Xenotransplantation: Plunging Headlong into Madness
Presentation by: Alan H. Berger, Executive Director, Animal Protection
Transplanting organs such as hearts, lungs, livers, kidneys, etc. from human donors to human patients seems commonplace today. In 1997, 20,006 organ transplants were performed in the United States1 but the waiting list at the end of 1997 was 56,678 patients.2 What we seem to have is an increasing demand for these prized organs and a seemingly limited supply.
With this perceived chronic shortage of human donor organs, the medical community has looked for a new source ... and thinks it has found it in animals! Yes, xenotransplantation, animal-to-human transplants is being touted as the perfect answer.
So What's Wrong with Xenotransplantation?
The proponents of xenotransplantation want you to envision a new world with an unlimited supply of fresh organs, available to anyone in need. What they don't tell you is the downside of xenotransplants. The cost -- to the animals whose organs are used, to the humans who pay for it financially and ethically, and to all animals (human and non-human) who face the real possibility of the potential catastrophic transmission of a fatal virus.
Animal Ethics: The first and most basic of the ethical considerations behind xenotransplantation still needs to be examined - is it morally acceptable to use animals as containers of spare parts for humans? Reluctantly and sadly, I accept the fact that the medical community simply doesn't care. To them, it is too bad, but after all, humans do come before all other living things. We are the masters of our universe. It is obvious that speciesism is just part of our cultural fabric which unfortunately incorporates discrimination in all of its ugly forms.
But even when using animals for research, investigators purport to be ethically bound to treat them humanely and to use the smallest number of animals to benefit the greatest number of people. Under this basic research protocol, sacrificing animals for xenotransplants -- where the number of people who "benefit" from one animal may only be one -- is not ethically acceptable.
The animals suggested for xenotransplantation are not regular animals, they are transgenic, genetically engineered to be more human. The ethical, moral, philosophical, and religious concerns over the creation of a "new" species never seems to be seriously addressed:
The public has increasingly questioned the use of animals by humans. In an Associated Press poll taken in November, 1995, 67% of those polled agreed somewhat or strongly that an animal's right to live free of suffering should be as important as a person's right to live free of suffering. Only 8% felt that it was always right to use animals to test medical treatment; 29% felt it was never or seldom right; and 62% said it was right under some circumstances. These opinions to protect animals have continued to get stronger.
It is unclear whether the public finds xenotransplantation acceptable. A 1998 study by the National Kidney Foundation (funded by Novartis) claimed that 62% of Americans accept the concept of xenotransplantation and nearly 75% would consider a xenotransplant for a loved one if the organ or tissue were unavailable from a human.3 Other studies show a different result. In a 1995 study in Australia, only 41.6% would accept an organ from a pig.4
The larger ethical question is the lesson we are presenting to future generations. Our society does not have a reverence for all life:
What National Health Care Policy? The census Bureau reported recently that 44.3 million Americans, 16.3% of the American population, were uninsured in 1998. The nation's uninsured were most likely to be found in low-income households, among minority groups, and in the ranks of full-time workers:
"Lack of health care coverage has reached epic proportions," charged Ron Pollock, Executive Director of Families USA.6 New medical technology, the rising cost of prescription medication and the increasing longevity of older people who require more care have combined to increase insurance premiums and to price many employers out of the medical insurance market, according to Richard Coorsh of Health Insurance Association of America.7
According to a 1996 study coordinated by the Harvard School of Public Health, approximately 50 million adults in the U.S. have difficulties with access to needed medical care and the affordability of medical bills. Almost 70% of those (equally divided between uninsured and insured adults) said that their problems in getting needed medical care are serious.8
In a 1993 Kaiser/Commonwealth Fund health insurance survey, 34% of the uninsured reported that they failed to receive needed care, and 71% postponed needed care. And the uninsured who have chronic illnesses "are least likely to receive proper maintenance and continuous care, with the result that untreated conditions such as hypertension or diabetes can lead to serious consequences."9
Access to medical care becomes much more acute in inner-city America. In the Bedford-Stuyvesant/Crown Heights area of Brooklyn, office-based doctor rate per capita is less than half the national average, even though medical needs are critical. For example, infant mortality rates are 40% higher than the national average and the rate of AIDS is nine times the national average.10
"In these times of managed care and a nationwide glut of hospital beds," reported The Wall Street Journal on the reluctance of state officials to authorize $300 million to overhaul an aging hospital in Brooklyn, "reviving these ailing medical centers may make little economic sense. Experts say it is time for a better way: lean clinics that provide out-patient and primary care."11
But when health care management takes services away from poorer neighborhoods, the "national glut of hospital beds" is not available to the people who need them most, as revealed in a recent study by the Harvard School of Public Health. There's virtually no access to health care for native Americans on reservations, for urban blacks, for the poor concentrated anywhere. For them, health is poorer, life is shorter. Health care access can vary life expectancies by as much as 15 years between areas as little apart as 12 miles.12
It is no wonder that people's confidence in our health care system is dwindling. In a National Coalition on Health Care poll, 80% believe something is "seriously wrong" with the system and 87% believe that the quality of care needs to be improved. Eight of ten blamed the profit motive for compromising quality.13
Meanwhile, health care costs are skyrocketing. We spend $425 billion a year -- two-thirds of all medical expenditures -- to treat the six leading chronic diseases that cause nearly three-quarters of all deaths:
Instead of allocating health costs to providing care to the millions who can't get it, our "baby boomer" bias concentrates on keeping that aging population bulge alive. If the mission of a national health care policy is to improve the quality of human health as well as saving lives, expensive experimental surgery such as xenotransplantation might never be considered.
Poor Use of Resources: In the year 2000 we will be spending nearly $4 billion on organ transplants in the U.S. According to the U.S. Institute of Medicine (IOM) in its June 1996 report, this per year cost could rise to $20.3 billion if all patients in need of organs receive xenotransplants, estimated at 100,000 per year.15 These cost figures do not include expensive follow-up care for the thousands who have already received transplants. The average costs for transplantation in 1996 were the following:
The IOM cost estimates look quite conservative when compared to estimates from a 1996 report issued by one of the leading investment banking companies in the world, Salomon Brothers.18 They estimated in the year 2010, there would be worldwide 507,992 transplants using pig donors and only 27,819 using human donor organs. The use of human organs would decrease worldwide from 46,831 in 1994 to an estimated 27,819 in 2010, a decrease of about 40%!
In 1994 the United States accounted for 37.8% of the world's transplantations. If this percentage remains constant for 2010, 192,021 of the 507,992 xenotransplants projected worldwide would be in the U.S.; almost twice projected by the IOM:
By using the transplant numbers from the Salomon Brothers report with the 1996 dollar costs for transplants, we get a frightening picture of the investment for xenotransplants:
The costs of these transplants would be $34.8 billion rather than the $20.3 billion estimated by the IOM. Also, follow-up costs each succeeding year for those 192,021 xenotransplants would be $3.7 billion. Based on historical evidence of annual increases in medical costs, these numbers could be increasing significantly each year. Assuming the Salomon Brothers' projections are accurate, over 5% of total annual medical expenditures in the United States will be for current transplantations!
Other cost increases and reductions may have an impact on these estimates, although it might not be significant in its net effect. The cost considerations are the following:
Although medicare, state medicaid, and private insurance are currently covering a significant portion of transplantation costs, it may take a long time before they will cover experimental surgery such as xenotransplantation. And even if xenotransplantation will be covered by medical insurance, at what cost?
Medicare and state medicaid may provide coverage for a variety of organ transplants; in 1988, about 90% of kidney transplants were covered through Medicare or state Medicaid programs.20 We already know that our federally funded health insurance programs are near bankruptcy. Will xenotransplantation cause it to explode? Or will we be forced to substantially increase premiums or, even worse, limit other coverages?
Private health insurance in the U.S. will be even more problematic. Costly medical procedures to a limited, select group will continually raise the overall cost of health care, limit insurance coverages, and increase insurance premiums. The result is that more and more people will not find adequate health care services available to them.
The cost simply outweighs the benefit, even given the assumption that the xenografts will be successful without any additional costly side effects. Do we save some patients with expensive medical procedures, and possibly lose even more patients by denying them access to adequate health care?
Transmission of Infectious Diseases: The World Health Organization (WHO) in 1996 stated that we are on "the brink of a global crisis in infectious diseases". About 30 infectious diseases are stalking the world today that weren't known 20 years ago including: AIDS, Ebola, Legionnaires' disease, and hantavirus. Infectious diseases killed 17 million of the 52 million people who died in 1995.21
Certain diseases jump from animals to humans (zoonosis). Recently, health officials in Hong Kong destroyed millions of chickens after a virus, A(H5N1), jumped directly from birds to humans.22 And lately, there has been much publicity over the occurrence of Creutzfeldt-Jakob disease (CJD), a fatal brain-wasting illness that has claimed a number of British humans' lives and which has been linked to mad cow disease (bovine spongiform encephalopathy).23
Xenotransplantation poses perhaps the greatest risk of exposing human populations to non-human primate viruses, and this possibility of transmission of a lethal virus has convinced many researchers to abandon primate-to-human transplants. The most frightening current example of zoonosis is AIDS; over 30 million people worldwide are infected with HIV. Even the Centers for Disease Control (CDC) scientists now acknowledge that HIV "resulted from the adaptation of simian retro viruses introduced across species lines into humans."24
In 1999 the Food & Drug Administration (FDA) published guidelines that effectively called for a "limited" ban on the use of nonhuman primates in xenografts. The FDA stated that nonhuman primates "raise substantial public health safety concerns" and the "public would be exposed to significant infectious disease risk."25
The concerns over using nonhuman primates as donors has made the pig the "animal of choice" for xenografts. But these will not be normal pigs, they will be transgenic (genetically altered) pigs. There will be attempts to raise them in a sterile environment, but pigs bring a whole new set of problems to the issue of xenosis (viruses transmitted during xenotransplants). Recent findings by researchers in the UK suggest that breeding virus-free pigs will be extremely difficult, if not impossible.
Sensitive molecular probes searched pigs from a range of breeds for copies of two inherited retro viruses, PERV-A and PERV-B (porcine endogenous proviruses), which can infect human cells.26 All the pigs tested possessed multiple copies of the viruses, 1023 copies of the PERV-A genes and 7-12 copies of PERV-B genes.27
"The existence of 20 to 30 copies per cell will make it very much harder to remove viruses from pig cells," said Dr. Jonathon Stoye of the National Institute of Medical Research in the UK, who led the research project. "It may actually be impossible."28 In the lab both viruses infect human cells, but nobody will commit with such little information to whether they will cause disease in people. Dr. Stoye, who wants further investigation before proceeding with pig-to-human transplants, says "We ought to know more about the pathogenic potential of these viruses."29
The "major" study of the transmission of pig viruses was published in August 1999. It was co-sponsored by Novartis and the CDC and tracked 160 patients in 9 countries exposed to living pig tissue over a 12 year period. It was highly touted as "encouraging" that transplants from pigs may be safe.30
Under further examination, the results were not encouraging at all. Consider this:
We do know that humans can already acquire approximately 25 diseases from pigs, including anthrax, influenza, scabies, rabies, leptospirosis (which produces liver and kidney damage) and erysipelas (a skin infection).31 Historically, the best known example is that of the 1918 influenza epidemic, which killed more than 20 million people worldwide and is now believed to have been a mutated swine virus carried to Europe by U.S. troops.32
Professor Frederick Murphy, a virologist at the University of California, has issued a warning about the risk of spreading diseases to humans in proposed transplants of transgenic pig organs. There are 4,000 known virus species, and 30,000 strains and variants that infect living creatures. Trying to identify potentially lethal viruses that might be transmitted to humans during a xenotransplant would be nearly impossible.33
The U.S. government intends to protect the public through cumbersome procedures that include screening donor animals for known viruses, constant surveillance of xenotransplant recipients and their contacts, maintaining tissue and blood samples from donor animals and human recipients, and establishing national and local registries of xenograft patients.34
Given the scope of xenotransplants expected, the number of patients will, most likely, quickly outstrip the capabilities of the necessary database and the surveillance procedures. As for screening for known viruses, what about the unknown ones? In February, 1998, Australian scientists discovered an unknown virus in pigs. It apparently came from a colony of fruitbats that lived nearby. Once it hit the piggery the virus attacked pig fetuses, which were either stillborn or had defects in the spinal cord and brain. It also infected two human workers, who recovered. "You can't screen for disease agents that you don't know about," said virologist Peter Kirkland.35
Earlier this year a new virus emerged that was transmitted to humans, the Nipah viral encephalitis virus. The result was that over 250 humans were infected and many patients had relapses. It killed 111 people and led to the mass slaughter of about one million pigs and thousands of dogs, cats, and sheep in Malaysia.36
How effective are our current surveillance techniques with an unknown virus? After a new virus is discovered, what can we really do about it? HIV has been known for decades, yet worldwide the AIDS epidemic is getting worse.37
The FDA acknowledges the seriousness of an infectious disease risk inherent in xenotransplantation from the comments in its 1999 guidelines:
Other Ethical Considerations: The ethical considerations seem almost infinite. Let's name just a few extra:
Just Say No to Xenotransplantation: Consider the Alternatives
We should all be convinced by now that xenotransplantation is not the answer to the perceived shortage of human organs for transplantation. Our first priority should be to reduce the need and we can do that. Before xenotransplantation should be even considered, intensified efforts to reduce the need for transplants and to enlarge the pool of human graft donors need to be adopted. Since we already examined the cost/benefit problem when we significantly increased the number of organ transplants, the enlargement of the human organ donor pool would need to be limited and other alternatives explored. It is a balancing act; reducing the need for transplantation while increasing the supply of organs to a manageable level.
Improve Human Organ Donor System: A study by the General Accounting Office in 1998 found that all available methods for increasing the number of potential organ donors had not been considered. The agency suggested that the number of available organs for transplant may actually be considerably higher than previously indicated.39
Many suggestions have been made to increase the supply of organs:
Mandated Choice/Presumed Consent Laws: Only about 20% of those individuals who die "healthy" have arranged for their organs to be used to help others. This seems remarkable based on the following 1993 Gallop Poll results measuring public perception:
The 1995 results of the most definitive study of our policy regarding organ procurement indicated a significant problem with the reluctance of families to agree to donate a family member's organs. In examining a number of cases in which family members were approached by health professionals, it was found that in only 34% of the cases the family members agreed to donate organs.41
A mandated choice law could be a very effective solution. Under this arrangement everyone would have to make a choice, yes or no -- it can be part of a driver's license renewal program where your answer is printed on your license. It is also essential that family members would not be able to change your selection. After all, it would hardly be your choice if someone else can change it when you are not able to speak for yourself.
Pennsylvania enacted a mandated choice program which also required hospitals to notify the region organ procurement organization upon each patient's death to determine potential for organ or tissue donation. This immediately increased referrals tenfold. An aggressive education program has also increased public awareness of the need for donors. In the first year of this mandated choice program, more than 820,000 drivers chose to have "organ donor" printed on the front of their licenses beneath their photograph.42
A presumed consent law may be the most appealing to increase organ donations. Many countries, especially in Europe, have successfully seen organ donation rates climb dramatically after the passage of this legislation. This law would assume, unless expressed otherwise before death, everyone is a potential organ donor upon his or her demise (minors or the infirm require parental or guardian consent). An opposite wish may simply be communicated in writing.
Presumed consent respects the majority opinion regarding donating organs. Without it, the presumption protects the minority and requires the majority to register their views expressively; an unfair system. Presumed consent shifts the responsibility of a decision about organ donation from the relatives to the individual, respecting his or her right to self determination. Grieving families are spared the stress and trauma of having to make this difficult decision at a time of such loss, especially since their response is often to deny permission, in many cases against the unvoiced preference of the deceased.
Other Medical Advances: The development of new surgical techniques to repair malformed or poorly functioning organs could have substantial long-term benefits. Ventricular remodeling is an example of a technique that can reshape a heart and avoid transplantation. Split organ transplants or kidney transplants from live donors are also being used. Bionic hearts and artificial organs are currently being developed.
Very interesting developments are also occurring with genetically engineered cells and tissue engineering. The Seattle Human Islet Transplantation Project has joined seven research facilities to develop human pancreatic islet cells for transplant of patients with diabetes I. The researchers are also working on a method to find a way to grow these cells in culture.43
Even more interesting is the possibility of actually growing your own organs. Dr. Michael Sefton of LIFE (Living Implants from Engineering) states, "Our intention is to grow large numbers of replacement hearts, kidneys and livers for transplantation and eliminate the need for a waiting list." He hopes to have a functioning heart available for preclinical testing in ten years.44
Prevention: Let's Take Better Care of Ourselves: While transplants may offer longer lives to the chronically ill, one form of "medicine" reigns supreme. "I really don't think that transplantation is going to be the answer," says Charles Porter, a Missouri cardiologist. "It's going to be rehabilitation and prevention."45 U.S. Representative Jim Moran, D-Va., agrees, pointing out that the nation spends far too much on curing illness and not enough trying to prevent them. "Prevention," he says, "is much less expensive and far more effective."46
Indeed, most illnesses are preventable. Changes in diet and increasing exercise can reduce blood pressure47, heart attacks48, and cancer.49 Unfortunately, most people don't heed the information about prevention that is before them every day. Of the enormous number of dollars spent on health care, only a fraction goes to prevention and control efforts -- about 3% of most state public health department budgets. In 1994, over $287 million was spent at the state level on prevention efforts aimed at the six leading chronic diseases. This was approximately 0.07% of the estimated $425 billion spent annually to treat these same diseases, according to a CDC study.50
According to a major study, a diet rich in fruits, vegetables, and low-fat dairy products can reduce blood pressure as much as the most commonly used hypertension drugs, eliminating the need for expensive drugs in many patients with mild hypertension. Widespread adoption of this combination diet could potentially reduce the risk of heart disease by 15% and the likelihood of stroke by 27%. "With nearly 50 million Americans having hypertension, and considering the billions of dollars spent each year on blood pressure medications, these findings have important public health considerations," says Dr. George Blackburn, President of the American Society for Clinical Nutrition.51
Recently the Centers for Disease Control and Prevention (CDC) announced that death rates from cardiovascular diseases have plummeted by 60% since 1950. The contributing factors for the decline are the decrease in smoking, better control of blood pressure, decreases in cholesterol levels, and improved treatments of heart attacks and strokes. Dr. Gilbert Omenn, Executive Vice President for Medical Affairs at the University of Michigan, predicted "that diseases like cancer, arthritis, Alzheimer's disease, gastro-intestinal diseases, and psychiatric diseases will be controlled, not by a wonder drug like a penicillin that cures patients, but by a mixture of preventive measures and treatments, some of which will involve changes in diet and behavior ..."52
The Harvard School of Public Health spent three years reviewing 4,500 scientific studies worldwide on nutrition and cancer. The fifteen member team led by Dr. Walter C. Willett concluded that between 30% and 40% of all cancers could be avoided by changing lifestyles and eating habits. The bottom line:
More education in health maintenance and disease prevention has proven to be the most effective use of research dollars, but our system still spends most of our precious research dollars on curing diseases.
The wholesale adoption of xenografts, using organs from genetically altered pigs, if successful, will generate enormous profits for the pharmaceutical industry, for the bioengineering firms that supply the pigs, and for the medical professionals involved. Because of the tremendous private investment from venture capital groups and large drug companies, the pressure to get approval for xenotransplantation is enormous. After all, it's all about money. Good for industry, bad for the consumer.
Are we placing profits ahead of public health?
Xenotransplantation is not the answer, despite all the rosy pictures over-optimistic researchers, genetic engineers, and pharmaceutical companies, paint of readily available organs. We cannot continue to cure human lives by the wholesale taking of animal lives. We cannot deny health care to others simply because where they live or their financial condition prevents them from having access to adequate health care. We must learn to take better care of each other, by becoming organ donors, and better care of ourselves, through diet and exercise.
1. Table 2 - U.S. Organ Transplants by Organ and Donor Type 1988 to 1977, 1998 UNOS Annual Report.
2. Table 6 - Waiting List Patient Characteristics at Year's End 1988 to 1977, 1998 UNOS Annual Report.
3. "Americans Recognize Organ Shortage, Support Animal-to-Human Transplants, New Survey Says." The National Kidney Foundation, January 21, 1998.
4. Paula J. Nohacsi, et al. "Patients' Attitudes to Xenotransplantation." Nature, Vol 378, November 30, 1995.
5. David Westphal. "Study: One million join the uninsured." Sacramento Bee, October 4, 1999.
7. Tony Pugh. "More of us lack health coverage." Contra Costa Times, October 4, 1999.
8. Karen Donelan, ScD, et al. "Whatever Happened to the Health Insurance Crisis in the United States?" JAMA, Volume 276 (1996), 1346-1350.
9. Karen Davis. "1996 AHSR Presidential Address: Uninsured in an Era of Managed Care." Health Services Research, Volume 31 (1997), 641-649.
10. Lucette Lagnado. "Inner-City Hospital Bergs for Life Support." The Wall Street Journal, February 12, 1997.
12. Steve Sternberg. "Study shows yawning gaps in U.S. health care." USA Today, December 4, 1997.
13. Edwin Chen. "Distress Over Health System Seen Growing." Los Angeles Times, January 24, 1997.
14. "Chronic Disease Costs Could Soar." San Francisco Chronicle, April 4, 1997.
15. Institute of Medicine. Xenotransplantation: Science, Ethics, and Public Policy. Washington, D.C.: National Academy Press, 1996.
16. Richard H. Hauboldt, F.S.A. Cost Implications of Human Organ and Tissue Transplantations, An Update 1996. Minneapolis, MN: Milliman & Robertson, Inc., 1996.
18. Peter Laing. Sandoz/The Unrecognized Potential of Xenotransplantation. Salomon Brothers, January 1996.
20. Congress of the United States. Outpatient Immunosuppressive Drugs Under Medicare. Office of Technology Assessment (OTA-H-452), September 1991.
21.World Health Organization (WHO). World Health Report 1996, Executive Summary. WHO.
22. Dr. Murray J. Cohen and E. Alix Fano."'Bird flu' a warning to stop animal organ transplants." Houston Chronicle, January 15, 1998.
23.Alicia Ault. "Brain grafts could pass on disease -- U.S. panel." Reuters, October 6, 1997.
24. Louisa A. Chapman, M.D., et al. "Sounding Board: Xenotransplantation and Xenogeneic Infections." New England Journal of Medicine, Volume 333 (1995), 1498-1501.
25. Food & Drug Administration (FDA). "Public Health Issues Posed by the Use of Nonhuman Primate Xenographs in Humans." Federal Register, April 6, 1999.
26. Clive Patience, et al. "Infection of human cells by an endogenous retrovirus of pigs." Nature Medicine, Volume 3 (1997), 282-296.
27. Associated Press. "Pig Organs May Bring Viral Risks." New York Times, October 21, 1997.
28. Michael Day. "Tainted transplants." New Scientist, October 18, 1997.
30. Khazal Paradis, et al. "Search for Cross-Species Transmission of Porcine Endogenous Retrovirus in Patients Treated with Living Pig Tissue." Science, Vol. 285, August 20, 1999.
31. Alix Fano, M.A., et al. Of Pigs, Primates, and Plagues: A Layperson's Guide to the Problems with Animal-to-Human Organ Transplants. New York: Medical Research Modernization Committee, n.d.
33. Frederick A. Murphy. "The Public Health Risk of Animal Organ and Tissue Transplantation into Humans." Science, Vol. 273, August 9, 1996.
34. Food & Drug Administration (FDA). "Draft Public Health Service (PHS) Guidelines on Infectious Disease Issues in Xenotransplantation." Federal Register, September 20, 1996
35. Reuters. "Pig virus sparks fears about animal transplants." February 25, 1998.
36. Alvin Ung. "Tropical Killer Virus in First of Its Kind; Experts Stumped." Associated Press, June 5, 1999.
37. Associated Press. "AIDS epidemic worsening, UN says." The Globe and Mail, November 27, 1997.
38. Food & Drug Administration.
39. General Accounting Office (GAO). Organ Donation: Assessing Performance of Organ Procurement Organizations. GAO, April 8, 1998.
40. Richard L. Worsnop. "Organ Transplants: Can the Number of Donors Be Increased?" CQ Researcher 5 (no. 30), August 11, 1995: 710.
41. Laura A. Siminoff, et al. "Public Policy Governing Organ and Tissue Procurement in the United States." Annals of Internal Medicine, Volume 123, Number 1, July 1, 1995.
42. "Organ Donations Experience Record Increase." PRNewswire, October 9, 1996.
43. Carol Smith. "Seattle Research Group Will Try Revised Cell Transplant Technique." Seattle Post, August 16, 1999.
44. Dorsey Griffith. "Future factory for body parts?" Sacramento Bee, July 15, 1999.
45. Alan Bavley. "Doctors pump life into new ideas for healing heart failure patients." San Francisco Chronicle, December 1, 1996.
47. Thomas H. Maugh II. "Study: Eat right, cut blood pressure." Sacramento Bee, April 17, 1997.
48. Geoffrey Cowley. "The Heart Attackers." Newsweek, August 11, 1997.
49. Brigid Schulte. "Cancer study says bad food is not key; diet and exercise are." Contra Costa Times, October 12, 1997.
50. "Chronic Disease Costs."
52. New York Times. "Death Rate for Heart Disease Cut Dramatically in the Past 50 Years." San Francisco Chronicle, August 6, 1999.