gender in research. "Partly because of the uproar that was generated [before the creation of the WHI, when the NIH realized that only about 13% of research funding was going to female-specific research], there are data now coming out that never would have come out before, because nobody ever bothered to divide data by men and women."
While Klein is enthusiastic about the initiative, she voices concern about its size. In this time of budget cuts, such a mammoth endeavor makes an easy target. Klein says she has seen other large studies discontinued prematurely and worries that the WHI could be another victim. "I hope they make it to the end and that modifications are made as needed," she said.
Since 1993, women ranging in age from 50 to 79 have been signing up to participate in this landmark study. Many may not live to see the final results. But as Ashley comments, "They're concerned about their children and their grandchildren. They [participate in] the examinations and the trial because they care about themselves and other women."
Mounting scientific evidence and recent media attention have heightened public awareness about endocrine disruptors, chemicals that mimick or interfere with the actions of hormones. Exposures to high doses of these chemicals, such as organochlorine compounds including DDT, PCBs, and dioxins, can be strongly associated with declines in offspring, increases in cancers, and reductions in reproductive functions in wildlife and humans. Because the various research projects on endocrine disruptors conducted by federal agencies lack cohesion, the government is working to coordinate and integrate research needs and goals.
The White House Office of Science and Technology Policy's Committee on Environment and Natural Resources (CENR) has created an interagency task force to develop a national strategy for research on endocrine disruptors. The goals of the working group include identifying key scientific questions about endocrine disruptors; developing an inventory of current federal research programs on endocrine disruptors; identifying research gaps in ongoing programs and assessing research needs to facilitate coordination across the federal government; initiating outreach efforts to public interest, private sector, and international groups; and promoting educational activities to disseminate information to the scientific community. The working group is chaired by Lawrence Reiter, director of the EPA's National Health and Environmental Effects Research Laboratory. George Lucier, director of the Environmental Toxicology Program of the NIEHS, serves as vice chair for human health and Michael Mac, program manager for status and trends for the National Biological Survey of the Department of the Interior, serves as vice chair for ecology.
Source: Adapted from Kavlock RJ et al., Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the U.S. EPA-sponsored workshop. Environ Health Perspect, 104(Suppl 4):715-740 (1996).
"Although trends in hormonally related diseases have not been clearly linked to environmental chemicals, it is probable that endocrine disruptors are contributing to human diseases and dysfunction. The question then becomes how much they are contributing," Lucier said. "What is needed is high-quality basic and applied research to examine a number of critical areas."
Many individual federal agencies have been working to develop research needs and priorities. In April 1995, the EPA sponsored an interdisciplinary workshop on the human health and ecological effects of endocrine disruptors to identify research gaps and determine future research priorities. According to the workshop summary, attendees concluded that research should focus primarily on effects on development of reproductive capability, on improved exposure assessment, and on the effects of mixtures. (See conference summary report, Environmental Health Perspectives, August 1996.)
The goal of the CENR working group is to evaluate and harmonize the needs and priorities of the various agencies. Lucier says that an interagency approach is important to the development of a national strategy. "The most effective way to utilize basic research to make sound policy decisions is to develop interagency approaches that maximize its application to multiple agencies," he said. "We will develop cross-cutting approaches useful to all agencies." An interagency approach also maximizes communication, Lucier added.
The CENR group has worked to put together a document prioritizing federal research needs. According to a preliminary draft of the strategy, the highest priority is determining the effects of endocrine disruptors on developing organisms, particularly on the reproductive system. Other priorities include assessing the potential carcinogenic effects and the toxicology of mixtures and assessing the nature and extent of contamination in the area of exposure. The group is also working to develop a comprehensive evaluation of all federally funded research projects on endocrine disruptors. According to Lucier, the group will also focus on how to link scientific activities to public policy decisions. The strategy is due out in September.
Alfred G. Knudson, Jr., and Joseph F. Fraumeni are this year's recipients of the Irving J. Selikoff Award for Cancer Research. Knudson and Fraumeni earned the award specifically for "research on the molecular origins of cancer and its application to the management of populations at high risk," said Sheldon Samuels, vice president for policy studies at the Ramazzini Institute, which was founded by Selikoff to promote occupational and environmental health research. The Ramazzini Institute sponsors the annual award.
Selikoff, who died in 1992, is remembered for his work at New York's Mt. Sinai School of Medicine in linking cancer and other diseases with environmental pollutants such as asbestos. The award consists of a plaque and a monetary prize given from a fund developed by Selikoff at the Ramazzini Institute. "We decided to keep the fund alive," Samuels said, adding that the fund is entirely privately endowed. The award is given to scientists who demonstrate excellence in expanding genetic research on how to repair cancer-causing damage--to prevent cancer from later appearing even though people have been exposed in the past. The award recipients are selected by a panel of officers at the Ramazzini Institute.
Selikoff standouts. Alfred G. Knudson, Jr. and Joseph F. Fraumeni (left to right holding boxes) are the 1996 winners of the Irving J. Selikoff Award for Cancer Research. They are flanked by Philip Landrigan (left) and Arthur C. Upton (right) of the Mt. Sinai School of Medicine.
Photo: P.E. Rogol
Knudson, a researcher at the Fox Chase Cancer Center in Philadelphia, Pennsylvania, was chosen for his research on developing models of carcinogenesis. "He is not only a great laboratory scientist, but he happens to be a conceptualizer, a theoretical biologist whose models of carcinogenesis are the basis of much of the research on the interface between the environment and our genetic inheritance," Samuels said. "Knudson was one of the conceptual pioneers who discovered the family of genes associated with retinal glaucoma, which is important in understanding cancer in general, because this same family is important in other cancers."
Fraumeni, who is director of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute (NCI) in Bethesda, Maryland, was given the award for his research in environmental and genetic factors in cancer, and in clarifying the role of genetic susceptibility.
According to Samuels, one of Fraumeni's most significant accomplishments has been the development of a program at the NCI in genetics and epidemiology. The program, links molecular biology, epidemiology, and prevention. "We are just now beginning to see the fruits of [Fraumeni's] work," Samuels said. "He deserves to be recognized for his achievement in pulling that program through." The awards were presented 21 May 1996 at the Mt. Sinai School of Medicine. "It's a great honor," said Fraumeni. "Both Dr. Knudson and I were delighted to receive the award given in memory of Dr. Selikoff, who contributed so much to the area of environmental cancer research.
In 1992, a Danish research team led by Niels Skakkebaek at the National University Hospital in Copenhagen published in the British Medical Journal the results of a meta-analysis of sperm count studies covering 50 years. The team concluded that human sperm counts had declined by as much as 50% during that time. Since then, many environmentalists, journalists, and reputable scientists have relied on this study to assert that environmental toxins are having an adverse effect on male fertility. Of special concern are both natural and manmade compounds called endocrine disruptors.
Three reports in the May 1996 issue of Fertility and Sterility challenge the assertion that sperm counts are declining worldwide. Sperm quality is measured by four factors: motility, morphology, semen volume, and sperm numbers. One of the studies, by C. Alvin Paulsen and colleagues at the University of Washington School of Medicine, looked at data from 500 Seattle-area men between 1972 and 1993 who met criteria for normal general and reproductive health. Results showed no decrease in sperm quality by any of the four standard measures.
Another study, by Harry Fisch and colleagues in the Department of Urology at the Columbia-Presbyterian Medical Center in New York, was based on data derived from the general U.S. male population. Using the records of the three oldest sperm banks in the United States, the Fisch team found that instead of a decline, results showed a statistically significant increase in sperm counts in the last 25 years (from 77x106/ml in 1970 to 89x106/ml in 1994). Fisch attributes the Danish study's conclusions to problems with nonuniformity of data and other methodological considerations.
The Fisch study did note marked geographical differences among the three data sources, with New York having the highest sperm counts and Los Angeles having the lowest. No explanation for this disparity was offered, and Fisch is currently investigating the issue.
Zoologist John Peterson Myers believes that Fisch's conclusions are "statistically challengeable" but agrees that "the emerging geography of sperm count change" deserves more research attention. In the genetic melting pot of the United States, he says, geographic variations point toward environmental rather than ethnic factors.
In certain geographic areas including Denmark, there has been a marked increase in male reproductive disorders such as testicular cancer, undescended testes, and hypospadia. Studies in France, London, and Scotland also suggest that sperm quality has declined in these areas in the last two decades. Skakkebaek believes these problems are connected to increased exposure of the male fetus to estrogens. There is also strong evidence from animal studies that suggests that environmental toxins, especially synthetic estrogens, can cause reproductive abnormalities. A new book, Our Stolen Future, written by World Wildlife Fund researcher Theo Colborn with journalist Diane Dumanoski and Peterson Myers, collects evidence from many sources to bolster the claim that environmental toxins are threatening reproductive health in many species including humans. The authors note that some 51 families of synthetic chemicals have been identified as hormone disrupters, including PCBs, dioxins, and furans.
Of the information in Our Stolen Future, Fisch warns that "you cannot extrapolate from animals to humans," and that while "there are definite environmental risks, . . . it's anecdotal evidence." Toxicologist Stephen Safe of Texas A & M University notes that the places where sperm counts have declined are "all Western world places where there's no apparent or obvious chemical gradient [known presence of unusual concentrations of chemicals] that I can see. These [new studies] would suggest that there are regional problems. We don't understand them, and we may want to come up with new hypotheses."
Despite their criticism of what they deem environmentalist alarmism and of the methodologies in earlier studies, even skeptics do not deny the general idea that human reproductive health may be threatened by environmental chemicals. Don Wolf of the Oregon Health Sciences University Andrology Laboratory believes the more extreme environmentalist claims are "trying to skew the data to support the hypothesis. The available data are simply insufficient to allow any hard and fast decisions." But he adds that it is "important that we don't completely ignore these concerns."
EHPnet
One-fourth of the money spent each year by Americans is spent on products regulated by the U.S. Food and Drug Administration; this amounts to over $1 trillion worth of goods--from eyeshadow to AZT--that must meet FDA guidelines for product safety and quality. Currently, all foods and drugs (for both animals and people), cosmetics, and radiation-emitting equipment are FDA regulated, and the agency seems poised to add the $2.8 billion tobacco industry to this list. From proposing tobacco regulation to researching the effects of the "morning after" pill, this obligation requires that the FDA study and debate some of the most divisive issues facing the nation. Part of the continuing dialogue between the FDA and the public consists of the agency's home page, located at http://www.fda.gov/, the entranceway to a well-designed resource on FDA programs and regulations.
From the home page, a user can choose one of eight icons to link to the home pages of specific FDA programs, read the FDA news, or change to another directory. Despite the aesthetic appeal of the site, however, the complex structure of the FDA can make it difficult to find the particular information being sought. The FDA search engine, which can be accessed from the bottom of the home page, offers another way to find FDA documents on specific subjects. Also located on the home page is a Comments link that allows users to correspond with the FDA via electronic mail.
Through the FDA News link, users can find information such as the text of proposed tobacco regulations and guidelines for protecting children from lead poisoning. The results of recent research studies are also presented here along with current press releases and product recalls (under the Latest FDA Enforcement Report link). This site also offers a calendar of upcoming meetings and symposia and a searchable archive of past press releases, papers, testimonies, reports, articles, and major speeches. Another link brings up the latest issue of FDA Consumer magazine, with full text of articles and back issues.
The Foods icon links users to information from the Center for Food Safety and Applied Nutrition, along with external biology-related resources that can be accessed from the CFSAN page via the Info link. Other links connect users to consumer advice on food handling, information on food additives like olestra and MSG, and facts about foodborne illnesses. The Bad Bug Book, which can be found under the Foodborne Illness link, provides descriptions of common pathogens as well as information about disease outbreaks and symptoms.
The Center for Drug Evaluation and Research site, linked through the Human Drugs icon, is evolving into a comprehensive resource on drug composition and regulation. Information on how the FDA screens new drugs, approves them for market, and ensures accuracy in testing, formulation, and labeling can be reached from the CDER home page by selecting the About CDER icon and following the Office of Compliance link to the Annual Report FY 95. Also within the annual report are pages on FDA drug recalls and a directory that lists FDA personnel by their area of expertise. The Division of Over-the-Counter Drug Products maintains lists of drug name changes and will soon host a complete database of active drug ingredients. The Drug Info icon on the CDER home page brings users to a list of approved drug products with therapeutic equivalence evaluations along with descriptions of drugs that have been approved in the last three years. Guidance documents for the drug manufacturing industry can be reached from the CDER home page via the Regulatory Guidance link.
The links to other FDA programs--Biologics, Devices and Radiological Health, Animal Drugs, Cosmetics, Field Operations and Imports, and Toxicology--all provide data pertinent to those particular fields. For instance, the Center for Biologics Evaluation and Research (Biologics link), which oversees the manufacture and sale of vaccines and blood products, provides a link to the Vaccine Adverse Response Reporting System. The Center for Devices and Radiological Health provides a useful list of safety alerts and advisories under the Program Areas link, and the National Center for Toxicological Research can be reached through the Toxicology icon. |
Errata
In the Forum article Fueling the Gas Debate, on page 689 of the July 1996 issue, Dr. Myron Mehlman was incorrectly identified as a staff scientist at the Environmental and Occupational Health Sciences Institute at Rutgers University. Dr. Mehlman is an adjunct professor of environmental and community medicine at the Robert Wood Johnson Medical School at the University of Medicine and Dentistry of New Jersey.
The NIEHS News article BRC Criteria Revised, on page 824 of the August 1996 issue, incorrectly stated that Donna Shalala, secretary of the Department of Health and Human Services, has approved a revision of the criteria for listing a substance in the Biennial Report on Carcinogens. The statement should have read that the Secretary "is expected to approve" such a revision.
Last Update: July 28, 1997