Devra (left) and Leslie were paired as college roommates more than 30 years ago. Today, Devra participates in the Avon Walk, not only to raise money for a cure, but to stay connected to her lifelong friend.

Nearly 2,000 of us gathered at the foot of the Washington Monument on an early May morning waiting for the opening ceremony of the 2012 Avon Walk for Breast Cancer to begin. Clouds of coffee and sunblock hung in the warm, humid air and a song about being strong against all odds thumped out from the loudspeakers like a hopped-up heartbeat.

A group of women wearing pink tulle skirts and black T-shirts embroidered ‘Tutus for Tatas’ across the chest moved toward me as I bent over to tie my sneaker. The fronts of their hats were inscribed in black sharpie: “For Mom”; “In loving memory of Susie”; “For Cathy, Barb and Allison.”

One of them greeted me when I stood up. “Hi, I’m Mary. Who are you walking for?” she asked, smiling and scanning my unadorned T-shirt for clues.

“My friend Leslie,” I said, who was diagnosed with breast cancer 10 years earlier.

The music faded as a man called our attention to the stage. “Good morning,” the speaker’s deep voice boomed. “My name is Mark and I’m walking for my three sisters who were all diagnosed with breast cancer at the same time and died within two years of each other.”

Some walkers stopped warming up their hamstrings to applaud. I reached into my fanny pack for a tissue and before anyone had a chance to recover a woman wearing a bright pink Nicki Minaj wig stepped up to the microphone. “Hello. My name is Margaret and I am 38 years old. This is my second Avon Walk. Four years ago I walked for my aunt Joanie, who is a 26-year survivor. Now, after being diagnosed with breast cancer in 2010, I am proud to say I am a survivor too.”

A woman from the Avon Foundation was the last to speak. She told us that every three minutes someone is diagnosed with breast cancer and every 13 minutes a life is lost to the disease, numbers many of us already knew by heart. I swallowed down the fear that I could become one of her statistics and applauded with the other potential victims around me as she officially opened the event.

As I started to walk, I thought about how lucky I was that Leslie and I were paired as college roommates more than 30 years ago. One evening, a month or two into our freshman year, Leslie and I walked back to our room after dinner to play backgammon, which had become a nightly ritual. We got to know each other over those games, taking turns asking questions about our families, our friends back home, and our likes and dislikes. We always sat on Leslie’s bed, made up with dark green flannel sheets and a red and black plaid wool blanket, all from L.L. Bean, a store based in Maine where her family had a vacation home. On the shelf next to her bed, she lined up three family photographs in matching black frames and a clock radio tuned to the local “Music of Your Life” station. Across the room, I had a rainbow striped quilt on my unmade bed and a poster of Tom Selleck in Magnum, P.I. taped to the wall above it.

About 15 minutes into our first game, the fire alarm went off, and as we rushed out of the room, I caught my finger in the door when I tried to slam it shut. The pain was instant and excrutiating.

Once outside, I began to panic. “I need a doctor, but I think the student health center closed at 6,” I sobbed to Leslie, holding up my swollen finger. My parents had always handled situations like this, and I wasn’t sure what to do.

“Come on,” Leslie said, taking charge. “There’s a hospital three blocks down the street that I pass every day on my way to class. We can walk.”

Five minutes later we were standing in front of the emergency room of the local Veterans Hospital. It was dark and looked closed except for the lighted sign indicating an ambulance entrance. We knocked on the locked door, and a nurse slid open a peek-a-boo panel. All we could see was her face, tilted upward as though she were standing on tippy toes.

“How can I help you?” she asked.

Leslie stepped in front of me and said, “My roommate slammed her finger in a door, and we think it’s broken. Is there a doctor we can see?”

“Is your roommate a veteran?” The nurse’s lips were thin and creased. She smiled, but only with the bottom half of her face.

“Should she be?” Leslie asked.

“If she wants to be treated here, either she or someone in her immediate family needs to be a veteran.”

Leslie looked at me. “Know any veterans, Devra?”

I shook my head, then asked, “What if I split my head open and was standing here with blood running down my face? Would I have to be a veteran to see a doctor?”

Leslie looked at her shoes and stifled a laugh while we waited for a reply. Her right leg started to shake, her tell when she was uncomfortable.

“There is a public hospital half a mile east of here. They take anybody,” the nurse said sharply. Then she lowered herself and snapped the panel shut, so hard it made my finger throb even more.

To distract me from the pain as we walked, Leslie started playing a game to see who could come up with the most gruesome injuries that the veterans-only hospital would turn away.

“What if I were carrying your severed leg while you hopped on one foot. Do you think they’d let us in?”

I knew it was my turn. “Or how about if I just swallowed a pencil and was experiencing stabbing pain in my stomach. Would she open the entire door?”

“Good one. Or what if your eyeball fell out and you showed it to the nurse through the peep hole. Would you get to see a veteran’s doctor? Get it? Peep hole? See a doctor?” Leslie’s words rode out on waves of laughter. We had to stop walking for a moment to give in to our giggles.

I was treated right away at the public hospital, and Leslie and I continued to make each other laugh throughout our friendship. In the late ’80s, we were in each other’s weddings, and when my marriage failed, Leslie offered the wisdom that helped me move on: “Dev, I’m sorry you’re hurting, but everything in life is a crapshoot, so quit your crying and live your life.”

And when she found out a long-term boyfriend dumped me around the same time she was diagnosed, she called and said, “In a lot of ways cancer is easier to deal with than a broken heart because there are treatments for cancer. You’re going to be fine. So am I.”

I participated in my first Avon Walk in 2004 to help Leslie in some way, as she helped me so many times since the night I slammed my finger in the door. Even though Leslie said she didn’t need anyone’s help, I wanted to raise money for the cure she felt we were “this close” to finding. At the opening ceremony I listened to the stories of loss and survival but didn’t relate, because even though Leslie had been fighting recurring cancer for two years, she had everyone convinced that she was going to be fine. I felt the same at the 2005 Walk, probably because Leslie was still alive.

Leslie died in 2006, a few weeks before my third Avon Walk and just shy of her 46th birthday. While leafing through an issue of Oprah magazine during my post-walk pedicure, a J. Crew ad caught my eye. The male model was our dorm manager from freshman year, a closeted, flirtatious blond artist who had a steady stream of boyfriends he didn’t think we noticed. I started to tear out the page to send to Leslie, who I knew would get a kick out of seeing it, but froze when I remembered that she was gone.

The more time passes, the more trouble I have recalling the smell of Leslie’s Clinique Happy perfume, or her quick laugh when I said something she thought was funny, or the way she made me feel safe and loved with her caring wisdom. I miss all of that. As long as she lived, she never lost her sense of humor; around her I always felt as bright and sparkly as she was to me. Gosh, I miss that, too. When she died, our story, our inside jokes, our friendship died with her, and I struggle to keep the image of us—of who I was with her and who we were together—clear in my mind. It’s as though a photograph of her is fading, which makes me feel like I am disappearing too.

I continue to participate in the Avon Walk every year, despite the unwelcome bond I now have with the other walkers who have lost someone they loved to the disease, because when I walk I replay my favorite moments with Leslie. Somehow my grief gives way to the joy I used to feel in her presence, and, for a brief time, I am whole again. Yes, I am committed to raise money to help find the cure that Leslie believed was just steps away. I fundraise and walk with the determination that breast cancer will become something that used to be, like eight-track tapes and rotary dial phones. But mostly I walk to stay connected to Leslie—my lifelong friend—and to keep the part of me that was a part of us alive.

A Walk To Remember The Saturday Evening Post

In this video, microbiologist Jonathan Eisen, professor at the University of California Davis Genome Center, explains how these good microbes may actually be our first line of defense against infection, disease, and lasting medical conditions—and how antibiotics may be doing more harm than good.

In Defense of Microbiomes The Saturday Evening Post

In this video from SoCal Connected, Murray explains the often undiscussed pain and discomfort terminal patients experience on life support, and what families might not consider when choosing to prolong a loved one’s life at all costs.

The Problem with Life Support The Saturday Evening Post

Parting the Wild Horse’s Mane The Saturday Evening Post

Waving Hands Like Clouds The Saturday Evening Post

Rooster Stands on One Leg The Saturday Evening Post

Stronger muscles and better weight control are among the many benefits of t’ai chi. “In contrast to the Western ‘go for the burn’ workout, t’ai chi conserves your life energy to balance mind, body, and spirit,” says David-Dorian Ross of the PBS program T’ai Chi, Health & Happiness.

T’ai chi techniques can be practiced one by one or as a short flowing routine. Try these relaxing yet strengthening moves from Ross’ latest DVD, Intro to T’ai Chi, available at gaiam.com.

How-to Video: Parting the Wild Horse’s Mane

This move (aka Tossing the Frisbee in a Lunge) coordinates arm and leg movements.

How-to Video: Rooster Stands on One Leg

This exercise requires some balance and will help you build strength in your leg muscles.

How-to Video: Waving Hands Like Clouds

New practitioners of t’ai chi will love this basic, fluid move that requires very little footwork.

5-Minute Fitness: T’ai Chi for Calmness and Strength The Saturday Evening Post

The story, recounted in a 1911 book The Bacillus of Long Life, describes healthy bacteria now called probiotics. Today, probiotics—defined by the World Health Organization as live microbes that confer a health benefit—are one of the hottest consumer health products. Last year, according to research firm Euromonitor International, more than 63,000 tons of probiotic cultures were consumed worldwide.

Americans are turning to probiotics in part to counter the sanitizing effect of modern food processing, which minimizes risks of pathogens in food but also kills natural flora which some scientists believe have health benefits. Live bacteria, originally marketed mainly in yogurt and dietary supplements, are now being added to breakfast cereals, juices, sports drinks, muffins, chocolate, and even pizza. Potential health benefits range from better digestive health to prevention of colds and flus.

Consider Herald Hollingshed, a 44-year-old technical director for a computer-services company, who felt his digestion started “slowing” when he hit middle age. He was frequently uncomfortable and bloated, but found relief with a Procter & Gamble product, Align. The pill “helps everything flow as it should,” says Hollingshed, who also switched to a healthier diet. “I feel in my best shape ever.”

For Cheryl Richardson, a 67-year-old retired lab technician from Chestertown, Maryland, probiotics over the years have helped balance the negative effects of antibiotics. Several years ago, after becoming ill from restaurant food while on vacation in the British Isles, a doctor prescribed an antibiotic that seemed to throw her digestive system out of whack. High doses of probiotics put it back on track.

“This replaces all the bacteria and helps your system digest food properly,” says Richardson.

For consumers, it’s simultaneously a cornucopia of choice and a confusing cacophony of marketing messages. The consumer “goes into a supermarket and has no idea which product to buy,” says Gregor Reid, professor of microbiology at the University of Western Ontario’s Lawson Research Institute. Despite the potential for confusion, scientists say probiotics hold great promise for human health. The evidence lies, in part, with the beneficial effects of breast milk. Beneficial gut flora called bifidobacteria are higher in breast-fed infants than in those fed by formula, says Glenn R. Gibson, professor of food microbiology at University of Reading in England, adding that the breast-fed infants have lower incidence of asthma and eczema. Good bacteria drop after babies are weaned, then remain stable through adult life until they drop precipitously around age 60 to 65. “They don’t go away completely, but they decrease and make us more prone to infections,” Gibson says. Low levels of good gut bacteria, he says, is likely at least part of the reason why the elderly suffer most during food-poisoning outbreaks.

The theory of how probiotics help us has for years been simple: The good bacteria crowd out the bad, resulting in better health. In recent years, scientists have learned that probiotic bacteria also take on many more useful tasks, says Philip M. Sherman, a scientist at the Hospital for Sick Children in Toronto. For example, scientists believe some types of probiotic bacteria help boost production of a protective mucus which lines the gut. Others, he says, produce cellular messages that calm harmful inflammation.

A growing number of scientists believe that gut microbes can change overall health. Scientists are beginning to study the use of probiotics to treat depression and even obesity. Benefits have already been shown for the digestive system, immune modulation, and dental health. There is even talk of the potential to increase longevity. “It’s exciting and there’s great promise,” says Joan Salge Blake, a clinical associate professor of nutrition at Boston University and a spokeswoman for the nonprofit Academy of Nutrition and Dietetics.

Meet the Healthy Microbes: These microorganisms have been shown to boost health in published scientific studies. (Click image to enlarge chart.)

If you want the benefits of probiotics, you need to select carefully. “It’s not one size fits all,” says Salge Blake. “The one that may help with constipation is different from the one that may help with immune support. Make sure you are getting the right strain for what you want.”

For example, Dannon Activia yogurt and Procter & Gamble Co.’s probiotic capsule Align have shown in scientific studies to improve gastrointestinal health. In four published studies, Activia improved food’s transit time through the gut. Align, shown to be effective in a chronic condition called irritable bowel syndrome, is also helpful for milder digestion problems.

Post Investigates Probiotics The Saturday Evening Post

What Are Probiotics? The Saturday Evening Post

That’s right. Zero. Statins—Lipitor, Crestor, Pravachol, Mevacor, Zocor, and their generic equivalents—today reside in the pill dispensers of a huge segment of the population over 45, but for heart-healthy patients, statins will not increase longevity, prevent a fatal heart attack, or avoid a life-ending stroke.

So if taking statins won’t keep you alive and healthy any longer than not taking the pills, Hadler asks—especially when you consider possible side effects ranging from muscle pain and fatigue to liver damage to increased risk of diabetes and even memory loss—what’s the point in knowing your cholesterol numbers?

Cardiologist Eric Topol is equally scathing about statins. Chief academic officer of Scripps Health, a nonprofit health care system based in San Diego, Topol has long believed that medicine must become personalized with treatments tailored to a patient’s DNA and other characteristics. Yet statins are the poster child of taking a drug that benefits some people and then prescribing it to many more. In his new book, The Creative Destruction of Medicine, Topol points out that only one or two out of 100 patients “without prior heart disease but at risk for developing such a condition will actually benefit” from a statin. To which he asks, “how about the 98 out of 100 patients who don’t benefit?”

To put these views in perspective, statins are associated with one of the greatest public health triumphs of the past 30 years: halving America’s death rate from coronary heart disease. From 543 per 100,000 men in 1980 the death rate fell to 267 deaths per 100,000 (adjusted for the aging of the population) in 2000. From 263 deaths per 100,000 women in 1980 it fell to 134 per 100,000 in 2000, data from the U.S. Centers for Disease Control and Prevention show.

Looking at it another way: As a result of the lower death rate from coronary heart disease, 341,745 fewer Americans died in 2000 alone.

That sounds pretty spectacular, but the crux of the debate lies in whether statins have a benefit in primary prevention—reducing heart attacks and strokes in patients without known heart disease. There’s no argument about the benefits of statins for secondary prevention—averting a heart attack or stroke in people who have already had one. For example, the 1994 Scandinavian Simvastatin Survival Study—still considered the definitive statin study—showed that treating patients with pre-existing heart disease decreased their chance of dying over five years from 12 percent without statins to eight percent with the drugs; their chance of cardiac death, heart attack, or needing heart surgery fell from about 30 percent without statins to about 20 percent with them also over five years. “If you’re in this category, you would definitely want to take a drug that decreased your chance of dying or having a major cardiac event by a third,” says Dr. Eli Farhi, an assistant professor of cardiology at the University at Buffalo School of Medicine and Biomedical Sciences.

Primary prevention is another matter, however. These are the people Hadler, Topol, and other critics focus on when they discuss the statin problem. Consider two of the most rigorous and widely cited clinical trials of statins: In one, three people of every 100 without pre-existing heart disease but with high cholesterol who took a placebo pill suffered a heart attack; two of every 100 such people taking the best-selling Lipitor did. In the other trial, four of every 100 volunteers taking placebo had a non-fatal heart attack or stroke while two of every 100 taking Crestor did. These results are typical of the findings of other studies. As Topol notes, the bottom line is that the most popular statins reduce the risk of having a heart attack or stroke from three or four percent to two percent.

That’s not very significant. A 2011 analysis that reviewed 14 randomized trials and over 34,000 patients compared the tiny benefit with the very real risks of diabetes and muscle pain or weakness the drugs pose and concluded, “there was no net overall benefit of statins for patients without pre-existing heart disease,” notes Topol.

The key phrase here is “without pre-existing heart disease.” But most general practitioners take their cue from cardiovascular specialists, and many of these experts believe that statins save lives, period. Theirs is a straightforward argument: Cholesterol is bad; therefore, lowering cholesterol is good. “If someone has high LDL as well as high blood pressure or a history of smoking or other risk factors such as age and gender, let’s take that one risk factor [elevated cholesterol] out of the equation,” says Cleveland Clinic’s Dr. Marc Gillinov, co-author of the new book Heart 411. (Indeed, Topol himself, once one of the fiercest advocates of statin drugs, wrote in The New England Journal of Medicine as recently as 2004 that “statin drugs have already surpassed all other classes of medicines in reducing the incidence of the major adverse outcomes of death, heart attack, and stroke” caused by atherosclerotic vascular disease.)

Statins, first introduced in 1987, lower blood cholesterol levels by affecting how much of the substance the liver produces, how much the intestines absorb, or how much circulates. Study after study, going back to the late 1980s, has concluded that statins lower the risk of heart disease, heart attacks, and stroke. Research into statins won the 1985 Nobel Prize in Medicine for Michael Brown and Joseph Goldstein. No wonder statins rang up U.S. sales of $14.3 billion in 2009. One-fourth of Americans 45 and older take statins according to the National Center for Health Statistics.

“Statins clearly decrease one’s chance” of having a heart attack or stroke, agrees Buffalo’s Farhi. But the real-life importance of the decrease depends on how high your risk is in the first place. If your 10-year risk is extremely slim—a value judgment, but many clinicians regard anything under 10 percent as low—then “it would be of minimal benefit to take a statin,” says Farhi. “You could treat thousands of such people without preventing a single event.”

One useful way to look at the data is to consider something called “number needed to treat” (NNT). NNT simply means how many people must be given a medication, undergo surgery, have a diagnostic test, or have any other medical intervention in order for a single one of them to benefit from it. That number can be surprisingly high even for interventions with unquestioned benefits. For instance, 16 people with open fractures need to receive antibiotics for one to benefit; eight people need to take inhaled steroids during an asthma attack to prevent one from going to the hospital. In each case the vast majority of people would not have developed infections or needed a trip to the ER, respectively, even without the intervention. The NNT in these cases is 16 and eight.

Statins for primary prevention have a stratospherically higher NNT. Sixty people would have to take a statin for five years for one to avoid a heart attack; 60 is the NNT for avoiding this outcome. And 268 people without heart disease would need to take a statin for five years for one person to be saved from a stroke; 268 is therefore the NNT for avoiding this outcome, explains Dr. David Newman of Mount Sinai Medical Center in New York, who maintains an NNT database at thennt.com.

It’s one thing to talk about population-wide research. The challenge, of course, is determining the risks or benefits to any individual. To use an extreme example, a person riding in an airplane that’s headed for the side of a mountain is at very low risk of dying from heart disease. On the other extreme, “If you’re a 50-year-old smoker with very high cholesterol and everyone in your family has died of a heart attack before the age of 40, you would probably be very interested in something that decreases the risk of a heart attack,” says Farhi. Most people fall between these two extremes. You can gauge your risk of having a heart attack in the next 10 years by visiting hp2010.nhlbihin.net/atpiii/calculator.asp.

The National Cholesterol Education Program calculator cited above can also be used to show why lowering cholesterol, as statins indisputably do, fails to make much difference in whether or not you will develop cardiovascular disease. After you’ve typed in your actual cholesterol, blood pressure, and other data, notice what happens if you change the cholesterol: In many cases, it alters the risk of a heart attack by little or nothing. A 55-year-old non-smoking woman with total cholesterol of 240 (high enough to make most physicians prescribe a statin), HDL (good cholesterol) of 50 (which is quite low), and systolic blood pressure of 110 has a 1 percent chance of having a heart attack over the next decade, for instance. Now change her total cholesterol to 190—a huge decline. Her risk is still 1 percent. A 65-year-old man with those first numbers has an 11 percent chance of having a heart attack over the next decade; lowering his cholesterol to 190 brings that down to 9 percent.

In other words, cholesterol levels are not as strongly predictive of cardiovascular disease as once thought. “This has shocked everyone,” says Newman. “Cholesterol levels are actually a fairly weak predictor of who will have a heart attack.”

Might statins provide benefits unrelated to cholesterol reduction? There is some evidence that they also decrease inflammation. (When inflammation occurs in the arteries, it is thought to increase the risk of heart disease.) A 2008 study called the JUPITER trial tested statins in about 18,000 people with normal LDLs but elevated C-reactive protein, a measure of inflammation. Statins reduced the risks of heart attack and stroke. That led proponents to conclude that by working through an additional mechanism—lowering inflammation, not just LDL—statins were helping even people with normal LDL levels. Critics of the study note that it was halted earlier than planned (when people on statins were having fewer cardiovascular events than those not taking the drugs), which can produce a misleading result.

Whether cutting your risk of having a heart attack over the next 10 years from 11 percent to 9 percent, as in our hypothetical 65-year-old man who slashed his cholesterol, is meaningful depends on your perspective. But physicians who question the benefit of statins note that no medication is without risk—and statins are no exception. One known side effect is muscle pain or weakness. About five percent of people taking statins develop this, though in most it goes away when they stop taking the drugs. Another is diabetes. One person in 167 who take a statin for five years will develop diabetes. Newman points out that among people taking statins for primary prevention, the risk of diabetes is greater than the benefit in stroke reduction. Indeed, a 2012 study by the Mayo Clinic as reported in the Archives of Internal Medicine found that the use of statins in postmenopausal women is linked to an increased risk of new-onset diabetes of 71 percent. And in February, the FDA announced what it called “important safety changes” in the labels required on statins. Beginning immediately, the labels will have to warn patients that the drugs have been reported to cause certain cognitive effects in some patients, including memory loss and confusion; when patients stopped taking statins, these problems disappeared. The labels will also have to warn that increases in blood sugar (hyperglycemia) have also been reported, and that the FDA is aware of studies showing that statins may increase the risk of type 2 diabetes.

As we were going to press, a new study was reported in The New York Times suggesting that taking statins makes it harder to exercise. The study, by French scientists, found that lab animals taking statins couldn’t run as far as a control group on a placebo. And a 2005 study that looked at human subjects had similar findings: “It seems possible that statins increase muscle damage” during and after exercise “and also interfere somewhat with the body’s ability to repair that damage,” Dr. Paul Thompson, the chief of cardiology at Hartford Hospital in Connecticut and senior author of the study, told the Times.

How many people might be taking statins despite having only a slim chance of benefiting? Experts can give only rough estimates, but the numbers are clearly in the millions. No one currently taking a statin should stop the medication without talking to his or her doctor, of course, but “it doesn’t make sense to treat all these low-risk people with statins,” says Farhi. “The effect is indeed ‘cosmetic,’ improving their cholesterol numbers without producing any measurable difference in clinical outcome.”

He adds: “Doctors who put everyone on a statin without considering whether they’re likely to benefit are doing their patients a disservice.”

The Cholesterol Conundrum The Saturday Evening Post

The suspicion that there is a connection between psychological stress and health—especially heart health—goes back to antiquity. In the mid-20th century endocrinologist Hans Selye coined the term “stress,” and described how the chronic, unrelieved kind can cause pathology, largely through the release of stress hormones including cortisol and adrenaline. Now advances in molecular biology and neuroscience have brought good news and bad news about stress and health. The bad news is that newly discovered mechanisms triggered by an overload of stress cause changes in neurons and the immune system that are more extensive than ever before suspected—with consequences for conditions as varied as asthma, arthritis, hypertension, and HIV/AIDS. The good news is that there are more ways than ever to reduce stress, even if you don’t feel like strapping on a pair of running shoes.

Anecdotal evidence of how stress impairs health is everywhere. Ed Rogers, 66, a public health consultant in Louisville, Kentucky, swears that whenever his wife yells at him for shirking his share of the housework he has to grab his inhaler to stave off an asthma attack. Whenever David, 64, of Breckenridge, Colorado, gets “tired and frustrated by the turkeys one is forced to work with/for,” he says, it causes “tension in the shoulders and neck tending toward headaches.” (Not wanting to offend those “turkeys,” David asks that his last name be withheld.)

But the evidence goes beyond anecdote. Chronic stressors such as financial, work, or marital problems plus the attendant depression, hostility, and anxiety account for about 30 percent of heart attack risk calculate a team of Swedish scientists. And high levels of the stress hormone cortisol strongly predict the likelihood that someone 65 or older will die of cardiovascular disease, as scientist Nicole Vogelzangs of VU University Medical Center and colleagues in The Netherlands found in a 2010 study. Previous research had “suggested that cortisol might increase the risk of cardiovascular mortality, but until now, no study had directly tested this,” said Vogelzangs. But her work found that people in the top one-third of cortisol levels are five times more likely to die of cardiovascular disease than those in the bottom one-third.

In one of the most elegant demonstrations of the link between stress and heart attacks, researchers at The University of Western Ontario (UWO) measured cortisol levels in hair, which is like examining tree rings to determine when droughts and other climate calamities occurred. Hair grows about 1 centimeter—just under half an inch—per month, explains UWO’s Gideon Koren, “so if we take a hair sample six centimeters long, we can determine stress levels for six months by measuring the cortisol level.” Using that approach on 56 men who had recently suffered a heart attack, he and colleagues found that the men had higher cortisol levels in the previous three months than comparable men hospitalized for other conditions, they reported last year.

“Experiments of nature” have offered dramatic demonstrations of the deadly effects of stress. Immediately after the 1994 Los Angeles earthquake, the number of cardiac deaths spiked two to five times the normal rate. And after the 9/11 attacks, the rate of defibrillator firings over the next month was two to three times normal, as the number of people whose heart needed to be shocked back into a normal rhythm soared as a result of chronic stress. But stress that falls short of the Richter scale and a terrorist attack can also harm health. Work, not surprisingly, is the stress mother lode. People working 50 hours a week or more are 13 percent more likely to report hypertension than people working 40 hours a week, and a stressful job with little decision-making authority raises blood pressure rates even during sleep.

Stress can harm health in two basic ways. One is by leading us to fall into unhealthy habits such as sleeping poorly, being less likely to exercise, smoking, and eating unhealthy foods (especially sugars and fats). The American Heart Association reports that 20 percent of Americans are worried that stress will affect their health—yet 36 percent of them say they deal with stress by drinking alcohol or eating. Result: a self-fulfilling prophecy. The poor health habits that result from stress account for an estimated two-thirds of the additional risk of heart attack and other cardiovascular illnesses in people with depression and anxiety, found a 2008 study in the Journal of the American College of Cardiology.

The other path from stress to illness winds through the endocrine, or hormone, system. Stress causes the brain’s hypothalamus to send a message to the adrenal glands, which sit just above the kidneys, to release cortisol. That may seem like a design flaw, but in fact cortisol helps the body recover from acute stress, including by raising blood sugar—the better to help you flee a saber-tooth cat. (The adrenals also release adrenaline, or epinephrine, and the related norepinephrine.) But trouble begins when too much cortisol is released, or when it is released unnecessarily—that is, not in response to an actual and immediate threat but to background anxiety—and remains chronically elevated. High cortisol levels cause chronic inflammation, which can cause arthritis to develop or worsen, and trigger the release of immune-system proteins called cytokines, implicated in such age-related diseases as Alzheimer’s, Parkinson’s, and type 2 diabetes.

How Stress Impairs Health

In Greek mythology, the monstrous Hydra terrorized visitors to a mystical lake. Beheading the Hydra was no easy task because it grew two new heads whenever one was cut off. The multiplying evil of the Hydra offers an apt analogy to the insidious ill-effects of stress in modern life. Chronic high levels of stress bring on a world of trouble on multiple body systems and can lead to…

When stressed, the body activates a tiny region in the brain called the hypothalamus that stimulates the suprarenal glands (red arrows) to release a surge of hormones, including adrenaline and cortisol (yellow arrows). Although the body’s stress-response system is typically self-regulating, returning to normal after a perceived threat passes, constant stress can seriously disrupt almost all the body’s processes, putting one at risk of a variety of serious health issues. Image © BSIP/Photo Researchers, Inc.

Worsening of Asthma symptoms
This condition is marked by inflammation of the airways, so it’s no surprise that stress, by causing inflammation, increases asthma symptoms. A University of Wisconsin study showed how. When students with asthma inhaled an allergen (ragweed, dust mites, or cat dander), lung inflammation was 27 percent higher during finals than during a low-stress period—even though the allergen exposures were identical.

Cardiovascular disease
Stress increases blood levels of inflammatory molecules (called IL-6, C-reactive protein, and fibrinogen). These bad actors promote the development of atherosclerosis, or hardening of the arteries. The inflammatory molecules that trigger atherosclerosis also make the fatty arterial deposits called plaques more likely to rupture, causing a heart attack or stroke. Stress also causes the nerves to flood the bloodstream with a molecule called neuropeptide Y (NPY), which raises heart rate and blood pressure. NPY stimulates the growth of abnormal smooth muscle in blood vessels, which leads them to become blocked with plaque-like deposits of microphages, thrombus, and lipids.

Faster weight gain
NPY also seems to be the culprit behind our tendency to overeat and gain weight when we’re stressed. It throws a monkey wrench into the brain’s appetite-regulation system, and can also “unlock” receptors in fat cells, stimulating them to grow in size and proliferate. That also seems to be an evolutionary adaptation—early humans benefited from putting on fat in response to stress, which tended to be of the “mammoths are scarce this year” variety rather than the “I can’t make my mortgage payment” kind. As a result, a physiological response that was adaptive in the past is harmful today: We put on a nice layer of fat that doesn’t actually help us cope with the source of our stress. The effect is so powerful that stressed mice on high calorie diets gained twice as much fat as unstressed mice on the same diet.

High cholesterol
One reason mental stress can raise cholesterol levels may be that stress encourages the body to produce more energy—to fight or flee—including fatty acids and glucose. Both substances cause the liver to produce and secrete more LDL, or bad cholesterol.

Impaired immune system
Although scientists have long suspected that stress undercuts the immune response, only now has the mechanism behind that connection become clear. When we are stressed, the flood of NPY impairs the immune-system cells whose job is to fight infections. As a result, colds, flu, and other viral diseases are more likely. So are virally caused malignancies such as cervical cancer, which can be triggered by the human papillomavirus (HPV). HPV infection alone is not sufficient; the immune response causes most HPV infections to disappear. But, with stress in the mix, precancerous cervical lesions are more likely to progress to cancer.

Weakened response to HIV
Stress can bring about changes that allow the HIV virus to replicate more quickly, accounting for much of the variability in how people respond to an HIV infection. By keeping stress under control or avoiding stressors an HIV-positive person is more likely to remain asymptomatic for long periods rather than progressing to AIDS and is less likely to suffer opportunistic infections.

Increased risk of dementia
Psychological stress in middle age can raise the risk of dementia, especially Alzheimer’s disease, in old age. Scientists at Sweden’s University of Gothenburg followed 1,400 women for 35 years, asking them about their levels of psychological stress in 1968, 1974, 1980, 1992, and 2000 to see who developed dementia. Women who reported repeated periods of stress in middle age were 65 percent more likely to eventually develop dementia than women who did not. In women who reported stress at all time points, the risk was more than twice that of women who had escaped stress. So what’s the connection? A solid body of research shows that stress hormones called glucocorticoids are toxic to neurons and to the synapses that connect them, a phenomenon dubbed “neurostress.” The fewer synapses in a brain, the less of a cognitive cushion it apparently has after age-related mental decline sets in.

Premature aging
Psychosocial stress can reach into our very DNA, altering the “telomeres” that sit at the ends of chromosomes like the plastic tips at the end of shoelaces. Telomeres become shorter as the cell (and the person) ages. When enough telomeres reach a critically short length, the chromosome unravels like a shoelace that has lost its tip, and the cell stops dividing. This can trigger or contribute to age-related diseases. People under chronic stress have shorter telomeres and less of the enzyme telomerase, which repairs that damage, find scientists led by Ronald Glaser of Ohio State University.

Increased risk of cancer
This one’s a big “maybe.” The problem for scientists is that it is almost impossible to know whether a stress-free immune system keeps nascent tumors in check. Micro-scopic tumors are almost impossible to detect, so researchers can’t tell whose are being quashed by a healthy immune system and whose are being allowed to proliferate by a stress-impaired immune system. A 2007 study found that, in cell cultures, the stress hormone norepinephrine can ratchet up biochemical signals that stimulate tumor cells to proliferate. And in multiple myeloma cells growing in lab dishes, norepinephrine can increase production of proteins that foster metastasis. “For years it was thought that the immune system plays no role in cancer,” says immunologist Peter Lee of Stanford. That’s because cancer is part of the “self,” and the immune system targets only “non-self”—viruses, bacteria, organ transplants. But now, he explains, “We and other labs have uncovered multiple immune deficits in cancer patients.”

Harm to the next generation
Stress can jump the generation gap. A mother’s stress during pregnancy can influence the baby’s developing immune system in such a way as to make the child’s immune response go into overdrive. For example, such children are at higher risk for asthma and for allergies to dust.

Illustration by Gianpaolo Pagni

Learn to be Stress Free!

As science keeps uncovering more ways that stress can impair health, there is also increasing confidence that you really can learn to lower stress levels. Researchers today understand more precisely than ever what it takes to control stress.

Aerobic exercise is an excellent place to start. Regular exercise, especially when combined with stress management training, can actually decrease cardiovascular risk in patients with heart disease.

The next step is to adopt principles of what’s known as cognitive behavorial therapy (CBT) focusing on stress management. CBT includes monitoring yourself for signs of stress and learning such stress-management skills as deep breathing and spiritual development. In studies, people receiving CBT had a 41 percent lower rate of both fatal and non-fatal heart events, 45 percent fewer recurrent heart attacks, and a 28 percent lower rate of death over the eight years that they were followed.

Stress management can improve physiological markers of cardiovascular health, found a 2011 study. It was the first randomized trial to show that something other than drugs can improve blood flow to heart, health of blood vessels, and ability of the cardiovascular system to regulate surges in blood pressure.

Even the way you fight can make a difference. A 2009 study found that when couples used words to indicate that they are thinking about their conflict in a rational way rather than making accusations they experienced smaller increases in cytokines after the fight compared to couples who fought irrationally.

Proper stress manage-ment can even impact your DNA. Herbert Benson, M.D., who coined the term “relaxation response,” finds that yoga, prayer, and a meditation-like exercise he developed—sitting quietly, relaxing your muscles, breathing rhythmically, and repeating a “focus” word when you exhale for 20 minutes—all lower heart rate, blood pressure, and inflammation. And, as he describes in his book The Relaxation Revolution, these calming activities affect DNA. Comparing experienced meditators to novices, he and colleagues found that 2,209 genes were expressed differently—that is, switched on or off—in the two groups. Among them: genes involved in the immune system, inflammation, premature aging, and oxidative decay implicated in heart disease and cancer. But after just eight weeks of stress-management training, Benson finds, hundreds of genes in novice meditators moved away from the stressed-out pattern and instead resembled one that has been “associated through past research with clear health benefits.”

The New Science of Stress The Saturday Evening Post

The notion that “insanity is infectious,” as virologist Ian Lipkin of Columbia University’s Mailman School of Public Health bluntly puts it, goes back to antiquity. As late as the 1800s, the mentally ill were locked away because, among other reasons, they were thought to be contagious. The notion wasn’t completely misguided. Until the discovery of penicillin ushered in the age of antibiotics, a major cause of mental illness was syphilis. But biomedicine is subject to fads and fashion no less than skirts are, and over the last 40 years disease detectives seeking the cause of mental conditions such as schizophrenia, bipolar disorder, autism, and obsessive-compulsive disorder have turned from microbes to genes as the cause. And now, a parade of discoveries suggests that viruses may be the culprit rather than your family tree. The new research indicates that viral infection can affect the developing brain and contribute to mental illnesses even before birth.

At first the evidence for a viral link to mental illness was spotty and inconsistent. Early studies piggy-backed on observations that when mothers suffered an infection during pregnancy, the children who were in utero at the time had an elevated risk of developing schizophrenia. But rigorous studies of whether that link was real produced contradictory results: Some found that maternal infection with influenza increased the risk of a child developing schizophrenia 20 years later, but others did not. Only in the last few years have scientists sorted it out. Instead of assuming that every child who had been in utero at the time of a flu outbreak had been infected, researchers began examining mothers’ blood for the telltale antibodies that indicate a past infection. With that advance, the link became clear: As researcher Alan Brown of Columbia University calculated in a 2010 paper, more than 30 percent of the risk of developing schizophrenia comes from prenatal exposure to the flu virus.

The flu virus is not the only culprit. In 2000, Brown and colleagues produced the first watertight evidence that young adults who had been exposed to the rubella virus (aka “German measles”) while they were fetuses less than three months old had a five-times-greater risk of developing psychosis—including schizophrenia—than their peers who had not been exposed to the virus.

Contrary to expectations, however, it is not rubella or other viruses, per se, that harm the developing brain. That became clear as scientists documented a veritable menagerie of maternal infections able to cause psychiatric and neurodevelopmental illnesses—not only flu and rubella but also toxoplasmosis and genitourinary infections. To their shock, scientists began to find that, although mothers had antibodies to flu in their blood (showing that the mother had been infected), the kids—in utero at the time—often did not: They were not infected with the virus.

“It is the reaction of the mother’s immune system to the infection, not the infection itself, that affects the developing brain,” says Columbia University’s Dr. Ian Lipkin.

So what was happening? It’s not that the fetus becomes infected. Instead, the infection triggers the mother’s innate immune system, the army of molecules that prime other cells to kill the invaders. “It is the reaction of the mother’s immune system to the infection, not the infection itself, that affects the developing brain,” says Lipkin. Specifically, a flood of antibodies and other immune-system chemicals with names like chemokines and cytokines surges through the placenta and into the fetus. “The result may be compromised fetal brain development,” explains Dr. Robert Freedman, a psychiatrist at the University of Colorado Denver Health Sciences Center.

Researchers put the final piece into the puzzle when they exposed pregnant mice to a molecular mimic of viral RNA (viral genes are often made of RNA instead of the closely related DNA). That exposure put the brakes on special stem cells that give rise to new nerve cells (neurons)—not just in the embryo but on into adulthood. Most egregiously, it blocked the growth of a specialized kind of neuron destined for the neocortex, the most advanced region of the brain.

How bad was the damage? The offspring of the virus-exposed mice could not even walk normally, reported epidemiologist Mady Hornig of Columbia and colleagues last year. And, after the mice grew to adulthood, they had other neurological abnormalities as well.

Because the mother’s immune system’s response to infection causes the harm to the fetus, almost any virus is a potential threat to the developing fetus. “The damage to neurons and neural stem cells might not be evident right away,” says Hornig, “but manifests later as cognitive and behavioral problems.”

How bad will those problems become? “The specific result depends on the timing,” says Lipkin. He explains that if neural stem cells are killed by the flood of immune-system molecules (the chemokines and cytokines) before they mature, they will not take their rightful place in the brain’s neural networks. Circuits that are forming at the time of the infection will be most vulnerable, while those already hooked up are spared. In schizophrenia, for instance, there are abnormally low numbers of neurons and incomplete clustering in a particular area of the brain, hinting that something went wrong when these regions were being constructed. The effect of the viral infection may be delayed even into adulthood if a circuit damaged by the cytokine flood is not recruited until that time.

The apparent link between prenatal viral infection and later brain disorders led Johns Hopkins Children’s Hospital to establish in 1998 the nation’s first pediatric research center to investigate links between severe mental illness and prenatal or early childhood viral infections. Last year, Robert Yolken, who heads the Stanley Division of Developmental Neurovirology at Johns Hopkins Medical School, and colleagues reported that in their study of all children born in Denmark since 1981, mothers who had been infected with herpes simplex 2 had a 56 percent greater risk of having a child who later developed schizophrenia.

Dr. Robert Yolken of Johns Hopkins Children’s Center believes that better understanding the role infections play in developing schizophrenia may lead to more effective treatments in the future.

Although current thinking holds that the mother’s immune response, not the virus itself, is the culprit behind viral causes of mental illness and neurodevelopmental disorders, there may be exceptions. Yolken, for instance, suspects that herpes and influenza viruses (as well as the Toxoplasma gondii parasite carried by cats and other warm-blooded animals) might invade the brain and lie dormant for years before triggering schizophrenia or bipolar illness.

The evidence that viruses can cause psychiatric illnesses and neurodevelopmental disorders does not mean they are the only causes. For example, bacteria can also trigger an immune response, which may explain why strep infection can damage the developing brain, leading to the constellation of tics, obsessive-compulsive disorder, and other symptoms called Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS). Additionally, many mental illnesses are more likely to arise in people with a family history of them, indicating that they are at least partly heritable. But the failure of geneticists to find genes that have a strong effect on the likelihood of developing schizophrenia, depression, bipolar disorder, or autism suggests that genes do not cause these complex disorders the way a single gene directly causes, say, sickle-cell disease. More likely, says Lipkin, genes make people more or less susceptible to other causes of these diseases—including viruses.

Although the research is still new, scientists believe that it is not too early for obstetricians to take the emerging findings into account. The most obvious step is to monitor pregnant women closely for infections—even those that seem mild—because what may be a minor inconvenience to the mother could be devastating to the unborn child. Women should be educated to be aware of when they might have contracted a viral infection and to tell their obstetrician, who may need to treat them more aggressively than is current practice. In animal studies, after pregnant females were exposed to virus genes, the damage to their unborn pups was prevented when the mothers were given nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen. That provides a rationale for using these drugs when a pregnant woman contracts an infection, says Hornig. Currently, obstetricians prescribe acetaminophen (Tylenol) for pain relief in pregnant women, but that compound does not have the anti-inflammatory effects needed to turn off the cytokine flood.

The old expression “take two aspirin—or ibuprofen—and call me in the morning” never had so much meaning.

Nathan Wolfe’s research on viruses has earned him the nickname “the Indiana Jones of virus hunters.”

The next deadly scourge—and where it’s most likely to originate.

It is no coincidence that the most widespread and dangerous viruses began infecting humans some 11,000 years ago, says virologist Nathan Wolfe, CEO of Global Virus Forecasting (GVF) Initiative. When animals and people live in close proximity, as they began to do with the advent of agriculture and animal husbandry, viruses from the former can jump the species barrier—as did HIV/AIDS, Ebola, Marburg, and more kinds of flu than you can count.

Wolfe, who founded GVF in 2008 and has been nicknamed the “Indiana Jones of virus hunters,” warns that our fellow mammals aren’t done with this problematic sharing. Some 60 percent of emerging viruses—that is, those new to medical science—come from animals. And as the world becomes smaller and more connected, allowing a traveler to get from the deepest jungles of Africa to London or New York or Tokyo in less than a day, the chance of a virus jumping from a monkey to a bush meat hunter to a western tourist and the entire developed world has soared. In his upcoming book The Viral Storm: The Dawn of a New Pandemic Age (to be published in October), Wolfe argues that this has made us sitting ducks for another global epidemic.

The greatest threats come from two sources: completely new viruses (such as HIV/AIDS) and viruses that mutate. Primates are the most likely reservoirs of the former because the closer the evolutionary relationship, the more likely a virus is to cross over. (For example, there are no cases of viruses jumping to humans from fish or insects, says Wolfe.) But viruses from mammals other than primates can also spread through the human population like wildfire. The H1N1 virus from pigs was so highly transmissible that it went from infecting zero percent of the human population to 10 percent in only a year, notes Wolfe, killing some 20,000 to 30,000 people. The only reason its toll has not been greater is that transmissibility and lethality are inversely related; that’s why Ebola, though deadly, is not highly transmissible.

An even greater threat is mutation of existing human viruses. If one that is deadly but not very transmissible or very transmissible but not deadly acquires genes for that second trait, the results could be catastrophic. That is most likely to happen when viruses from widely separated regions come into contact—as is more and more likely in what Wolfe calls “this viral mixing vessel” caused by global travel.

“Viruses aren’t static,” he says. “They change over time; they exchange genes with other viruses, which can make them more likely to develop deadly recombinants. The greatest threat is probably something we don’t even know is out there.”

Medical Breakthrough: The Viral Link to Mental Illness The Saturday Evening Post

When he was working at the National Cancer Institute (NCI) in the 1990s, Dr. Hwu and colleagues decided they needed an innovative way to retrain the immune system. What if they could inject into cancer patients the very “markers” that stud the surface of malignant cells? That’s how vaccines for infectious diseases such as measles and smallpox work, by training the immune system to recognize and attack the markers on disease-causing viruses. In this case, Dr. Hwu and others reasoned that injecting “tumor antigens” might train the immune system to recognize the tumor cells as foreign and destroy them. It would be a “cancer vaccine” — not a vaccine like that for measles, which prevents a disease, but one that treats it. (These cutting-edge cancer vaccines are not to be confused with Gardasil, a vaccine that primes the immune system to attack the virus that causes cervical cancer. Very few human cancers are known to be caused by viruses, so “cancer vaccine” has come to mean one that treats existing cancer.)

The NCI scientists were hardly alone in dreaming of a cancer vaccine. The appeal was obvious: Oncologists’ cancer-fighting arsenal consisted of surgery, radiation, and chemotherapy — or as critics like to say, cutting, burning, and poisoning. Not only did the three weapons come with serious side effects, but they were far from universally effective. Perhaps harnessing the immune system would vanquish tumor cells with little to no collateral damage to the rest of the body. The idea took hold in a serious way in the 1970s, recalls Dr. Len Lichtenfeld of the American Cancer Society, “and it was going to be a slam dunk. We were going to cure cancer.” Obviously, that did not happen. Instead, vaccine after vaccine failed. But with advances in their understanding of both cancer and immunology, scientists finally scored some notable successes: Three large-scale studies, called Phase III clinical trials, presented at the 2009 meeting of the American Society of Clinical Oncology (ASCO), suggest that cancer vaccines may one day play a role in cancer treatment.

Vaccine Renews Hope—Dr. Patrick Hwu meets with Hilde Stapleton, who credits the trial vaccine plus interleukin-2 with knocking her melanoma into remission. In May 1999, Stapleton found a suspicious mole behind her left knee. After surgery to remove the mole and lymph nodes (the cancer had spread) at M.D. Anderson, she enrolled in an early cancer vaccine study. But by 2006, the melanoma had returned. Because the cancer had metastasized to her lungs, her earlier experience in a vaccine trial led her to volunteer for Hwu's trial the following spring. She has been in full remission ever since. "I'm, pleased with the results," she says. Image: © AP Photo/David J. Phillip.

In one study, a vaccine based on the work of Dr. Hwu and his NCI colleagues extended what’s called progression-free survival — how long patients live before a cancer that has been treated with chemotherapy or radiation returns — in people with advanced melanoma, one of the most lethal cancers. The vaccine consists of antigens that stud melanoma cells. By injecting these “gp100” molecules into patients, “the vaccine activates the T cells of the immune system to recognize the antigens on the surface of the tumor,” says Dr. Hwu. “The T cells then secrete enzymes that poke holes in the tumor cells’ membrane, causing it to disintegrate” and the cancer cells to die.

This was the first time a melanoma vaccine had shown any benefit in a Phase III trial, but even with this distinction, it was no “slam dunk.” The 93 patients who received a standard therapy called interleukin-2 and no vaccine remained in remission for an average of 1.6 months. The 86 patients who received the vaccine plus interleukin-2 remained in remission for just under three months; hardly a big improvement. And on what every cancer patient cares about most — staying alive — the vaccine fell short. Vaccinated patients lived 17.6 months, on average, while unvaccinated patients lived 12.8 months, a difference that statistical analysis determined could be due to chance.

Why wasn’t the benefit greater? It’s possible that the patients did not have enough T cells to mount an effective immune response, says Dr. Hwu. Or maybe, for some reason, the T cells do not find the melanoma cells. Perhaps the tumor disguised itself, hiding the antigen that the T cells were trained to look for. “It’s possible that we did not have enough soldiers, or that they were not well-enough trained, or that they were not able to find the battlefield,” says Dr. Hwu. It’s also possible that a vaccine needs to contain more than the gp100 antigen. “Unique antigens specific to a patient’s cancer do exist, and using them might stimulate a more effective immune response,” he says. “But it would take months to synthesize such a custom-made vaccine,” and advanced melanoma patients do not have months.

Another study unveiled at ASCO this year, however, took the customization approach. Invented by M.D. Anderson’s Larry Kwak when he, too, was at NCI, the vaccine contains markers from each patient’s cancer — in this case, a form of non-Hodgkin’s lymphoma called follicular lymphoma, which is a cancer of (ironically) immune-system cells called B cells. After a biopsy harvests a patient’s malignant B cells from the lymph nodes, it takes about one month to make the vaccine. “The vaccine uniquely recruits the patient’s immune system to seek and destroy only tumor B cells,” said Stephen Schuster of the University of Pennsylvania, who led the study.
“It’s the ultimate in personalized therapy,” adds Dr. Kwak. “Even if patients have the same type of lymphoma, the tumors will still have different antigens, and that’s what you want your vaccine to contain.” The 76 patients who received the custom-made vaccine after a standard course of chemo remained disease-free just over one year longer than the 41 patients who received the chemo alone (44.2 months compared to 30.6 months). In an earlier Phase II study at NCI, patients have remained disease-free for an average of eight years.

Crucially, all the patients in the latest study were in complete remission or had no detectable cancer when they received their personalized vaccine. That is, they had responded to standard chemo and sustained a remission for six months. To skeptics, that raises the possibility that these patients’ cancer might have been less aggressive, and that fact — not the vaccine — accounts for their longer survival. In addition, the vaccine was compared to chemo that has now been superseded by something more effective. Oncologist Ron Levy of Stanford University, a founding father of cancer vaccines, gives BioVax ID “a qualified yes” in terms of effectiveness, but only a “maybe” on whether it will find a meaningful role in treating patients with follicular lymphoma.

Dr. Larry Kwak from M.D, Anderson are working on "personalized" vaccines that prime the immune system to go after a unique biological tag found only on tumor cells. Photo © Wyatt McSpadden Photography.

Dr. Kwak sees it differently. He admits that the vaccine — and possibly all cancer vaccines — work best in patients whose tumor has shrunk to almost nothing or who are in complete remission. “Then you bring in the vaccine to mop up any remaining cancer cells,” he says. “That’s the strategy, and it should work for other cancers.” If he’s right, then the failures of other cancer vaccines might be because the patients in those studies had active and sometimes widespread cancer. “We now suspect that cancer vaccines will not work very well against advanced tumors,” says Dr. Kwak. “Tumors have the ability to turn off the immune response, and the more tumor you have, the more factors that can do that.”

That may explain why a vaccine for prostate cancer has fallen short. Called Provenge, it failed to beat back disease, let alone improve survival, in early tests, and the Food and Drug Administration refused to approve it in 2007. But the manufacturer, Dendreon, has spent an estimated $560 million on it and isn’t giving up. In a new trial, also presented at ASCO this year, the company announced that among men whose prostate cancer was no longer responding to hormone treatment or chemo, those who received Provenge lived four months longer than those who did not, 26 months versus 22 months. Just under one-third of the Provenge men were still alive after three years, compared to just under one-quarter of the men who did not receive the vaccine — 31 percent versus 23 percent. That’s far from a cure, but Dendreon is hopeful that it will get a green light from the FDA in 2010.

But don’t expect that to open the floodgates for cancer vaccines. So many have failed that it seemed as if they were going to be yet another therapy that looked terrific on paper, and even in lab animals, but which crashed and burned when tested in people. For instance, in 2006 a pancreatic-cancer vaccine called PANVAC-VF failed to improve overall survival. Considering that it was being compared to chemotherapy that keeps patients alive for a median three months, the result was a big disappointment.

The encouraging results for the melanoma and follicular lymphoma vaccines — and, to a lesser extent, for Provenge — have definitely been heard, breathing new life into a field that had been hanging by a thread. “Looking to the future, I think we’ll see a role for vaccines where the cancer is found very early, when the disease burden is small [because the patient is in remission], or when there are circulating cancer cells that can’t be eliminated any other way,” says Dr. Lichtenfeld. “But it looks unlikely that cancer vaccines will produce a response in people who have cancer throughout their system.” The latter, of course, are the sickest of the sick, so there is no small irony in the likelihood that this most innovative of cancer treatments will help not those who need it most, but those with an already hopeful prognosis.

The Post Investigates: Cancer Vaccines The Saturday Evening Post