How Coffee Can Galvanize Your Workout

Can a cup of coffee motivate you to relish your trips to the gym this winter? That question is at the heart of a notable study of caffeine and exercise, one of several new experiments suggesting that, whatever your sport, caffeine may allow you to perform better and enjoy yourself more.

Scientists and many athletes have known for years, of course, that a cup of coffee before a workout jolts athletic performance, especially in endurance sports like distance running and cycling. Caffeine has been proven to increase the number of fatty acids circulating in the bloodstream, which enables people to run or pedal longer (since their muscles can absorb and burn that fat for fuel and save the body’s limited stores of carbohydrates until later in the workout). As a result, caffeine, which is legal under International Olympic Committee rules, is the most popular drug in sports. More than two-thirds of about 20,680 Olympic athletes studied for a recent report had caffeine in their urine, with use highest among triathletes, cyclists and rowers.

But whether and how caffeine affects other, less-aerobic activities, like weight training or playing a stop-and-go team sport like soccer or basketball, has been less clear.

So researchers at Coventry University in England recently recruited 13 fit young men and asked them to repeat a standard weight-training gym regimen on several occasions. An hour before one workout, the men consumed a sugar-free energy drink containing caffeine. An hour before another, they drank the same beverage, minus the caffeine. Then the men lifted, pressed and squatted, performing each exercise until they were exhausted.

Exhaustion arrived much later for those who’d had caffeine first. After swallowing the caffeinated beverage, the men completed significantly more repetitions of the exercises than after the placebo. They also reported feeling subjectively less tired during the entire bout and, in perhaps the most interesting finding, said that they were eager to repeat the whole workout again soon.

“Essentially, we found that with the caffeinated drink, the person felt more able to invest effort,” says Michael Duncan, a senior lecturer in sports science at the University of Exeter in England and lead author of the study. “They would put more work into the training session, and when the session was finished, in the presence of the caffeinated drink, they were more psychologically ready to go again.”

How caffeine influences the physiology and psychology of weight trainers isn’t fully understood, Dr. Duncan says. In contrast to endurance sports, an increase in fats in the blood wouldn’t provide much benefit in this kind of exercise.

Instead, Dr. Duncan says, he believes that caffeine “antagonizes adenosine,” a substance in muscles that builds up during exercise and blunts the force of contractions. The more adenosine in a muscle, the less force it generates. Caffeine reduces adenosine levels, “which then enables more forceful muscular contractions and delays fatigue,” Dr. Duncan says. “That’s the theory, anyway,” he adds.

Additional mechanisms may also be at work, other research suggests. For an experiment published last month in The Journal of Applied Physiology, researchers asked a group of volunteers who regularly play team sports to complete a grueling workout designed to simulate the physical exertion of a soccer or basketball game. Such sports commonly involve repeated bouts of intense sprinting, but little prolonged slower running. Most of the effort is anaerobic.

In the test, the volunteers performed about 16 percent better if they had ingested a caffeine capsule 70 minutes beforehand. They also, as it turned out, had far less potassium in the fluid between their muscles afterward. “We believe that potassium buildup is involved” in the kind of fatigue that occurs during anaerobic activities, like team sports and weight training, says one of the study’s authors, Magni Mohr, an exercise physiologist affiliated with both the University of Exeter and the University of Copenhagen in Denmark.

At the same time, caffeine, while affecting muscles, seems also to have a striking effect on the central nervous system and on those parts of the brain involved in mood, alertness and fine motor coordination during exercise. In astudy published last month in The British Journal of Sports Medicine, soccer players dribbled, headed and kicked the ball more accurately if they’d had caffeine than if they hadn’t.

All of which would seem to indicate that a grande Americano is the ideal sports beverage. But, Dr. Mohr cautions, many questions remain. “We don’t know the best dose” of caffeine to provide performance benefits without undesirable side effects, he says, like heightened blood pressure or the jitters. In his study, volunteers consumed the equivalent of more than five large cups of brewed coffee before their workout.

Similarly, it’s not known whether people who swill cappuccinos and green tea all day get the same benefits from dosing themselves just before a workout as people who only occasionally drink caffeine, or whether the hour before a workout is the ideal moment to imbibe. Dr. Mohr suspects “it’s likely that you get more effect” if you’re not habituated to the drug, but he and others are currently studying those and similar issues and expect results soon.

In the meantime, “probably everyone can get some” fatigue-delaying and mood-enhancing benefits from caffeine, Dr. Mohr says — meaning that your gym gear should probably include a travel mug.

FDA Targets Homeopathic Weight Loss Products

TUESDAY, Dec. 6 (HealthDay News) -- U.S. officials on Tuesday said that they are taking action to remove controversial, unapproved and illegally labeled HCG weight loss products from the market.

HCG stands for human chorionic gonadotropin, a hormone made by the human placenta and found in the urine of pregnant women. The products are typically given in conjunction with an extremely low-calorie diet -- as low as 500 calories per day -- which has some experts worried about possible health effects.

According to the U.S. Food and Drug Administration, companies marketing over-the-counter HCGweight loss products labeled as "homeopathic" were sent warning letters on Tuesday by the FDA and the U.S. Federal Trade Commission. The letters cautioned that the companies are violating federal law by selling the unapproved drugs, and by making unsupported claims for their products.

HCG is approved in the United States as an injectable drug for treating some cases of female infertility and other medical conditions, but is not approved as a weight loss aid.

The FDA said that HCG weight loss products are sold online and in stores as oral drops, pellets and sprays, despite no proof as to either their effectiveness or safety.

Visitors to the website for one maker included in the FDA action, The Original HCG Drops, are told they can "lose 20-30 pounds in 30-40 days," as they take the product. The company also claims that HCG "tells the body to release abnormal fat" and "hold on to lean muscle. All this is designed to establish a new body weight and reset your metabolism."

The FDA is especially concerned, however, because labeling on homeopathic HCG weight loss products typically advises consumers to take the products in conjunction with a very low calorie diet. However, there is no substantial evidence that the HCG products help people lose weight, the agency said, and people on these types of severely restricted diets put themselves at heightened risk for problems such as gallstones, electrolyte imbalances and heartbeat disorders called arrhythmias.

"These products are marketed over-the-counter on websites and in some retail stores, and can be found in the form of oral drops, pellets and sprays," Elizabeth Miller, acting director of the Division of Non-Prescription Products and Health Fraud in the FDA's Office of Compliance, Center for Drug Evaluation and Research, said during a late morning news conference.

"Currently there are no FDA-approved HCG drug products for weight-loss," she said. "FDA thinks it is important for consumers to understand that these products are potentially dangerous if taken as directed."

Neither the FDA nor the Federal Trade Commission (FTC) know how many people use these products.

"The indication is that they are being heavily marketed on the Internet and that suggests to us that there are purchasers out there," Richard Cleland, assistant director of the FTC'S Division of Advertising Practices, said during the news conference. "A survey we conducted several years ago of all types of diet products indicated that there were almost 5 million Americans a year that are victimized by weight-loss fraud."

One expert agreed with the FDA's move.

"The HCG diet is a typical fad diet that preys on people's desperation for fast weight loss," said Samantha Heller, a dietitian, nutritionist, exercise physiologist and clinical nutrition coordinator at the Center for Cancer Care at Griffin Hospital in Derby, Conn. "Not only is it dangerous for people to consume only 500 calories a day over time but the safety and efficacy of taking HCG for weight loss has not been established. A near starvation diet can result in emotional, psychological and physiological damage."

The companies have 15 days to notify the FDA of measures they've taken to correct the violations outlined in the warning letters. If they fail to respond, the companies may face legal action, including seizure and injunction, or criminal prosecution, the FDA said.

"Deceptive advertising about weight loss products is one of the most prevalent types of fraud," David Vladeck, director of the FTC's Bureau of Consumer Protection, said in the statement. "Any advertiser who makes health claims about a product is required by federal law to back them up with competent and reliable scientific evidence, so consumers have the accurate information they need to make good decisions."

Companies receiving warning letters are: HCG Platinum, LLC makers of "HCG Platinum," "HCG Platinum X-30," and "HCG Platinum X-14"; HCG Diet Direct, LLC, makers of HCG Diet Homeopathic Drops; theoriginalhcgdrops.com and resetthebody.com, marketers of "Homeopathic Original HCG" and "Homeopathic HCG"; Natural Medical Supply, whose products include "Alcohol Free hCG Weight Loss Formula," "hCG Diet Pellets Weight Loss Formula," and "hCG Diet Drops Weight Loss Formula"; Nutri Fusion Systems LLC, makers of "HCG Fusion 30" and "HCG Fusion 43"; and hcg-miracleweightloss.com, marketers of "HCG Extra Weight Loss Homeopathic Drops."

Nebraskan Loses Half Her Body Weight

Natalie Strawn of Omaha, Neb., had struggled with her weight since childhood.

"I was a depressed child growing up, so I used food as comfort," Strawn, 20, told "Good Morning America." "I didn't have any friends but I had food, so I ate.

"I would make nachos and I would take half a can to a whole can of refried beans, a whole bag of chips, whole pound bag of cheese and smother it in ranch dressing and that would be my breakfast," she said of her typical eating routine.

By sixth-grade, Strawn weighed 333 pounds, and as her weight increased, so did the bullying at the hands of her classmates.

"I would hear 'tub of lard,' I would be mooed at, that was what hurt the most, being mooed at when I walked down the hallways. I'd be called Shamu [the whale] if I was swimming at the local pool in the summertime. … I was bullied so bad. … I started being home schooled and when I turned 16, I dropped out and decided to get my GED," she said.

By age 17, Strawn weighed more than 550 pounds. She had difficulty walking, and couldn't learn to drive because she couldn't fit behind the wheel of a car.

"When you're 562 pounds, they don't make cars for people that size," Strawn said.

Finally, she decided that she had missed out on enough. Determined to change her life, she joined Weight Watchers. She attended weekly meetings, set small, 5-pound goals and chronicled her progress online in a video blog.

"The thing I like about the plan I'm doing is the freedom and flexibility it gives me," Strawn said of her success with Weight Watchers. "There's no food that's off limits so I can eat basically whatever I want. I just have to watch the portion control."

Strawn also began to exercise, something she says was almost impossible at first.

"It wasn't until I lost about 100 pounds that I could start exercising," she told "GMA." "I started doing chair aerobics and it was 18 minutes long and it was the longest 18 minutes of my life. The first time I did it I was so out of breath and I was drenched in sweat."

In the course of three years, she lost 282 pounds and, today, is far removed from both the exercise restrictions she faced, and the size 44 jeans she used to wear.

"Now I walk, I do a 2-mile DVD exercise every day," Strawn said.

Despite already losing more than her body weight, Strawn says, she'd like lose another 100 pounds.

"My dream weight is 168," she said, adding that 382 pounds is the total amount of weight she'd like to lose.

Helping Strawn achieve her goal in the past three years has been her mom, Rita, who has been on a weight-loss journey of her own, losing nearly 100 pounds herself.

"My mom, and I'm determined," Strawn told "GMA" of the two sources where she finds the strength to continue her weight-loss journey.

She also hopes her story is an example to others struggling with their weight as she once did.

"I don't like things that are hard, so if I can do it, anyone can do it," she said. "I'm determined

Talking to Parents About Fat Babies

Obesity in teenagers and adolescents is a major concern for pediatricians. But the discussion gets tricky when it turns to a weight crisis in infants. As Dr. Perri Klass explains in this week’s Science Times, experts on child nutrition are debating whether some of the standard infant feeding practices and attitudes may be in need of revising, particularly the notion of getting infants to eat as much as possible.

My grandmother’s attitude — stuff food into the baby, be proud of a “good eater” — may not make sense in an environment of abundant food and rising obesity.

But it gets medically controversial, and emotionally sticky, when doctors start talking about obesity in babies. Is there an epidemic of infant obesity? Are fat babies at greater risk of turning into fat children at higher risk for medical consequences later on in life? And what can doctors advise parents about feeding a baby — which ought, after all, to be one of the basic joys of parenthood?

The answers to those questions aren’t always clear. Scientists do know that the number of obese children has been on the increase. But not the proportion of those under age 2 whose weight-for-length curve is at the 95th percentile or above — that has held pretty steady since 1999.
Perhaps more important, no one wants to see babies on diets, no one wants to see hungry babies not given food.

Drug Scarcity’s Dire Cost, and Some Ways to Cope

When Jenny Morrill, who has been battling ovarian cancer since 2007, went to the hospital for her scheduled chemotherapy treatment in June, the nurse greeted her with both good news and bad.

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Ellen Weinstein

“She said, ‘The good news is that you’re doing really well on this drug Doxil. The bad news is that we have no Doxil to give you,’ ” said Ms. Morrill, 55. “My jaw dropped.”

Ms. Morrill, a mother and a former arts administrator who lives near Kingston, N.Y., is one of thousands of patients with ovarian cancer, multiple myeloma, AIDS-related Kaposi’s sarcoma or other cancerwho were left in the lurch last summer when supplies of Doxil, a chemotherapy drug less toxic than many comparable agents, ran out because of production problems at the only plant that made it.

In recent years, about 7,000 patients in the United States were using the drug at any given time. But by November, the factory had shut down completely.

The shortage has disrupted treatment plans and has upset patients.

“A lot of things can go wrong when you’re in cancer treatment — your white count can go down, you can become too frail to get treatment, the chemo can stop working. One of the things you never consider is that treatment might just not be available,” said Ms. Morrill, who has suffered from severe nausea since being switched to another chemotherapy drug.

“It’s like you’re out in the ocean and the guy on the lifeboat says, ‘Sorry, they ran out of life rings.’ ”

Doxil is hardly the only drug disappearing from pharmacy and hospital shelves. More than 251 drugs have been in short supply this year, including about 20 chemotherapy agents, according to the American Society of Health-System Pharmacists, which has been tracking the problem.

The vast majority are generic injectable medications widely used in hospitals, including drugs used to relieve pain, fight cancer or infections, anesthetize surgical patients, treat cardiovascular disease and manage psychiatric conditions. Critical intravenous nutritional supplements and oral drugs for controlling diabetes, high blood pressure and attention-deficit hyperactivity disorder are difficult to find, said Cynthia Reilly, the director of practice development at the pharmacists’ organization.

Roslyne Schulman, a director of policy at the American Hospital Association, said: “This is very serious. This is a public health crisis. The shortage cuts across all treatment categories. It affects bread-and-butter drugs that hospitals have depended on for many years.”

Nearly all hospitals in an A.H.A. survey in June reported that they had struggled with one or more drug shortages in the previous six months, and nearly half had experienced shortages of more than 20 drugs. Three out of four hospitals reported rationing or restricting drugs that were in short supply.

The scarcity drives up health care costs as hospitals turn to more expensive substitutes and must spend time and money teaching staff how to use unfamiliar drugs. The risk of medical errors and complications also increases, experts say; many procedures have been delayed or canceled.

A number of complex factors have contributed to the shortages, according to Ms. Reilly, who called the situation a “perfect storm.”

Recent consolidation in the pharmaceutical industry has reduced the number of factories; most of the drugs in short supply are made by just one or two companies. That means greater repercussions when any single plant experiences production problems, cannot obtain ingredients or fails an inspection, as happened with Doxil.

Shortages often beget more shortages as health facilities stockpile supplies. Prices often spike when unethical distributors take advantage of the panic.

Indeed, some observers have blamed manufacturers of generic drugs, suggesting that they are trying drive up prices. But industry representatives say their business is to sell in large quantities.

“It’s to our advantage not to have shortages and to keep the products flowing,” said Ralph G. Neas, the president and chief executive of the Generic Pharmaceutical Association. “We sell affordable medications at a very good prices. We have to do more of that, not less.”

Most of the missing drugs are generic simply because the vast majority of drugs in use are generic, he said.

The shortages will not be solved easily, most experts believe. “There is no silver bullet,” said Maya J. Bermingham, assistant general counsel at the Pharmaceutical Research and Manufacturers of America, a trade group.

The consequences for patients can be varied and unexpected.

While alternative drugs are usually available, they may pose hazards. Physicians who turn to a second- or third-line drug may be less familiar with dosing and side effects. They are often unaware of the shortages and may be caught by surprise, increasing the risk of a medical error.

The substitute drugs also may be more toxic for frail, elderly or very young patients or — for pain medication, in particular —take longer to work.

Second-choice anesthesia drugs can lead to longer hospital stays because patients may not wake up as quickly, said Dr. Jane C. Fitch, the vice president of the American Society of Anesthesiologists.

“For procedures that can be put off and don’t have to be done right then and there, some patients have made the decision to wait and defer the surgery,” Dr. Fitch said.

Substituting a brand-name drug for a generic is also likely to drive up the patient’s out-of-pocket costs.

How to Picture the Size of the Universe

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Space, as Douglas Adams once so aptly wrote, is big.

To try imagining how big, place a penny down in front of you. If our sun were the size of that penny, the nearest star, Alpha Centauri, would be 350 miles away. Depending on where you live, that’s very likely in the next state (or possibly country) over.

Attempting to imagine distances larger than this quickly becomes troublesome. At this scale, the Milky Way galaxy would be 7.5 million miles across, or more than 30 times the distance between the Earth and the moon. As you can see, these are rather inhuman dimensions that are almost impossible to really get a sense of.

But that doesn’t mean it’s completely impossible. Astronomers have made observations and simulations that in some way capture the enormity of our cosmos. In this gallery, Wired will look at the size and scale of the universe’s largest, farthest, and most mysterious objects.

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Size of the Universe

No one knows exactly how large the universe is. It could be infinite or it could have an edge, meaning that traveling for long enough in one direction will bring you back to where you started, like traveling on the surface of a sphere.

Scientists argue over the exact shape and size of the universe but they can calculate one thing with good precision: how far away we can see. Light travels at a specific speed, and because the universe is approximately 13.7 billion years old, we can’t see anything farther away than 13.7 billion light years away, right?

Wrong. The strange thing about space is that it’s expanding. And that expansion can occur at more or less any speed — including faster than light speed — so the most distant objects we can see were in fact once much closer to us. Over time, the universe has shuffled distant stars and galaxies away from us as if they were on an extremely rapid conveyor belt, and dropped them off in far away locations.

Strangely, this means that our observational power is sort of “boosted” and the furthest things we can see are more than 46 billion light years away. While we are not the center of the universe, we are at the center of this observable portion of the universe, which traces out a sphere roughly 93 billion light years across.

Holiday Gifts From Your Kitchen

Andrew Scrivani for The New York TimesHomemade granola, lemon olive oil and an oatmeal pancake mix make delicious holiday gifts.

Some of my favorite holiday gifts, both given and received, have come from the kitchen. One year I made homemade bread, flavored with cherries and nuts and twisted to look like a candy cane. A good friend of mine regularly gives decadent raspberry chocolate truffles.

But while many edible holiday gifts tend to be sweet, like cookies and candies, this year Recipes for Health author Martha Rose Shulman is gifting on the savory side, offering flavored oils and marinated foods. She also suggests homemade granola and dry-ingredient mixes. Here are Ms. Shulman’s picks for delicious and healthful edible gifts.

Marinated Goat Cheese: Package in a jar and add a note reminding the recipient that these are especially nice to have on hand for adding to salads and quick toasted open-faced sandwiches. Suggest they place a round on a piece of bread, pop it in a toaster oven and toast 3 to 4 minutes.

Harissa: Harissa is that fiery paste used in Tunisian cuisine. You can get it in tubes, but the homemade version tastes much fresher. “Make a note on the label to top up with olive oil whenever the harissa is used so that it will keep for a long time,” she advises.

Sweet Peppers Conserved in Oil: Roasted peppers always look beautiful in a jar of olive oil. Feel free to add other herbs, like oregano or basil, to the mix.

Oatmeal Buttermilk Blueberry Pancakes: The reason people buy mixes is to save the time it takes to measure and sift ingredients. “So why not take the dry ingredients called for in this recipe, put them in a nice bag and put a label on the package,” suggests Ms. Shulman. The label should say something like: “Beat together 2 extra-large eggs with 1 1/2 cups buttermilk, 3 tablespoons canola or grapeseed oil and 1 teaspoon vanilla. Whisk in the pancake mix. Add berries, chopped fruit or dried fruit as desired.”

Buckwheat and Amaranth Muffins: Same idea; mix up the dry ingredients and package them, then write out the missing ingredients and instructions on your homemade label. Or consider giving dry mix gifts for a variety of Ms. Shulman’s muffin recipes or Cornmeal Cranberry Scones.

Holiday Granola: “I used to make a rich holiday granola, but often it burned and stuck to the baking sheets,” says Ms. Shulman. “One of the reasons: I used wheat germ, which browns more quickly than oats. Now I keep the heat low in my oven and line my baking sheets with parchment. Be sure to stir the granola every 10 to 15 minutes, and switch the trays from top to bottom each time you stir. If you want to make a smaller amount, you can halve this recipe.”

Lemon Olive Oil: “The lemon oil goes beautifully with vegetables or fish, and is lovely on a salad or drizzled over bread,” says Ms. Shulman. Food safety experts advise keeping homemade flavored oils in the refrigerator and using within 10 days.

Pili Pili (Spicy Herb Oil): “This spicy oil with an African name is popular throughout Provence. It’s usually on the table in pizzerias for drizzling, but it’s also terrific drizzled over vegetables, grilled meats or fish, grains and bread – whatever you want to add a kick to,” explains Ms. Shulman. “In France it is made with very hot bird chilies. You could use fresh Thai chilies for this, but I’m using dried chiles de arbol, because that’s what I have on hand.”

Thousands Sterilized, a State Weighs Restitution

LINWOOD, N.C. — Charles Holt, 62, spreads a cache of vintage government records across his trailer floor. They are the stark facts of his state-ordered sterilization.

The reports begin when he was barely a teenager, fighting at school and masturbating openly. A social worker wrote that he and his parents were of “rather low mentality.” Mr. Holt was sent to a state home for people with mental and emotional problems. In 1968, when he was ready to get out and start life as an adult, the Eugenics Board of North Carolina ruled that he should first have a vasectomy.

A social worker convinced his mother it was for the best.

“We especially emphasized that it was a way of protecting Charles in case he were falsely accused of having fathered a child,” the social worker wrote to the board.

Now, along with scores of others selected for state sterilization — among them uneducated young girls who had been raped by older men, poor teenagers from large families, people with epilepsy and those deemed to be too “feeble-minded” to raise children — Mr. Holt is waiting to see what a state that had one of the country’s most aggressive eugenics programs will decide his fertility was worth.

Although North Carolina officially apologized in 2002 and legislators have pressed to compensate victims before, a task force appointed by Gov. Bev Perdue is again wrestling with the state’s obligation to the estimated 7,600 victims of its eugenics program.

The board operated from 1933 to 1977 as an experiment in genetic engineering once considered a legitimate way to keep welfare rolls small, stop poverty and improve the gene pool.

Thirty-one other states had eugenics programs. Virginia and California each sterilized more people than North Carolina. But no program was more aggressive.

Only North Carolina gave social workers the power to designate people for sterilization. They often relied on I.Q. tests like those done on Mr. Holt, whose scores reached 73. But for some victims who often spent more time picking cotton than in school, the I.Q. tests at the time were not necessarily accurate predictors of capability. For example, as an adult Mr. Holt held down three jobs at once, delivering newspapers, working at a grocery store and doing maintenance for a small city.

Wealthy businessmen, among them James Hanes, the hosiery magnate, and Dr. Clarence Gamble, heir to the Procter & Gamble fortune, drove the eugenics movement. They helped form the Human Betterment League of North Carolina in 1947, and found a sympathetic bureaucrat in Wallace Kuralt, the father of the television journalist Charles Kuralt.

A proponent of birth control in all forms, Mr. Kuralt used the program extensively when he was director of the Mecklenburg County welfare department from 1945 to 1972. That county had more sterilizations than any other in the state.

Over all, about 70 percent of the North Carolina operations took place after 1945, and many of them were on poor young women and racial minorities. Nonwhite minorities made up about 40 percent of those sterilized, and girls and women about 85 percent.

The program, while not specifically devised to target racial minorities, affected black Americans disproportionately because they were more often poor and uneducated and from large rural families.

“The state owes something to the victims,” said Governor Perdue, who campaigned on the issue.

But what? Her five-member task force has been meeting since May to try to determine what that might be. A final report is due in February.

This week, the task force set some priorities. Money was the most important thing to offer victims, followed by mental health services.

How much to pay is a vexing question, and what North Carolina does will be closely watched by officials in other states. In a period of severe budget cuts and layoffs, money for eugenics victims can be a hard sell to legislators.

Treatment for Blood Disease Is Gene Therapy Landmark

Medical researchers in Britain have successfully treated six patients suffering from the blood-clotting disease known as hemophilia B by injecting them with the correct form of a defective gene, a landmark achievement in the troubled field of gene therapy. Hemophilia B, which was carried by Queen Victoria and affected most of the royal houses of Europe, is the first well-known disease to appear treatable by gene therapy, a technique with a 20-year record of almost unbroken failure.

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University College London

A virus carrying a replacement gene for blood clotting was used by University College London researchers to help six patients.

“I think this is a terrific advance for the field,” said Dr. Ronald G. Crystal, a gene therapist at Weill Cornell Medical College. “After all the hype in the early 1990s, I think the field is really coming back now.”

Gene therapy has had minor successes in very rare diseases but suffered a major setback in 1999 with the death of a patient in a clinical trial at the University of Pennsylvania. Another gene therapy trial treated an immune deficiency but caused cancer in some patients.

The general concept of gene therapy — replacing the defective gene in any genetic disease with the intact version — has long been alluring. But carrying it out in practice, usually by loading the replacement gene onto a virus that introduces it into human cells, has been a struggle.

The immune system is all too effective at killing the viruses before the genes can take effect.

The success with hemophilia B, reported online Saturday in The New England Journal of Medicine, embodies several minor improvements developed over many years by different groups of researchers.

The delivery virus, carrying a good version of the human gene for the clotting agent known as Factor IX, was prepared by researchers at St. Jude Children’s Research Hospitalin Memphis. The patients had been recruited and treated with the virus in England by a team led by Dr. Amit C. Nathwani of University College London; researchers at theChildren’s Hospital of Philadelphia monitored their immune reactions.

Hemophilia B is caused by a defect in the gene for Factor IX. Fatal if untreated, the disease occurs almost only in men because the Factor IX gene lies on the X chromosome, of which men have only a single copy.

Women who carry a defective gene on one X chromosome can compensate with the good copy on their other X chromosome, but they bequeath the defective copy to half their children. About one in 30,000 of newborn boys have the disease, with about 3,000 patients in the United States.

Dr. Nathwani and his team reported that they treated the patients by infusing the delivery virus into their veins. The virus homes in on the cells of the liver, and the gene it carries then churns out correct copies of Factor IX. A single injection enabled the patients to produce small amounts of Factor IX, enough that four of the six could stop the usual treatment, injections of Factor IX concentrate prepared from donated blood. The other two patients continued to need concentrate, but less frequently.

Treating a patient with concentrate costs $300,000 a year, with a possible lifetime cost of $20 million, but the single required injection of the new delivery virus costs just $30,000,Dr. Katherine P. Ponder of the Washington University School of Medicine in St. Louis notes in her commentary in The New England Journal of Medicine, calling the trial “a landmark study.”

The patients have continued to produce their own Factor IX for up to 22 months, said Dr. Edward G. D. Tuddenham, director of the Hemophilia Center at the Royal Free Hospital in London. One patient, a geologist, had a good response at first, but his level of Factor IX has declined to 1 percent of normal, the level at which the disease kicks in.

“We attribute this to the fact that he had an inflammation, and although we treated it promptly, we should have been quicker off the mark,” Dr. Tuddenham said.

The patient cannot be injected again with the same virus because his immune system is now primed to attack it. “He’s very philosophic about it, but he’s a scientist, and his motivation is to help the science,” Dr. Tuddenham said.

Twenty more patients will be treated to assess the best dose of the virus, the goal being the highest dose that does not set off an immune system attack, Dr. Tuddenham said. “We are pretty close to the sweet spot,” he said. If all goes well, a genetic treatment for hemophilia B “could be available for widespread use in a couple of years.”

In a trial in 2006, a patient injected with a corrective gene produced his own Factor IX but only for 10 weeks. The designer of that treatment, Dr. Katherine A. High of Children’s Hospital of Philadelphia, said the new therapy had worked because the delivery virus had been made more efficient and because the research team had treated the patients withsteroids to suppress immune system attacks on the virus.

“I think it’s incredibly exciting, and I say that even though these people are my competitors,” she said. Dr. High is listed as a co-author of the report because her laboratory helped monitor the patients and provided proof for regulators that the virus would not insert its human gene into the patients’ sperm and make the change hereditary.

A serious problem with other delivery viruses is that they insert themselves randomly into chromosomes, sometimes disrupting a gene. The virus used by Dr. Nathwani’s team, known as adeno-associated virus-8, generally stays outside the chromosomes, so it should not present this problem. Still, patients will need to be monitored for liver cancer, a small possibility that has been observed in mice.

“I don’t think it’s a showstopper, but it’s a critical safety issue that has to be assessed,” Dr. High said.

Patients have little or no immunity to the adeno-associated virus, which infects rhesus monkeys. The virus has a propensity for making liver cells its target, which is good for the therapy because these cells are the natural producers of Factor IX. However, liver cells do not live forever and slowly replenish themselves, possibly limiting how long the therapy will last.

About 80 percent of hemophilia cases are of the type known as hemophilia A, which is caused by defects in a different blood-clotting agent, Factor VIII. Researchers have focused on hemophilia B, in part, because the Factor IX gene is much smaller and easier to work with.

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