The measure of the land and the measure of our bodies are the same . . . I never said the land was mine to do with as I chose. The one who has the right to dispose of it is the one who created it.
Chief Joseph, Nez Perce
EPA Releases Mercury Report
December 19 was a big day for the U.S. EPA. On that day, after several years of debate and angst, the EPA released the draft copy of its Report to Congress on Mercury, an eight-volume review of the hazards of mercury, including an inventory of exposures and health effects caused by mercury emissions. The EPA calls its report a "snapshot" of the current state of mercury emissions--and of the current body of knowledge on the topic, which only very recently expanded to include information from studies conducted in the Seychelle Islands and the Faroe Islands.
There is no longer any doubt that exposure to mercury, particularly to the organic form methylmercury, causes damaging health effects, but there is fierce debate over what level of exposure should be considered dangerous. The EPA report, which was originally due in 1994, was repeatedly held up in hopes of including data from more recent studies, such as the Seychelles study. The agency finally decided to release the report without those data; the report relies instead largely upon a study from the early 1970s of Iraqi mother-child pairs, which found that the presence of mercury in the mother's hair at levels over 10 parts per million appears to be related to developmental and/or neurological abnormalities in her offspring. Based upon those findings, the EPA proposes a reference dose for methylmercury of 0.1 µg per kilogram body weight per day--a figure that is five times more stringent than that proposed by the Agency for Toxic Substances and Disease Registry (ATSDR) and over four times as tough as that of the Food and Drug Administration.
The Seychelle Islands study was designed as a follow-up to the Iraqi study. Its purpose was to test the Iraqi findings on a population that was both much larger than the Iraqi population and that received its mercury exposure through the most common route of consumption of fish (the Iraqi subjects had eaten contaminated grain). The findings of the Seychelles study, published in volumes 16 and 18 (1995 and 1997, respectively) of Neurotoxicology, found no evidence that prenatal methylmercury exposure is linked to childhood defects. However, a companion study of subjects from the Faroe Islands, published in the November-December 1997 issue of Neurotoxicology and Teratology, indicates that methylmercury exposure in utero does cause negative health effects--but not at the rates noted in the Iraqi study.
The ATSDR has just issued its own draft report on the health effects of mercury. Christopher T. DeRosa, director of the division of toxicology at the ATSDR, says of the EPA report, "We feel it's a significant body of work. . . . Its conclusions are consistent with conclusions reached by the ATSDR in our 1993 report." DeRosa says that the newest ATSDR report includes data from the Seychelle Islands study. The final form of the report will include the data from the Faroe Islands study, which were not available at the time the draft was drawn up.
Opponents of the EPA report say the agency is being overreactive in its play to have mercury labeled as a significant health threat. Many of these opponents feel the EPA report will alarm U.S. citizens unnecessarily by leading them to believe that less, rather than more, mercury will cause health problems, particularly to those exposed in utero.
Humans are exposed to methylmercury primarily through eating fish that have accumulated amounts of the compound in their muscle tissue. In general, U.S. fish fanciers are less likely to eat contaminated fish than consumers in other nations. Still, there is some danger to those who eat large amounts of seafood, particularly large predatory species such as shark and swordfish, which are more likely, through their position in the food chain, to have been exposed to mercury pollution.
The birth of the industrial age gave rise to increased releases of mercury, thanks to such developments as electricity, nuclear energy, and fossil fuel combustion. Mercury tends to spread widely and easily because it can remain suspended in the atmosphere for up to a year. The organic forms of mercury such as methylmercury are the more dangerous to humans because these forms tend to bioaccumulate, as opposed to the inorganic forms, which tend to be less well absorbed and more easily discarded by the body.
The uncertainty over whether it is safe to eat fish and in what amounts is frightening to many people. To alleviate these fears, DeRosa says, representatives from a number of government agencies, including the EPA, the ATSDR, and the FDA, will issue a joint statement later this year that will attempt to provide a consensus of where the science of mercury poisoning is heading.
Fighting Disease with Disease
For nearly 200 years, people have observed that cancers occasionally regress in patients who contract a bacterial infection. However, purposely infecting cancer patients with the same bugs that cause food poisoning and toxic shock syndrome in order to control their tumors has never seemed like a very sensible treatment regimen--until, perhaps, now. In October, researchers at the Yale University School of Medicine in New Haven, Connecticut, announced they had developed a strain of Salmonella typhimurium with an unusual affinity for malignant tumors. Not only does this strain limit cancer growth while posing a minimal risk of serious infection, it also can be used to deliver anticancer agents to the site of the tumor.
The result is a Salmonella that attacks tumors via a two-pronged method, but that does little or no harm to the patient. In the Yale study, cancerous mice that received the bacteria treatment lived up to twice as long as cancerous mice that did not, and were found to have tumors less than half the size of those in the untreated mice. The researchers showed the method to be effective against a wide range of tumors, including those caused by inoculating mice with human lung, colon, breast, kidney, and liver cancers. The Salmonella even effectively battled multiple tumors within the same animal, the researchers reported in the 15 October 1997 issue of Cancer Research.
The mechanism by which bacterial infections slow cancer growth is not known, but investigator John Pawelek and colleagues Brooks Low and David Bermudes at Yale reasoned that if such an infection was localized to the tumor site, it would slow the cancer growth more effectively while reducing the risk of infection elsewhere in the body. By using different growth substrates, the team was able to isolate a mutant form of Salmonella that needs an unusual mix of metabolites to grow--a mix found in abundance within malignant tumors but scarcely anywhere else in the body. Once injected into a cancerous mouse, the mutant Salmonella seeks out the tumor and thrives there, while the immune system easily controls the bug in the rest of the body. Sacrificed mice that had undergone treatment had Salmonella populations in their tumors that were 250-9,000 times as dense as those found in the animals' livers.
The deliberate infections dramatically reduced tumor growth, but the authors decided to take the research a step further. They reasoned that, because their Salmonella strain tended to concentrate itself around tumors, it would make a good vehicle for delivering anticancer drugs. In this vein, the researchers further modified the strain by introducing into the bacteria the herpes simplex virus gene that codes for thymidine kinase. While thymidine kinase does not fight cancer on its own, it is deadly to cells when combined with ganciclovir, a prodrug used to fight herpes in AIDS patients. By a very poorly understood process, cells that produce thymidine kinase, such as the Yale team's modified Salmonella, will not only die upon contact with ganciclovir, they will take their nearest neighbors with them. This so-called "bystander effect," which was first noted a decade ago, has been observed in many instances of cell death.
Salmonella soldiers? Mice injected with Salmonella show that the bacteria make their way into melanoma tumor cells and multiply, slowing the growth of the tumor.
The researchers injected mice with the Salmonella that incorporated the thymidine kinase gene, and then treated them with ganciclovir. As expected, additional tumor regression due to the bystander effect was noted. However, the researchers reported, this effect was small in comparison to the much more radical effect of the bacterial infection on the tumor, despite the efficacy of the drug. Nonetheless, the use of Salmonella as a drug delivery device still represents an important breakthrough. Getting drugs into tumors has always been a difficult challenge for doctors because, among other barriers, tumors have high internal pressure pushing outward. But the Yale scientists showed that for motile Salmonella such obstacles are no problem.
The October report by the Yale group was the culmination of four years of research on this radical new method to fight cancer. Now the scientists are preparing the invention for use in clinical trials, the next step in drug development.
Is Airborne Manganese a Hazard?
Public health officials, scientists, and regulators worry that a gasoline additive containing manganese, claimed by its maker to boost engine performance, may cause physical harm by increasing the amount of manganese in the air. Ethyl Corporation of Richmond, Virginia, which makes methylcyclopentadienyl manganese tricarbonyl (MMT), disputes such worries, and says the manganese emitted into the air when MMT is burned poses no risk to human health.
The concerns about the additive come as the Agency for Toxic Substances and Disease Registry (ASTDR) is completing a toxicological profile of manganese to assess sources of exposure and the metal's impact on health. The agency is required to prepare such profiles for hazardous substances found at the nation's most serious hazardous waste sites--those on the EPA's National Priorities List of Superfund sites. Of 1,430 sites on the list, 644 (or 45%) have "excessive levels of manganese," according to the ATSDR. Excessive levels are those greater than background in the environment.
A trace element, manganese is an essential part of the diet and can easily be obtained from grains and nuts. Manganese deficiency can lead to bone problems and stunted growth. Excess dietary manganese is simply excreted. A number of studies have shown that occupational exposure to manganese can lead to Parkinson's disease-like symptoms such as muscle tremors.
Manganese is used to give strength to steel and aluminum. Manganese levels in the air can vary widely, being higher near foundries and metal plants and lower away from such facilities. But it's chronic exposure to manganese compounds emitted in the exhaust of vehicles fueled by MMT-boosted gas that has raised the most concerns.
Canada banned the import of MMT this year--none of the additive is made there--due to concerns over possible health effects. MMT had been used in Canadian gasoline for nearly 20 years. Ethyl is fighting the ban. A U.S. appeals court in Washington, DC, overturned an EPA ban on MMT in 1995, saying the agency acted illegally by attempting to ban the additive on health grounds under the Clean Air Act (CAA). The court said that under the CAA, the EPA could only consider MMT's effect on engine performance. But California has successfully kept the additive out of unleaded gasoline sold in that state for approximately 20 years because of a "lack of data on the health effects of breathing manganese," says Richard Vincent, a spokesman for the California Air Resources Board.
Widespread exposure to manganese, says Michael Davis, senior health scientist and acting chief of the EPA's Hazardous Pollutant Assessment Branch, may cause neurological damage, as well as harm to the lungs and the reproductive system. "We didn't feel like those areas were adequately evaluated [in considering exposure from MMT]," he says. Davis notes studies that show workers who were occupationally exposed to manganese were subject to pneumonia and coughs. He also cites a 1973 study that suggested an increase in respiratory illnesses in Japanese students living near a factory emitting manganese.
A draft toxicological profile for manganese prepared by the ATSDR cites studies showing that men occupationally exposed to manganese have impaired fertility as well as impotence and loss of libido. However, data on the health effects of manganese exposure are scanty and inconclusive, according to the profile.
Moreover, says Monica Campbell, a Toronto toxicologist and spokesperson for the Ontario Public Health Association, studies of MMT have failed to consider the impact of manganese from MMT on people living near major arterial roads. They are a vulnerable population more exposed to vehicle exhausts, she says.
A study of laboratory rats, presented at the Arkansas conference by researchers Hans Tjälve and Jörgen Henriksson of the Swedish University of Agricultural Sciences in Uppsala, found that, when inhaled through the nose, manganese can enter the brain and reach the spinal column. Says EPA neuroscientist Kenneth Hudnell, "This is a whole new route of exposure that hasn't been considered before. It bypasses all protective barriers that we have."
And in an EPA-funded study, Donna Mergler, a neurophysiologist at the Université du Québec at Montréal, and colleagues found a relationship between manganese levels in the blood and neuromotor slowing problems in people who lived near, but did not work in, a former manganese alloy production plant. Higher blood manganese levels were also linked to learning and memory problems in men over the age of 50. But the findings from this research are preliminary, cautions Hudnell, who was a researcher on the study. "It simply points out the need for more research," he says.
Donald Lynam, an Ethyl vice president and scientist, takes a different view. Lynam says that MMT adds virtually no manganese to the air. He points to the conclusions of an Ethyl-sponsored study, also presented at the Arkansas conference, that found that MMT's contribution of manganese to the air in Toronto was trivial.
He further points to a review by the Canadian agency Health Canada that concludes that it is impossible to assess the impact of MMT on manganese in the air. The 1994 review, however, did recommend monitoring for MMT because use of the additive has increased substantially in recent years.
Ethyl's position on the potential health hazards of manganese generated by MMT is unambiguous. According to a statement on the Ethyl Web site, "[N]o evidence exists suggesting that MMT presents any risk to public health, much less a significant risk."
Meanwhile, MMT can be and is being added to gasoline in the United States. According to the EPA, MMT was added to 11 million gallons of gasoline during the summer of 1997. That is an extremely small portion of the billions of gallons of gas that are sold each year, according to the agency. But the EPA's concern over the manganese MMT puts into the air isn't assuaged. The agency is still talking with Ethyl Corporation to decide what types of health effects testing it wants done on animals exposed to the manganese generated when MMT is burned in gasoline.
New Test Speeds Detection of E. coli
A mutant form of Escherichia coli called O157:H7 continues to make headlines for causing sometimes-fatal illnesses in those who eat contaminated foods. Three children died in Washington State in 1993 after eating contaminated hamburgers at a Jack-in-the-Box fast food restaurant. In the summer of 1997, 25 million pounds of hamburger, potentially tainted with E. coli O157:H7, were recalled by Hudson Foods in Columbus, Nebraska, after making consumers ill.
The present way to detect E. coli O157:H7 requires growing the bacteria in laboratory cultures, which takes days. And some stubborn bacteria refuse to grow in the laboratory, yet still infect people, giving false-negative results. This time-consuming and inaccurate method limits the detection of disease-causing bacteria.
Now, Montana researchers have created a new technique that detects E. coli O157:H7 in four hours, is highly sensitive, and works in food, feces, and water. The method could be adapted to detect other foodborne pathogens such as Salmonella, or even biological warfare agents. "You can use this method on any organism. It's not just for E. coli," says Gordon McFeters. He and fellow microbiologist Barry Pyle of Montana State University in Bozeman invented the technology with funds from the National Aeronautics and Space Administration (which is looking for new ways to check the safety of food and water on space missions), then teamed up with Montana ImmunoTech, Inc., in Bozeman to perfect their test.
The patent-pending technology uses antibodies to detect unique molecules on the surface of E. coli O157:H7. The antibodies are attached to tiny (0.1 micron) magnetic beads that bind bacteria, then are concentrated by passing them through a magnet before staining with fluorescent dyes for detection. In laboratory trials, as few as 10 E. coli O157:H7 bacteria were detected in slurried samples of raw hamburger. "The organism is so virulent, just ten can cause an infection," says immunologist John Jutila, president of Montana Immunotech. The magnetic beads are also coated with antibodies that detect the toxins or virulence factors produced by E. coli O157:H7, making the test doubly discriminating.
With a new two-year $750,000 Small Business Innovation Research (Phase II) grant from the National Institutes of Health, the researchers will convert the prototype antibody/bead method into an easy-to-use dipstick test for field use. The prototype requires cumbersome laboratory equipment such as a fluorescent microscope. The researchers face the challenge of applying their technology to a dipstick. "The dipstick technology is conceived and under development," says Pyle. Once perfected, a dipstick, similar to a home pregnancy kit, could check feces of cattle at slaughterhouses to stop infected animals from slipping in. Or farther along, meat ground at local supermarkets could be checked before being packaged for consumers.
Microbiologist Dick Wilson, director of the E. coli reference center at Penn State University in University Park, an international repository holding 34,000 strains, says that a test kit for E. coli O157:H7 should be highly specific and sensitive, rapid, and eliminate the need for a high-tech laboratory. He's watched the development of a burgeoning number of such kits and the Montana technology stands out, he says, because it also detects virulence factors. "An increasing number of E. coli strains with the same virulence factors as O157:H7 are evolving and infecting animals and people," says Wilson.
In designing their dipstick for field use, the Montana team needs to overcome two possible limitations, says Wilson. First, the dipstick must be highly sensitive to detect small numbers of infectious bacteria, and substances in food, water, and feces must not interfere with the antibody binding. Second, little has been determined about the environmental ecology of E. coli O157:H7 since it first appeared in 1982. No one knows how cattle become infected with E. coli O157:H7 before passing it to people. Tom Besser, a veterinarian and microbiologist at Washington State University's College of Veterinary Medicine in Pullman, suspects water or feed are contaminated, because outbreaks in cattle herds resemble foodborne epidemics. A dipstick could help track the source of E. coli O157:H7 on farms and eliminate it. "This area has received little attention," says Besser. If contaminated water proves to be the source, "we could learn how to design or clean tanks to prevent infections," he says. In the future, a dipstick could monitor water and feed to prevent new contaminations on farms.
Big Hair News
A study published in the August 1997 issue of Annals of Epidemiology has revealed an unexpectedly high incidence of salivary gland cancers among female hairdressers. The study, conducted by G. Marie Swanson, director of the Cancer Center at Michigan State University in East Lansing, was designed to assess the relationship between a variety of occupations and industries and the risk of this somewhat uncommon cancer.
Salivary gland cancer is extremely rare: fewer than 1 in 100,000 people develop such tumors. It occurs more often in men than women and overall five-year survival rates are relatively high, averaging 72.8% among men and women combined. Most cancers of the major salivary glands (the glands that actually produce saliva) occur in the parotid gland--located below and in front of the ear--but women's tumors are more often characterized as benign acinar cell adenomas, while men's are more often characterized as malignant squamous cell carcinomas or adenocarcinomas.
Because the cancer occurs so rarely, it has been difficult to ascertain what factors contribute to its growth. It is thought that exposure to Epstein-Barr virus (which causes infectious mononucleosis) or an abnormal hormone status (as might occur in a breast cancer patient) may contribute to development of the cancer. Radiation to the head is also believed to be a prime culprit. Now, Swanson's findings offer another explanation.
Swanson began the study with the intention of focusing on the occupational hazards peculiar to women and blacks because these groups had traditionally been excluded from studies on occupational hazards, which typically focus on white males. The group of salivary gland cancer patients interviewed included 163 men and women of both races who were diagnosed with the disease between November 1984 and March 1991. These patients, along with a group of control subjects, were chosen from enrollees in the Occupational Cancer Incidence Surveillance Study, an investigation of occupational risk factors for cancers among residents of the three-county area surrounding Detroit, Michigan. Swanson conducted telephone interviews with the subjects and controls, eliciting information on each person's job history, smoking history, adult medical history, residence history, education, and birthplace, as well as other demographic variables.
The results showed that the disease occurs more frequently among employees such as hairstylists, oil and gas salespeople, railroad workers, and postal service personnel--all of whom are exposed on the job to inhaled chemicals and fumes, and all characterized in the study as occupations at high risk for developing salivary gland cancers. Of these professions, hairdressers had the highest rate of the cancers, with the disease appearing in approximately 13% of the stylists. Swanson believes that the exposures that led to the development of salivary gland cancer among the group of hairdressers probably occurred 20-30 years ago when, she says, products such as turpentine and lacquer were routinely used in beauty salons as ingredients in hairdressing preparations. She points out that the median age at the time of diagnosis with salivary gland cancer is the early 60s, and that 20 or 30 years ago, the majority of hairstylists probably were female. Even though turpentine has been largely supplanted by safer beauty aids, stylists today are still exposed to hairsprays, solutions, and dyes; a study published in the Archives of Otolaryngology--Head and Neck Surgery in 1990 indicated a relationship between the use of self-applied hair dyes and the incidence of salivary gland cancers.
The next step, says Swanson, is to design a study that will isolate the specific inhaled exposures faced by hairdressers. This step is expected to shed light on what causes the salivary gland tumors and possibly also identify other occupational risks in the hairdressing industry--and indicate what, if anything, needs to be changed in the work environment of the modern-day stylist.
Dirty Snow
The pristine beauty of the snow-covered Arctic landscape may suggest that this is one part of the earth that has not yet been marred by human activity. But recent studies by the Arctic Council's Arctic Monitoring and Assessment Programme (AMAP) paint a far different picture. Though the Arctic remains a clean environment when compared to many other places in the world, it is also a fragile environment, and, AMAP reports, it is being inundated with pollutants carried by water and air from the world's industrial centers in Europe, North America, and Asia. In many cases, these pollutants accumulate in the fish and birds that supply sustenance to the region's indigenous peoples, resulting in diets dangerously high in cadmium, mercury, and organic pollutants, according to AMAP.
AMAP's recent report, Arctic Pollution Issues: A State of the Arctic Environment Report, is the product of six years of research by the world's eight Arctic nations. Scientists and leaders from Canada, Denmark, Finland, Iceland, Norway, Sweden, Russia, and the United States first began to discuss concerns about the Far North in 1991 under the auspices of the Arctic Environmental Protection Strategy (AEPS). In June 1997, the AEPS was integrated into the Arctic Council, an intergovernmental forum that will supply the infrastructure for addressing the concerns raised in the AMAP report.
Much of the work of the council and its member countries to protect the Arctic is described on the Arctic Council's World Wide Web site, located at http://www.nrc.ca/arctic/. Under the What's New link on this page, visitors can find the conclusions and recommendations of the AMAP report, including the report's 13-page executive summary. Also linked to the What's New page is information on obtaining documents from the council's last panel discussion, which sought to answer the question of whether the Arctic environment is now improving or continuing to deteriorate.
If the Arctic environment is showing signs of improvement, some credit must be given to the Arctic Council and its predecessor, the AEPS. In their short histories, these organizations have produced four declarations in which the governments of the Arctic countries committed themselves to protecting the Far North and its people. The text of these declarations, along with the Arctic Council's founding document, can be found by following the Documents & Reports link on the home page.
Information about the programs that have been implemented by the Arctic Council to address the concerns raised in the AMAP report and the intergovernmental declarations can be found by following the Arctic Council Members & Programs link. The four programs described here focus on protecting the marine environment, conserving the Arctic's fauna and flora, responding to emergencies, and assessing the Arctic's environmental status. Also available on the site is a comprehensive list of links to sites about the economy, society, culture, environment, and science above the Arctic Circle.
Last Update: February 5, 1998