To all our readers: we wish you a very happy and healthy new year!
"The real goal is to keep people alive forever."
-- William Haseltine, head of Human Genome Sciences in Rockville, MD, at a conference in Washington, DC on 4 Dec. 2000, marking the creation of the Society of Regenerative Medicine to promote research on "the human body's natural ability to build, repair and maintain itself."
[As a result of genome mapping,] "we will be able to increase the complexity of our . . . DNA without having to wait for the slow process of biological evolution. It is likely that we will be able to completely redesign [the human genome] in the next 1000 [years]."
-- Physicist Stephen Hawking, addressing the eyeforpharma 2000 meeting in Basel, Switzerland in December 2000
(The above news items/quotes from Haseltine and Hawking reported in the 22 December 2000 Science.)
HELP! WE NEED SOMEBODY!!
We need somebody who regularly visits a major university biomedical library to make copies of scientific papers for us. We will pay $6.00 per paper (or make offer) plus shipping. Please write to us care of this magazine or website.
A paper in the 29 September 2000 Science1 reports that the maximum age at death in Sweden rose from about 101 years during the 1860s to about 108 years during the 1990s. The pace of increase was 0.44 years per decade before 1969 but accelerated to 1.11 years per decade after that due to a faster pace of old-age mortality decline. The authors were able to attribute more than 70% of the rise in the maximum age at death during the period of 1861 to 1999 to reductions in death rates above age 70. (The rest is due to increased numbers of survivors to old age.) The lead author, John Wilmoth, was quoted in the October 7, 2000 The Lancet:2 "Contrary to the common belief that has been stated in many scientific papers, there is no 'fixed limit' to the human lifespan." "People have been saying for a long time that humans can't live beyond 120 years, but that number was taken out of thin air. We've already had a well-documented case of someone who lived to age 122 [Jeanne Calment]. It wouldn't surprise me if the world record is 125 or 150 by the year 2050."
By now the news has gotten around that grilling or frying hamburgers, steaks, and other meats at high temperatures results in the formation of heterocyclic amine carcinogens. However, although cooking at lower temperatures or for shorter lengths of time does result in the formation of less of these carcinogens, a different health problem may result because bacteria in the meat, such as E. coli, may not be adequately thermally inactivated. A new study1 of the optimum temperatures for cooking hamburgers that both minimizes formation of carcinogens but destroys bacteria has reported that at 70° C (158° F) or higher, colony forming bacteria were completely inactivated. When patties were turned just once, heterocyclic amine levels increased as cooking temperatures increased. However, when patties were turned over every minute, the levels of the carcinogens were statistically lower. The internal temperature of the patties also reached 70° C sooner when they were turned over every minute, thus destroying harmful bacteria while creating far less of the heterocyclic amine carcinogens.
So, turn your hamburgers or steaks over every minute until they reach an interior temperature of 70°C (158° F) and enjoy healthier results.
A new and pleasant way to increase HDL levels was reported recently.1 Sixteen healthy men and 9 healthy women with elevated plasma total and LDL cholesterol and normal triacylglycerol (triglycerides, fats in the blood) concentrations took part in the study. Results showed that incorporation of 750 mL (3 cups), but not 250 or 500 mL, of orange juice daily increased HDL cholesterol by 21%, triacyglycerol concentrations by 30%, and folate concentrations by 18%, as well as decreasing the LDL/HDL ratio by 16%. (The orange juice was Tropicana Pure Premium orange juice.)
Although there was an increase in triacylglycerol, the increased levels did not exceed the normal range and the authors suggest that this may not be clinically significant or result in increased cardiovascular risk. The increase in HDL and reduction in LDL/HDL ratio are likely to be cardioprotective; importantly, it is easier to reduce LDL than it is to increase HDL. The authors do not recommend that consumption of large amounts of orange juice (which they estimate at approximately 20% of daily energy level) should be recommended to hypercholesterolemic individuals. Instead, they suggest that cardioprotective nutrients in amounts similar to those found in 750mL of orange juice should be ingested daily from a variety of foods. We will look forward to more studies that provide concrete information on appropriate combinations of other foods and on the active phytochemical constituents.
At the March 1999 meeting of the American Chemical Society, chemist Joe Vinson (University of Scranton, Pennsylvania) reported that a single candy bar's worth of milk chocolate (40 grams) contains more than 300 mg. of polyphenols, equivalent to a day's worth of fruits and vegetables. Indeed, he reported, if the candy bar is dark chocolate, it holds the equivalent of 2 days' worth of fruits' and vegetables' polyphenols. This reported in the 2 April 1999 Science.
A new study1 reports very exciting results in a chocolate feeding study in humans. Procyanidins found in chocolate are polyphenolic flavonoids. Ten healthy subjects (4 men and 6 women) ate 37 grams of a high procyanidin chocolate bar (DOVE Dark Chocolate, a commercially available confection containing 4.0 mg./g. of procyanidin) or of a low procyanidin chocolate bar (0.09 mg./g. procyanidin) after an overnight fast. Relative to the low procyanidin chocolate, the high procyanidin chocolate induced 32% increases in plasma prostacyclin and 29% decreases in plasma leukotrienes. The ratio of leukotrienes to prostacyclin, a measure of proinflammatory to antiinflammatory eicosanoid balance, decreased by 58% in cultured human aortic endothelial cells, similar to the 52% decrease in plasma of the human subjects. These results suggest protection of the vascular system, since prostacyclin prevents formation of abnormal blood clots within blood vessels, while leukotrienes stimulate them.
The reported effects were transient, however, suggesting that (as the authors note) "consumption of polyphenolics many times each day might be necessary for optimal vascular protection." It would certainly be inadvisable to eat 37 grams of chocolate "many times" per day, but it is good to know that chocolate is yet another source of the healthful procyanidins.
A little over a year ago, there was a flap over whether tobacco companies were producing nicotine-enriched tobacco, a type called Y-1. A story in The New York Timesreported that the government was investigating Brown & Williamson tobacco company executives "about efforts to genetically engineer seeds to produce plants with higher nicotine levels."
"In January 1998, DNA Plant Technology pleaded guilty to a misdemeanor count of conspiring to illegally export the Y-1 seeds and agreed to cooperate in the Government's continuing inquiry. Brown & Williamson officials were soon brought to testify before a grand jury in Washington. But that inquiry also died. Raymond C. Marshall, a lawyer in San Francisco who represented DNA Plant Technology, said he never heard from Justice Department officials again."
The facts bear little relationship to the newspaper report. In fact, DNA Plant Technology Corporation did accept a contract in 1983 from Brown & Williamson, but it had nothing to do with genetically engineering high-nicotine tobacco, a very difficult project even today. Rather, the company took Y-1 seeds for tobacco containing 5% more nicotine in its leaves that had been developed in the 1970's at a USDA agricultural research station in Oxford, NC using ordinary breeding techniques of genetic crosses and engineered it for male sterility, a necessary commercial prerequisite for legal export. All the above was reported in an unsigned editorial in the 17 November 1999 Nature Biotechnology.As the editorial noted, "Agricultural biotechology has enough public perception problems without being used as a pawn in the political crusades of mass media journalists." However, this is par for the course concerning unpopular segments of the population, such as tobacco companies, and a continuing danger in a political system in which 51% make decisions that can be imposed upon the other 49% (or in which 51% can vote themselves perceived benefits at the expense of the 49%). Another serious problem, not discussed in the editorial, is that much of basic biomedical research and most environmental research (such as the issue of "global warming") is funded by the federal government, which can, by funding those scientists who produce results consistent with the chosen direction of the government's public policies (eg. its agenda), find scientific support for whatever policies they prefer while ignoring data inconsistent with those policies.
Systemic lupus erythematosus (SLE) is an autoimmune disease primarily affecting young women (the female/male ratio of patients with SLE is 9:1) that can be very severe and even fatal. Studies suggest that it is associated with a hyperestrogenic state. It is known that estrogen exacerbates autoimmune diseases, which is why so many more women than men suffer from these diseases.
A new clinical study2 reports on the effect of reducing prolactin, a hormone released in response to estrogen, which is an immunostimulatory molecule that may worsen autoimmune conditions. Activated B cells that are autoreactive are causative factors in SLE.
Earlier small human trials had found that the prolactin secretion blocking drug bromocriptine had had beneficial effects in patients with mild to moderate SLE. The purpose of the new study was to learn more about the mechanism of the bromocriptine effects. The results showed that in estrogen treated BALB/c mice the activation of the B cells involved in autoreactivity was mediated by prolactin. Hence, reducing prolactin levels with bromocriptine resulted in improvement in the disease.
This is a very exciting finding for autoimmune SLE and ought to be considered in other estrogen/prolactin related autoimmune conditions. Unfortunately, bromocriptine (Parlodel)® is long past patent protection and, hence, this SLE treatment may not receive the attention it deserves.
Methoxsalen, a drug already approved for treating psoriasis, has been found to reduce the rate of metabolic destruction of nicotine. A liver enzyme called CYP2A6, a member of the P-450 enzyme family, governs the metabolism of nicotine to cotinine in a two step process. As the enzyme removes nicotine from the bloodstream, a smoker needs to replete supplies by smoking another cigarette. It has been found that individuals with a defective CYP2A6 enzyme are protected from heavy dependency on nicotine because it is removed so slowly from their bloodstream. These people simply smoke a lot less and, because CYP2A6 converts procarcinogens found in tobacco smoke into their carcinogenic form, they are also less likely to develop smoking related cancers.
Methoxsalen turned out to be an effective inhibitor of CYP2A6. In one study, 17 smokers who had no intention of quitting were given tablets containing 30, 10, or 3.5 mg. of methoxsalen or a placebo orally, along with a 4 mg. nicotine tablet. Blood nicotine levels were measured at 30 minute intervals over 3 hours. Those who received the higher doses of methoxsalen had nicotine levels that were twice as high as those who took the 3.5 mg. dose of the drug or placebo. Those on the higher doses reported that they lost the urge to light up as often.
This may make it easier for those who make a new year's resolution to quit smoking to actually do so. Note, however, that methoxsalen is a powerful photosensitizer, so a high SPF sunblock would be needed for any skin areas exposed to sun. Hopefully, non-photosensitizing analogs can be developed.
Since the discovery of telomeres, the chromosome ends that shorten with each cell doubling, and of telomerase, the enzyme that increases the length of telomeres, there has been considerable speculation and some experimentation concerning whether telomerase can be used to extend the lifespan of cells, tissues, or even organisms without an excessive risk of developing cancer.
A new study1 reports that a transient exposure to human telomerase resulted in a very small average telomere elongation and yet extended the lifespan of normal human fibroblasts by 50%. The cells that were used were normal diploid foreskin fibroblasts that, at population doubling 85 (near senescent) had an insertion of DNA for telomerase. At population doubling 92, the telomerase DNA was removed, at which point the cells lost telomerase activity and showed telomere shortening over an additional 50 population doublings. The authors suggest that transient exposure to telomerase maybe a safe method for using the enzyme in producing tissue made of cells with a longer lifespan.
This may also be potentially useful for local treatment of skin cells in vivo, which are readily accessible. The $6.4 billion dollar question: Will it work as a hair restorer? It is interesting to note that mature hair follicles contain stem cells that appear to be essential for renewal of the skin.
The much loved chicken soup used as a medicine when we have mild upper respiratory tract infections, such as "colds," continues to yield its "secrets" to investigators. Researchers thought that chicken soup might work by having anti-inflammatory effects in the diverse conditions that it seems to help. To evaluate this, a traditional chicken soup was tested for its ability to inhibit neutrophil migration and was found to significantly do so in a dose dependent manner. (When a little chicken soup inhibited neutrophil migration, a bit more worked even better . . .) The activity was present in a non-particulate part of the soup. In fact, all the vegetables and the chicken in the soup had inhibitory activity.1
A possibly therapeutic ingredient in chicken soup that we have reported on before is the amino acid arginine, found in relatively large amounts in chicken and turkey meat and known to be an immune system stimulant in adequate quantities. If you are a vegetarian or do not care for chicken soup, you might try taking arginine as a nutritional supplement.
The important role of folic acid in preventing neural tube defects in fetuses and in reducing human bloodstream homocysteine levels thereby reducing the risk of cardiovascular disease is becoming more widely known. (No thanks to the FDA, however, which prohibited the communication of the neural tube defect information for years after other federal government agencies, such as the U.S. Centers for Disease Control and the U.S. Public Health Service, were trying to get the information to all women of childbearing age. We and our co-plaintiffs had to sue the FDA to force them to approve a folic acid/neural tube defects health claim and have had to sue them again because the FDA approved claim is grossly misleading; for example, the FDA claim does not permit the inclusion of the truthful and important information that synthetic folic acid in a supplement or a fortified food is twice as bioavailable as natural food folates. The FDA continues to prevent accurate information on the relationship between homocysteine and cardiovascular disease from being communicated in dietary supplement labels and advertising and we and co-plaintiffs have an ongoing First Amendment suit against the FDA on this issue, too. See www.emord.com.)
Much less well known, however, is the importance of folic acid in the proper regulation of genetic expression. (The FDA hasn't even begun its molasses-like thinking process about this additional effect of folic acid.) Folic acid (as N5-methyl tetrahydrofolate) is required for the methylation of homocysteine to methionine (an important means of getting rid of cytotoxic homocysteine). The methionine is then modified to S-adenosylmethionine, a universal methyl donor in a variety of biochemical reactions, including the methylation of DNA. Hypomethylation (a deficiency of methylation) of DNA can result in the expression of genes that, with adequate amounts of methylation, would be suppressed. Hypermethylation, on the other hand, can prevent expression of genes, such as tumor suppressor genes, that should be expressed. Hence, methylation is a critical process in the control of gene expression and folic acid is an essential part of that process.
In a new study,1,2 researchers investigated the use of a DNA methylation assay as a way to measure a functional consequence of marginal folic acid intake. As the authors noted, though the assay does indeed provide useful information concerning folic acid intake, a definition of DNA hypomethylation still needs to be established as there are no currently set normal ranges for DNA methylation. The study followed 33 healthy postmenopausal women (aged 60-85 years) on a moderately folate-depleted diet for 7 weeks, followed by 7 weeks of folate repletion with either 200 or 415 mcg. of folic acid per day (doses equivalent to 400 and 830 mcg. of natural food folates daily). Leukocyte DNA methylation was determined on the basis of the ability of DNA to incorporate methyl groups from labeled S-adenosylmethionine in an in vitro assay.
Results showed that moderate folate depletion in the subjects resulted in a significant increase in overall mean methyl incorporation into leukocyte DNA, with a total of 27 of 33 subjects showing an increase at week 7 compared with baseline. This suggests that there was a deficiency of methylation in the depleted leukocyte DNA. During repletion, a significant proportion of the subjects continued to respond with increasing methyl incorporation, which the authors interpret to mean that leukocyte DNA methylation may be slow to respond to folate repletion after depletion. They suggest that a longer repletion period or repletion with higher amounts of folic acid (larger than 415 mcg. per day) may have been required to observe significant increases in the methylation status of hypomethylated DNA in these women.
1,2. Rampersaud et al, "Genomic DNA Methylation Decreases in Response to Moderate Folate Depletion in Elderly Women," Am. J. Clin. Nutr. 72:998-1003(2000); Jacob, "Folate, DNA Methylation, and Gene Expression: Factors of Nature and Nurture," Am. J. Clin. Nutr. 72:903-4 (2000)
Wow! The election is finally over but the Second American Civil War may still be heating up! We think that the razor thin margin of victory by Bush did not reflect a lack of difference between the two Presidential candidates, as some have proposed, but a nation sharply divided between two different sets of values that boil down to the tax payers versus the tax money takers (another way to put it is the gimmees versus the wealth producers.) The basis for this war between the roughly equal (in numbers)*segments of society is that, while there is virtually unlimited potential for government to tax and redistribute income, there is little to restrain anyone from demanding more and more benefits at the expense of those who pay, obviously an unstable and morally hazardous situation. (The reason that direct taxes, such as income taxes, were not included as part of the federal government's powers in the original Constitution and why a Sixteenth Amendment was needed to institute direct taxes was that the founders feared that direct taxes would give the federal government too much power. How right they were. Note that under our current laws, there is absolutely no entitlement by anybody to a penny of his or her own earnings, while there are numerous entitlements to other people's money.)
Equality is often used as a moral basis for government to redistribute income. Whether people have a right to the fruits of other people's labor simply by virtue of having been born is a question of value. However, whether equality can actually be achieved by government manipulation is an economic question that can be answered without resort to value judgements. Note that: 1) The faster technology changes, the less likely that there can be equality in the distribution of its benefits. That's because the faster changes take place, the farther the system of constantly changing human choices is from the equilibrium (stasis) that would be required for equality to exist. An example of perfect equality is death. 2) At the same time, though, the faster technology changes, the faster that products of advanced technology become available to all, including the less well off. As an example of "trickle down" economics, a personal computer that cost $3,000 a decade ago can now be purchased for $30 at a garage sale. 3) Hence, you can have a dynamic economy with lots of opportunities and no guarantee of equal outcomes or you can have a stagnant economy within which to politically jockey for equality.
We fear that we have seen a fundamental change in the nature of American elections with the entrance of large-scale legal litigation and the open use of widespread fraud in ballot counting as a political strategy. All sorts of clever things are being hatched by lawyers. For example, think about the impact of an emerging battle in several states, including Florida, Pennsylvania, and Washington, over re-enfranchising felons, who are likely to vote overwhelmingly - perhaps 70-90% - Democratic. (In many low population rural counties where prisons are often built, the majority of residents may vote Republican, but the felons could dominate the results of local elections.) There are about 4 million convicted felons out there who are currently disenfranchised by state laws.
Criminologist Chistopher Uggen of the University of Minnesota says, "Democrats have successfully co-opted Republican policies on crime. One unanticipated cost of that strategy has been an erosion of the Democratic voter base."
Nancy Northrup, director of the Democracy Program at New York University's Brennan Center for Justice, is the lead attorney for the Florida ex-felons. "Disenfranchised felons used to represent 1% of Florida's voting age population," she says. "Now it’s 5%." (Here is yet another social problem resulting from the "War on Drugs" which has disenfranchised many for non-violent drug offenses. Is it wise public policy to treat non-violent drug offenses as harshly as violent crimes?) Counting both inmates and ex-inmates, 24% of Florida's voting age black males cannot vote. (See Goldhaber, "The FelonVote," The National Law Journal, Oct. 30, 2000, pg. A1)
* A 50/50 split is predicted by game theory.1,2 Deviations from 50/50 are probably due to credibility differences between the candidates. For example, after Bush Sr. moved his lips on taxes, his base no longer supported him, and Bob Dole really was (as he was called) a tax collector for the welfare state. Clinton, despite being an exceptionally good liar and willing to use whatever means, even unconstitutional ones, to achieve his ends, remained a credible source of government goodies for his constituencies. In the 2000 election, the credibility of the two candidates appeared to be about equal to their respective constituencies; hence, the almost perfect 50/50 voter split predicted by game theory. It is easier to follow this argument if you consider, as an analogy, the relationship between populations of predator and prey. Increasing numbers of prey allow for increasing numbers of predators. If predators increase in numbers too rapidly in response to the increased prey, though, the ratio of predators to prey become too great and prey are depleted, followed by a die-back of predators.
Until recently, one of the big problems in mathematical models of predator-prey ecology is that they were inherently unstable. The models predicted that the predators would either completely consume all prey and then starve or consume nearly all of the prey and then starve. Of course, this rarely happens in nature. The flaw in the prior mathematical models was that they ignored differences in the spatial distributions of predators versus prey.The ability of prey to move away from a high predation area to an area of less predation has a profound stabilizing effect.3 That is exactly what is happening in the United States. Ten years ago we moved from Southern California, an area of high taxes and heavy land use regulations, to Central Nevada, a rural area with few regulations in a state with no income tax. If you examine the USA Today election map of counties won by Bush versus those won by Gore, you can see clearly a dramatic distinction between the urban areas where most of the tax predators live and rural areas where tax prey can still escape to. It is because of the careful design of the electoral college by the founders that the U.S. is not dominated by a few large population centers.