NATURALLY DANGEROUS: Surprising Facts About Food, Health, and the Environment.
By James P. Collman, Professor of Chemistry, Stanford University
Chapter 5 Cancer and the Environment
© James P. Collman, 2003. All rights reserved
There may be a revolution coming in the treatment of cancer. For some time it has been recognized that both cancer cells and stem cells have similar characteristic features. Both types are able to grow perpetually and both are immune to switches that initiate cell suicide. This similarity has long been recognized, but only recently have cancer stem cells been identified in several types of cancer. Stem cells are only a tiny subset of the cells in a tumor, but the cancer stem cells very important because they enable a damaged tumor to completely reconstruct itself. For example when irradiation, or chemotherapy nearly destroys a tumor, but don't kill the cancer stem cells, the tumor grows back. This is a common occurrence. An even more dangerous possibility is that such drastic treatments, may create cancer stem cells by transforming normal stem cells. That possibility is speculation, but some scientists fear this could happen. There is preliminary evidence that this phenomenon may be true.
Beginning in the early 1990s, John E. Dick at the University of Toronto isolated a blood stem cell, and subsequently showed that this cell could generate leukemia in mice, but other malignant cells could not. Following that initial research, other groups isolated cancer stem cells from different solid tumors. Proteins on the surface of these cancer stem cells are used to identify them. One can speculate that in the future, such diagnostic proteins may be used to identify cancer stem cells and mark them for destruction. Stem cells are now being studied in a variety of tumors: colon, bone, cervical, lung, and prostate. The existence of cancer stem cells may help understand why, even with the development of improved chemotherapeutic drugs, very little advance has been made in the long-term survival of cancer patients. Cancer stem cells are apparently not destroyed by these drugs, so the tumors grow back. A new strategy may be required to destroy cancer stem cells. Consider the example of a remarkable new cancer drug, Gleevec, which is used to treat a leukemia with few side effects. But Gleevec apparently does not kill the cancer stem cell. Gleevec keeps the cancer suppressed if it is taken regularly, but if treatment is stopped, the cancer returns.
There is some evidence that cancer stem cells may be more resistant to radiation than other cancer cells. It appears that cancer stem cells can repair themselves more efficiently. This is especially disturbing in the case of brain cancers where radiation is the principal method of treatment. Reduction of the tumor is taken as a sign of success - but it may be only temporary! Thus the current method of treating brain tumors seems destined to failure.
Studies of both cancer stem cells and ordinary stem cells may provide new
strategies for treating cancer. These important subjects are in their infancy.
(Taken from an article by Sarah Everts, Chemistry & Engineering News,
January 15, 2007, page 28)
Both animal experiments and surveys of people gathered over the past two decades support the hypothesis that nighttime illumination which interrupts the body's production of the hormone, melatonin, increases the risk for breast cancer. A recent Harvard study of nurses estimated the nightly concentration of melatonin by measuring the concentration of this hormone in the first urine void upon rising. Those subjects having higher melatonin levels were found to have a lower risk of breast cancer. Light at night is clearly a risk factor for cancer. Beyond light, age and obesity, both known risk factors for cancer, were also found to influence melatonin levels. It is speculated that smoking may also reduce melatonin levels.
Recall from Chapter 3, that melatonin forms in the pineal gland, which is located in the brain and that melatonin circulates in the bloodstream. After dark, blood concentrations of this hormone rise above low daytime levels and usually reach a peak value in the middle of the night. Sleep is not necessary for melatonin release, but darkness is. Because the pineal gland responds to the optic nerves, when a person's eyes are exposed to bright light at night the usual surge of melatonin is dampened.
The relationship between low melatonin levels and breast cancer is supported
by a plethora of circumstantial evidence. Breast cancer is increasing everywhere
in the world, but it is most prevalent in industrialized countries where electric
lights are widely used. The rate of increase is greatest in countries that
are generating more electric power and presumably more electric light. Breast
cancer is less common in women who sleep over 9 hours per night compared with
women who sleep less. Blind women have very low rates of breast cancer, but
women working on night shifts have twice the risk of developing breast cancer
compared with women who do not work at night. (Science News, January 7, 2006,
Vol. 169, page 8) .
A nationwide Japanese study found men who alternate between working in the day and at night have three times the normal rate of prostate cancer!! Previous studies on women who work on schedules that disrupt their biological sleep rhythms have an increased risk of breast cancer. This study of men was a little different than previous studies of nurses in the U.S. The Japanese data was gathered for over a decade in the late 1980s on 14,000 cancer-free men between 40 and 65 years of age. A large group worked only in the day; a smaller group worked solely at night and a similar group rotated between night and day shifts. The first two groups had about the same cancer rates and were used as a control group. The prostate cancer rates were found to be three times higher for the rotating shift worker. These studies took into account smoking habits, alcohol consumption, and other variables. Different levels of the hormone melatonin are suspected to be involved in these results. People produce less melatonin when they are exposed to light during their usual sleep periods (see pages 77-79 in Naturally Dangerous). It is speculated that melatinin might protect men against prostate cancer, and that hypothesis is now being tested by giving patients melatonin supplements. (American Journal of Epidemiology, September 15, 2006 ; Science News, September 23, 2006 , Vol. 170, page 195)
The rate of the most common form of breast cancer in the U.S. fell an astounding 15 percent between August 2002 and December 2003! That good news has been ascribed to the same period when women abandoned hormone treatment for the unpleasant symptoms of menopause. Women stopped taking these prescribed hormone supplements following a large national study indicating that such “therapy” is associated with a small increase in the risk of breast cancer. This ill-advised hormone therapy was based on a theoretical concept, but had never been tested in a statistical double-blinded manner. The new promising findings need to be confirmed by examining data from other countries. The association between this drop in the rate of breast cancer and cessation of hormone therapy is logical but unproven, because epidemiology can never prove causality. However, this was the first time that breast cancer rates had ever fallen significantly.
When the large clinical trial from the Women’s Health Initiative of Wyeth’s menopause hormone drug, Prempro reported slightly increased breast cancer rates, that drug’s sales fell by 50 percent over the next six months. It is known that hormones can promote the growth of estrogen positive tumors. It is also interesting that black women got fewer breast cancers than white women, since black women were less likely to use hormones to treat menopause symptoms. Moreover, the largest fall in breast cancer rates was found among women between the ages of 50 to 69, the exact group that was most likely to have been taking hormones to treat menopause symptoms. The drop in breast cancer rates accounted for about 14,000 women in the U.S. The drop was largest in affluent Marin County California, a place where high breast cancer rates had been identified and blamed by some on environmental factors. There are many lessons in these findings. (New York Times, story by Gina Kolata, December 14, 2006 ).
Vitamin D, the “sunshine vitamin” is really not a vitamin but an intermediate created by sunlight or obtained from foods and subsequently forms a hormone in your body. There is increasing evidence that many people, especially those living in less sunny climates are deficient in vitamin D. Moreover it appears that vitamin D protects us from several different cancers so that vitamin D deficiency can result in higher incidences of cancer: Several thousand premature deaths from colon, breast, ovarian, and prostate cancers are proposed to result from vitamin D deficiency. Much of the evidence supporting vitamin D deficiency and its role in cancer is epidemiological (statistical), but it seems convincing.
Vitamin D is formed in our skin upon exposure to UVB, the type of high energy sunlight that can cause skin cancer. The most active, hormone-like, metabolite made from vitamin D in the body is 1,25(OH)2D, which is regulated by parathyroid hormone in the kidney. This active form (1.25(OH)2D) is made by enzymes in the colon, prostate, breast, and in other tissues. UVB sunlight increases the amount of the precursor of this active form thus stimulating production of higher levels of 1,25(OH)2D. Curiously, physical activity also results in higher levels of this most active form of vitamin D. The most accurate levels of vitamin D are those measured in the serum, and these have been obtained by studying individuals from geographic locations rather than from determining the dietary habits of subjects. Convincing statistical studies have associated vitamin D markers in the serum with sunlight and associated these with incidences of colon, rectal, breast, and prostate cancers. Residents of sunny climates have been found to have lower incidences of prostate cancers. Genetic factors are also important; a genotype bb, occurring in 35% of men in the US population, is associated with lower circulating concentrations of 1,25(OH2)D. Compared with the rest of the population, such men have twice the incidence of prostate and colon cancers. A similar association has been found with breast cancer among women who have the same bb genotype
Blacks have levels of 25(OH)D that are half that of whites, but thus far the NAS has not recommended higher supplements of vitamin D for blacks, perhaps because of political correctness. In Northern cities with large black populations, Blacks have higher incidences of colon, breast, and prostate, cancer mortality rates compared with whites and this may be the result of lower vitamin D levels.
How much sunlight would a person need to get sufficient vitamin D? In summer 15 minutes and in early fall 20 minutes between 11:00 AM and 2:00 PM exposure of arms, shoulders, and backs under clear skies should be sufficient. But blacks need more exposure. However, in the winter months in the Northern half of the US, no amount of solar exposure is enough for either group!! Moreover, some light-skinned people cannot risk so much exposure to UVB because many such individuals are more subject to skin cancer. Other people who choose to wear sunscreens may also become deficient in vitamin D.
Individuals who cannot get sufficient vitamin D from exposure to strong sunlight are advised to take vitamin D supplements or to eat foods that are rich in vitamin D. How much vitamin D should these individuals obtain from foods or supplements? The National Academy of Sciences (NAS) recommends 200 international units (IU) for individuals up to 50 years old, 400 IU from 51 to 70 years and 600 IU for those above 70 per day. There seems to be less concern about any danger from raising the recommended vitamin D levels to daily intakes of 800 to 1000 IU.
hat foods are rich in vitamin D? Cod liver oil is the richest; a teaspoon each day contains more than an adequate intake. Chinook salmon, either boiled or baked has over 400 IU per serving; shrimp has about 162 IU in a 4 oz. serving. Milk is fortified with vitamin D, but one glass has only about 120 IU so that many individuals could not get enough vitamin D unless they drank 4-5 glasses a day. Ice cream is not made from milk that has been fortified with vitamin D. Some varieties of orange juice are fortified with vitamin D. Eggs contain a small amount of vitamin D: about 70 IU each. Some foods have vitamin D levels marked in micrograms. Note that 1 microgram of vitamin D is that same as 40 IU. Some long-term studies have demonstated the efficacy of taking vitamin D supplements in reducing cancer risk, when combined with calcium, which reduces the incidence of fractures. These costs are minor compared with the cost of treating cancer or a fracture. A daily dose of 1000 IU of vitamin D is less than 5 cents! (Adopted from American Journal of Public Health, February 2006, Vol. 96, No. 2, page 252)
Genetic analysis of moles reveal that these harmless pigmented cells were once cancer-like tumors, but they have been rendered harmless so that they cannot divide and grow and progress into malignant melanomas. Mole cells have a cancer gene called BRAF, but they do not become immortal. The “guardian protein”, P53 halts forever the division and proliferation of these cells so that they become benign. Of course moles are pigmented and occur on the skin, but scientists believe that this sort of behavior, inactivating cancer cells occurs in many parts of the body, where tiny tumors heading towards cancer are rendered harmless by P53. The resulting small, colorless cells are difficult to detect. For example this sort of process may occur in the prostate. If protective proteins such as P53 are turned off these mole-like cancer cells proliferate and can become malignant. We need to learn more about how the proliferation of early cancer cells can be arrested; successful treatment of cancers might be developed from such knowledge. (New York Times, D1, 9/19/06 )
Identical twins inherit identical genes, which have a huge influence on the twins’ nearly identical appearance, susceptibility to disease such as cancer, and even to the twins’ personalities. But the environment, the foods they eat, chemicals they are exposed to, and the emotional care they receive can influence twins in different ways, especially if they live apart in different environments. Many of these differences also have genetic origins; their genes are modified, usually with enzymes. These “epigenetic” marks result from chemical groups, usually single carbon methyl groups near the beginning of a gene and can keep that gene from being turned on. Genes are often activated or turned on by proteins, which do this by binding to specific sections of the gene; epigenetic marks keep such proteins from binding so that a marked gene stays switched off. These chemical modifications of genes affect how genes are expressed and can play a role in diseases ranging from cancer to schizophrenia. Much of the origin of “nature versus nurture” controversy can be traced to epigenetic modification of genes. The majority of these epigenetic marks are put in place before an animal’s birth. External factors can influence the epigenetic modification of genes before and after birth. Animal studies have shown that particular food supplements in an animal’s diet during pregnancy can mark and control a gene thus determining particular traits of that animal’s offspring. For example, feeding pregnant mice food that contains vitamin B12, folic acid, choline and a nutrient called betaine caused their pups to develop an unusual bridled fur. In control experiments, mothers that had not received these supplements in their food, gave birth to offspring with normal fur. In other experiments, giving pregnant mice genistein supplements from soybeans changed their babies coat colors and reduced the incidence of these mice from becoming obese and developing diabetes or cancer. These changes are thought to arise from altering the methylation pattern of the pup’s genes, and shutting off particular genes. In other examples the degree of attention mother mice give to their offspring has been shown to affect epigenetic marking and possibly the behavior of their babies.
These methylation events are catalyzed by enzymes. Molecules that inhibit these methylating enzymes alter epigenetic marking. By shutting down these enzymes, dividing cells are unable to pass on their epigenetic marks. Drugs that are methylating enzyme inhibitors can have either negative or positive effects on diseases, such as cancer, but the detailed mechanisms are obscure. An article in the April 15, 2006 issue of Cancer reported that when 170 patients suffering from a blood cancer was treated for 6 weeks with a “demethylating drug”, decitabine, 9% went into complete remission and another third of these patients showed significant improvement. This strategy may lead to an important cancer drug therapy.
The way in which the environment effects genetically-controlled physiology is suggested by the fact that these epigenetic markers shift during a person’s lifetime, and in the case of identical twins, differences in these epigenetic patterns increase with age, much more so if the twins have been living in different environments for long periods. Some of these epigenetic changes can have negative health effects, especially the occurrence of cancer. For example, in a study of cells taken from cancer patients it was discovered that epigenetic marks are associated with silencing tumor-suppressor genes. The study of epigenetic marks is an important emerging field of bio-medical science. (Science News, June 24, 2006 , vol. 169, page 392)
Recall from reading Chapter 5 that some cancers can be traced to viruses and that viruses can be warded off by vaccines. In 2006 the FDA (Food and Drug Administration) approved Merck's new vaccine, Gardasil, which is intended to prevent cervical cancer by blocking infection from the sexually transmitted human papillomavirus. Worldwide, only breast cancer strikes more women than cervical cancer. In the U.S., where Pap smear screening is widely performed, each year about 14,000 women are diagnosed with deadly cervical cancer and 3,900 women die from it. Related cancers of the vagina and the vulva should also be blocked by Gardasil. In the U.S. annually 6,000 women are diagnosed and 1,700 die from these cancers. The development of this vaccine is therefore a major development in preventative medicine and should become a major source of earnings for Merck, with projected annual earnings of $3 billion.
Of course such a development brings some problems. How long will these shots last? Current estimates are only 3 1/2 years. Who should get this vaccine? So far it has only been approved for females ages 9 through 26; because this disease is sexually transmitted that raises politically charged questions as to whether the vaccine should be required for school girls. When will Gardasil be approved for older women? Should it be given to men, who develop genital warts and transmit cancer via papillomavirus.
Further improvement may come from an oral version of this vaccine and to
prevent it from having to be refrigerated. Competition is coming from GlaxoSmithKline,
which is developing a competing vaccine called Cervarix. Such developments
may restrain the cost. The development of these vaccines represents a major
advance in public health that within a generation may greatly reduce a major
malignancy, N. 2 among women worldwide.
The "wasting-disease" is another of the fatal diseases called transmissible spongiform encephalopathies, which include mad cow disease and sheep scrapie that are discussed under prion diseases in Chapter 5. It is now accepted that several people acquired mad cow disease in England by eating infected beef. The process by which animals such as cows, sheep, monkeys, or other animals are infected with prions has been worked out: these animals eat feed contaminated with prions and derived from other infected animals. Human-to-human transmission occurred similarly by cannibals in New Guinea, resulting in a prion disease called Kuru. But wild deer and elk do not eat such contaminated feed; moreover, the chronic wasting disease is known to spread rapidly between deer and between elk, or between deer and elk, either in game farms, or in the wild. Now evidence has appeared that seems to explain this mysterious, rapid transmission. Dr. Richard Bessen, a professor of veterinary medicine at Montana State University discovered infectious prions in deer and elk tongues and believes this is probably the method by which the disease is transmitted via saliva. Other experiments with hamsters had shown that prions travel to taste buds on the tongue. Moreover, infections prions have also been found in sheep tongues. When deer or elk lick or slobber on each other, which is common among elk, it is thought that infections prions may be shed from their tongue. Alternatively when these animals graze on grass infectious saliva may contaminate the grass or soil with these indestructible proteins. Other grazing animals would then become infected through their own tongues and saliva. This method of transmission is very plausible and is consistent with the rapid transmission of the wasting disease that has been observed between grazing wild and domestic deer and elk. Recently a bull moose, another member of the cervid family to which deer and elk belong, was discovered for the first time to have the wasting disease. Among deer and elk the chronic wasting disease has thus far been found in a dozen states ¨C including New York and in two Canadian provinces. I worry about the bison in the U.S., because they sometimes graze along side deer or elk. On the consumer side, slaughterhouses remove tonsils, a tissue that is near the tongue, but they allow the root of the tongue to enter the food supply; beware of hot dogs or other sausage products. British scientists have reported finding prions in cattle tonsils. Hunters are advised to take the whole deer or elk heads to state laboratories for prion testing before eating the animal. Of course, hunters should avoid eating deer or elk tongues. (New York Times, October 4, 2005, page D2 )
There is strong evidence that omega-3 fatty acids found in certain fish oils have a beneficial effect on cardiovascular health. It has been assumed and a few small statistical studies have indicated that eating oily fish or taking dietary supplements containing omega-3 fatty acids reduce the incidence of cancer. However, such epidemiological studies are more reliable when many people are studied over a long period of time and other possible interfering factors are ruled out. Now comes a new, large study of this issue published in the January 25 issue of the Journal of the American Medical Association. This analysis was based on 38 previous studies of over 700,000 people from several countries, having diverse demographic characteristics. The conclusion is that there is no or a weak link between consumption of omega-3 fatty acids and a reduced risk of 11 types of cancer: breast, colorectal, prostate, ovarian, lung, pancreatic, stomach, skin, and bladder, as well as aerodigestive and lymphoma. Some previous studies indicated that diets rich in fish oils can reduce the risk of bowel cancer. Additionally, a large study of 478,000 men and women from 10 European countries found that eating large amounts of fish were less likely to get cancer than those eating smaller quantities. Overall, the evidence seems inconclusive or weak. Remember that omega-3 fatty acids such as EPA and DHA are found in oily fish such as salmon and mackerel, and in flaxseed, walnuts, and canola oil.
A large study of 23 types of cancers reported for 9 major ethnic groups in California over the period 1988 through 2001 showed some remarkable group differences. South Asians had the lowest incidence of cancers among all groups; Korean women had the lowest breast cancer rate. Blacks, as expected, have the highest prostate cancer mortality, about 10 times higher than Asians. One plausible explanation involves differences in androgen receptors between races. These statistical data are yet another indication that diverse races have different medical responses, which is “politically incorrect”, but nevertheless true. (Science, Vol. 307, 7 January 2005)
It is estimated that 5.5 trillion cigarettes are smoked every year throughout the World. This amount is so large that it is difficult to imagine. Stretched end to end that many cigarettes would reach from the earth to the sun and back and have enough left for some trips to Mars. The World Health Organization estimates that 5 million people die each year over the World from diseases such as cancer that result from smoking cigarettes. This situation is slowly improving in some places; in California all public buildings, including restaurants and even bars are smoke free. But in most parts of Europe, one cannot avoid second-hand smoke in a restaurant, even if local ordinances require no-smoking areas.
Large epidemiological studies in the UK and in California indicate that childhood leukemia probably arises as a consequence of an abnormal immune response to one or more common infections for children who have unknown genetic defects acquired during fetal development before birth. The ongoing British study took data over 15 years from 1,737 children diagnosed with leukemia and compared these with 7,629 children who did not have cancer. These data suggest an abnormal immune response to infection, but found that children who attended day care centers or otherwise had a wide range of social contacts outside the home had lower rates of leukemia. Such contact has been shown to enhance normal immune responses. A similar finding, that attendance in day care centers lowers the incidence of leukemia, was uncovered in a study carried out in Northern California. These epidemiological studies revealed other interesting results. Exposure to a range of environmental factors such as household levels of ionizing and electromagnetic radiation, parental smoking and occupation, breastfeeding, and neonatal vitamin K administration do not appear to be related to the incidence or probability of childhood leukemia. (Health News, April 23, 2005, by Ron Gara)
The relationships between various lifestyles and longevity are difficult to measure. But a California study of Seventh-day Adventists gives realistic insights into this complex issue. Recall that a fully reliable measure of a pharmaceutical drug in the context of benefits and risks can only be measured by statistical studies of large numbers of patients who take these drugs over years and comparisons with other similar people who did not take that medicine. One must also be cautious about the effect of genetic factors. A total of 34,194 Adventists, who were over 30 years of age were studied since 1976. The Adventists are genetically homogeneous, which means they are like average Californians. But members of this religious sect share many habits that are considered healthy; for example most Adventists do not smoke, some eat meat, but many others are vegetarians. This group provided detailed information about their weight, physical activity, diet, tobacco use, and medical histories. Epidemiologists calculated how each health habit affected life expectancy.
Adventists were found to live longer that average Californians. A typical 30-year-old male Adventist has a life expectancy of 81.2 years, which is 7.3 years longer than other 30-year-old California men. Adventist women gained less in terms of life expectancy, 4.4 years compared with average California women. There is still a gender gap, but a smaller one; California women live about 5.7 years longer than California men. The Adventist gap is only 2.1 years. Vegetarians have an advantage, about 1.2 years for the average 65-year-old Adventist. The vegetarians were leaner, which is a known advantage for several diseases such as cancer and heart problems. Adventists tend to eat more nuts compared with other Californians. Eating nuts on a regular basis was shown to add an extra 2.7 years of life expectancy. High levels of exercise produced a gain of 2.3 years, and non-smoking netted 1.75 years (less than your Author would have guessed). The effect of exercise in this study was similar to an earlier one of Harvard college alumni and a Finnish study. The similarities add credence to this well-controlled study of California Adventists. Readers have a choice: choose healthy habits and live longer and live better. (Harvard Men’s Health Watch, Harvard Medical School, Volume 9, number 2, September 2004)
The news is full of warnings about the obesity epidemic. For example, obesity has been correlated with a greater risk of cancer and of type-2 diabetes. But hold up, a recent large, high-quality statistical study shows that people who are a little overweight, but not obese, actually live longer!! Moreover, individuals who are underweight have a higher risk of death, about that of the obese (who are at risk). Five categories of weight, measured by the body mass index, B.M.I. were used in these statistical studies. The results from these studies are as follows: underweight (B.M.I. up to 18.4) 33,000 more deaths; normal weight (B.M.I. 18.5 – 24.9) average or baseline number of deaths; overweight (B.M.I 25 – 29.9) 86,000 fewer deaths; obese (B.M.I. 30 – 34.9) 30,000 more deaths; extremely obese (B.M.I 35+) 82,000 more deaths. Readers may recall that the B.M.I equals your weight in lbs., divided by your height in inches squared; the resulting ratio must be multiplied by 703. Try this equation on yourself. About 8% of Americans are extremely obese, which is a large number. This rigorous statistical study was adjusted for factors such as smoking, age, race, and alcohol consumption. It is probable that family history (genetic factors) is important. Individuals should consider whether they are susceptible to or have heart disease or type-2 diabetes before adjusting their weight up, to the overweight category. The advent of new medicines such as the statins, which lower cholesterol levels, and ACE inhibitors, which lower blood pressure may have influenced these results. It has been suggested that overweight should now be referred to as normal weight. (New York Times, April 20, 2005, page A1)
Long-term use of some pain-killing medicines have been linked to increased risks of heart attacks. Now a large statistical study tracking the health of 114,000 women aged from 22 to 85 years over a six-year period has indicated that regular consumption of aspirin and/or ibuprofen raises the risk of breast cancer. These results were the opposite of what was expected. This study was supported by the National Cancer Institute and was conducted by Sarah F. Marshall from the University of Southern California. Daily use of aspirin was found to increase the risk of estrogen receptor/progesterone receptor (ER/PR)negative breast cancers, whereas continuous use of ibuprofen (a non-steroid anti-inflammatory) appeared to enhance the risk of non-localized breast cancers. (International Reporter, Vol. XXXII (No. 6) June 2005)
No one understands a statistical connection between increased levels of breast cancer and exposure to artificial light. For example, it is known that women in developed countries have a higher rate of breast cancer compared with women in underdeveloped countries. Night-shift workers such as nurses are more susceptible to breast cancer, but blind women are less susceptible. There is an unverified theory to explain this: artificial light could trigger a “clock gene”, which influences pre-menopausal women’s risk of cancer. Artificial light is only about 150 years old, but data from that time are not sufficiently accurate to give a clue about the historical record of breast cancer. This mystery needs careful study. (Richard Stevens, cancer epidemiologist at the University of Connecticut, February 10, 2005)
Salt (sodium chloride) is essential for life, but people typically get enough in their diets by consuming other foods that contain salt. Because of this, actual salt deficiency is very rare, however in New Zealand a campaign against table salt has resulted in iodine deficiency. Recall from pages151-152 in Naturally Dangerous that iodine, a chemical cousin of chlorine, is required for good health because iodine is used to produce an essential hormone in our thyroid gland. People who do not get sufficient iodine develop mental retardation; pregnant women tend to miscarry or have a still-borne child. Many people living in Third World countries experience enlarged thyroid glands, a sign of iodine deficiency. Because of the fact that iodine is essential for good health, New Zealand, the United States, and many other developed countries have long required that iodine be added to table salt. In the 1990s, a study in New Zealand revealed that 11% of 9- to 10-year old children showed signs of iodine deficiency. This appears to be the result of their health authorities demonizing the use of table salt.
Some people have been flavoring their food exclusively with sea salt, which they imagine to be “natural” and therefore better for you than refined white salt. Not so! Refined salt from the supermarket is fortified with iodine and is thus healthier. Sea salt may not contain much iodine. About 15% of an average person’s salt intake comes from adding salt while cooking food or while eating it. About 75% of salt we consume comes from processed foods, and the remaining 10% is present in the raw foods. Why have health authorities warned against salting one’s food? There has long been a controversy over whether excess salt intake causes high blood pressure. This has been the subject of several very large, lengthy statistical studies. An emerging consensus is that salt consumption has a small effect on increasing blood pressure, but other factors such as eating potassium-rich fruits and vegetables, whole grains, nuts, and low-fat dairy products will lower blood pressure even when people consume substantial amounts of table salt. Particular groups of individuals are more or less susceptible to their salt consumption in the sense of blood pressure. Moreover, older people are more salt sensitive than younger people. The whole subject is complicated and not well understood, but it is clear that people must take in sufficient iodine for good health. (Noel O’Hare, Listener-The Things That Matter, November 27, 2004)
A major environmental impact from China’s rapidly growing economy derives from a Worldwide buildup of mercury and other pollutants spewing from their coal-fired power plants. Plumes of air pollution such as soot, ozone, sulfates, and mercury are now being tracked as these pollutants drift eastward from China crossing oceans and continents. Currently China has over 2,000 coal-fired power plants and many more are coming on line as the result of China’s rapidly expanding economy and the fact that they have a large supply of coal, which is their major energy source. Greenhouse gases such as carbon dioxide have received the greatest attention, even though China is exempted from the Kyoto Agreement. But the toxic, neurotoxin, mercury is a much greater danger. Asia, mostly China, constitutes over 50% of the global emissions of mercury; North America and Europe each contribute about 10% more. We are all breathing each other’s air; the eastward flow of the atmosphere resulting from the jet stream and the Earth’s rotation, carries plumes of dirty air from China to Massachusetts. Over 30% of the mercury that is falling on lakes, streams, and land in the U.S. is coming from China. The Chinese spew 600 tons of mercury into the air, compared with about 120 tons in the U.S. This situation will get worse as the Chinese expand their coal-fired power plants. Pollution control devices are slowly being installed in U.S. power plants, but of antipollution devices not being installed in China, either in older coal-fired plants, nor-in the newest ones. There are also natural sources of mercury, which cannot be controlled. It is estimated that about one third of the atmospheric mercury comes from volcanic eruptions and evaporation from the Earth’s surface. Atmospheric mercury becomes most hazardous when it is converted into blood-soluble methyl mercury by water-borne, anaerobic microorganisms. Fish acquire methyl mercury by eating smaller creatures and humans become contaminated by eating the fish. Infants are at greatest risk, but adults can suffer if their mercury levels get too high. For example, a professional hockey player, Joel Bouchard, suffered dizziness, headaches, insomnia, and blurred vision seemingly from the mercury he picked up by eating tuna every day in what he believed was a healthy diet. Of course Chinese living in the vicinity of coal-fired power plants are subjected to very high, unhealthy levels of mercury. Even their local rice crop contains potentially dangerous levels of mercury. There are other air-pollutants coming from the Chinese coal-fired power plants, such as soot, and nitrogen and sulfur oxides. But these are less hazardous than mercury. With a rapidly growing economy and a 200 year supply of coal, this situation will get worse unless there is international pressure to clean up the stack gases from these coal fired power plants. (Matt Pottinger, Steve Stecklow, and Jon Fialka, Wall Street Journal, December 17, 2004, page A1)
A simple test for early Alzheimer’s disease is a patient’s inability to smell and recognize certain odors such as strawberry, smoke, soap, menthol, clove, pineapple, lilac, lemon, and leather. There are already scratch-and-sniff tests for this incurable disease, which presently affects about 4.5 million Americans. Alzheimer’s starts out with mild memory loss, but eventually leads to brain damage, confusion, and a patient’s inability to care for themselves. There is no cure for Alzheimer’s but early diagnosis and some treatments slow the progression of this disease, which is ever increasing as the population ages. (Reuters Limited, 2004)
You will be reading a lot about a protein called P53. This protein is now recognized as a main line of natural defense against cancer. P53 acts by preventing the proliferation of cells with damaged DNA. This guardian protein also enhances DNA repair, stops excessive cell growth, and induces badly damaged cells to commit suicide, by a process called apoptosis. Recall from Chapter 5 that a characteristic of cancer cells is that they are immortal, such malignant cells avoid natural and healthful cell death. It is very interesting that P53 is activated (turned on) by damage to a cell’s DNA or by stressful conditions such as low oxygen concentration. For example, when cancers are treated with radiation, or with chemotherapy both of which damage some of the cancer cell’s DNA, P53 is activated so that the cell can be repaired, or if it is damaged beyond repair, P53 signals the cell to be destroyed by the natural suicide process, apoptosis. What happens if the guardian protein, P53 itself becomes damaged? In that situation cancer cells proliferate and grow without control. For example, if the organism suffers too much radiation damage, this can ruin P53. Certain types of viruses can also cripple P53, resulting in uncontrolled cancer. Inherited mutations to the gene coding for P53 can result in genetic susceptibility towards cancer because that mutated P53 is inactive and cannot respond to DNA damage. Another naturally occurring protein called Mdm2 is termed “anti-P53” because this protein disrupts the action of P53. A new class of anti-cancer drugs called nutlins is designed to tie up Mdm2 so that P53 becomes active and effective. Inventing drugs that restore P53 function is an active and promising area of cancer research. Such drugs can be more effective and have fewer side effects than chemotherapy or radiation treatment. Keep tuned, a lot is going on in cancer research. (see: “Genetics: From Genes to Genomes”; McGraw Hill, NY, 2004, 2nd edition, pages 621-646)
News reports warning about dangers from eating fish because they may contain toxic mercury compounds are alarming the public. But all mercury is not alike. Diverse species of fish contain different levels of mercury; moreover, it is the chemical nature of the mercury in fish that is important! Until August, 2003 (Science, vol. 301, page 1203) the chemical identity of mercury in fish was unknown. As discussed on page 133 in Naturally Dangerous, diverse mercury compounds have widely different neurotoxic activities. For example dimethylmercury is toxic at such low levels that it is considered supertoxic; on the other hand, the mineral, mercury selenide is relatively safe. These differences in toxicity are reasonable because the oily, reactive compound, dimethylmercury is soluble in the blood and can pass into the brain through the blood brain barrier, whereas mercury selenide is very stable and is insoluble. The usual mercury compound, which is assumed to be in fish is methylmercury chloride. The actual type of mercury compound that has recently been identified in fish is a derivative of the amino acid, cysteine. The toxicity of this compound is intermediate between the two extremes. The mercury-cysteine complex found in fish is estimated to be about 20 times less toxic than methylmercury chloride. Another complication is that upon ingesting fish, mercury compounds might be transformed into a more toxic form by stomach acids. Whether this occurs is presently unknown.
The amount of mercury that accumulates in fish depends on the particular fish and their eating habits. Three different, widely-eaten fish: swordfish, orange roughy, and sand sole have substantially different mercury concentrations: 6, 1.2, and 0.4 micromolar, respectively. These difference scan be correlated with the fish’s diets. Swordfish is a top predator, eating exclusively other fish and squid, whereas orange roughy is midway in the food chain, feeding on shrimps, small squid and some small fish.
A recent study of Seattle area men showed a clear relationship between consuming red wine and cutting the risk of prostate cancer. A group of 750 men, between 40 and 64 years old, who had been diagnosed with prostate cancer, was compared to a control group of 703 men. One glass of red wine a day reduced an individual’s risk of prostate cancer by 50%! White wine and other alcoholic drinks showed no benefit. Something in the red wine is special, perhaps it is the anti-aging chemical, resveratrol, which is found in red, but not in white wines. (New York Times, page D6, September 28, 2004)
There is growing evidence that parasitic worms, or substances derived from them may be useful in treating autoimmune diseases. This so called worm therapy is still experimental, because it has not been tested with large double-blind trials. But promising results have been achieved with small human tests and this idea has been well documented with animal studies. The concept behind such treatment is consistent with an old theory known as the hygiene hypothesis: too much cleanliness may cause immune system diseases and that microbes have a role in calming the immune system. One of the first target diseases to be studied in human patients is a painful bowel disease called IBD. A gastroenterologist, Joel Weinstock from the University of Iowa is giving volunteers Gatorade drinks containing 2500 live eggs from parasitic worms in an attempt to treat IBD. Earlier mouse studies using eggs or extracts from a variety of parasites such as flukes, flat warms, tape worms, and pinworms were shown to reduce or prevent several autoimmune disorders including type-1 diabetes. One of the first parasites to be tested with humans are eggs from the pig whipworm, Trichuris suis, which does not fully develop in humans and should not have side effects. Small studies by Weinstock using live parasitic egg shave shown promising results for patients having ulcerative colitis, an inflammation of the large intestine that produces persistent diarrhea. Similar positive results have been achieved in a small study of patients having Chrohn’s disease, another painful autoimmune disorder. A group of children in Gabon Africa who were treated with medications to kill their helminth parasite infections resulted in them developing allergies. There are substantial ethical problems using parasitic worms as a medical treatment, but the development of medicines to reduce serious autoimmune diseases could counterbalance these concerns. (Science, Vol. 305, 9 July, 2004, page 170)
In Chapter 5, the immune system is compared to a two-sided creature from science fiction, who is both the benevolent Dr. Jekyll and the evil Mr. Hyde. Similarly, our immune system protects us by fighting infection and malignancy, but it can also become treacherous, attacking tissues within our body resulting in autoimmune diseases such as rheumatoid arthritis, type 1 diabetes, lupus, and multiple sclerosis. A recent issue of Science (Vol. 305, 9 July, 2004) presents the present status of immunotherapy, methods for enhancing our immune system in fighting infections, cancer, and autoimmune diseases. The details are complex, well beyond most readers of Naturally Dangerous, but some facets should interest non-scientists.
It may surprise you that the immune system can be stimulated to fight autoimmune diseases, which are caused by a malfunction of the immune systemitself. About 5% of Americans and Europeans suffer from autoimmune diseases; two-thirds of the victims are women. No one knows for sure howthese autoimmune diseases come about, but the most probable cause is thought to originate from an infectious microbe that has some similarity to a region oftissue in the victim’s body, so that the immune system is provoked to attack a particular site in its own body. A difficult problem in developing treatments for autoimmune diseases is that the treatment may simultaneously disarm the patientŐs entire immune system, thus making that person susceptible to infections or even to cancer. Very recently there has been some success by employing a particular factor derived from the immune system: “mono-clonal-antibodies” to attack and neutralize an inflammatory immune factor, called TNF that destroys tissue in rheumatoid arthritis sufferers. These new antibody drugs, such as Remicade, do ameliorate rheumatoid arthritis in about 50% of patients. This treatment, given by direct introduction into the blood stream, “infusion” in the doctor’s office, approximately every two months, is covered by Medicare for eligible patients. Readers will remember that since antibodies are proteins, which would be digested and destroyed in the stomach, these antibodies must be introduced directly into the blood steam. Such treatments, although miraculous for many patients, are not without side effects. For example these medicines worsen MS, multiple sclerosis, and can also place some individuals at risk for infections such as tuberculosis. These expensive treatments add a large burden to national health costs, up to $5 billion annually in the U.S.
It is now accepted that our immune system protects us against some early cancers. Because of this have been multiple attempts to use diverse immunotherapies to treat more advanced human cancers, but in each instance these therapies have failed. Nevertheless, this is currently a very active arena of cancer research. Even though the immune system does attack cancer cells, these cells have several mechanisms to evade the immune response. When these evasive methods are better understood, useful anti-cancer immunotherapies may evolve, but such methods seem distant at this time.
In 1796, the famous French scientist, Louis Pasteur, cured a boy from rabies, a fatal viral disease, after the boy had been bitten by a rabid dog. Such “post-exposure” vaccinations, although painful, are still used today to treat rabies victims. The same strategies are also used today to prevent severe illness after tetanus and diphtheria infections. However, this technique has many problems and is ineffective with other infectious diseases such as human immunodeficiency virus (HIV), hepatitis B virus, and human papilloma virus. Work continues to develop long-term therapeutic vaccines against diseases which have no effective alternative therapies.
As discussed in Chapter 5, chemotherapy and radiation attack the DNA in all cells, but are more destructive to rapidly growing cancer cells. These traditional treatments have very unpleasant side effects. Many new strategies for treating cancers are being developed; new drugs are being designed to attack targets that are characteristic of cancer cells. The new drugs take aim at traits that are specific to cancer cells so that such drugs should have fewer side effects and greater efficacy.
One characteristic of cancer is hyperactive growth. This property is stimulated by growth signals that promote rapid cell division. An epidermal growth factor, EGF, is involved. Some drugs are being developed to prevent EGF from binding to a receptor on the cancer cell or to disable an enzyme that is required in this signaling pathway. Gleeve is an example of a drug that binds and blocks the EGF receptor.
Because of their rapid growth, cancer cells need large amounts of food and oxygen to fuel this growth; this requires that cancer cells grow new blood vessel capillaries to bring in additional oxygen and nutrients. Signals to develop these new capillaries such as VEGF (vascular endothelial growth factor) might be blocked to reduce or destroy tumors. Avastin is just such an anti-angiogenesis drug.
In contrast to normal cells, which have genetically programmed cell death or apoptosis cancer cells are immortal. New drugs are being designed to restore apoptosis to cancer cells.
Cancer cells can become resistant to attack by the immune system, which is the body’s natural defense. A monoclonal antibody, Rituxan marks certain cells for destruction, but both normal and cancer cells are thus attacked by the immune system. The hope is that normal cells can be restored by stem cells in the bone marrow. A new vaccine called TRI-CON has been developed to target a protein, CEA that is normally displayed only on the surface of tumor cells. The immune system is drawn to attack and destroy those cells.
These new therapies are not magic bullets; they do attack processes that occur in normal cells and therefore have side effects. Cancer cells are very resourceful and eventually develop resistance, but there is an effective strategy to avoid resistance by employing a cocktail of different drugs. This has become a useful tool; for example the bicycle racing champion, Lance Armstrong was successfully treated for testicular cancer by such a chemotherapy cocktail. A survey of these treatments and some of the new drugs being developed can be found in the article by Bernadette Tansy, San Francisco Chronicle, July 6, 2003, page 11.
Prostate cancer is the second most common cancer; skin cancer is the first. Each year in the U.S. about 220,000 men are diagnosed as having prostate cancer, and about 29,000 men die of this disease. A recent double-blinded seven-year study of 4,300 healthy older men reported that those who were taking finasteride experienced a 25% reduction in their incidence of getting prostate cancer. This would seem to be great news, for Merck, which sells this drug under the trade name Proscar, and for older males, but there is a complication. About 1.5% more of those taking finasteride developed more aggressive cases of prostate cancer compared with those taking the placebo. This creates a dilemma: should an older man take this prophylactic medicine and risk getting a more dangerous case of prostate cancer? Until further studies are complete each patient and his physician must make this choice. This drug prevents the transformation of the hormone testosterone into a more active form. The same drug sold under a different name: Propecia, has been used to treat baldness, but it is used at one-fifth the dose employed in the above study. There are several lessons in this situation: taking hormones has consequences that are not easily predicted. Moreover, healthy patients taking a prophylactic medicine assume risks along with the possible benefit.
There is an old saying: “you can dig your grave with your teeth”; this seems to be true! A huge statistical study in the New England Journal of Medicine evaluating 900,000 initially cancer-free people over 16 years revealed a powerful connection between cancer and excess weight. The conclusion is remarkable: being overweight might account for 14 percent of all cancer deaths in men and 20 percent in women! As many as 90,000 cancer deaths each year in the U.S. could be prevented by losing weight! Smaller, earlier studies had indicated a link between obesity and certain cancers(breast, uterus, colon, kidney, esophagus, and gall bladder). This recent, very large study linked excess weight to these and cancers of the cervix, ovary, myeloma, non-Hodgkins lymphoma, pancreas, liver, and, in men, the stomach and prostate. No link was apparent between being over weight and brain, skin, and bladder cancers. Why would an increased risk of cancer correlate with weight? The principal explanation is that levels of endogenous hormones such as sex hormones, insulin, and insulin-like Growth Factor I, are increased in overweight people. These natural hormones stimulate the growth of cancer cells. Increased exercise may decrease the risk, but it is important to keep one’s body-mass index (B.M.I.) in a healthy range. The increased risks are substantial: the risk of dying from breast cancer varies from 34%, to 63%, to 70% for individuals who are obese, very obese, and morbidly obese, respectively! Similar correlations were found for both men and women with many other types of cancer. Why the higher numbers for women? They tend to be more often overweight, and breast cancer is a common one that is nearly unique to women. (New York Times, May 6, 2003, page D7)
Our immune system can protect us or it can attack us. Allergic reactions are one example of the immune system malfunctioning. Certain individuals experience dangerous allergic reactions to a particular food. I know a famous Harvard professor who is violently allergic to seafood. My sister-in-law is allergic to shrimp and other shellfish. A recent report described a woman who had an allergic reaction from kissing her boyfriend, who had just eaten shrimp. She was allergic to the shrimp, but not to her boyfriend! This incident is not a laughing matter; it is life threatening. She experienced cramps and nausea and her throat swelled up sending her to the emergency room.
Following chance observations that people with arthritis, many of whom take aspirin, seem to have less cancer, a large, double blind study has shown that taking aspirin regularly, reduces the incidence of colon cancer by 40 percent. There is preliminary evidence that aspirin may give some protection against breast cancer. Aspirin is also being studied with other types of cancer. Because aspirin is a cheap nonprescription drug, pharmaceutical companies have not been interested in financing studies of aspirin. But aspirin’s cousins, anti-inflammatory prescription drugs called cox-2 inhibitors seem to have the same effect on cancer cells as aspirin. There may be money in studying the effect of cox-2 inhibitors on cancer. Recall from pages 46 and 47 in Naturally Dangerous that aspirin blocks two similar enzymes, cox-1 and cox-1, but the new prescription drugs, Vioxx and Celebrex, selectively inhibit only cox-2. Recent studies show that pre-cancerous polyps make huge amounts of cox-2. Thus inhibiting cox-2 may slow cell grown, promote cell death, and inhibit tumors from growing the blood vessels they require for nourishment. (New York Times, science section) See also Super-aspirins in Chapter 2.
For non-scientists interested in cancer I strongly suggest that you look at the book: “One Renegade Cell ”, by Robert A. Weinberg, director of one of the leading cancer centers in the World. The medical and biochemical history of cancer is presented in simple terms. He begins by describing the triggering of cancer by exposure to chemical carcinogens and radiation and continues to present the discovery of oncogenes and suppressor genes. The latter controls malignant cell proliferation. With little prior biochemical knowledge, the reader can understand the current problems in diagnosing and treating human cancers. Medical researchers have a long ways to go, but they are making steady progress.
A new drug: imatimib, market under the name Gleevec, is close to being approved for chronic myeloid leukemia (CML). After 18 months over 97 percent of patients getting imatimib were in leukemia remission, although most still showed signs of cancer. In the United States about 200,000 people have CML. These promising results must be followed up over at least five years before the effectiveness of Gleeve can be fully evaluated. (Science News, December 14, 2002, Vol. 162, p. 372)