RACHEL'S ENVIRONMENT & HEALTH WEEKLY #702 / July 6, 2000
The human genome -- the blueprint for making a human being -- has been almost completely cataloged. "Today we are learning the language in which God created life," said President Clinton, announcing the accomplishment June 26.[1] Under a banner headline on page 1, the NEW YORK TIMES called it "an achievement that represents a pinnacle of human self-knowledge."
The 3 billion genetic instructions that form a blueprint for human life have now been cataloged, but the meaning of most of those instructions remains unknown. Therefore, the practical significance of deciphering the book of human life remains murky except in one area: many new pharmaceutical drugs will soon be possible. Unfortunately, this is a mixed blessing. A raft of new drugs may benefit those humans who need and can afford them, but new drugs make serious trouble for the natural environment and for many of the non-human creatures living there. Even for humans, drugs already represent a major environmental challenge -- arguably the most difficult chemical challenge that we face. The environment is already heavily polluted with drugs and personal care products that have passed through humans, entered sewage treatment plants and then been discharged into waterways. (See REHW #614.) Increased drug pollution of our waterways -- including our drinking water -- is one of the dark sides of the human genome project -- a dark side that few acknowledge.
News reports of the human genome achievement have been dominated by "gee whiz" predictions of accelerating pharmaceutical advances, with no hint of any problems. The NEW YORK TIMES said, "The successful deciphering of this vast genetic archive attests to the extraordinary pace of biology's advance since 1953, when the structure of DNA was first discovered and presages an era of even brisker progress."[1] The TIMES went on to quote Dr. Gillian R. Woollett, representing the Pharmaceutical Research and Manufacturers of America, a drug manufacturers' trade association: "The rate of change is absolutely incredible. It's actually changing the way drug development is even conceived," said Dr. Woollett.[3]
The next day the business section of the TIMES explained how companies are "finding gold in scientific pay dirt: ...Genomics companies are using different methods to build businesses out of the genome," the TIMES said, offering three examples: "Incyte Genomics Inc. of Palo Alto, Calif., sells access to a database about genes to drug companies. Millennium Pharmaceuticals of Cambridge, Mass., is using genomics to understand disease processes to develop drugs. Human Genome Sciences of Rockville, Md. is developing drugs and selling its information," the TIMES wrote.[5] Notably, all three examples of commercial exploitation of the genome involve new drugs.
Last December two scientists -- Christian G. Daughton and Thomas A. Ternes -- writing in ENVIRONMENTAL HEALTH PERSPECTIVES, a respected, peer-reviewed journal, pointed out the relationship between the human genome project and new drugs: "The enormous array of pharmaceuticals will continue to diversify and grow as the human genome is mapped. Today there are about 500 distinct biochemical receptors at which drugs are targeted.... The number of targets is expected to increase 20-fold (yielding 3000 to 10,000 drug targets) in the near future...."[6] Daughton and Ternes go on to say, "Escalating introduction to the marketplace of new pharmaceuticals is adding exponentially to the already large array of chemical classes, each with distinct modes of biochemical action, many of which are poorly understood."
Daughton and Ternes say that the quantity of pharmaceuticals and personal care products entering the environment each year is roughly comparable to the amounts of pesticides used each year. Huge quantities of prescription drugs and biologics, diagnostic agents, "neutraceuticals," fragrances, sun-screen agents and numerous other classes of compounds enter the environment each year, without any government agencies taking notice. As daughton and Ternes point out, these chemicals tend to have several worrisome characteristics:
** Many are very long-lived, many break down into other long-lived compounds with their own peculiar chemical characteristics, and almost nothing is known about their movement in the environment;
** Pesticides tend to enter the environment in seasonal pulses. In contrast, pharmaceuticals and personal care products (PPCPs) enter the environment continuously via domestic and industrial sewage systems and via wet-weather runoff (for example, from confined animal feeding operations such as hog factories).
** Unlike many pesticides, most drugs and personal care products have not been examined for adverse environmental effects. Daughton and Ternes comment, "This is surprising especially since certain pharmaceuticals are designed to modulate [change] endocrine and immune systems and cellular signal transduction and as such... have obvious potential as endocrine disruptors in the environment."[6,pg.908]
** Many of these chemicals are designed to have profound physiologic effects, so it would not be surprising if they were found to affect fish, shellfish, birds, worms, frogs, insects, and other forms of life.[6,pg.925]
** With pharmaceuticals, unpredicted and unknown side effects are often the norm: "The possible actions and biochemical ramifications on nontarget aquatic biota are even less understood; many are totally unknown," Daughton and Ternes say.
** "It is important to recognize that for many drugs, their specific modes of action even in the target species are also unknown. For these drugs, it is impossible to predict what effects they might have on non-target organisms." [6,pg.923]
** Most drugs don't cure illnesses, they control symptoms -- they lower cholesterol levels or blood pressure, or they alleviate pain or depression, or they revive limp libidoes. However, to achieve these results, they must be taken continuously, often for many years. Therefore, even relatively short-lived PPCPs can cause chronic exposures because they are continuously infused into the environment;
** Aquatic organisms are captives of their aquatic environment so must endure perpetual exposure;
** The bioaccumulation/bioconcentration potential for at least some PPCPs matches that of organochlorine compounds;[6,pg.910]
** Some PPCPs show "very high acute aquatic toxicity" while others "can elicit constellations of significant but subtle effects across numerous species."[6,pg.910]
** It must also be recognized that even though individual concentrations of any drug might be low, the combined concentrations from drugs sharing a common mechanism of action could be substantial."[6,pg.925]
** Most chemical researchers don't have the tools needed to look for these chemicals in the environment. Researchers use gas chromatography (GC) and mass spectrometry (MS). The signals produced by such analytic equipment are compared to "spectral libraries," allowing unknown chemicals to be identified. But the standard spectral libraries available from U.S. Environmental Protection Agency (EPA), the National Institute of Standards and Technology (NIST), and the National Institutes of Health (NIH) do not include most pharmaceuticals. Therefore typical researchers are not prepared to identify pharmaceuticals in the environment.
** Daughton and Ternes list 66 classes of pharmaceuticals, including antidepressants; cancer chemotherapy drugs; tranquilizers and psychiatric drugs; pain killers of many kinds; anti-inflammatory drugs; many kinds of antihypertensives (blood pressure reducers); antiseptics; fungicides; anti-epileptics; bronchodilators (such as albuterol); many lipid regulators or anti-cholesterol agents; chemicals to increase the contrast in x-rays; muscle relaxants; anti-psychotic drugs; oral contraceptives; anorectics (diet pills); antibiotics; and synthetic hormones (estrogen and thyroid). Details about the 200 most popular prescription drugs in the U.S. in 1999 can be found at www.rxlist.com/top200.htm. These 200 reportedly account for two thirds of all the prescriptions filled each year in the U.S.
** Most exposure to drugs and personal care products occurs in the aquatic environment, but it also occurs on land: "...the primary source for terrestrial exposure is probably from disposal of biosolids [sludge] from [sewage treatment plants] and from animal wastes both applied to land and stored in open-air pits (waste lagoons)..." [6,pg.925]
** Daughton and Ternes say, "Theoretically, [pharmaceuticals and personal care products] in sewage sludge applied to crop lands could be taken up by plants."[6,pg.921] Surely everyone can agree that this problem should be examined carefully BEFORE allowing sewage sludge to be mixed with soil.
Is this a new problem? Daughton and Ternes show that, "It therefore was clearly recognized over 20 years ago that the continual, daily introduction of kilogram quantities of drugs from a given [sewage treatment plant] into receiving waters could result in sustained concentrations with the potential to lead to exposures in aquatic organisms." [6,pg.925]
But for 20 years regulatory officials and drug corporations have pretended that the problem does not exist, perhaps because they have no idea what to do about it. Now the problem seems about to get worse for three reasons: (1) The genome-induced gold rush to produce new drugs, mentioned above; (2) the Internet, which is allowing people to purchase drugs that they previously could not get their hands on; and (3) recent public hearings by the U.S. Food and Drug Administration (FDA) to consider allowing many prescription drugs to be sold without a prescription. The last time FDA held such hearings, in 1972, 600 drugs switched from prescription to non-prescription status.[7]
Christian Daughton, a scientist with U.S. Environmental Protection Agency, is aggressively urging environmental scientists to pay more attention to this problem. However Daughton acknowledges that the problem may already be too large for detailed scientific analysis: "In the final analysis, given the vast array of mechanisms of drug action and side effects, the total number of different toxicity tests possibly required to screen the effluent from a typical [sewage treatment plant] could be impractically large." [6,pg.923]
In June of this year, Daughton and others organized a scientific conference in Minnesota.[8] There, Glen R. Boyd, a civil engineer from Tulane University in New Orleans reported finding drugs in the Mississippi River, in Louisiana's Lake Ponchetrain, and in Tulane's tap water. In all the waters tested, Boyd and his team found low levels of the anti-cholesterol drug clofibric acid along with the pain killer naproxen and the hormone estrone. In Tulane's tap water, estrone averaged 35 parts per trillion with a high of 80 parts per trillion.
Naturally, the water-dwelling creatures will bear the brunt of all this because they cannot escape civilized peoples' habit of urinating and defecating in all the available fresh water. At the Minnesota meeting in June a team of scientists reporting finding male carp and walleyes producing "sky high" quantities of vitellogenin, an egg-yolk protein normally made only by females. In 1998, Environment Canada, Canada's federal environmental agency, reported high levels of estrogens and birth control compounds in the effluent of sewage treatment plants nationwide. Chris D. Metcalfe of Trent University in Peterborough, Ontario created laboratory conditions similar to those found by Environment Canada and he reported in June that those conditions cause some fish to become intersex -- having the characteristics of both males and females. Metcalfe has found intersex white perch in the Great Lakes.
** Daughton and Ternes say, "A major unaddressed issue regarding human health is the long-term effects of ingesting via potable waters very low subtherapeutic doses of numerous pharmaceuticals multiple times a day for many decades." [6,pg.923] What will it mean to raise our babies on water contaminated with low levels of birth control drugs and athlete's foot remedies plus Viagra, Prozac, Valium, Claritin, Amoxicillin, Prevachol, Codeine, Flonase, Ibuprofen, Dilantin, Cozaar, Pepcid, Albuterol, Naproxen, Warfarin, Ranitidine, Diazepam, Bactroban, Lotrel, Lorazepam, Tamoxifen, Mevacor, and dozens of other potent drugs, along with hair removers, mosquito repellants, sunburn creams, musks and other fragrances? No one knows, but evidently we're going to find out, learning by doing.
--Peter Montague
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[1] Nicholas Wade, "Genetic Code of Human Life is Cracked by Scientists," NEW YORK TIMES June 27, 2000, pg. 1.
[2] Nicholas Wade, "Now the Hard Part: Putting the Genome to Work," NEW YORK TIMES June 27, 2000, pg. D1.
[3] Kenneth Chang, "Incomplete, Project Is Already Paying off," NEW YORK TIMES June 27, 2000, pg. D1.
[4] Andrew Pollack, "Is Everything for Sale?" NEW YORK TIMES June 28, 2000, pg. C1.
[5] Andrew Pollack, "Finding Gold in Scientific Pay Dirt," NEW YORK TIMES June 28, 2000, pg. C1, C12.
[6] Christian G. Daughton and Thomas A. Ternes, "Pharmaceuticals and Personal Care Products in the Environment: Agents of Subtle Change," ENVIRONMENTAL HEALTH PERSPECTIVES Vol. 107 Supplement 6 (December 1999), pgs. 907-938.
[7] Sheryl Gay Stolberg, "U.S. May Ease Sale of Drugs Over the Counter," NEW YORK TIMES June 28, 2000, pg. A1.
[8] Janet Raloff, "Excreted Drugs: Something Looks Fishy," SCIENCE NEWS June 17, 2000, pg. 388.
(posted without permission)
