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1997 REVIEW--PART 1: SOMETHING IS TERRIBLY WRONG
During 1997, accumulating evidence indicated that something is disrupting normal sexual development and function in humans.
Baby Boys Disappearing
The year began with a report from Canadian researchers that an abnormal excess of baby girls were born in Canada and the U.S. during the period 1970 to 1990.[1] Normally, about 1057 males are born for every 1000 females[2] for a sex ratio of 0.514, but in Canada and the U.S. after 1970 the number of male babies declined, according to nationwide birth records in both countries. The reasons for the shifting sex ratio are not known.
In Canada, over the 20 years the cumulative loss was 2.2 males per 1000 live births; in the U.S., the cumulative loss was 1.0 males per 1000 live births. These losses were statistically significant. (In the U.S. the loss was greatest in the Atlantic coastal region where 5.6 males were lost for each 1000 live births.) Overall, in Canada during the period 1970 to 1990, 8639 liveborn males were lost. In the U.S., with its much larger population (250 million vs. 30 million), the total loss of liveborn males was 37,840 during the 20 years. The sex ratio can be affected by many factors including:[2] hormonally induced ovulation, which tends to produce more females; race (African-American couples tend to have more females); season of the year (more males born in summer, more females in winter); timing of fertilization in relation to the day of ovulation; social class has a small observable effect (in England, royalty tends to produce males and domestic servants tend to produce females); war, which tends to produce more males; smoking, which tends to produce more females; prostate cancer (tends to produce males); non-Hodgkin's lymphoma in either parent (tends to produce females); various drugs (some tend to produce males, others females); toxemia during pregnancy or pre-eclampsia (tends to be associated with male births); and DBCP (a pesticide used against nematodes) diminishes sperm count and strongly tends to produce females.
In 1986, William H. James of the Galton Laboratory (University College London) hypothesized that sex ratio was determined by hormone levels in the blood of the parents at the time of conception.[3,4] Sex ratio has been James's research specialty for many years, and he has presented considerable evidence to support his hypothesis.[5,6,7]
In 1996, a team of Italian and U.S. researchers provided additional evidence supporting James's hypothesis: the sex ratio of babies born after the explosion at Seveso, Italy, which spread dioxin over a large area on July 10, 1976. The researchers studied live births from April 1977 (9 months after the explosion) to December, 1984, among couples living in the most contaminated area. Of 74 births, only 26 were male and 48 were female, for a sex ratio of 0.35 instead of the normal 0.514. After 1984 the Seveso sex ratio returned to normal.[8]
Sperm Counts Have Declined
Toward the end of 1997, a re-analysis of sperm counts in the U.S., Europe, and the rest of the world concluded that sperm counts among men in the U.S. and Europe really have declined steadily for 50 years.[9] In 1992, Elisabeth Carlsen and co-workers had analyzed 61 separate studies of sperm counts and reported a 50% average decline in sperm count in Europe, the U.S., and elsewhere over the last 50 years. (See REHW #343, #369, #372, #432, #446, #448, and #492). Carlesen's study was criticized from various viewpoints (though not by anyone who had actually reviewed the 61 studies that formed the basis of the British report). In 1996 new studies revealed that enormous differences existed in sperm counts in geographic regions. After that, skeptics concluded that the whole decline in sperm counts was an artifact of statistical modeling and had no basis in reality. The NEW YORK TIMES favored the skeptics, leaving the impression that the whole dispute resulted from math errors.[10]
Now Shanna H. Swan, chief of the reproductive epidemiology section of the California Department of Health Services, has re-examined the original 61 studies. Swan conducted straightforward statistical analyses that took account of regional variations (which are, indeed, large --sperm counts in New York are 131 million sperm per milliliter vs. 72 million per milliliter in California.) Swan's conclusion: AVERAGE sperm counts in the U.S. and Europe during the past 50 years have declined more steeply than the British first reported, but no decline was found in less-industrialized countries of Asia and Latin America. In the U.S., sperm counts have declined 1.5% each year and in Europe the annual decline has been twice as great. Dr. Swan's study was published in ENVIRONMENTAL HEALTH PERSPECTIVES (a U.S. government scientific journal) in November.[9] Swan told the LOS ANGELES DAILY NEWS, "My hope is, this study will change the question of concern from if there is a decline, to why there is a decline. I think it's time we looked at that."[11] (The NEW YORK TIMES has so far ignored Dr. Swan's new study.)
In the early 1980s, researchers with U.S. Environmental Protection Agency identified 16 industrial chemicals that reduce sperm counts.[12] In 1995, European researchers showed that common industrial chemicals widely present in U.S. foods (because of contact with plastics) cause reductions in size of testicles and diminished sperm counts in exposed mice.[13]
Male Genital Defects Increasing
In late 1997, researchers with the federal centers for Disease Control and Prevention in Atlanta reported that the occurrence of hypospadias doubled in the U.S. between 1968 and 1993.[14] Hypospadias is a birth defect of the penis. Nine to 12 weeks after conception, as a male grows inside the womb, the penis develops a channel for urine, called the urethra; hypospadias is a birth defect in which the urethra does not close but remains open for a certain distance on the underside of the penis, sometimes all the way to the scrotum. Typically, hypospadias is corrected surgically.
The new hypospadias data were gathered from two separate surveillance systems, the Metropolitan Atlanta Congenital Defects Program, and the Nationwide Birth Defects Monitoring Program. The researchers found that, not only did hypospadias double during the 25-year period, but the most serious forms of the defect increased faster than the average. They concluded that the increases are unlikely to result from improved sensitivity of the surveillance systems. They could not rule out the possibility that the increases resulted from better identification of mild cases by physicians; however, they noted that this explanation should have increased the number of mild cases compared to severe cases when, in fact, their data showed the opposite trend.
Hypospadias has been reported increasing in England and Wales, Hungary, Sweden, Norway, and Denmark, but most recently the trend has leveled off in England, Sweden, and Hungary.
Our good friend Pat Costner, a chemist with Greenpeace International, points out that hypospadias is considered a form of hermaphroditism --a person having both male and female reproductive organs.
Consider these trends: cancers of the reproductive system (prostate, testicles, ovaries, endometrium and female breast) account for 30% of all cancers, and are increasing in many countries;[15] ectopic pregnancies increased nearly fourfold in the U.S., 1970-1987;[16] in many countries, the incidence of undescended testicles is increasing;[17] and now these 1997 studies reveal declining sperm, increasing hypospadias, and disappearing baby boys. Together, they suggest a picture of something going terribly wrong with human sexual development and function.
All of these aspects of human sexuality share one common feature: all are strongly influenced by hormones. Therefore, many researchers have suggested that industrial chemicals that interfere with hormones may be responsible.[18]
One thing is certain: the chemical industry is conducting a large-scale experiment on humanity. Does this experiment --conducted without our informed consent --not violate the principles established at Nuremburg after World War II? Does this experiment not violate the Universal Declaration of Human Rights, which the United States signed in December, 1948?
Students of government, politics, administration, environmental studies, gender studies, racial studies, chemistry, engineering, philosophy, humanities, history, ethics, business, anthropology, sociology, and law (among other relevant fields of study) might do well to debate one question: where did the chemical industry obtain the right to put us in the position we all now find ourselves in: forced to wonder, "Is our children's health and future being take from them as they are slowly poisoned?"
It seems reasonable and prudent to be asking, "Where did chemical corporations obtain the right to do these things?" A national debate on that subject seems long overdue. In 1997, we inched forward toward that debate.
--Peter Montague
Cancer occurs when a cell goes haywire and starts multiplying uncontrollably. Modern cancer theory says a cancer is initiated when damage occurs to the cell's genetic material, its DNA.[1] Such damage can arise spontaneously (translation: we don't have any idea what causes it) or it can result from an encounter with a carcinogen, such as an x-ray or a cancer-causing chemical.
Damaged ("initiated") cells are likely to be removed from the body by a natural process called apoptosis. (Therefore anything that interferes with apoptosis may encourage cancer without being recognized as a carcinogen.)
An "initiated" cell that survives apoptosis does not begin to grow uncontrollably until several more things happen to it. The cell has to be "promoted" by agents (such as x-rays or certain chemicals) that interfere with the ordinary messages being transmitted back and forth between the cell and the body it inhabits. In some instances, estrogen (female sex hormone) can "promote" cancer cells. The result of "promotion" is an expanded cluster of abnormal cells, waiting to become true cancers.
Still these promoted cells do not multiply uncontrollably unless something ELSE happens to them. The "something else" is called progression and it results from more physical injury to the cell's DNA --and progression in all likelihood requires more than one physical injury. Again, x-rays and certain chemicals (in cigarette smoke, for example), might cause progression. Thus cancer is a multi-step process, requiring perhaps 5 or 6 (or more) "insults" to a cell before cancer develops.
A cell that has been sufficiently damaged takes on fearsome properties --it becomes more sensitive to hormones, it can spread and invade other parts of the body, and it develops a knack for attracting blood vessels to nourish the growing tumor. It is now a cancer and, left alone, it will multiply (grow) until it kills its host.
Very few things have the ability to initiate cancer AND promote it AND make it progress. Things that can do this are called "complete carcinogens." Radiation is a "complete carcinogen" (including cosmic radiation from outer space, which we cannot avoid) but most carcinogens are not --most carcinogens EITHER initiate cancer OR promote it OR cause it to progress.
In any case, you can compare cancer to a rope hanging from a tree branch. If the rope is cut, then you have a cancer. You can think of carcinogens as bullets being fired at the rope. Most bullets miss the rope completely. A few hit the rope and damage it. As time passes and more and more carcinogens are fired at the rope, eventually the rope may be cut and cancer develops. Luck plays a part here (which is another way of saying we don't understand what's going on).
In sum, cancer prevention means avoiding contact with carcinogens --avoiding the bullets. This is the truth about cancer, including breast cancer. What percentage of cancers are avoidable?
In 1981, Richard Doll and Richard Peto --famous British researchers --looked at cancers in every country where statistics were available.[2] They looked for the lowest rates for each type of cancer and on that basis they estimated that the "natural" level of cancer in humans is about 1/5 of the current cancer rate in the U.S. In other words, they estimated that 80% of U.S. cancer cases are avoidable and preventable.[3]
To review the situation with breast cancer: In the U.S., the occurrence of breast cancer has been increasing at the rate of 1% per year since about 1950.[4] The same rate of increase is visible in Canada, Japan, Denmark, the Nordic countries, and elsewhere in the "developed" world.[5] The reasons for this steady increase are not understood. In 1982 mammography screening became widespread and many breast cancers were suddenly discovered earlier. This led to a 3% to 4% annual rate of increase in the incidence of breast cancers during the period 1982-1987, but by 1991 the "mammography effect" had passed and the rate of increase had dropped back to its historical rate of 1% annual rise. Thus when someone says, "The incidence of breast cancer is dropping" they are describing the end of the mammography effect (the shift from the 4% annual increase back to the 1% annual increase). The incidence of breast cancer is not really dropping --it is still increasing at about 1% each year, for unknown reasons. (On the other hand, the DEATH rate from breast cancer IS dropping slightly because tumors are now being found earlier, so earlier and more successful therapies (surgery, chemotherapy and radiation treatments) are keeping more women alive, at least for the 5 years that officially define a "cure.")
As we have seen (REHW #571, #572, #573, #574), 30% to 50% of breast cancers can be explained by exposure to naturally-occurring estrogens (sex hormones), which a woman's body produces as part of the monthly menstrual cycle. However, this still leaves 50% to 70% of breast cancers unexplained.
In recent years, Devra Lee Davis and Leon Bradlow at Cornell University have suggested that xenoestrogens might account for 10% or 20% of the unexplained breast cancers. Xenoestrogens are industrial chemicals that mimic natural sex hormones. Davis and Bradlow initially proposed their hypothesis in 1993 and they have elaborated upon it since. In the body, estrogen is metabolized into two different chemicals --"good" estrogens and "bad" estrogens (analogous to "good" cholesterol and "bad" cholesterol). Evidence is mounting that some organochlorines and other xenoestrogens help create bad estrogens, which contribute to breast cancer.[6,7,8]
So far, most of the human studies of this subject have focused on DDE (a breakdown product of the pesticide DDT) and PCBs. Last week, we pointed out that these are inappropriate chemicals for determining whether or not xenoestrogens cause breast cancer. PCBs represent a group of 209 chemicals, some of which are estrogenic and others of which are ANTI-estrogenic. (Some ANTI-estrogens, such as tamoxifen, are used for breast cancer therapy, to stop a cancer from spreading. Some women have even been given tamoxifen in an attempt to prevent breast cancer. Unfortunately, tamoxifen has caused other cancers in some of these women.[9]) Regarding DDE, we overstated the case somewhat last week, saying flatly that DDE is not estrogenic. There are two kinds of DDE and one is estrogenic (o,p'-DDE) and the other is not (p,p'-DDE). However, the human studies that have provided the basis for claims that organochlorines don't cause breast cancer have all reported total DDE or p,p'-DDE (the non-estrogenic form).[10] Therefore, our point remains valid: studies of total DDE or mixed PCBs provide no basis for claiming that xenoestrogens aren't implicated in breast cancer. They are not studies of clearly-estrogenic substances.
There are at least three aspects of hormone-disrupting chemicals that make them exceedingly difficult for science to study:
1. Chemicals that interfere with hormones may only be effective at a particular moment in the development of a baby in the womb. In the laboratory, exposing a pregnant rat to dioxin on the 15th day of pregnancy dramatically affects the sexual characteristics of her male offspring after they mature. Dioxin exposure on other days has no such effect. (See REHW #290.) It may be that exposure to organochlorines or other hormone-disrupting chemicals at a particular moment in the womb primes a baby girl's breast cells for later growth of cancer.[8]
2. Furthermore, some hormone disrupters (such as the common pesticide, atrazine) only stay in the body for a few months or a few years. By the time a baby grows into childhood or adulthood, these chemicals are gone and can't be studied. DDE and PCBs are convenient to study because they remain in the body for a long time, but they are not necessarily important chemicals for breast cancer. The important ones may well be gone by the time the research begins.
3. Many of these chemicals work in combinations. Their effects are additive. Two chemicals present at ineffective levels may combine to produce an effect. This has been conclusively shown.[11] Scientists almost never study combinations of chemicals --and most of us have combinations of HUNDREDS of different organochlorines and other xenoestrogens in our bodies, as a result of continuous chemical trespass by corporations.
For these (and other) reasons, science may never solve the puzzle of breast cancer --or it may find answers only after many more decades of research.
In the meantime, prevention can begin now. Breast cancer activists could be advocating a ban on every chemical that shows any tendency to interfere with hormones, or to cause cancer, in any form of life. Activists' determination to ban harmful chemicals should not wax and wane as new studies of DDE and PCBs are misleadingly reported (or ignored entirely) by the NEW YORK TIMES.
The rationale for banning hormonally active chemicals, and carcinogens, is ethical. The molecular biologist and physician, John Gofman, has argued, "If you pollute when you DO NOT KNOW if there is any safe dose, you are performing improper experimentation on people without their in-formed consent.... If you pollute when you DO KNOW that there is no safe dose with respect to causing extra cases of deadly cancers, then you are committing premeditated random murder."[12] Either way, our human rights are being violated by corporate polluters.
As an ethical principle, the burden of proof should be shifted to the polluter to demonstrate --BEFORE the pollution begins --that living things will not be harmed.
Cancer --including breast cancer --is a political disease. Corporations have hijacked our sovereign power and are using it against us, contaminating our air, water, and food with cancer-causing, hormone-disrupting chemicals. If we are to survive as a species, we will need to reassert the sovereign power of the people to "promote the general welfare" (as the preamble to our Constitution says). We simply have no other choice.
--Peter Montague
THE TRUTH ABOUT BREAST CANCER--PART 4
Late last month the NEW ENGLAND JOURNAL OF MEDICINE (NEJM) published a study (by David J. Hunter) comparing the levels of DDE and PCBs in the blood of two groups of women, one group with breast cancer, the other without.[1] The Hunter study failed to find a positive relationship between breast cancer and DDE or PCBs in the blood. DDE is a breakdown product of the organochlorine pesticide DDT, which was banned in the U.S. in the mid-1970s; PCBs are a group of 209 chlorinated industrial chemicals, also banned in the U.S. The Hunter study is the largest of its kind to date, comparing 236 pairs of women for DDE and 230 pairs for PCBs.
The NEW ENGLAND JOURNAL OF MEDICINE put a far-reaching title on the new study: "Plasma Organochlorine Levels and the Risk of Breast Cancer." (Plasma is the part of the blood that contains fat-soluble chemicals such as organochlorines.) The title seemed to suggest that a study of two chemicals --DDE and PCBs --could tell us something definitive about all of the 15,000 different organochlorine compounds in relation to breast cancer.
In case we missed the message, the editors of the JOURNAL provided an editorial that spelled it out. The editorial, by Stephen H. Safe, a Texas researcher whose work is often funded by the Chemical Manufacturers Association, had a slightly different though equally far-reaching title: "Xenoestrogens and Breast Cancer." (Xenoestrogens are industrial chemicals that interfere with normal sex hormones such as estrogen.)
Dr. Safe's editorial in NEJM began, "Chemophobia, the unreasonable fear of chemicals, is a common public reaction to scientific or media reports suggesting that exposure to various environmental contaminants may pose a threat to health." Surely this is an odd message from a scientist. He is saying, if you fear chemicals because scientific reports indicate that they might harm your health, you are suffering from an irrational phobia. Perhaps Dr. Safe did not write the editorial in his capacity as a scientist.
Dr. Safe concludes his chemophobia editorial saying it is time we all stopped worrying about organochlorines and breast cancer. He writes, "The results of Hunter along with those of other recent studies should reassure the public that weakly estrogenic organochlorine compounds such as PCBs, DDT and DDE are not a cause of breast cancer."[2] Estrogenic organochlorine compounds such as DDT, DDE and PCBs are not a cause of breast cancer. Case closed.
If we still didn't get the point, Gina Kolata of the NEW YORK TIMES interviewed Dr. Safe, giving him an opportunity to amplify his message. Dr. Safe told Ms. Kolata it is time to quit researching the relationship between organochlorine chemicals and breast cancer: "For advocates [of the idea that the two are connected], it's never ending. But for other people, there may be times when we want to spend our money on other things," Dr. Safe said.[3] No more research needed. Case closed.
Three days later in the Sunday TIMES, Gina Kolata delivered the message once again, summarizing the Hunter study this way: "One more environmental scare bit the dust last week as scientists from the Harvard School of Public Health reported that their large and meticulous study found no evidence that exposure to the chemicals DDT and PCB's [sic] are linked to breast cancer."[4] Another scare bit the dust. Case closed.
Including the recent Hunter study, there are now 11 published studies of organochlorine compounds (DDE, PCBs, methoxychlor, beta-hexachlorobenzene, and chlordane --the last 3 being pesticides) in relation to breast cancer. Four studies, including the largest two of the 11, have shown no relationship between DDE, PCBs and breast cancer.[1,5,6,7] Six smaller studies have indicated a positive relationship, suggesting that some organochlorines may be implicated somehow in breast cancer.[8,9,10,11,12,13] One additional study was equivocal, subject to differing interpretations.[14]
The equivocal study was by led by Nancy Krieger, who examined DDE and PCB levels in the blood of 150 women with breast cancer and 150 women without breast cancer. The 300 women were chosen to represent racial/ethnic groups: 100 whites, 100 African-Americans and 100 Asian-Americans. Taken together, the 300 women showed no statistically-significant relationship between DDE, PCBs and breast cancer. However, when the racial/ethnic groups were studied individually, the whites and the African-Americans with breast cancer showed elevated levels of DDE in the blood, compared to whites and African-Americans without breast cancer.[14] Asian and recently-immigrated Asian-American women tend to have a much lower incidence of breast cancer than white Americans, perhaps because of a protective effect from their diet.[15,16] Omitting the Asian-Americans from the Krieger study essentially reverses the study's conclusions.
Thus out of 11 studies, 4 are negative and 7 show elevated levels of organochlorines of one kind or another in tissues of women with breast cancer. One of those seven were not statistically signficant. Is it time to close the book on this inquiry?
Stephen Safe and Gina Kolata obviously want us to think so. Dr. Safe and Ms. Kolata both try to make us believe that recent work has revealed that breast cancer can be completely explained by "known risk factors." Listen to Dr. Safe: "Robbins and coworkers recently showed that the high incidence of breast cancer in women from the San Francisco Bay area can be accounted for by known risk factors, including parity [how many children they've had], age at first full-term pregnancy, months of breast-feeding, age at menopause, age at menarche [when a woman's period commences], and alcohol consumption."[2] Ms. Kolata takes the argument even further: "Dr. Hunter said that perhaps it was time to question the assumption that much breast cancer is caused by unknown environmental agents. A recent study, for example, found that the high rate of breast cancer in the San Francisco Bay area can be completely attributed to known risk factors like a woman's age when she start to menstruate, has a first child, and when she begins menopause."
Dr. Safe and Ms. Kolata both make it sound as if this new study of women in San Francisco has revealed that all breast cancer can be explained by "known risk factors." If true, this is important news.
In fact the Robbins study of women in the San Francisco Bay area did not even try to explain the origins of all breast cancer.[17] Robbins observed that white women near San Francisco Bay have a 14% higher incidence of breast cancer than the national average (and African-American women in the Bay area are 10% above the national average), and he set out to see if he could explain the 14% and 10% increases. He and his coworkers found that women in San Francisco tend to have fewer children, have them later in life, breast feed them less, and so forth, thus explaining the 14% and 10% increases by "known risk factors." The 50% to 70% of breast cancer that can't be explained anywhere else in the U.S. also can't be explained in San Francisco --despite the false impression that Dr. Safe and Ms. Kolata managed to create.
What about Stephen Safe's conclusion (amplified by Ms. Kolata), that, based on four negative studies of DDE and PCBs, we should stop trying to find the links between environmental estrogenic chemicals and breast cancer?
Stephen Safe knows that DDE is not estrogenic. DDT is estrogenic, but DDE is not. DDE is a potent anti-androgen (it blocks the action of male hormones).[18] DDE DOES interfere with sex hormones, but it doesn't mimic estrogen and there's no good reason to think it would make a major contribution to breast cancer. Likewise, many PCBs are not estrogenic --on the contrary, they are ANTI-estrogenic. Dr. Safe's own research has shown this again and again.[19] Thus there is no good reason to think that DDE and a randomly-selected group of mixed PCBs will cause breast cancer. Listen once more to Dr. Safe's editorial (titled "Xenoestrogens and Breast Cancer"). He writes, "The results of Hunter along with those of other recent studies should reassure the public that weakly estrogenic organochlorine compounds such as PCBs, DDT and DDE are not a cause of breast cancer." But DDE is not estrogenic, and neither are many PCBs. This is a false argument and Dr. Safe --and the editors of the NEW ENGLAND JOURNAL OF MEDICINE --know it.
There are good, strong reasons to think that many estrogen-mimicking chemicals, some of them organochlorines, might be associated with breast cancer, and these should be carefully examined. But DDE and mixed PCBs are not in that category. They have been studied because they are convenient to study, not because they are particularly estrogenic. When Stephen Safe tells Gina Kolata we might want to end research on organochlorines and breast cancer based on studies of DDE and mixed PCBs, Dr. Safe is sounding like a camp follower of the Chemical Manufacturers Association, not like a scientist.
--Peter Montague
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