Longevity Pill Tested in Humans

What if I told you there was a pill that slows aging and allows you to live a healthy life to age 100?

Such a pill may exist right now. It's being tested in people in very early-stage human clinical trials. Today, the company making the pill, Sirtris Pharmaceuticals, announced its findings from preclinical testing in cells and animals, and also from tests conducted on 85 male volunteers this summer.

The verdict: so far, the pill works, although it will be years before we know how well it works, or if it can actually extend the life span of people in the same way that it has bumped up the life span of mice.

Speaking today at the Annual Metabolic Diseases Drug Discovery and Development World Summit in San Diego, Sirtris's senior director of biology, Jill Milne, announced that the drug, SRT501, reduces glucose and improves insulin sensitivity in animal and in vitro studies of the drug's effect on type 2 diabetes. In people, the drug was tested for dose, safety, tolerability, and pharmacokinetics--that is, how well the drug was absorbed, distributed, metabolized, and removed from the body.

Phase 1b trials are already under way to test safety and pharmacokinetics on patients with type 2 diabetes. Later-phase trials will test to see if the drug actually works in diabetics.

SRT501 is a proprietary chemical developed by Sirtris that's based on the naturally occurring resveratrol that company cofounder David Sinclair of Harvard University has been studying for its effects in extending life span in a number of organisms, including yeast, flies, and mice. Last year, Sinclair created a sensation when he published a paper in Nature detailing how mice on a high-fat diet that were fed large doses of resveratrol were as healthy as mice on a regular diet. Resveratrol also sharply extended life span, produced positive changes in insulin sensitivity and other diabetes-preventing mechanisms, and increased energy production in cells. The mice were given very high doses of resveratrol--22 milligrams per kilogram of weight. In comparison, a liter of red wine delivers 1.5 to 3 milligrams. To match the results in the mice, a 150-pound human would need to drink 750 to 1,500 bottles of wine a day.

Sinclair says that SRT501 is a thousand times more potent than naturally occurring resveratrol, which gives it the same punch as the resveratrol in all those bottles of wine.

Sinclair believes that resveratrol activates a gene called SIRT-1, which is associated with the regulation of life span in several animals. This contention is disputed by some critics: they argue that the mechanism by which resveratrol works is still poorly understood.

Because humans are so long-lived, SRT501 can't be easily tested for longevity in humans--nor does the Food and Drug Administration recognize "increased life span" as an allowable indication for an approved drug. This is why Sirtris is testing SRT501 for diseases related to aging, such as type 2 diabetes. However, should the drug be approved for diabetes, it will undoubtedly be used to extend life span by many people without diabetes.

The drug still has years of testing to go and faces many hurdles. It may not work. But if it does, the consequences will be profound. For instance, it will mean that more people will be alive on the earth. Age 90 will be the new 70, and 70 the new 50, with profound impacts on everything from social security to retirement age. It may also mean fewer people with diabetes, Alzheimer's, and some cancers.

Can one pill do and cause all that? Critics have long said no--that such a compound will not work in humans. But they also said it wouldn't work in mice--until it did work. (At least in fat mice.)

So let's sip some pinot noir and wait for more results from Sirtris. After all, we're not getting any younger.

Look for my profile of longevity researcher David Sinclair in the September/October issue of Technology Review.

Sirtris press release

A Hand for the Wounded

A new hand: The i-LIMB hand is a prosthetic device with five individually powered fingers to give users a prosthesis that comes very close to looking and acting like a real human hand. Credit: Touch Bionics

A new bionic hand is now available that, for the first time, allows users to operate the fingers independently, using the muscles in the remaining part of their arm. The fingers also have an increased level of sensitivity that enables the user to pick up a Styrofoam cup with little effort, or a business card off a table. A skinlike coating makes the hand feel and look more human than other artificial hands.

The new hand, called the i-LIMB, is made by United Kingdom-based Touch Bionics. The company plans to unveil the device at the 12th World Congress of the International Society for Prosthetics and Orthotics in Vancouver, Canada, held from July 29 through August 3. According to the company's website,

"The i-LIMB Hand is controlled by a unique, highly intuitive control system that uses a traditional two-input myoelectric (muscle signal) to open and close the hand's life-like fingers. Myoelectric controls utilize the electrical signal generated by the muscles in the remaining portion of the patient's limb. This signal is picked up by electrodes that sit on the surface of the skin. Existing users of basic myoelectric prosthetic hands are able to quickly adapt to the system and can master the device's new functionality within minutes."

The hand is already being used by soldiers wounded in Iraq and Afghanistan by improvised explosive devices (IEDs). A few months ago, I attended a dinner in New York sponsored by the Wounded Warriors, a group that supports soldiers wounded in the line of duty, and I was able to see a next-generation prosthetic arm. A major focus of the Warriors is to provide soldiers, who have lost arms, legs, or both, with prosthetic limbs, therapy sessions, and services to meet their needs.

Much to my surprise, a uniformed marine at my table was missing part of an arm and both legs. I say I was surprised because he walked and interacted normally. Although I noticed that his hand was artificial--it was made out of white plastic--he used it almost like a real human hand to eat, pick up things, and greet others. When I shook his hand, I could tell it was metal and plastic, but the grip felt natural.

I don't remember the marine's name, but I am truly amazed by his courage. He had been a sniper in Iraq and was wounded when his lightly armored Humvee was hit by a roadside bomb. Far from angry or bitter, he was recently married and is able to water-ski and participate in other sports and activities. At the time I spoke with him, he was gung ho about life.

Fortunately, those who are wounded and lose limbs during combat now have the benefit of advanced electronics, materials, and biotech to provide them with prosthetics like none ever seen before. Tragically, many more soldiers may need them before the war in Iraq and Afghanistan is finished.

Extraterrestrial Life Begins at Home

If we ever find aliens on other planets, they might look like Romulans or Wookies, though it's far more likely that extraterrestrial creatures will eat acid and breathe methane. They may have genetic codes containing six, eight, or twelve nucleotides instead of the four we have here on Earth--or they may operate with systems entirely different than DNA.

Life may be so bizarre beyond our world that we may not even recognize it, says a new report from the National Academy's National Research Council. The authors found that life as it commonly exists on Earth--based on being biosolvent in liquid water, requiring a carbon-based metabolism, and having a molecular system that evolves and the ability to exchange energy with the environment--is not the only basis for life elsewhere in the universe.

The report, commissioned by NASA as part of its mission to search for life in outer space, suggests that astrobiologists turn their eyes toward Earth to study creatures found in its extreme environments.

"It is critical to know what to look for in the search for life in the solar system," said committee chair John Baross, a professor of oceanography at the University of Washington, Seattle, in a press release about the report. "The search so far has focused on Earth-like life because that's all we know, but life that may have originated elsewhere could be unrecognizable compared with life here. Advances throughout the last decade in biology and biochemistry show that the basic requirements for life might not be as concrete as we thought."

While some of this may seem obvious--that life might be different in outer space--this report adds yet another reason to explore life in extreme places on Earth, such as volcanic vents and deserts that resemble conditions on Mars and other planets. In metagenomics, there are scientists putting their efforts toward finding bacteria that employ novel methods to store and use energy that might be mimicked by humans.

The report suggests that space missions and exploration should be aimed at more than just planets where conditions seem most favorable to Terran life. Likewise, probes should be built to look for exotic evidence of life-forms. For instance, Titan, one of Saturn's moons, seems to have liquid mixtures of water and ammonia that might contain life, according to the committee.

Perhaps most interesting is the report's suggestion that humans who most often think geocentrically might gain a better understanding of fundamental philosophical questions about the nature of life. This kind of thinking may also hasten the discovery of life beyond our small planet. These life-forms may not speak to us in a low growl like Chewbacca, but they will most likely reveal a great deal about the nature of life, including our own.

The Anti-Science President

The news just gets worse about how politics has trumped science throughout the current White House administration's tenure. Pick a topic--embryonic stem cells, global warming, mercury levels in the environment--and on each one, this administration has denied science when it interfered with the president's ideology.

Now the former surgeon general, Richard Carmona, who held office from 2002 to 2006, is telling Congress in considerable detail how he was muzzled on everything from stem cells and sex education to a report on secondhand smoke. He was also told to mention President Bush at least three times on each page of every speech, and was directed to give speeches in support of Republican candidates.

According to a front-page article in Tuesday's New York Times,

On issue after issue, Dr. Carmona asserted, the Bush administration made decisions about important public health issues based solely on political considerations, not scientific ones.

"I was told to stay away from those because we've already decided which way we want to go," Dr. Carmona said.

He described attending a meeting of top officials in which the subject of global warming was discussed. The other officials concluded that global warming was a liberal cause and dismissed it, he said.

Politicians have always tried to manipulate facts to suit their agendas, and they will again, though the scale attempted by this administration is truly astonishing. So is the hubris that somehow people wouldn't notice that the administration's ideology contradicted facts and empirical proof.

Inevitably, facts have a nasty habit of being, well, real--for example, the fact that abortions do not cause breast cancer, despite a government website that kept making this claim against all scientific evidence. Or that carbon-dioxide levels in the atmosphere are rapidly rising. Or that most Americans support embryonic stem-cell research.

Yet there is a curious twist here in the sheer breadth and audacity of the effort. Most presidents manipulate science, or try to, but they keep quiet about it, following T. S. Eliot's observation that "Between the idea / And the reality / Between the motion / And the act / Falls the shadow." This White House did not hide in the shadows with its science policies. It stayed firmly in the spotlight.

Almost from the beginning--certainly in August 2001, when President Bush announced his restrictive policy on stem-cell research--George W. Bush made little effort to hide his disregard for science that didn't agree with his ideology. This is what is revealing about Carmona's testimony to the Senate yesterday, which paints a picture of a surgeon general who was essentially told to ignore reality on many issues. For instance, he was simply told not to mention scientific studies that questioned a sex-education policy that relies solely on abstinence.

In an area I'm more familiar with, embryonic stem-cell research, the administration's policies disregarded reality on two issues. First, the president's core constituency was quite vocal about its wish to ban the use of embryonic stem cells for research and its hope that their use could be criminalized. This is despite the fact that the science is readily accessible to trained scientists around the world and that most Americans want the potential treatments and cures promised by stem-cell research. Second, the president's policy to allow research only on stem-cell lines created before August 2001 was problematic because the lines in question were fewer than promised and mostly unusable.

Despite the president's anti-science stances during his first term, George W. Bush was reelected in 2004, in part because science is seldom a determining factor in election outcomes. In 2004, the electorate was more concerned about the threat of terrorism, the war in Iraq, and other front-burner issues.

Perhaps Americans in 2004 should have paid a bit more attention to the science policies of the Bush administration. One can only hope that in 2008 science and facts have a bit more influence with both the candidates and the electorate.

Smoke-Free United Kingdom: The Morning After

A few days ago I was in Purton, an ancient village in the Cotswolds, just west of London, where people have smoked tobacco since it started arriving from the Virginia Colonies. But on the evening of June 30, in a haze of smoke, the last legal cigarette was stubbed out at the end of a party, called the Last Night for Tobacco, held in the Angel Pub.

Smoking is not a usual topic for this blog, although I do write about risk factors--such as smoking--for diseases, along with their treatment and possible cures. The toxins and particles in smoke are environmental factors that in many smokers can cause a cascade of harmful effects, from triggering cancerous growths to causing damage to the p53 gene and other DNA.

Britain now becomes the 20th nation in the world, give or take, that has instituted a ban on smoking in public places. The trend started with Ireland in 2004. An article in News@Nature.com recently assessed how well this trend, which is becoming a major movement, is doing in terms of improving health.

For me, banning tobacco in the United Kingdom's bars and restaurants could not have happened soon enough. Coming from California, where tobacco has been banned in public places since 1998, I have always found it shocking to walk into the soupy air of a British pub and suck in the fumes of someone else's cigarettes. It stings my eyes and makes me cough, among other things. It also makes me wonder, as I sip an Old Speckled Hen or some other frothy ale, how many of the people I'm mingling with will one day end up with diseases caused by smoking--or if deep inside me some subtle shift in my own DNA is under way as a result of breathing in secondhand smoke.

Reportedly, the health impact--that is, the cost of health care--of smoking was a major reason for the British ban. The National Health Service crunched the numbers and determined that the public health hazard and the cost of caring for smokers outweighed the freedom to light up.

Some Brits protested the smoking ban, and many vigils like the one at the Angel Pub were held, but overall, the day went smoothly. This may have had more to do with the distraction of attempted terrorist bombings in London and Glasgow than with a universal acceptance of the ban. Still, Brits I talked to seemed either happy (nonsmokers) or resigned (smokers).

The impact of bans on smoking in different parts of the world is already being felt. For instance, in California, rates of lung and bronchial cancer have decreased four times as fast as in the rest of the United States. Also in California, the bans are credited with helping people quit smoking, as the number of smokers has fallen from 23 percent of the state's population in 1988 to 13 percent in 2006. (In 1988, antismoking efforts began with pushes such as advertising, which led to a partial ban in 1995; a complete ban took effect in 1998.) In Scotland, cigarette sales fell 8 percent in the first year of its ban; in Ireland, the number of smokers has dropped 5 percent since 2004.

Surprisingly, according to the News@Nature.com article, many gaps remain in the science of how much damage secondhand smoke does to nonsmokers:

But the data supporting the link between second-hand smoke and cardiovascular disease are more controversial. The surgeon general's report states that "pooled relative risks from meta-analysis indicate a 25-30% increase in risk of coronary heart disease from exposure to second-hand smoke." Although most epidemiologists think there is a link, it's the size of the effect that surprises them.

"It seems to me that a 25% increase is not plausible," says John Bailar, a biostatistician at the National Academy of Sciences in Washington DC, who thinks the effect should be proportional to exposure, as it is for lung cancer. "Regular smoking only increases the risk of cardiovascular disease by 75%, so how could second-hand smoke, which is much more dilute, have an effect one-third that size?" Bailar says that even if a non-smoker took in 10% as much smoke as a smoker, which is a high-end estimate, his increased risk would be only 7.5%.

Supporters of the ban argue that secondhand "sidestream" smoke is actually more toxic per gram of total particulate matter than is smoke inhaled by the person smoking the cigarette. Another explanation is that in some people, the threshold of smoke to trigger disease is small. According to the article,

Despite these concerns, the surgeon general's report takes a hard line on exposure, stating that there is no "safe" level. According to Terry Pechacek, one of the authors of the report and associate director at the Office on Smoking and Health at the US Centers for Disease Control and Prevention in Atlanta, Georgia: "Exposure to second-hand smoke for even a short time can have adverse health effects--this is not subject to debate. Compounds in tobacco smoke have the ability to cause cancer in humans, it's just a probabilistic game of whether they will cause death in a certain individual."

Meanwhile, back in the United States, there are still numerous states where the fog of smoke remains in bars, restaurants, and workplaces. This includes our nation's capital, Washington, DC, which has no ban. I was there recently in a posh pub in a neighborhood within DC, Georgetown sitting near a woman who was waving her cigarette behind her and in my face--strategically out of the way of her friends. I didn't say anything, but I did wonder if this cigarette, which she was apparently enjoying, would be the one that would trigger that p53 mutation in her or in one of us in the room.

A nerdy, uncool thought, perhaps, but it's sad nonetheless that in the country that launched the antismoking movement with the 1964 Surgeon General's report, the fog remains.

David Ewing Duncan's website.

Saving the Banana

In 2003, I met Geoffrey Arinaitwe, a Ugandan plant geneticist training at Belgium's Catholic University of Leuven--one of the early research centers developing genetically modified (GM) crops. Regardless of what you think about GM food, Arinaitwe had a compelling story: without genetic modification, the main food source of his country and many others in the tropics would die off, impacting the diet of 10 million Ugandans and hundreds of millions more poor people from Brazil to Indonesia.

Now Arinaitwe is back in Kampala, where he is poised to test the first modified bananas to be planted in Ugandan soil. A researcher at Kawanda Agricultural Research Institute,, this shy scientist with a gentle voice and slight build is waiting for GM plants to arrive from Leuven; they are expected within the month.

In 2003, I wrote a story for Seed magazine about the plight of the edible banana. Since it's seedless and therefore sterile, all bananas come from mutant plants discovered some 8,000 years ago, probably in Papua New Guinea. They have been grafted, or cloned, ever since, and developed into dozens of varieties, colors, and sizes. Bananas are ideal for the developing world because they are compact, easy to grow and transport, and highly nutritious. In these parts of the world, they are eaten raw and cooked and used to make beverages. In Uganda, they are so important that the word for banana, matooke, also means "food."

Unfortunately, with an 8,000-year-old genome, the edible banana hasn't evolved to keep up with new pests. These include the black sigatoka, a leaf-destroying fungus, which has devastated vast acres of bananas. It cripples plants and reduces output by 50 percent. Close to half the banana crop in Uganda has been afflicted as this fungus spreads around the world.

Scientists at Leuven have been working to combat the problem. Led by Rony Swennen, a team discovered that inserting a gene from rice provides significant protection for the banana with apparently no danger to either humans or the environment. Because the banana is sterile, it can't get loose in the environment, nor is there a seed allowing Monsanto or other corporations to sell it. In fact, Swennen and banana organizations around the world are prepared to provide the initial plants to farmers at a cost. Once a farmer has the plant, he or she can graft more.

Another advantage, according to Swennen and Arinaitwe, is that the GM banana greatly reduces the need to use pesticides that fend off the black sigatoka in export crops going to markets in the West. Most Ugandan farmers growing bananas for local consumption can't afford expensive pesticides, but on huge plantations in Africa and Latin America, growers use some of the highest levels of chemicals sprayed in the world to fend off fungi and other pests. This has led to reports of higher than normal instances of leukemia and sterility in growers.

By the way, organic bananas sold in the West are grown without pesticides. They are raised either in areas unaffected by the black sigatoka or are harvested out of the reduced yields of afflicted plants, further reducing the amount of fruit available to locals.

None of this convinces opponents of GM foods, who responded to my Seed article with astonishing vitriol and even some personal attacks. I'll leave it to readers to decide if inserting a rice gene into a cloned banana is repugnant and undesirable.

Almost certainly, though, critics are correct that acceptance of the modified banana may make other forms of GM foods more palatable, so to speak, particularly in much of Africa, which has largely opposed GM crops. As modified corn, cotton, and other crops become more prevalent in the West and elsewhere, it's obvious that GM creep has already begun.

As for safety, the scientists at Leuven say that their GM bananas are harmless. Now Arinaitwe will test them in Uganda to see if he and the Ugandan government agree. Hurdles remain before a rice-banana hybrid is approved and accepted. Protests are also expected, although in the end the withering, decimated crops that cover hill after hill in this country, which has an entire culture built on the banana, may make this banana update stick. We'll see.