Making Research a Political Issue
This year promises a lot of political debate about how many tax dollars should be committed to fighting terrorism. Yet the issue of cancer research is unlikely to be raised. For fiscal year 2004, the federal government has authorized a record defense budget of $401.3 billion. At least one independent study, however, estimates the true cost of defense and anti-terror expenditures to be an astonishing $754 billion in 2004—or 88% more than the much-publicized $401.3 billion defense budget.16 This includes the Department of Homeland Security budget, security-related portions of other federal departmental budgets, and interest attributable to past debt-financed defense outlays. By contrast, the federal government has allocated a paltry $4.8 billion for cancer research, even less for research on other killer diseases, and only a miniscule $2.2 billion for anti-aging research.17
Since aging is the underlying cause of age-related diseases—including most cancers—the lack of funding for this type of research is truly inexcusable.
As our polls clearly indicate, the vast majority of Americans fear cancer more than terrorism. Since government spending eats up a huge percentage of the gross national product, it would appear prudent for citizens participating in the democratic process to let both incumbents and challengers know that medical research is a critical public issue. It would be nice to know at least which politicians favor spending more money on extending the healthy human life span. By making this a political issue, there is a chance that politicians may realize that taxpayers want tangible benefits from government that are in the best interests of the people.
We suggest that Life Extension members write candidates of all parties and demand to know their positions on issues such as funding more life extension research, allowing scientists in the private sector more freedom to explore new research vistas, and speeding the pathway from the research lab to the clinic. These letters should also demand FDA reform that would provide seriously ill Americans with the freedom to try experimental drugs without bureaucratic interference. You need not say you are against fighting terrorism, but rather that you are far more terrorized by the prospect of aging and disease than by political or religious extremists.
According to a groundbreaking special investigation published in the March 22, 2004 issue of Fortune magazine, America is losing the war on cancer and it is time to overhaul the battle plan.
Fortune reports that the percentage of Americans dying from cancer is about the same as it was in 1970, and reveals systemic problems that are making cancer so difficult to defeat.
The article begins by showing how researchers have amassed an enormous amount of knowledge essential to the war on cancer. The problem is that a dysfunctional cancer culture has made the search for knowledge an end unto itself rather than a means to an end. The result is a research and grant culture focused on finding the tiniest improvements to treatment rather than genuine breakthroughs, i.e., cures.
The most revealing example of this system-wide failure is that cancer researchers focus most of their effort on shrinking tumors in terminally ill patients. The bulk of research money is spent on this goal and not on understanding and arresting the process of metastasis, which kills 90% of patients. According to a Fortune examination of National Cancer Institute (NCI) grants going back to 1972, less than 0.5% of study proposals focused on metastasis. Of nearly 8,900 NCI grant proposals awarded last year, 92% did not even mention metastasis.
Fortune criticized the failure of the cancer establishment to recognize that human tumors have quickly changing DNA characteristics that enable them to mutate and develop new growth factors in order to escape eradication by most single-agent experimental therapies employed today.
All of these failures come to a head, says Fortune magazine, when the FDA obstructs progress by mandating rigid three-phase clinical trials that are often designed to fail. One example of this problem is the FDA’s requirement that experimental drugs be given only to end-stage cancer patients. This often precludes scientists from learning whether promising drugs could be effective in early-stage cancers that are more readily curable. The FDA clinical trial process remains the only way to get a new cancer drug approved, yet Fortune magazine found that scientists in the cancer community are maddeningly frustrated by it.
The Fortune article points out that even as research and treatment have intensified, cancer’s annual death toll has risen 73% — over one and one-half times the growth of the US population. By contrast, deaths from heart disease and stroke have slowed dramatically.
Fortune concludes its in-depth report with a proposal for a radical overhaul of how America fights the war on cancer, including a transformation in the way the NCI funds research, a consolidation of the federal war chest into one bureaucracy (from five), and an overhaul of the FDA drug-testing and approval process.
The mainstream media are now recognizing what the Life Extension Foundation exposed years ago about the failure of conventional oncology research. The question is, will anyone in the federal government pay attention?
Our Work to Extend Your Life Span
Life Extension is funding millions of dollars of research each year to help keep you alive and healthy. Included in this research is the most promising approach to the control of aging and age-related diseases, which involves the use of high-density microarrays (gene chips) to measure gene expression in thousands of genes at a time. Conducted by BioMarker Pharmaceuticals, this research is based on the idea that gene expression is a fundamental process that underlies the aging process and the killer diseases related to aging.
BioMarker is using gene chips made by Affymetrix, which measure the expression of thousands of genes at a time in mice and monkeys.
The research objective is developing gene-expression profiles for the tissues of normally aging animals and comparing them with gene profiles in life span-extending models, such as mice fed a calorie-restricted diet.
Radical Effects of Caloric Restriction
Caloric restriction has produced anti-aging effects and extended maximum life span in many species, including mice, rats, and dogs. Caloric restriction has been shown to extend the maximum life span of both mice and rats up to 60%.18-25 BioMarker is collaborating with scientists at the National Institute on Aging, who have been conducting a study of caloric restriction in monkeys to compare its effects on gene expression in monkeys and mice. This kind of comparison is helping BioMarker’s scientists uncover genes that affect aging in mammals on different rungs of the evolutionary ladder. Thus far, it appears that many of the anti-aging gene-expression effects found in mice are also found in monkeys, which share about 98% of their genome with humans.
There are two models, Ames and Snell dwarf mice, where a single gene mutation that markedly reduces the output of three pituitary hormones (growth hormone, prolactin, and thyroid-stimulating hormone) has been shown to extend maximum life span up to 70%.26,27 That a single gene change can extend maximum life span so radically is strong evidence that only a few genes may be involved in the control of aging. BioMarker is actively searching for these genes.
Researchers Andrezej Bartke of Southern Illinois University, Richard A. Miller of the University of Michigan, and others have shown that Ames dwarf mice, which live 50% longer than normal mice, lived an additional 25% longer when fed a calorie-restricted diet.28,29 BioMarker is collaborating with Dr. Bartke to analyze gene expression in long-lived dwarf mice. A gene chip study of the liver in dwarf mice has demonstrated that these animals show some changes in gene expression that are similar to calorie-restricted animals, but also show changes that are different. These findings, which will soon be published in a peer-reviewed scientific journal, support the finding that caloric restriction and dwarfism extend life span in somewhat different ways,30 and that the combination of these two approaches is synergistic.
Quick Screening for Anti-Aging Therapies
In an extraordinary breakthrough, BioMarker scientists found that most of the changes in gene expression caused by long-term caloric restriction (over two years) occur in the liver in only two to four weeks after placing mice on a calorie-restricted diet.31 This finding makes it possible for BioMarker to screen potential anti-aging therapies in less than a month—25 times faster than any other technique currently available!
The ability to screen for anti-aging therapies quickly and inexpensively is an enormous breakthrough. Pharmaceutical companies spend billions of dollars trying to discover new drugs for the treatment of cancer, heart disease, stroke, Alzheimer’s disease, and other killers. They usually have to conduct lengthy, highly expensive studies on thousands of drugs in order to find even one promising new drug candidate.
Is Metformin an Anti-Aging Therapy?
BioMarker may have already found an anti-aging therapy with its unique technology platform. When BioMarker scientists screened several glucoregulatory agents used to treat diabetes, they found that the undisputed star of the group was metformin, which was twice as effective as the other drugs in reproducing the gene-expression effects of caloric restriction.32
Further evidence that metformin may be an authentic anti-aging therapy is that a similar drug—phenformin—was found in the late 1970s to extend life span in mice by 23%. This study by Russian researchers also demonstrated a fourfold reduction in cancer incidence in the phenformin-treated mice.33 In 2002, scientists at the National Institute on Aging presented data showing that metformin extended the life span of mice by 20%.
BioMarker is currently conducting its own study of metformin in 40 mice, seeking to determine the extent to which metformin can extend life span and reduce the incidence of age-related diseases in these animals. This study is being conducted at the University of California at Riverside under the direction of Dr. Stephen Spindler.
New BioMarker Studies of Resveratrol
Resveratrol is an antioxidant and anti-inflammatory agent found in red wine and red grapes that has been shown to protect against heart disease and cancer.34-47 Gene chip studies have demonstrated that resveratrol produces a striking effect on cancer-related genes. Among other effects, resveratrol activates tumor suppressor genes and genes that detoxify chemicals. It also suppresses genes that enable cancer cells to communicate with each other.
BioMarker is now preparing for a gene chip study to determine if resveratrol can mimic the gene-expression effects of caloric restriction. BioMarker scientists are collaborating with scientists at Harvard Medical School in Boston and Critical Care Research in southern California to find the best forms of resveratrol to test, and will probably also test one or two analogs of resveratrol developed at Harvard.
Is Rejuvenation Possible?
One of BioMarker’s most important findings is that life-extending regimens such as caloric restriction can rapidly induce a rejuvenation profile of gene expression. Over 70 years of studies have led to the conclusion that caloric restriction gradually prevents age-related decline and that it must be followed throughout the life span to be effective. BioMarker’s gene chip studies have challenged this dogma by showing that in less than a month after a calorie-restricted diet, mice generated a gene-expression profile consistent with rejuvenation.31
Another BioMarker study has bolstered the likelihood that anti-aging therapies may be effective in older people, who need to be rejuvenated if they are to have their healthy life spans extended. Recently, a paper by BioMarker scientists was accepted for publication in the Proceedings of the National Academy of Sciences USA. This paper reports the results of an experiment that demonstrated, for the first time, that caloric restriction can be initiated late in life in mice (19 months old) and still be as effective in extending life span and reducing the onset of tumors as caloric restriction begun early in life. This study also closely associates the genomic response, as measured by gene chip assays, with the health and longevity effects of caloric restriction, suggesting that caloric-restriction mimetics such as metformin should be able to reproduce the physiological effects of caloric restriction.
These studies are very good news for those of us who are past our physical prime. They provide striking evidence that it should be possible to develop rejuvenation therapies that are capable of making us younger, healthier, and longer lived than ever before.