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Calories, bias, and ethics

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Calories, bias, and ethics

From Primate Research
August 2012

For 25 years, the rhesus monkeys were kept semi-starved, lean and hungry. The males’ weights were so low they were the equivalent of a 6-foot-tall man who tipped the scales at just 120 to 133 pounds. The hope was that if the monkeys lived longer, healthier lives by eating a lot less, then maybe people, their evolutionary cousins, would, too. Some scientists, anticipating such benefits, began severely restricting their own diets.

If you are one of the few people in the world who pay attention to both the industry’s claims and the actual results from experiments on animals, then you’ve likely already read something about a recent report from the NIH.

The story was covered in the New York Times and starts this way:

Severe Diet Doesn’t Prolong Life, at Least in Monkeys
By GINA KOLATA
Published: August 29, 2012

For 25 years, the rhesus monkeys were kept semi-starved, lean and hungry. The males’ weights were so low they were the equivalent of a 6-foot-tall man who tipped the scales at just 120 to 133 pounds. The hope was that if the monkeys lived longer, healthier lives by eating a lot less, then maybe people, their evolutionary cousins, would, too. Some scientists, anticipating such benefits, began severely restricting their own diets.

A 23-year study comparing calorie restricted rhesus monkeys, left, to normally-fed monkeys, has shown that calorie restriction may not increase one's lifespan.

The results of this major, long-awaited study, which began in 1987, are finally in. But it did not bring the vindication calorie restriction enthusiasts had anticipated. It turns out the skinny monkeys did not live any longer than those kept at more normal weights. Some lab test results improved, but only in monkeys put on the diet when they were old. The causes of death — cancer, heart disease — were the same in both the underfed and the normally fed monkeys.

The article goes on to point out the UW, Madison’s involvement in this research:

Like many other researchers on aging, he had expected an outcome similar to that of a 2009 study from the University of Wisconsin that concluded that caloric restriction did extend monkeys’ life spans.

But even that study had a question mark hanging over it. Its authors had disregarded about half of the deaths among the monkeys they studied, saying they were not related to aging. If they had included all of the deaths, there was no extension of life span in the Wisconsin study, either.

What you might not be aware of if you don’t read the Wisconsin State Journal is just how frequently the university has called attention to its research in this area. Media often swallows whole the reports that are so straightforwardly propaganda – written by spin-doctors whose only reason for writing about the university’s use of animals appears to be, well, propaganda – cultivating the public's misunderstanding and delusion that they themselves planted originally in misleading press releases.

Below, I’ve pasted in a few of the university’s releases over the years regarding its caloric restriction tax-payer-funded gravy train. The university’s spin seems at odds with the third party report in the NYT.

This is a good example of the problem of bias in science. Assuming that the UW, Madison scientists involved actually believed the things they said, their fiddling with the data they used to draw conclusions is the reason for blinding and double blinding in research design. Even knowing the risks of bias, it seems that many, maybe most scientists are unable to keep from seeing success when it simply isn’t there.

This seems to be a situation-based version of a universal human foible. We aren’t good, or even moderately fair judges of anything when the thing that we are trying to judge is something we are involved in more or less directly. We can’t accurately judge even our own morality when we are part of a system that condones and encourages our behavior.

This explains why people will commit atrocities when ordered to so. The work of people like Milgram, Zimbardo, Bandura, and many others has made it exquisitely clear that human endeavors that include opportunities for willfully hurting others will almost always do so unless their is vigorous third-party oversight. The harm done often has the energetic support and cooperation of nearly everyone in the system.

So researchers are unable to fairly draw conclusions from their own data and must blind themselves to many details behind the data if they are to have any hope of fairly judging their own results.

And people who experiment on animals and approve the experiments are also hopelessly biased and can see only pie when they look up at the sky.

The part of all this that is doubly depressing is the plain fact that most of the people who approve experiments on animals are supposed to know the inherent unavoidable bias they bring to their work. But when deciding whether to approve an experiment, they do nothing to avoid their blinding biases. They decide to approve someone’s invasive brain experiments on dogs or cats or monkeys not because there is any evidence that similar experiments have provided some benefit to human patients, but solely because the experiments come with a bucket of money for the institution or else the vivisectors whose experiment they are “considering” for approval, is well-known to them.

The failure to make any effort to avoid bias is unethical and dirties everyone involved.

Anyway, below are snippets from the university’s press releases touting the work that the NIH study now seems to refute:

University Communications
News releases

FOR IMMEDIATE RELEASE

6/13/06

PHOTO EDITORS: High-resolution images are available at http://www.news.wisc.edu/newsphotos/monkeyRC.html

CONTACT: Richard H. Weindruch (608) 263-3503, rhweindr@wisc.edu; Sterling Johnson (608) 256-1901, Ext. 11946, scj@medicine.wisc.edu

WISCONSIN DIET AND AGING STUDY GAINS $7.9 MILLION GRANT

MADISON - A pioneering long-term study of the links between diet and aging in monkeys will continue through 2011 with the help of a new $7.9 million grant from the National Institutes of Health (NIH).

First initiated at the National Primate Research Center at the University of Wisconsin-Madison in 1989, the study examines the effects of a reduced-calorie diet on the aging process and health of 76 rhesus monkeys. It is one of only two long-term studies of its kind, and during the course of 16 years has shown that a nutritious but reduced-calorie diet has multiple benefits for health and aging.

The project, according to Richard Weindruch, the UW-Madison School of Medicine and Public Health professor who has led the research since 1994, is in a critical phase as the monkeys in the study are entering late middle age, which for rhesus macaques is their early to mid-20s. In captivity, rhesus monkeys can live up to 40 years.

Late middle age, Weindruch notes, is the time of life when a host of age-related conditions such as diabetes, heart disease, cognitive deficits and arthritis, among other things, begin to manifest themselves. This is true, he says, for both monkeys and humans.

"This is a very interesting time in the study," says Weindruch, who also is an investigator at the Geriatric Research, Education and Clinical Center at the William S. Middleton Memorial Veterans Hospital. Because the animals have reached this stage of life, "it's show time for dietary restriction."

At this point in the study, the disparities between the monkeys on a diet reduced in calories by 30 percent and those allowed to eat as much as they wish are clearly evident. "Most importantly, we're starting to see the separation of the survival curves," Weindruch says, noting that 90 percent of the animals who began the study on a reduced diet are still alive, while only 70 percent of the animals allowed to eat freely have survived to this stage.

Of those animals who have died, most have succumbed to the same age-related conditions that kill many humans with colon cancer claiming the most, and diabetes and heart disease also taking a high toll. Says Weindruch: "Whether these trends will continue, time will tell."

The idea that fewer calories can extend lifespan and improve health has a long experimental history. The notion has been tested in animal models ranging from spiders and mice to, more recently, fledgling studies in humans. But the rhesus macaques in the Wisconsin study, according to Weindruch, offer perhaps the best window into a phenomenon that is the only proven dietary way to extend lifespan. Rhesus macaques have much in common with humans, including a similar genetic makeup and susceptibility to many of the diseases and conditions that affect human health.

University Communications
News releases

FOR IMMEDIATE RELEASE
July 20, 1999
CONTACT: Richard Weindruch, (608) 256-1901, Ext. 1642, rhweindr@facstaff.wisc.edu

((Editor's note: We've put together a news media resource web page at http://www.news.wisc.edu/newsphotos/aging.html for organizations wishing to download high-resolution images to accompany this story.))

$6.75 MILLION TO EXTEND PRIMATE STUDIES OF DIET AND AGING

MADISON - A decade-long study of how diet affects the process of growing old, will continue and be expanded at the University of Wisconsin-Madison with the help of $6.75 million from the National Institutes of Health (NIH).

Begun in 1989 at the Wisconsin Regional Primate Research Center (WRPRC),
the study of rhesus macaques on controlled diets is one of only two such studies in the world. The research, according to Richard Weindruch, a UW-Madison Medical School professor and the lead scientist for the project, is intended to answer a central question of biology: Can aging be held at bay by cutting down on calories?

"Dietary restriction offers a powerful experimental strategy to explore mechanisms of aging because it is the only intervention which has repeatedly and strongly increased maximum life span and retarded the rate of aging in laboratory rodents," said Weindruch. "But the study of calorie restriction and aging in non-human primates is in its infancy, as compared to the body of work done in rodents."

The new grant will enable scientists to continue studies in rhesus macaques, a much-studied and long-lived animal whose genetic and physiological characteristics parallel those of humans. The work is being conducted in several groups of primates whose calorie intake for the past five to 10 years has been reduced by about 30 percent, as well as monkeys whose diets permit them to eat as much as they wish.

The study of rhesus monkeys builds on extensive research in rodents, spiders and other animals that shows life span can be significantly extended and the rate of aging slowed by maintaining a nutritious but restricted diet, according to Weindruch.

UW-Madison Home
News from UW-Madison

UW-Madison News Releases
University Communications
News releases

FOR IMMEDIATE RELEASE
7/9/09

PHOTO EDITORS: Images are available for download at http://www.news.wisc.edu/newsphotos/monkeyDiet09.html

CONTACT: Richard Weindruch, 608-256-1901, ext. 11642, rhweindr@wisc.edu; Ricki Colman, 608-263-3544, rcolman@primate.wisc.edu; Sterling Johnson, 608-256-1901 ext. 11946, scj@medicine.wisc.edu

REDUCED DIET THWARTS AGING, DISEASE IN MONKEYS

MADISON - The bottom-line message from a decades-long study of monkeys on a restricted diet is simple: Consuming fewer calories leads to a longer, healthier life.

University Communications
News releases

FOR IMMEDIATE RELEASE
6/4/08

CONTACT: Tomas Prolla, (608) 265-5204, (608) 556-0175 (cell), taprolla@wisc.edu; Richard Weindruch (608) 256-1901 ext. 11642, (608) 556-0176 (cell), rhweindr@wisc.edu

AGENT IN RED WINE FOUND TO KEEP HEARTS YOUNG

MADISON - How, scientists wonder, do the French get away with a clean bill of heart health despite a diet loaded with saturated fats?

The answer to the so-called "French paradox" may be found in red wine. More specifically, it may reside in small doses of resveratrol, a natural constituent of grapes, pomegranates, red wine and other foods, according to a new study by an international team of researchers.

Writing this week (June 3) in the online, open-access journal Public Library of Science One, the researchers report that low doses of resveratrol in the diet of middle-aged mice has a widespread influence on the genetic levers of aging and may confer special protection on the heart.

Specifically, the researchers found that low doses of resveratrol mimic the effects of what is known as caloric restriction - diets with 20-30 percent fewer calories than a typical diet - that in numerous studies has been shown to extend lifespan and blunt the effects of aging.

"This brings down the dose of resveratrol toward the consumption reality mode," says senior author Richard Weindruch, a University of Wisconsin-Madison professor of medicine and a researcher at the William S. Middleton Memorial Veterans Hospital. "At the same time, it plugs into the biology of caloric restriction."

UW-Madison Home
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University Communications
News releases

FOR IMMEDIATE RELEASE
11/18/10

CONTACT: Tomas A. Prolla, 608-556-0175, taprolla@wisc.edu; John M. Denu, 608-265-1859, jmdenu@wisc.edu

SCIENTISTS FERRET OUT A KEY PATHWAY FOR AGING

MADISON - For decades, scientists have been searching for the fundamental biological secrets of how eating less extends lifespan.

It has been well documented in species ranging from spiders to monkeys that a diet with consistently fewer calories can dramatically slow the process of aging and improve health in old age. But how a reduced diet acts at the most basic level to influence metabolism and physiology to blunt the age-related decline of tissues and cells has remained, for the most part, a mystery.

Now, writing in the current online issue (Nov. 18) of the journal Cell, a team of scientists from the University of Wisconsin-Madison and their colleagues describe a molecular pathway that is a key determinant of the aging process. The finding not only helps explain the cascade of events that contributes to aging, but also provides a rational basis for devising interventions, drugs that may retard aging and contribute to better health in old age.

"We're getting closer and closer to a good understanding of how caloric restriction works," says Tomas A. Prolla, a UW-Madison professor of genetics and a senior author of the new Cell study. "This study is the first direct proof for a mechanism underlying the anti-aging effects we observe under caloric restriction."  

University Communications
News releases

HOLD FOR 5 P.M. EASTERN TIME RELEASE OCTOBER 28, 2002

CONTACT: Tomas Prolla, (608) 265-5204, taprolla@facstaff.wisc.edu; Richard Weindruch, (608) 256-1901, Ext. 11642, rhweindr@.wisc.edu

NOTE TO PHOTO EDITORS: To download high-resolution photos that accompany this story, visit: http://www.news.wisc.edu/newsphotos/age.html

EVEN IN MIDDLE AGE, CUTTING CALORIES SLOWS AGING OF THE HEART

MADISON - To remain young at heart, eat less.

That, in short, is the message drawn from research published today, Oct. 28, by a team of researchers from the University of Wisconsin-Madison.

Writing in the Proceedings of the National Academy of Sciences (PNAS), a research group led by UW-Madison genetics Professor Tomas A. Prolla, and Medical School Professor Richard Weindruch, reports the results of a study in which middle-aged mice, put on a calorie-restricted diet, exhibit signs of a remarkable uptick in heart health in old age.

"It looks like caloric restriction just retarded the whole aging process in the heart," said Prolla whose group employed powerful molecular techniques to study nearly 10,000 genes at work in the heart. The work represents the first global analysis of gene expression in the aging heart.  

FOR IMMEDIATE RELEASE
August 26, 1999

CONTACT: Tomas A. Prolla (608) 265-5204, taprolla@facstaff.wisc.edu; Richard Weindruch (608) 256-1901, Ext. 1642, rhweindr@facstaff.wisc.edu

(NOTE TO PHOTO EDITORS: High-resolution images of Prolla and Weindruch are available for downloading at: http://www.news.wisc.edu/newsphotos/age.html )

STUDY DETAILS GENETIC BASIS OF AGING-- AND HOW IT MIGHT BE DELAYED

MADISON - Scientists at the University of Wisconsin-Madison have, for the first time, profiled specific genetic changes during the aging of experimental animals, a discovery that could aid work to extend life span and preserve health.

The work conducted with mice combines a powerful new genetic technique with dietary restriction, the only known way to delay the aging process. The research will be published Friday, Aug. 27, in the journal Science.

The study is a milestone in aging research, providing scientists with an intimate look at the ebb and flow of genetic activity with age, and the roles individual genes play in the process of growing old.

Moreover, it reveals how a low-calorie diet, the only known method of slowing aging in several animal species, works at the most basic level to extend life span and preserve health. Such knowledge, used in concert with new technologies capable of rapidly surveying the activity of thousands of genes at once, promises to accelerate the development of drugs that mimic the age-retarding effects of a low-calorie diet, according to the Wisconsin scientists.