November 2006 Archives

Mars Global Surveyor Bites the Dust

National Aeronautic and Space Association (NASA) scientists fear that the suddenly silent Mars Global Surveyor (MGS) is lost forever. MGS orbited Mars for over 9 years transmitting information and over 240,000 images to Earth from Mars, before failing a few weeks ago because of a solar panel malfunction. NASA launched the craft 10 years ago and it was only expected to last 2 years -- or 1 Martian year -- but the orbiter remained active until now, so scientists emphasize that MGS has had a productive existence.

Over the past two weeks NASA valiantly attempted to revive the floundering craft, at times employing the Mars Reconnaissance Orbiter (MRO) and a rover called Opportunity to locate MGS, but all attempts were to no avail. Ground controllers who tried to communicate with MGS "were met with a silent response from the misbehaving probe", according to a a space.com report.

The Mars Global Surveyor was the oldest of five NASA spacecraft currently in use on Mars, which also include the 2001 Mars Odyssey, Mars Reconnaissance Orbiter (MRO), Mars Express, and two Mars Exploration Rovers called Opportunity and Spirit. Spirit was the subject an October profile by the satirical news journal The Onion titled: "Mars Rover Beginning to Hate Mars". (link fixed 10/11)

The Onion wrote of an increasingly hostile rover sending belligerent messages ("STILL NO WATER") and the occasional obscene gesture back to the Earth. The paper said that an irate Spirit was jealous of the orbiting spacecrafts because they got to fly and suspected that the other rover, Opportunity, "has found water and isn't telling anyone". The fictional report quoted an ever optimistic Spirit management team:

"Hopefully these malfunctions will straighten themselves out," one of the lead scientists commented about the robot and its spiteful messages..."In the meantime, we'll simply have to try to glean what usable data we can from 'OVERPRICED SPACE-ROOMBA AWAITING MORE BULLSHIT ORDERS.'"

Even scientists become a little sentimental about these robots it seems, anthropomorphizing the robots not only in fiction but real life. "We may have lost a dear old friend and teacher," said Michael Meyer, chief scientist for Mars exploration at NASA, according to non-fiction news reports. No doubt it will be a sad final farewell, but along with "ashes to ashes and dust to dust", I'm sure scientists and long time friends will say that the Mars Global Surveyor (MGS) died doing what (s)he loved best.

FDA Approves Silicone Breast Implants: Safe Decision?

Notice: This article was written in 2006 and might be outdated. It is not medical advice, does not endorse recommend/not recommend any product, nor recommend/not recommend any procedure.

FDA Approves Sale of Silicone Implants to Applause and Criticism

The Food and Drug Administration (FDA) approved the sale of silicone breast implants on Friday. This type of implant, but not the saline ones, had been banned for sale in the U.S. since 1992. The New York Times reported yesterday that "supporters" of the FDA decision, "including leading surgeons, applauded" this week's approval of silicone breast implants. Others apparently "lambasted" the decision. The products are manufactured by Allergan Corp. (formerly Inamed), and Mentor Corp., both in California. The FDA reviewed clinical trial data from the two manufacturers for "up to four years", and studied "a wealth of other information to determine the benefits and risks of these products", according to Daniel Schultz, M.D., Director, Center for Devices and Radiological Health, FDA.

Risks

Women who contemplate the operation to have implants inserted will most likely come across marketing data from the implant makers and plastic surgeons. However there are real risks to the implants, described in the 44 pages of consumer information on Mentor's product, in "Important Information for Augmentation Patients About Mentor MemoryGelTM Silicone Gel-Filled Breast Implants"--available here. (This is a separate document from the breast reconstruction document for Mentor, and also separate from Allergan's augmentation and reconstruction documents). The most common risk is re-operation. According to Mentor's data 15.4% of primary augmentation group and 28% of the revision-augmentation patients were reoperated during the three years of the study. For the Mentor reconstruction group, those numbers were 27% and 29%. For the Allergan augmentation group, studied over 4 years, those numbers were 23.5" and 35%. For the Allergan reconstruction group over 4 years 41% and 33% of patients were reoperated.

Rupture is another risk. Rupture is often silent (unnoticed by the wearer) therefore most reliably detected with regular Magnetic Resonance Imaging (MRI) examinations, which the FDA recommends after 3 years and once every 2 years after that. Unfortunately, compression during mammographic imaging increases the risk of rupture. In the Mentor Core Study the rupture rate was 7.7% over 3 years for the MRI cohort¹.

When the breasts rupture, the silicone gel can "remain within the scar tissue capsule surrounding the implant", or it may migrate, which has possible health consequences. The report summarizes the health consequences, "which have not been fully established", but include change in breast shape or size, pain, and "rare" reports of nerve damage, granuloma formation, tissue breakdown, and lymphadenopathy due to migration of the gel into the liver, arm, groin, chest wall, armpit or upper abdominal wall. A study released in April, 2005 in the study, published in the American Journal of Surgical Pathology, reported on the pathology of lymph node biopsies of women 96 who had breast implants removed and 14 controls. Rare foamy macrophages were found in 91 implant women and 4 controls. Refractile studies showed the presence of polyurethane in 16 women, and silicone in 86 women. Spectroscopy confirmed the presence of silicone in 71 patients with implants, and the presence of 2 polyurethane in 2 patients with implants. Silicone and polyurethane were not found in the control group's lymph nodes.

Capsular contracture is separate side effect, classified by Baker Grades which help physicians determine the severity of the side effect that can necessitate removal. The implants usually aren't removed in cases of Baker Grades I and II, however in Baker Grade III, where the breast hardens and changes shape, and Baker Grade IV that involves "hard, obvious distortion, and tenderness with pain", the implants usually need to be changed. The two company's clinical trials showed slightly different results for side effects. In the Mentor study 8% of the women who received first time augmentation experienced severe capsular contracture in the first three years. In the revision-augmentation cohort the risk was 19% in three years. Nipple complications and scarring/hypertrophic scarring occurred in approximately 10% and 8% of the population, respectively. Other complications occurred much less frequently, such as sagging, lactation complications, infection, hematoma, etc.

The studies also followed self-reported signs and symptoms of which there were 100. There were 50 reports of rheumatological symtoms and a few other frequently reported conditions that were not necessarily caused by the implants including:

"significant increases...[in] fatigue, exhaustion, joint swelling, joint pain, numbness of hands, frequent muscle cramps and the combined categories of fatigue, pain and fibromyalgia-like symptoms in primary augmentation patients, and for joint pain in revision-augmentation patients. These increases were not found to be related to simply getting older over time.

The FDA decision also requires the two companies to follow 40,000 women who receive breast implants for 10 years. The patient information listed on the FDA site notes that the breast implants are not permanent, and need to be periodically replaced. The older they are the more likely they will need to be replaced.

High Patient Satisfaction

According to Mentor's own survey on patient satisfaction, when asked by their surgeon at 3 years: "Would the patient have this breast surgery again? 81% of the 146 revision-augmentation patents, and 83% of the 456 primary augmentation patients answered. Of those, Mentor said, 94% and 98% respectively, said they would.

Acronym Required wrote about silicone implants last year in Silicone Implants -- A Health Risk to Choose?, which looked at documents obtained by the New York Times showing that ruptures probably more common than Mentor reported and that the company falsified data. In "Silicone Implants and the FDA (more)", Acronym Required looked at different opinions about why the FDA had at one point approved Mentor's application, but not Inamed's. The NYT had reported that Mentor may have falsified data. In addition, the Boston Globe reported that there were different numbers of plastic surgeons on the review committees for each company.

Some Disapprove

Some think the decision is a travesty. The National Organization for Women, (NOW), said, "sadly, we are not shocked that this agency is swayed more by money and politics than science and medicine." Among other health issues, NOW expressed concern for the health of the women and children, and especially evidence that platinum leaks from the silicone implants. Research on this issue was published in Analytical Chemistry. Acronym Required wrote about this several months ago in "Platinum Bonds and Silicone Implants". Plastic surgeons are elated by the news. "For us, it's a triumph of science," said Dr. Richard A. D'Amico of Engelwood, N.J., who is president-elect of the American Society of Plastic Surgeons.

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¹ This consumer information said that the non-MRI cohort had "0%" rupture rate, however elsewhere the report makes it clear that silent ruptures can only be detected by MRI. The presentation of information was confusing -- it's not "0"- it's unknown. As well, will the juxtaposition of the data discourage women from getting MRI's, even though the FDA recommends them?

Britain's science path: brilliant lights?

When science is cool & scientists are stars

Prime Minister Tony Blair says he's trying to revive science. He admits he was a "refusnik" at school, but now he's a "born-again" and "evangelical" (scientist). Although his choices got him to the position of Prime Minister, he now wishes when he was in school he hadn't eschewed laboratory and thought all scientists were boffins. "This is Britain's path to the future, lit by the brilliant light of science", he said recently. Many people in the UK have voiced concern about the drop of students in the hard sciences -- math, engineering and physics. Blair forever tries to entice students to study science, and now promises they will be rewarded with rainbows, bright lights and stardom. Blair spoke passionately on the subject earlier this month:

"We need our scientists today to be as celebrated and famous as our sportsmen and women, our actors, our business entrepreneurs. Scientists are stars too....Science today abounds both with noble causes and with glittering prizes: reach out for them."

Could stardom be arranged? Maybe instead of being abruptly awakened by a phone call at the ungodly hour of 4:00AM and told of their award in front of a tiny sleepy audience, a spouse or dog -- Nobel Laureate nominees could gather somewhere in Hollywood, at a reasonable time of day, for a grand awards ceremony that lasted hours and hours. Crowds worldwide would see bejeweled scientists with plunging necklines and scientists in tuxedos parading down the red carpet for photographers. Someone famous could emcee (who's funny, maybe British), and we'd listen to dramatic uplifting music. In between the numerous awards, pomp and circumstance, they'd screen retrospective films of the scientists' careers in the lab -- producers would edit the footage to highlight the exciting moments. Or maybe scientists could be like music stars, which would entail racier awards ceremonies where the scientists would slouch around and wear sunglasses. Of course some people, hearkening back to the events like the stem cell debacle, argue that science and fame are too combustible for prime time.

Nature makes a great point in their current issue, that Time International's recent "60 years of heroes" has nine musicians, but only one scientist.That scientist is Andrei Sakharov, a thermonuclear physicist listed under the "Rebels and Leaders". We do wonder why they left out Linus Torvalds, a computer scientist, who Time also included in "Rebels and Leaders". Computer scientists seem to have achieved the cool/nerdy thing, perhaps we should include them in our science mix to raise our stature. Notice that Linus was placed between Margaret Thatcher and King Juan Carlos on the Time's eclectic list, and I believe Linus managed to make them seem cooler. We might consider the strategy.

Describe "evidence based science"

Despite his rhetoric about make scientists "stars", some people say that Blair is only interested in science that furthers industry, and that he complains too much about "campaigners" and the anti-science brigade" who protest that nuclear energy or genetically modified foods "threaten our future". Others say Blair sends mixed messages about science, for example by promoting homeopathy but scorning people who question the safety of the MMR vaccines. In general people welcome the sentiments but criticize Labour's actual science policies:

  • In "UK Civil Servants Accused of Warping Science", Nature reports this week that in the Labour government "political interference in science policy is far greater in the United States".
  • The Guardian said that members of Parliament reported earlier this month that government used the words "evidence based science" and "hides behind a figleaf of scientific respectability when spinning unpalatable or controversial policies to make them acceptable to voters"
  • A Science and Technology report by the House of Lords earlier this month criticized science teaching. The report suggested that science curriculum is too test-oriented and narrow. Students avoid science for easier subjects. There is a shortage of chemistry, physics and math teachers, and teachers should be incentivized for the long-term instead of with golden hellos.

Britain seems to have the same issues with science as Australia, the U.S., and many Western countries. Blair forever champions science, but it's unclear what the outcome of all the talk will be. In a speech to the Labour Party Conference last month he covered a gamut of science topics -- curing cancer, "lab-on-a-chip technologies", early diagnoses for Alzheimer's and glaucoma and cataracts, "DNA vaccines for AIDS and malaria and Hepatitis B and some cancers", information technology for reduced technology fraud, nanotechnologies, in fact everything from climate change to cars that would keep drivers in the correct lane.

However, the audience reacted listlessly to the myriad of science topics and action items, according to the The Guardian's "clapometer" readings. Only two science topics elicited much excitement from the Labour audience. The first was Blair's call for nuclear power: "without it we are going to face an energy crisis" (6.01 seconds of clapping). The other was his mention of stem cell research: "we welcome it here" (12.2 seconds). The other 27 clap-worthy topics ranged from nationalistic: "Identity cards ... are an essential part of responding to the reality of modern migration" (10.74 seconds), to personal: "At least she's [Cherie] not going to run off with the bloke next door" (17.30 seconds), hyperbolic war cries: "Withdrawal from Iraq: "A craven act of surrender" (11.44 seconds), to FDR-ish polyptotons: "They will lose faith in us only if first we lose faith in ourselves" (13.93 seconds).

We know that a clapometer is a cheap surrogate for predicting future policy and assume/hope it fails to measure Labour's true level of commitment to all the science issues on the table. However the level of politicians' enthusiasm for science, including basic science, will no doubt register with budding scientists and perhaps influence their choice to believe the hype that as scientists they will lauded as stars, or even paid sufficiently.

Healthcare IT: The Perfect Storm

The Perfect Storm, Corporate IT vs. Determined Employee

Kaiser Permanente employee Justen Deal noticed few months ago that the custom implementation of the health care provider's Epic Systems records management system, dubbed "HealthConnect", was costing billions of dollars but was plagued by persistent problems that effected health care delivery. In addition, the employee projected future operating expenses and expected revenues and asserted that Kaiser faced a $7 billion dollar deficit in the next couple of years. He wrote some letters to individuals in charge of corporate oversight, to the board, and to various internal parties who he thought should be concerned. They said they'd investigate his concerns, they warned him not to talk to the board, they said he was mistaken, and at times claimed they didn't understand his complaints. He sent more evidence. Finally Kaiser lawyers said they investigated his complaints and said they were all baseless. Not satisfied, he sent letters to several California state agencies. All of these communications are now posted at his site called www.fixkp.org, and make for very interesting reading. Finally he sent a letter to over 50,000 employees, again listing his concerns.

In response, the CEO of Kaiser, George Halvorson, wrote a letter of his own to all 151,000 employees refuting Justen Deal's allegations. "The person who wrote the e-mail is a young man relatively new to KP whose job involves publications...", he starts out. "Overall, the e-mail was an unfortunate combination of partial facts, old data, incomplete data, "conspiracy" thinking, and naivete´.", he ends. He addresses the complaints. Responding to Justen's comments about his replacement of the board right after he was hired at Kaiser, he says, "I suspect he hasn't evaluated very many Boards."

He dismisses Justen's questions about an audit of his position at a previous employer, a Minnesota managed healthcare organization called Health Partners. The Minnesota Attorney General's Office's audit was "critical" his $5.5 million dollar compensation package when he left and his financial oversight as the CEO. But Halvorson said the 'routine' audit cleared him: "no actions, no citations, no regulation violations and no mandatory results of any kind."

Justen Deal also criticized the CIO of Kaiser for simultaneously serving as a director of a company hired as a consultant for Kaiser, while he was employed at Kaiser. Halvorson's letter declared that the CIO "was not, in fact, a principal or Board member of the "Tanning" company when they did our systems evaluation work. However, "J. Clifford Dodd", the CIO of Kaiser, was indeed at Kaiser when he hired Tanning Technologies, a consulting company that lists him as director "John C. Dodd", at least according to Tanning's own SEC filing in 2002.

Mr. Halvorson also addressed the technical problems implementing Epic Solutions system that Deal outlined: "KP HealthConnect issues are both inaccurate and wrong". The HealthConnect system is working well, he said. However a ComputerWorld author wrote an article titled "Problems abound for Kaiser e-health records management system: An internal report details hundreds of technical issues and outages", which details a few of the hundreds of problems listed in the 722 page internal report on the system's issues and outages. The system has been down for hours at a time causing various critical disruptions within the Kaiser healthcare system:

  • "On May 10, a power outage that lasted for 37 hours and 9 minutes affected multiple facilities [causing pharmacy and tracking problems]..If a patient were transferred during this time they would need to track their location manually [and]....users are reporting that multiple patients are showing in the wrong beds"
  • March 26, for 3 hours and 51 minutes, "users in multiple locations..were unable to access patient info or update patient info"
  • April 10 for 1 hours and 23 minutes, drug information is not population for nurses, pharmacists, and technicians in one office and they "cannot see patient updates for new [drug] orders or changes in meds, such as stopping orders..."
  • "On June 7, for 6 hours and 34 minutes, labs were unable to collect data, run tests and provide test results."
  • "On Oct. 10, for 3 hours and 24 minutes, doctors and nurses in several facilities were unable to retrieve critical medical information to treat patients."

These were only a few of the issues. IT is tough business, especially for critical systems in healthcare and banking. Clearly, this is a massive system subject to significant challenges. Kaiser Permanente has 151,000 employees, 37 medical centers, 12,000 physicians, 8.6 million members and $31 billion in operating revenue. The plan to get the system up and running in three years was ambitious. So someone like Justen, who is not accustomed to the thorny business of IT would be rightly shocked at the messiness of it all. That the system was supposedly written in "MUMPS (Massachusetts General Hospital Utility Multi-Programming System) -- a health care programming language originally developed in the 1960s", may or may not be relevant, but the software had certainly never been scaled to this size organization. Various sources report different issues, architecture, planning, personnel and management failures.

Throughout his communications, Justen Deal expressed concern about a projected $7 billion dollar deficit that Kaiser was facing. Halvorson said in his letter, "The memo leads off with a mention of our financial future. Interestingly, that's the one area where the e-mail may have done us all a service". Halvorson says he warned about the looming deficits in internal memos. The projected deficit was news to the San Francisco Chronicle, which published a story about Deal's email and the impending deficit titled: "Kaiser: Critical need to cut rising costs $7 billion in losses if no action taken, HMO report says". Halvorson told the Chronicle that Kaiser has started cutting costs -- that wouldn't affect patient care.

Many, many of the details of this story are unknown. In the end, similar to Katrina, if there's a massive hurricane brewing off the coast, then FEMA's assurances that they're prepared and everything is fine will only subdue the masses until the storm hits. Kaiser will hopefully get the system up and running -- and if so it will be a feat. In the meantime, the turmoil is very real. The CTO, Cliff Dodd, resigned the day after Deal sent his mass email. Kaiser denies that the Chief Technology Officer's resignation is at all related to Justen's allegations.

Business and the Web 2.0 Generation?

On one hand Justen Deal believes he's preventing another Enron, which is arguably an idealistic or grandiose idea. Its easy to imagine that he was infected by disgruntled IT employees whose project was canned in the decision to license Epic. It's easy to argue that he's young and naive, which is the tack that Kaiser took in their correspondence. However, while anyone can make these points, a reading of the letters on the www.fixkp.org website shows that the organization handled him abysmally. One letter written by outside counsel addresses just one of his complaints by curtly listing about 30 other organizations using the Epic System, followed by: "Do you have any concerns that you can list with us about the decision-making process used by these providers to select Epic?".

It was clearly a fishing expedition and Deal quickly questioned why the lawyer, who Kaiser used to defend itself against wrongful termination suits, was fielding operations questions addressed to the board. He writes back in a letter posted on his site that his opinions of Kaiser's Epic selection processes are "irrelevant" and that engineering documents addressed this. Obviously he couldn't answer her question about other organizations' decisions, he said. He did offer information about the relative sizes of some of the organizations she listed. Some had several hundred members, compared to Kaiser's 8.6 million, others had several hundred doctors, compared to Kaiser's 13,000, doctors, etc.. In this view then, the system wasn't proven to scale or architected to an organization the size of Kaiser.

Clearly, his opinions of the system aren't isolated, since outages have caused turmoil across the organization. A recent article in Harvard Business Review talks about different IT implementations including enterprise systems that impose process changes at all levels of the organization. The author gives the example of another health care organization that failed:

"In 2002, a Boston-based hospital set up an IT system that replaced handwritten prescriptions with online orders. ...Even though studies had demonstrated that the system would reduce medication errors, physicians bitterly resisted. They complained that the computer-based process was slower and less convenient than paper-based ordering and that the built-in error checking didn't work. They protested so strongly that the hospital was able to roll out the system in only a few departments. Today, most of the doctors continue to write prescriptions on paper and fax them to the hospital's pharmacy..."

It wasn't the only Healthcare IT project to fail. On a larger scale, Britain's 2002 healthcare initiative evidently wasted $24 billion, and apparently two Members of Parliament say the project is "sleepwalking toward disaster." The author of the Harvard Business Review article says, "In fact, the biggest mistake business leaders make is to underestimate resistance when they impose changes in the ways people work." He quotes a CIO, who said '"I can make a project fail, but I can't make it succeed. For that, I need my [non-IT] business colleagues."' Successful system implementations need to broad support at all levels. This may be even more important in the future.

Deal was definitely a thorn in Kaiser's side, someone who was young, unintimidated, and apparently not yet appropriately practical (or cynical, depending on your view). Kaiser's tactics, aimed at quieting him, seemed to have the opposite effect. The internet gave easy public access to SEC statements, newspaper articles, attorney generals' audits. He dug deeper, found more evidence, wrote precise, articulate letters, and did not back down. He thought he had important insight that was being ignored. In a way, Kaiser executives underestimated both technology and Mr. Deal.

Twenty somethings virtually grew up with the internet. Deal's identity is available at his blog, and anywhere else on the internet, which is typical to many people his age, who for better or worse, have markedly different attitudes about privacy then previous generations. The attitude that information, personal, corporate or otherwise is free and accessible, flies in the face of a certain corporate theology in which information is coveted and hoarded, and top down management restricts open exchange especially between personnel levels. In this age, is this an effective way to manage? Is it an effective structure with which to implement an enterprise wide system? The corporation's attitude about information clashed with today's information accessibility.

Is Justen Deal and Kaiser an isolated event or a new trend? Either way, it could be a wake up call for organizations. But whether Kaiser is contemplating this, or as we speak rewriting the employee handbook rules and toiling over their public relations effort, remains to be seen.

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Acronym Required has written other articles about management issues here.

Calorie Reduction or Resveratrol, Which Path?

Is the future thin monkeys or chubby mice? Gerontology is having a productive week, as the results of two anti-aging studies promise greater longevity -- or do they? In one study, researchers fed Rhesus monkeys a reduced calorie (CR) diet to counter the effects of aging. In the other mice were given large doses of resveratrol, a compound found in grape skins and wine, which apparently countered the ill-effects of a high fat diet. Both the mice and the monkeys thrived on their respective regimens.

When researchers reduced Rhesus monkeys' daily caloric intake, allowing the monkeys far fewer food pellets than the animals might have liked, as the animals aged they suffered less arthritis, heart disease, cancer, Alzheimer's diabetes, and Parkinson's than the cohort fed the regular diet. This result isn't surprising. There is well known longevity effect attached to under eating, and mice, rats, fruit flies, roundworms and other species have all taken a turn at proving this theory. But although "systematic under eating", "under nutrition without malnutrition", and "long-term under nutrition" have been around for almost a century, scientists forever hedge when it comes to recommending such a regimen for humans. In April, 1990 the New York Times wrote in "Diet Offers Tantalizing Clues to Long Life":

"initial observations that an extremely low-calorie diet extends life span in animals date back to the 1930's, but they were long shrugged off as mere laboratory curiosities."

In that 1990 article scientists had yet to study monkeys so they warned that people should be careful about under eating:

"..researchers warn against people undertaking an ascetic regimen too hastily. They stress that experimental animals are fed carefully measured and planned menus that are difficult to translate into human fare, and that it is easy to become malnourished."

Despite the warnings, the CR *movement* has gained a dedicated group of followers in the past decade, although certainly hordes of people aren't clambering aboard the semi-starvation bandwagon. New York Magazine offered a a glimpse of the lifestyle of the CR group this week in "The Fast Supper". Between the magazine's profile and the New York Times article, One for the Ages: A Prescription That May Extend Life", you can get a taste of the ascetic lifestyle choices of CR diet adherents.

Newspaper reports about the studies feature pictures of the lab animals in different states of aging, some graceful, posing for photographers next to plates of food and wine. The animals peer out from the pages of the newspaper, as if taunting the reader -- that supposedly brainy human species which spends millions of dollars seeking anti-aging remedies and pursuing immortality yet flirts with mortality incessantly by eating so much as to become quite fat, and ill and decrepit. Acknowledging the sometimes ironic senselessness of it all, nevertheless, one might endure such deprivation -- if it worked.

But even if you're convinced (or not) by CR advocates who say they enjoy their three leaf salads with a spot of dressing and a scallop and if you don't find the gaunt, bony aesthetic off-putting, doctors' conclusions about the diet might dissuade you from forgoing today's breakfast, lunch and dinner. Tuesday's article reports that "despite initially promising results, some scientists doubt that calorie restrictions can ever work effectively in humans." (emphasis ours). Of course that's the "initially" that means "after decades of conclusive research". The article cited "mathematical models", and also the not so empirical statements from scientists like Dr. Jay Phelan:

"calorie restriction is doomed to fail, and will make people miserable in the process...have you ever tried to go without food for a day"?

Never mind those humans who find this diet quite rewarding, or that decades of research shows that it (more by less) works. Red wine and resveratrol, by comparison, seem to have a more optimistic future -- at least according to the pundits. In 1990-1991 French researchers and scientists at Cornell found that resveratrol might lower cholesterol. People cheered the idea that red wine might actually be "healthy", although scientists coached "moderation". In the current study, mice who were fed large doses of resveratrol and a high fat diet somehow weren't afflicted with heart disease, diabetes, and liver damage. (Interestingly though, cholesterol levels remained high.)

The resveratrol researchers write that the effect of the chemical was similar to calorie reduction and in fact shared 19 pathways, including increased insulin sensitivity and increased hepatic mitochondrial number. They report that it reversed the effects of the unhealthy diet and put the mice who took ample doses of the compound on par with the regular diet control mice. The principle author, Dr. David Sinclair, of Harvard University and Sirtris Pharmaceuticals Inc.(a company with a stake in the research) says that although the mice are chubby, their organs looked younger than the control mice.

The journal Nature, which published the resveratrol paper, was cautious about the results and about extending these results to humans. The mechanism of resveratrol's action aren't precisely known (or published), its safety is untested, and the study used a relatively small sample size of mice. Scientists didn't test whether the chemical could reverse previous liver damage since the mice always took the the chemical. The paper's author thinks that resveratrol may act on SIRT1, as it does in vitro, but that's still speculative. Despite the caution, Nature briefly dares to indulge in cavalier bursts of enthusiasm such as, "of course, the mechanism isn't so important if the drug works." The New York Times notes optimistically:

"very large daily doses of resveratrol could offset the unhealthy, high-calorie diet thought to underlie the rising toll of obesity in the United States and elsewhere, if people respond to the drug as mice do".

Both the mice and the monkeys lived longer lives, but if humans get to pick their poison, we could bet which path will appeal to the most people. It's clearly cheaper to just forgo eating (the CR method). But if people could live a gourmand's life and supplement their gluttony with pills that counteracted the results of overindulgence, we think they might prefer that route. If they could preserve normal physiological functions but not sacrifice that burger, those fries, that croissant, then the popularity of Sirtris Pharmaceutical pill would prevail. Unfortunately, one can't get the same effect from wine -- it would take excessive amounts to get the dose of resveratrol that the mice were given, but you can ignore that you now know that, and just drink wine "because of the resveratrol".

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