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Space Shuttle Rescue Scenarios

Follow, day by day, how a high-risk effort to save the crew of the Space Shuttle Columbia might have unfolded.

The RNAi Cure?

<p>
<figure class="richtext-image full-width">
<img alt="glowing test tube" class="richtext-image full-width" src="https://staging.pbs.org/wgbh/nova/media/images/rnai-cure-01.width-990_UZDTPYi.jpg"/>
<figcaption>It may work in the lab, but will RNAi radically change the practice of medicine?
        
        <div class="credit">© Ted Spiegel/CORBIS</div>
</figcaption>
</figure>
</p>
<p>
	How close are we to seeing RNAi transform medicine, if it will at all? There have been hundreds of successful experiments in petri dish cell cultures, dozens in lab animals, and in late 2004, an RNAi therapy was tested in humans for the first time. Yet experts in the field still see daunting obstacles ahead for treating most diseases. The chief hurdles are how to deliver RNAi drugs to the right targets, how to avoid veering "off-target" and shutting down good genes or cellular processes, and how to ensure that the drugs stay active long enough to help patients.</p>
<p>
	Despite these challenges, researchers are optimistic that many RNAi therapies will enter clinical trials in the next five years and possibly get FDA approval in the next decade. Here, get a glimpse of some of the most promising areas of research.</p>
<p>
<figure class="richtext-image full-width">
<img alt="eye exam" class="richtext-image full-width" src="https://staging.pbs.org/wgbh/nova/media/images/rnai-cure-02.width-990_L0DRjXu.jpg"/>
<figcaption>Macular degeneration is the leading cause of adult blindness in the developed
world.
        
        <div class="credit">© Ed Kashi/Corbis</div>
</figcaption>
</figure>
</p>
<h3>
	Macular degeneration</h3>
<p>
	The first RNAi therapy to reach patients in clinical trials is a treatment that aims at a debilitating eye disease called macular degeneration. Biotech firms had focused on the disease for many reasons: Most critically, RNAi drugs can be delivered directly to the diseased tissue—literally injected into the eye. This direct delivery helps ensure that "naked" RNAi drugs—short strands of RNA that aren't packaged and protected in membranes and which quickly break down in the bloodstream—can reach their target intact. Local delivery also makes it less likely that the drugs will have unanticipated, harmful effects elsewhere in the body.</p>
<p>
	What's more, the disease is triggered by a well-known culprit—a protein called VEGF that promotes blood vessel growth. In patients with macular degeneration, too much of this protein leads to the sprouting of excess blood vessels behind the retina. The blood vessels leak, clouding and often entirely destroying vision. The new RNAi drugs shut down genes that produce VEGF.</p>
<p>
	The first clinical trial, involving about two dozen patients, launched in the fall of 2004. While intended primarily to assess safety issues, this ongoing trial shows promising results. Two months after being injected with the drug, a quarter of the patients had significantly clearer vision, and the other patients' vision had at least stabilized. If subsequent trials prove they are effective, RNAi drugs for this condition could hit the market by 2009.</p>
<p>
<figure class="richtext-image full-width">
<img alt="mouse with glowing stomachs" class="richtext-image full-width" src="https://staging.pbs.org/wgbh/nova/media/images/rnai-cure-03.width-990_KU71eNq.jpg"/>
<figcaption>To test their RNAi treatment, Stanford researchers used mice infected with a
specially crafted, "glowing" version of a hepatitis C gene (left). The
treatment effectively turned off the glowing gene (right).
        
        <div class="credit">Courtesy Dr. Mark A. Kay</div>
</figcaption>
</figure>
</p>
<h3>
	Hepatitis C</h3>
<p>
	The RNA interference system that cells naturally possess likely evolved millions of years ago, as organisms survived the onslaught of dangerous invading viruses. So it makes sense that researchers are now trying to harness the cell's RNAi machinery to fight a wide range of viruses. One of the most noteworthy is hepatitis C, which infects roughly 200 million people worldwide and causes an often fatal disease of the liver.</p>
<p>
	In 2002, geneticists Anton McCaffrey and Mark Kay at Stanford University announced that their RNAi treatment had controlled the virus in laboratory mice. It was the first time an RNAi approach had worked not just in lab cell cultures but in living animals. In their initial experiments, the researchers injected "naked" RNA strands into the tail veins of mice using a high-pressure, rapid-transfusion method to ensure that the RNA strands were taken up in the liver.</p>
<p>
	But the delivery method McCaffrey and Kay used, which doubled the mice's blood volume within eight seconds, isn't feasible for humans. And even if it were, the effects of naked RNA are likely to wear off in a matter of days. So these researchers are exploring ways to use viral vectors—viruses stripped of their harmful genes—to ferry RNA-making molecules into liver cells. It's a technique that has been refined over a decade of gene therapy research and, if successful, would provide long-term protection.</p>
<p>
<figure class="richtext-image full-width">
<img alt="brain slice" class="richtext-image full-width" src="https://staging.pbs.org/wgbh/nova/media/images/rnai-cure-04.width-990_89hSfqQ.jpg"/>
<figcaption>A brain devastated by Huntington's disease, a genetic disorder for which there
is now no effective treatment or cure
        
        <div class="credit">Courtesy Dr. Christine Hulette, Duke University</div>
</figcaption>
</figure>
</p>
<h3>
	Huntington's disease</h3>
<p>
	To defeat hereditary diseases like Huntington's, doctors ideally want to shut down the operation of a harmful gene over the lifetime of an individual. It's another case where, rather than repeatedly administer "naked" RNAi drugs, researchers hope to employ safe, stripped-down viruses to transport RNA-making molecules to target cells. Once embedded in the cell's machinery, these RNA-making molecules could continuously silence the troublesome gene.</p>
<p>
	In 2004, Beverly Davidson and colleagues at the University of Iowa used this technique to treat mice with spinocerebellar ataxia, a neurological disorder akin to Huntington's. It was a landmark—the first time that an actively troublesome gene was put out of commission in such a way. Soon after, Davidson treated mice with Huntington's, a disease that affects more than 30,000 people in the U.S. alone.</p>
<p>
	But in the Huntington's experiments, there was a critical catch: in addition to silencing the harmful gene, the treatment also shut down the healthy version of the Huntington's gene. (Patients carry both.) While Davidson and other researchers are optimistic that they can tweak the design of RNAi drugs to overcome this obstacle, such "off-target" affects could hinder many RNAi therapies.</p>
<p>
<figure class="richtext-image full-width">
<img alt="" class="richtext-image full-width" src="https://staging.pbs.org/wgbh/nova/media/images/rnai-cure-05.width-990_aLCph9r.jpg"/>
<figcaption>As with the best current HIV drug regimes, new RNAi therapies must attack the virus on multiple fronts at once to counter the problem of drug resistance.
        
        <div class="credit">© WGBH Educational Foundation and Medical Library</div>
</figcaption>
</figure>
</p>
<h3>
	HIV </h3>
<p>
	Almost as soon as RNA interference was discovered in human cells, scientists began exploring how it could be recruited to battle HIV. By late 2002, Phillip Sharp and colleagues at MIT announced they could interrupt various steps in the HIV life cycle with RNAi molecules. But these and other experiments were largely "proof-of-principle" studies, stopping the virus in cell cultures, not human patients.</p>
<p>
	HIV mutates and evolves resistance so rapidly that any single target for an RNAi therapy won't be sufficient. Molecular biologist John Rossi of City of Hope Medical Center and colleagues at Colorado State University have engineered an RNAi therapy aiming at multiple HIV genes. And to build up the multipronged attack even more, Rossi combines this RNAi therapy with two other RNA technologies (called ribozymes and RNA decoys) to block HIV's replication and invasion of the immune system.</p>
<p>
	Rossi's group is tackling the critical issue of drug delivery in yet another way. If it works, doctors might one day extract stem cells from a patient's bone marrow, genetically alter these cells with the RNA therapy, then transfuse them back into the patient, where they would develop into healthy immune-system cells safeguarded against HIV. Rossi has established the therapy with mice and rhesus monkeys, and hopes to move into clinical trials in 2006.</p>
<p>
<figure class="richtext-image full-width">
<img alt="X-ray of lung" class="richtext-image full-width" src="https://staging.pbs.org/wgbh/nova/media/images/rnai-cure-06.width-990_P47aIJQ.jpg"/>
<figcaption>A child's lungs, infected with RSV. The virus prompts as many as 125,000 pediatric hospitalizations in the U.S. each year.
        
        <div class="credit">Courtesy Dr. Simon Kao/Virtual Children's Hospital</div>
</figcaption>
</figure>
</p>
<h3>
	Respiratory Infections</h3>
<p class="caption">
	For biotech firms aiming to bring RNAi therapies to market quickly, diseases of the lung, like those of the eye, are prime candidates. It's relatively simple to deliver RNAi drugs directly to the respiratory system—patients can inhale them. One day, we may breathe in RNAi drugs for a host of different viruses, including SARS and influenza. The first virus to be defeated in this way, though, will likely be respiratory syncytial virus, or RSV.</p>
<p>
	RSV, while not commonly known by name, infects almost every child in the U.S. by the age of two. Infection typically leads just to cold-like symptoms, but it can have far graver consequences, including croup, pneumonia, and respiratory failure. RSV also endangers the elderly and people with weak immune systems.</p>
<p>
	By early 2005, biochemist Sailen Barik at the University of South Alabama had engineered RNAi molecules to shut down various RSV genes. Like the treatment for macular degeneration, these molecules were short strands of "naked" RNA that would rapidly break down in the bloodstream. When inhaled by mice, though, the short RNA strands reached their targets intact and controlled the virus. Clinical trials for RSV are slated to begin in the first half of 2006.</p>
<p>
<figure class="richtext-image full-width">
<img alt="cells of body" class="richtext-image full-width" src="https://staging.pbs.org/wgbh/nova/media/images/rnai-cure-07.width-990_rOinr4l.jpg"/>
<figcaption>Because diseased cells of the blood system are relatively accessible, leukemia may be among the first forms of cancer treated with RNAi drugs.
        
        <div class="credit">Courtesy National Cancer Institute</div>
</figcaption>
</figure>
</p>
<h3>
	Cancer</h3>
<p>
	Cancer often involves mutant genes that promote uncontrolled cell growth. In the last few years, researchers have silenced more than a dozen known cancer-causing genes with RNAi. Yet, once again, most of this success has been with cell cultures in the lab, and delivery poses the key hurdle in moving from the lab to the bedside of patients. Researchers are just beginning, for instance, to sort through how RNAi therapies might reach and penetrate tumors.</p>
<p>
	Rather than take a leading role, some RNAi therapies may help defeat cancers by supporting chemotherapy. Drug resistance is a major problem in chemotherapy, thwarting between 20 and 50 percent of all current treatments. In many of these failures, the guilty agent is a protein called P-glycoprotein. Like a misguided housekeeper, this protein sweeps drugs out of diseased cells. In 2004, a team of scientists at Imperial College London showed that RNAi can stop production of the protein in multidrug-resistant leukemia cells, restoring their sensitivity to existing drugs.</p>
<p>
	RNAi also provides a powerful new way for scientists to discover and learn more about genes that trigger or inhibit cancer. Greg Hannon and his group at Cold Spring Harbor Laboratory are part of an effort to decipher the function of 15,000 genes in a variety of human cancer cell lines. Such efforts might pinpoint genes never before linked to cancer and generate novel ideas for treatments.</p>

Will RNAi, already in human clinical trials, treat a host of diseases, including AIDS, cancer, and Huntington's?


Fit to Go the Distance

<p>
	NOVA wanted to investigate these questions, and with the help of a dozen enthusiastic recruits, we set out to see if "ordinary people" could transform themselves into marathoners in just a matter of months. The results, on display in the program <a href="http://www.pbs.org/wgbh/nova/body/marathon-challenge.html">Marathon Challenge</a>, were extraordinary.</p>
<p>
<figure class="richtext-image full-width">
<img alt="Uta Pippig running" class="richtext-image full-width" src="https://staging.pbs.org/wgbh/nova/media/images/fit-distance-01.width-990_onzplA7.jpg"/>
<figcaption>Uta Pippig makes it look easy. Like most elite marathoners, though, she has trained her naturally gifted body to perform at its peak.
        
        <div class="credit">© Victah Sailor</div>
</figcaption>
</figure>
</p>
<h3>
	A test of fitness</h3>
<p>
	A range of physical traits and well-honed skills distinguishes elite distance runners from huffing joggers—lean yet muscular bodies, a linear and efficient stride, and a high threshold for pain and muscle fatigue among them. Yet exercise physiologists often focus on one measure of fitness, called VO<sub>2</sub>max, as the key to a person's aptitude for endurance sports. It's also a good gauge of overall cardiovascular health. Because it's quantifiable, it also offered a way to assess how much progress NOVA's runners made from start to finish of their nine-month training for the Boston Marathon.</p>
<p>
	VO<sub>2</sub>max, theoretically, is the volume of oxygen a person can consume in one minute as he or she exercises at maximum exertion. In practice, it's measured by hooking up test subjects (in our case, NOVA runners) to a breathing apparatus and having them run as hard as they can.</p>
<p>
	Oxygen is essential for converting the fuel you get from food into energy for your muscles, and endurance athletes process oxygen efficiently to keep themselves going. VO<sub>2</sub>max is not simply a matter of oxygen consumption, however—it's usually expressed in terms of body weight (milliliters of oxygen per kilogram of body weight), so merely losing weight can improve your score over time.</p>
<p>
<figure class="richtext-image full-width">
<img alt="oxygen consumption" class="richtext-image full-width" src="https://staging.pbs.org/wgbh/nova/media/images/fit-distance-02.width-990_NrNyI0H.jpg"/>
<figcaption>The NOVA runners had their oxygen consumption measured with an apparatus similar to this one, which includes a heart monitor to check for signs of dangerous
overexertion.
        
        <div class="credit">© Dimitri Iundt; Jean-Yves Ruszniewski/TempSport/Corbis</div>
</figcaption>
</figure>
</p>
<h3>
	Nurturing what nature gave you</h3>
<p>
	Elite endurance athletes, including distance runners and cyclists, consume vast amounts of oxygen when they compete; they can have VO<sub>2</sub>max scores twice as high as most of us mere mortals. Lance Armstrong once registered at 83.8 ml/kg/min; the average man his age would measure between 40 and 50. Even if Armstrong had never taken up cycling or any sport, he likely would have scored exceptionally high.</p>
<p>
	We are all born with a genetic predisposition for a certain VO<sub>2</sub>max range, and most of us, even if we work out daily, will never hit the marks of champions. Yet where we fall within our own ranges hinges on how often and how strenuously we exercise. More critically, this exercise, like a wonder drug, can boost our physical and emotional well-being.</p>
<p>
	So what innate physiological factors determined the NOVA runners' scores, how could training change them, and what impact could this have on their health? For the answers, it helps to trace how oxygen moves from the air you breathe all the way to the mitochondria of your muscle cells, where it is ultimately consumed.</p>
<h3>
	Into the lungs</h3>
<p>
	Given that VO<sub>2</sub>max is a measure of oxygen consumption, you might think that lung capacity—the volume of air a person can inhale—plays a major role in determining VO<sub>2</sub>max scores. Indeed, Lance Armstrong is renowned, among many more significant things, for having strikingly large lungs. However, lung size isn't a limiting factor; even people with smaller-than-average lung capacity breathe in far more oxygen than the rest of their bodies can process.</p>
<p>
	From the lungs, oxygen diffuses into the bloodstream. For most of us, the rate at which the oxygen moves at this point is also insignificant. Only elite athletes might have their VO<sub>2</sub>max scores hampered by the rate of diffusion, because their blood flows so rapidly that it might not have time to pick up all the oxygen it could carry. In any case, no amount of training will alter the lungs to make the oxygen flow from them any faster or make them healthier in general.</p>
<p>
<figure class="richtext-image full-width">
<img alt="cardiovascular system" class="richtext-image full-width" src="https://staging.pbs.org/wgbh/nova/media/images/fit-distance-03.width-990_wpQScUC.jpg"/>
<figcaption>Regular aerobic exercise, whether it's marathon training or simply brisk walking, can dramatically enhance the health of your entire cardiovascular system.
        
        <div class="credit">© Howard Sochurek/CORBIS</div>
</figcaption>
</figure>
</p>
<h3>
	Red-blooded athletes</h3>
<p>
	Exactly how much oxygen your blood can absorb and deliver to your muscles is critical to your VO<sub>2</sub>max and your performance in endurance sports. At the lungs, oxygen attaches to hemoglobin, a protein complex in red blood cells. Oxygen-enriched, the blood turns bright red and remains this vivid color until the oxygen is "dropped off" in all the various tissues of your body that need it—not just to power muscles, but to keep the heart, brain, and other vital organs functioning.</p>
<p>
	The sheer volume of blood in your body, the number of red blood cells it contains, and the quality of hemoglobin within these cells all affect the amount of oxygen your blood can shuttle to your muscles. If you are anemic and your hemoglobin lacks iron, for instance, it is less able to bond with oxygen. And cigarette smoking can dramatically compromise oxygen delivery, because tobacco smoke's carbon monoxide, rather than oxygen, holds onto hemoglobin.</p>
<blockquote>
	With sweat and perseverance, all of us can strengthen our hearts.</blockquote>
<p>
	"Born" runners may naturally generate high numbers of red blood cells that are particularly effective at transporting oxygen. World-class athletes also frequently train at high altitudes, where their bodies make more red blood cells in response to "thin" (low-oxygen) air. All too often, competitive athletes also temporarily boost blood oxygen levels through illicit means, including blood transfusions and doping with EPO (Erythropoietin), a hormone that triggers red blood cell production.</p>
<p>
	Team NOVA, of course, never turned to such underhanded tactics. Fortunately, legitimate training, even at sea level, could enhance the ability of their blood and vascular systems to carry more oxygen to hard-working muscles.</p>
<p>
<figure class="richtext-image full-width">
<img alt="red blood cells in capillary" class="richtext-image full-width" src="https://staging.pbs.org/wgbh/nova/media/images/fit-distance-04.width-990_iZmgwsD.jpg"/>
<figcaption>Red blood cells within a capillary. Such tiny blood vessels directly feed oxygen and nutrients to muscle and other tissues of the body.
        
        <div class="credit">© Visuals Unlimited/Corbis</div>
</figcaption>
</figure>
</p>
<p>
	Regular and fairly intense training like the NOVA runners experienced spawns the growth of new capillaries, tiny blood vessels that supply oxygen and nutrients to skeletal muscles, the heart, the brain, and elsewhere. What's more, such exercise can make blood vessels throughout the body less stiff, improving blood flow and reducing risk of arteriosclerosis. By improving cholesterol levels, exercise also helps keep the vascular system, including vital coronary arteries, free of clogs.</p>
<h3>
	The heart of the matter</h3>
<p>
	Perhaps the greatest determiner of VO<sub>2</sub>max scores is cardiac output, the amount of oxygen-rich blood your heart sends through your body in a single minute. Elite endurance athletes have extraordinarily powerful, and often unusually large, hearts. A typical jogger might pump over 15 quarts of blood per minute, while a frontrunner in the Boston Marathon is capable of pumping twice that.</p>
<p>
	Cardiac output is the product of heart rate (the number of beats per minute) times stroke volume (how much blood the heart ejects with each contraction). For champions and recreational runners alike, even the most arduous training won't increase maximal heart rate, and this rate inevitably drops as we get older.</p>
<p>
	On the other hand, with sweat and perseverance, all of us can strengthen our hearts and increase stroke volume. Elite marathoners rack up thousands of training miles each year to extend the muscles of the heart and increase stroke volume. Even Team NOVA's workouts—which eventually had the runners pounding pavement (and dirt) about 30 miles a week—could improve the efficiency of their hearts.</p>
<h3>
	Muscle work</h3>
<p>
	Elite distance runners may look almost waif-like, certainly not muscle-bound. Yet they have muscles that are exceptionally good at processing oxygen and propelling them through 26.2 miles—muscles that, despite maintaining nearly a five-minute-per-mile pace, don't seem to tire. How is it possible?</p>
<p>
	Part of the answer lies in the type of muscle fiber that predominates in their bodies. Physiologists call it "slow-twitch" fiber (as opposed to bulkier "fast-twitch" fiber that helps sprinters and weightlifters with quick bursts of power). Team NOVA's athletic muse, Uta Pippig, is likely graced with an abundance of slow-twitch fiber, while fast-twitch muscles probably contour NOVA runner Steve DeOssie, a former NFL linebacker.</p>
<p>
<figure class="richtext-image full-width">
<img alt="bodybuilder biceps" class="richtext-image full-width" src="https://staging.pbs.org/wgbh/nova/media/images/fit-distance-05.width-990_T4N9j7W.jpg"/>
<figcaption>While bodybuilders relish the bulky muscles created by resistance training, marathoners covet a different type of muscle adept at using oxygen.
        
        <div class="credit">© Bryan Smith/istockphoto.com</div>
</figcaption>
</figure>
</p>
<p>
	A person's tendency to develop either slow- or fast-twitch muscle is largely genetic, yet specific training techniques—long runs verses bench presses, for instance—practiced over many years may change the balance of fiber types slightly. Endurance training can also alter the physiology of either muscle type, in essence making fast-twitch muscles perform more like slow-twitch, and making slow-twitch muscles do better at what they already do well, namely use oxygen for energy production.</p>
<p>
	The key is mitochondria, tiny structures that act as power plants within all cells. Mitochondria combine oxygen with glucose or other food fuels to make ATP (adenosine triphosphate), the so-called "universal energy molecule" that powers cellular work. In muscle cells, ATP is essential for muscle contraction. Slow-twitch fiber inherently contains more mitochondria than fast-twitch. But endurance training increases the number of mitochondria in both types of muscle. It also can make mitochondria larger and more metabolically active.</p>
<h3>
	No pain, no gain?</h3>
<p>
	Bigger and more active mitochondria don't just produce extra energy to keep muscles moving, they also cut down on muscle fatigue. Tired, sore muscles during exercise are linked to a buildup of lactic acid, and mitochondria can sweep up and consume lactic acid as a fuel source. Once again, champion athletes may have an innate edge; their mitochondria might be particularly well suited for this cellular housekeeping. But anyone can condition his or her muscles to be less crippled by lactic acid.</p>
<blockquote>
	It's possible that some of the positive change evident in Team NOVA's scores has little to do with red blood cells or mitochondria or any other physiological factor.</blockquote>
<p>
	The members of Team NOVA conditioned their muscles over nine months of rigorous training, and they were capable of runs at the end that would have been excruciating for them at the start. In the summer of 2006 some of them couldn't even make it through a single mile without cramping up and stopping. By the spring of 2007, they were aiming to take on the grueling 26.2-mile course of perhaps the world's most famous marathon, Heartbreak Hill and all.</p>
<h3>
	"Winning" the NOVA challenge</h3>
<p>
	Shortly before they made their way to the starting line on the outskirts of Boston, the runners on Team NOVA stepped onto a treadmill to have their VO<sub>2</sub>max measured for the second time. Here are the results, comparing how well they did prior to their nine-month training adventure with how they did post-training:</p>
<p>
<figure class="richtext-image full-width">
<img alt="" class="richtext-image full-width" src="https://staging.pbs.org/wgbh/nova/media/images/fit-distance-06.width-990_opJhVb5.jpg"/>
<figcaption>Results for men on Team NOVA
        
    </figcaption>
</figure>
</p>
<p>
<figure class="richtext-image full-width">
<img alt="" class="richtext-image full-width" src="https://staging.pbs.org/wgbh/nova/media/images/fit-distance-07.width-990_0cFLPqE.jpg"/>
<figcaption>Results for women on Team NOVA
        
    </figcaption>
</figure>
</p>
<p>
	To understand these results, it helps to put them in the context of normal VO<sub>2</sub>max scores for men and women of various ages:</p>
<p>
<figure class="richtext-image full-width">
<img alt="" class="richtext-image full-width" src="https://staging.pbs.org/wgbh/nova/media/images/fit-distance-08.width-990_nUrzMUN.jpg"/>
<figcaption>VO<sub>2</sub>max ratings for men
        
    </figcaption>
</figure>
</p>
<p>
<figure class="richtext-image full-width">
<img alt="" class="richtext-image full-width" src="https://staging.pbs.org/wgbh/nova/media/images/fit-distance-09.width-990_MX7Bh0m.jpg"/>
<figcaption>VO<sub>2</sub>max ratings for women
        
    </figcaption>
</figure>
</p>
<p>
	Clearly, some members of Team NOVA made tremendous advances in VO<sub>2</sub>max, others less so. Both Jonathan Bush and Ray Rassi started with relatively high scores and therefore had less room for improvement. But all the tested runners upped their scores, reflecting a positive change in their cardiovascular and respiratory fitness.</p>
<p>
<figure class="richtext-image full-width">
<img alt="Betsey Powers-Sinclair" class="richtext-image full-width" src="https://staging.pbs.org/wgbh/nova/media/images/fit-distance-10.width-990_tGjm9QT.jpg"/>
<figcaption>Betsey Powers-Sinclair transformed her body, and clearly her mindset as well, by taking on the NOVA challenge.
        
        <div class="credit">Courtesy Don Megerle</div>
</figcaption>
</figure>
</p>
<p>
	Betsey Powers-Sinclair's standout gain—more than doubling her VO<sub>2</sub>max—may be somewhat artificial, because her first test was stopped short due to concerns about her heart. But even had she scored slightly higher the first time, she still would have made a tremendous advance. By the time of her second test, she had dropped 45 pounds, largely due to changes she had made in her diet. Her final score is also a testament to her ability to rise nearly every morning at 5 a.m. to attend an exercise "boot camp," pushing herself far beyond even what Coach Megerle prescribed in his training regimen. Sama ElBannan also made a lifestyle change that may have boosted her VO<sub>2</sub>max and certainly changed the entire outlook for her future health—she gave up smoking.</p>
<h3>
	The power of positive thinking</h3>
<p>
	It's possible that some of the positive change evident in Team NOVA's scores has little to do with red blood cells or mitochondria or any other physiological factor. Perhaps some psychological "X Factor" contributed to the improvement. VO<sub>2</sub>max is, after all, oxygen consumption at "maximum" exertion, measured when people run on a treadmill as fast as they <em>think</em> they can. Did NOVA's runners, at the end of their adventure, have greater willpower and confidence to keep going on the treadmill at points where, nine months earlier, they might have felt they were too exhausted?</p>
<p>
	Whatever the answer, if the men and women of Team NOVA can retain some of the exercise practices and the mindset they gained through this experience, they likely will be not just fit to go the distance of future marathons, they will be better fit for life. A mountain of medical studies has shown that regular exercise decreases risk of heart disease, high blood pressure, and Type II diabetes, helps people maintain a healthy body weight, and can ward off mild depression and possibly even Alzheimer's.</p>
<p>
	Do you have to train for a marathon to see such health benefits? Not at all. For Team NOVA, taking on the challenge served as an impetus to get some of them off the proverbial couch. However, as Tufts University physiologist and Team NOVA advisor Roger Fielding notes, even brisk walking five or six days a week for 30 to 40 minutes at a time can impart many of the same health benefits. That's something almost all of us can do.</p>
<p>
<figure class="richtext-image full-width">
<img alt="Team NOVA" class="richtext-image full-width" src="https://staging.pbs.org/wgbh/nova/media/images/fit-distance-11.width-990_n7VjVG9.jpg"/>
<figcaption>Team NOVA's Daniel Williams, Ray Rassi, Jane Viener, and Steve DeOssie—all presented by a smiling Sama ElBannan.
        
        <div class="credit">Courtesy Don Megerle</div>
</figcaption>
</figure>
</p>

How does regular exercise transform your body and enable even novice runners to finish a marathon?

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Galactic Explorer Andrea Ghez

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Friendly Robots

Engineer Cynthia Breazeal talks about some of her favorite non-human companions in this audio slide show.

Traces of the Donner Party

Archeologist Julie Schablitsky describes what she and colleagues discovered at the Donner family campsite.

Hotter Oceans, Fiercer Storms

In this audio slide show, examine the link between rising sea surface temperature and more intense storms.

Susan Lewis

Articles