Thursday, January 19, 2012

A Doctor in Your Pocket



What does the future of medicine hold? Tiny health monitors, tailored therapies—and the end of illness


Take a moment to imagine what it would be like to live robustly to the ripe old age of 100 or more. You wouldn't die of any particular illness, and you wouldn't gradually waste away under the spell of some awful, enfeebling disease that began years or decades earlier.
It may sound far-fetched, but it is possible to live a long, disease-free life. Most of the conditions that kill us, including cancer and heart disease, could be prevented or delayed by a new way of looking at and treating health. The end of illness is near.
Today, we mostly wait for the body to break before we treat it. When I picture what it will be like for my two children to stay in good health as independent adults in 10 or 20 years, I see a big shift from our current model.
I see them being able to monitor and adjust their health in real time with the help of smartphones, wearable gadgets—perhaps like small, invisible stickers—to track the inner workings of their cells, and virtual replicas of their bodies that they will play much like videogames, allowing them to know exactly what they can do to optimize every aspect of their health. What happens when I take drug x at dosage y? How can I change the expression of my genes to stop cancer? Would eating more salmon and dark chocolate boost my metabolism and burn fat? Can red wine really lower my risk of heart attack?
From a drop of their blood, they will be able to upload information onto a personal biochip that can help to create an individualized plan of action, including both preventive measures and therapies for identified ailments or signs of "unhealthiness." (Other body fluids—like tears and saliva—might be routinely tested, too.) They would be on the lookout for problems like imbalances in blood-sugar control, a risk factor for diabetes, and uncontrolled cell growth, which could signal cancer. Their doctors won't just examine them once a year; they will continually monitor the next generation of patients, offering advice along the way.
What is equally exciting is that this patient data will be added to a universal database that can be aggregated by powerful search engines like Google and constantly fed into new trials and experiments—speeding up our understanding of which drugs work best for which people. The database might show, for example, that people with a particular genetic profile respond to one type of cancer treatment but not another. As more people anonymously add their health data, this database would become more and more effective as a tool for preventive medicine.
Today, most people who are concerned about their health follow sweeping, general guidelines. If you want to lose weight, you are likely to pick a diet that advises eating more fibrous vegetables and cutting back on processed sugar. If you want to reduce your risk for cancer, you avoid tobacco smoke, exercise regularly and take early detection seriously.
The problem with health care today is that we don't know enough about the body to practice preventive medicine actively. With limited knowledge, diagnostic medicine makes sense. If we don't know what we're trying to prevent or how best to do it, we have to wait for an obvious symptom to emerge in order to take action. At that point, we're usually treating a disease that has had ample opportunity to progress.
We can do better. To start, we need to appreciate the body for what it is: a very complex network, much of which we don't yet fully understand. When you look at the body from this systemic point of view, you begin to see that a lot of what we know about health is gravely misunderstood.
In 2009, my colleague Danny Hillis—a former Disney engineer who pioneered the development of so-called parallel supercomputers—and I set up a way to measure 100,000 different types of proteins from a single drop of blood. The goal is to evaluate and make sense of the body's intricate inner workings in a way that's much more dynamic and insightful than what DNA alone can provide. Proteins change in your body every minute, depending on what's going on internally. Our ultimate plan is to develop tests, based on protein levels, for illnesses like cancer. Such tests could take the place of invasive techniques like biopsies.
With each passing year, the technology necessary for this revolution in medicine is growing less expensive. Last week, Life Technologies of Carlsbad, Calif., announced that it will be able to map an individual's entire genetic sequence in one day, for $1,000. Similar tests today cost many thousands of dollars. The ability to follow day-to-day changes in your body's proteins and metabolites is not far behind.
So how do we get to this future?
It has to start with data collection. In 2004, Dell launched a company program called Well at Dell to encourage healthy lifestyles. Employees receive alerts and information customized to their health issues, incorporating their latest test results and treatments and allowing them to make more informed decisions. A newly diagnosed diabetic, for example, might get information about how to monitor blood sugar and watch out for the circulatory problems that often accompany the disease.
Not surprisingly, these corporate health-management tools have come under fire, with most critics worrying about privacy. But we can't expect the health-care industry to continue to innovate and grow if we continue to hoard health information.
The federal agency that administers Medicare pays over half of the medical bills in the U.S., but it doesn't retrieve, organize or mine that data. Imagine how much better the Medicare system could be if all this data were analyzed to improve public health. Or imagine databases from many different sources, private and public, coming together in a centralized network that would look for patterns and try to translate them into new ideas for anticipating and preventing health problems.
Personalized medicine isn't as far away as you might think. Consider what's already happening in genetic profiling for individuals, which is available today for several hundred dollars. I co-founded a genetic screening company and am a big proponent of the technology. It allows us to take a broad look at DNA variations and to assess your risk for certain ailments and what medications, at what dosages, might work best, based on your metabolism. Just because you have one or two markers of genetic risk does not mean that you will definitely develop a particular condition, but the outcome can be affected by changes in lifestyle, or in some cases, by taking medication.
As these and other technologies advance, it will become progressively easier to monitor and maintain our overall health. Then it will be up to us. The promise of personalized medicine depends, finally, not on the tools that become available but on our determination to be informed and willing patients.

http://online.wsj.com/article/SB10001424052970204124204577155162382326848.html?mod=djemWMPIndia_h

A Gut Check for Many Ailments


What you think is going on in your head may be caused in part by what's happening in your gut.
A growing body of research shows the gut affects bodily functions far beyond digestion. Studies have shown intriguing links from the gut's health to bone formation, learning and memory and even conditions including Parkinson's disease. Recent research found disruptions to the stomach or intestinal bacteria can prompt depression and anxiety—at least in lab rats.
Better understanding the communication between the gut and the brain could help reveal the causes of and treatments for a range of ailments, and provide diagnostic clues for doctors.

"The gut is important in medical research, not just for problems pertaining to the digestive system but also problems pertaining to the rest of the body," says Pankaj J. Pasricha, chief of the division of gastroenterology and hepatology at Stanford University School of Medicine.
The gut—considered as a single digestive organ that includes the esophagus, stomach and intestines—has its own nervous system that allows it to operate independently from the brain.
This enteric nervous system is known among researchers as the "gut brain." It controls organs including the pancreas and gall bladder via nerve connections. Hormones and neurotransmitters generated in the gut interact with organs such as the lungs and heart.
Like the brain and spinal cord, the gut is filled with nerve cells. The small intestine alone has 100 million neurons, roughly equal to the amount found in the spinal cord, says Michael Gershon, a professor at Columbia University.
The vagus nerve, which stretches down from the brainstem, is the main conduit between the brain and gut. But the gut doesn't just take orders from the brain.
"The brain is a CEO that doesn't like to micromanage," says Dr. Gershon. The brain receives much more information from the gut than it sends down, he adds.
Many people with psychiatric and brain conditions also report gastrointestinal issues. New research indicates problems in the gut may cause problems in the brain, just as a mental ailment, such as anxiety, can upset the stomach.
Stanford's Dr. Pasricha and colleagues examined this question in the lab by irritating the stomachs of newborn rats. By the time the animals were eight to 10 weeks old, the physical disturbance had healed, but these animals displayed more depressed and anxious behaviors, such as giving up more quickly in a swimming task, than rats whose stomachs weren't irritated.
Compared to controls, the rats also showed increased sensitivity to stress and produced more of a stress hormone, in a study published in May in a Public Library of Science journal, PLoS One.
Other work, such as that of researchers from McMaster University in Hamilton, Ontario, demonstrated that bacteria in the gut—known as gut flora—play a role in how the body responds to stress. The exact mechanism is unknown, but certain bacteria are thought to facilitate important interactions between the gut and the brain.
Electrically stimulating the vagus nerve has been shown to reduce the symptoms of epilepsy and depression. (One treatment approved by the Food and Drug Administration, made by Cyberonics Inc., is already on the market.)
Exactly why such stimulation works isn't known, experts say, but a similar procedure has been shown in animal studies to help improve learning and memory.
Earlier this month, researchers made a small step toward understanding a gastrointestinal ailment that typically affects children with autism.
In a study of 23 autistic children and nine typically developing kids, a bacterium unique to the intestines of those with autism called Sutterella was discovered.
The results, published online in the journal mBio by researchers at Columbia's school of public health, need to be studied further, but suggest Sutterella may be important in understanding the link between autism and digestive ailments, the authors wrote.
Dr. Gershon, professor of pathology and cell biology at Columbia, has been studying how the gut controls its behavior and that of other organs by investigating the neurotransmitter serotonin.
Low serotonin levels in the brain are known to affect mood and sleep. Several common antidepressants work by raising levels of serotonin in the brain.
Yet about 95% of the serotonin in the body is made in the gut, not in the brain, says Dr. Gershon. Serotonin and other neurotransmitters produced by gut neurons help the digestive track push food through the gut.
Work by Dr. Gershon and others has shown that serotonin is necessary for the repair of cells in the liver and lungs, and plays a role in normal heart development and bone-mass accumulation.
Studying the neurons in the gut also may also help shed light on Parkinson's disease. Some of the damage the disease causes to brain neurons that make the neurotransmitter dopamine also occur in the gut neurons, researchers say.
Researchers are now studying whether gut neurons, which can be sampled through a routine colonoscopy, may help clinicians diagnose and track the disease without invasive brain biopsies, says Pascal Derkinderen, a professor of neurology at Inserm, France's national institute of health.

http://online.wsj.com/article/SB10001424052970204468004577164732944974356.html?mod=djemWMPAsia_h

Wednesday, January 18, 2012

Omelets: The Ultimate Fast Food

For some time now the medical literature has been countering the myth that the cholesterol in eggs goes straight to the arteries and that eggs should be shunned by anybody committed to healthy eating. Studies have shown that only a small amount of dietary cholesterol passes into the blood and that saturated fats and trans fats have much bigger effects on cholesterol levels. In fact, according to the Harvard School of Public Health, the only large study that looked at the effect of egg consumption on heart disease found no correlation between the two, except among people with diabetes, who were a bit more likely to develop heart disease if they ate an egg a day.

That’s great news, because eggs are an excellent and delicious source of nutrients, rated by some nutritionists as the gold standard for protein, as one egg has only 75 calories but 7 grams of protein. They are also a great source of the carotenoids lutein and zeaxanthin, which have been associated with protection against vision loss.
It’s also great news because eggs cook quickly. Make an omelet if you need a quick, utterly satisfying meal. Omelets are my response to people who tell me that they’d like to eat a healthier diet but that it’s too time-consuming. In addition to the fillings in this week’s recipes, think of using up leftovers or little hunks of cheese that are lingering in your refrigerator, or search through your pantry for something that looks delicious.
Beet Green and Feta Omelet
At this time of year I don’t let a week go by without buying beets at the farmers’ market. I cook up the greens when I get home so that I can make meals like this one in minutes.
For each omelet:
1/3 cup chopped blanched or steamed beet greens (about 1 ounce; see below)
1 garlic clove, minced
1/2 teaspoon red wine vinegar or sherry vinegar
Salt and freshly ground pepper
2 eggs
2 to 3 teaspoons low-fat milk
2 teaspoons extra virgin olive oil
1/2 ounce feta cheese, crumbled
1. In a bowl, toss the chopped blanched beet greens with the garlic, vinegar and salt and pepper to taste.
2. Break the eggs into another bowl and beat with a fork or a whisk until eggs are frothy. Whisk in salt and pepper to taste and 2 to 3 teaspoons milk.
3. Heat an 8-inch nonstick omelet pan over medium-high heat. Add 2 teaspoons olive oil. Hold your hand an inch or two above the pan, and when it feels hot, pour the eggs into the middle of the pan, scraping every last bit into the pan with a rubber spatula. Swirl the pan to distribute the eggs evenly over the surface. Shake the pan gently, tilting it slightly with one hand while lifting up the edges of the omelet with the spatula in your other hand, to let the eggs run underneath during the first minute or two of cooking.
4. As soon as the eggs are set on the bottom, sprinkle the beet greens over the middle of the egg “pancake” and top with the feta. Next, jerk the pan quickly away from you then back toward you so that the omelet folds over onto itself. If you don’t like your omelet runny in the middle (I do), jerk the pan again so that the omelet folds over once more. Cook for a minute or two longer. Tilt the pan and roll the omelet out onto a plate.
Another way to make a 2-egg omelet is to flip it over before adding the filling. Do this with the same motion, jerking the pan quickly away from you and then back toward you, but lift your hand slightly as you begin to jerk the pan back toward you. The omelet will flip over onto the other side, like a pancake. Place the filling in the middle. Use your spatula to fold one side over, then the other side, and roll the omelet out of the pan.
To blanch beet greens: Bring a pot of water to a boil while you wash and stem the beet greens. Rinse in 2 changes of water to rid the leaves of sand. When the water comes to a boil, salt generously and add the greens. Blanch for 1 to 2 minutes, until just tender, and transfer to a bowl of cold water. Drain, squeeze out excess water, and chop. To steam the greens, place them in a steamer basket above 1 inch of boiling water. Cover and steam for 2 minutes or until wilted. Rinse and squeeze out excess water.
Yield: Serves 1
Advance preparation: The blanched beet greens will keep for 4 to 5 days in a covered bowl in the refrigerator.
Nutritional information per serving: 275 calories; 7 grams saturated fat; 3 grams polyunsaturated fat; 11 grams monounsaturated fat; 385 milligrams cholesterol; 4 grams carbohydrates; 1 gram dietary fiber; 369 milligrams sodium (does not include salt to taste); 16 grams protein.

It Could Be Old Age, or It Could Be Low B12

Ilsa Katz was 85 when her daughter, Vivian Atkins, first noticed that her mother was becoming increasingly confused.

“She couldn’t remember names, where she’d been or what she’d done that day,” Ms. Atkins recalled in an interview. “Initially, I was not too worried. I thought it was part of normal aging. But over time, the confusion and memory problems became more severe and more frequent.”
Her mother couldn’t remember the names of close relatives or what day it was. She thought she was going to work or needed to go downtown, which she never did. And she was often agitated.
A workup at a memory clinic resulted in a diagnosis of early Alzheimer’s disease, and Ms. Katz was prescribed Aricept, which Ms. Atkins said seemed to make matters worse. But the clinic also tested Ms. Katz’s blood level of vitamin B12. It was well below normal, and her doctor thought that could be contributing to her symptoms.
Weekly B12 injections were begun. “Soon afterward, she became less agitated, less confused and her memory was much better,” said Ms. Atkins. “I felt I had my mother back, and she feels a lot better, too.”
Now 87, Ms. Katz still lives alone in Manhattan and feels well enough to refuse outside assistance.
Still, her daughter wondered, “Why aren’t B12 levels checked routinely, particularly in older people?”
It is an important question. As we age, our ability to absorb B12 from food declines, and often so does our consumption of foods rich in this vitamin. A B12 deficiency can creep up without warning and cause a host of confusing symptoms that are likely to be misdiagnosed or ascribed to aging.
A Vital Nutrient
B12 is an essential vitamin with roles throughout the body. It is needed for the development and maintenance of a healthy nervous system, the production of DNA and formation of red blood cells.
A severe B12 deficiency results in anemia, which can be picked up by an ordinary blood test. But the less dramatic symptoms of a B12 deficiency may include muscle weakness, fatigue, shakiness, unsteady gait, incontinence, low blood pressure, depression and other mood disorders, and cognitive problems like poor memory.
Labs differ in what they consider normal, but most authorities say a deficiency occurs when B12 levels in adults fall below 250 picograms per milliliter of blood serum. Like all Bvitamins, B12 is water-soluble, but the body stores extra B12 in the liver and other tissues. Even if dietary sources are inadequate for some time, a serum deficiency may not show up for years.
If the amount of B12 in storage is low to begin with, a deficiency can develop within a year, even more quickly in infants.
Recommended dietary amounts of B12 vary: 2.4 micrograms daily for those age 14 and older, 2.6 micrograms for pregnant women and 2.8 micrograms for nursing women. Barring circumstances that impair B12 absorption, these are levels easily obtained from awell-balanced diet containing animal protein.
In its natural form, B12 is present in significant amounts only in animal foods, most prominently in liver (83 micrograms in a 3.5-ounce serving). Good food sources include other red meats, turkey, fish and shellfish. Lesser amounts of the vitamin are present in dairy products, eggs and chicken.
Those at Risk
Natural plant sources are meager at best in B12, and the vitamin is poorly absorbed from them. Many strict vegetarians and all vegans, as well as infants they breast-feed, must consume supplements or fortified breakfast cereals to get adequate amounts.
Certain organisms, like the bacterium Spirulina and some algae, contain a pseudo-B12 that the body cannot use but may result in a false reading of a normal B12 level on a blood test. Despite claims to the contrary, laver, a seaweed, and barley grass are not reliable sources of B12.
In animal foods, B12 is combined with protein and must be released by stomach acid and an enzyme to be absorbed. Thus, chronic users of acid-suppressing drugs like Prilosec, Prevacid and Nexium, as well as ulcer medications like Pepcid and Tagamet, are at risk of developing a B12 deficiency and often require a daily B12 supplement.
Stomach acid levels decline with age. As many as 30 percent of older people may lack sufficient stomach acid to absorb adequate amounts of B12 from natural sources. Therefore, regular consumption of fortified foods or supplementation with 25 to 100 micrograms of B12 daily is recommended for people over 50.
Synthetic B12, found in supplements and fortified foods, does not depend on stomach acid to be absorbed. But whether natural or synthetic, only some of the B12 consumed gets into the body. Treatment to correct a B12 deficiency typically involves much larger doses than the body actually requires.
Free B12 from both natural and synthetic sources must be combined with a substance in the stomach called intrinsic factor to be absorbed through the gut. This factor is lacking in people with an autoimmune disorder called pernicious anemia; the resulting vitamin deficiency is commonly treated with injections of B12.
Although most doctors are quick to recommend injections to correct a B12 deficiency, considerable evidence indicates that, in large enough doses, sublingual (under-the-tongue) tablets or skin patches of B12 may work as well as injections for people with absorption problems, even for those with pernicious anemia.
Most often, a daily supplement of 2,000 micrograms is recommended for about a month, then lowered to 1,000 micrograms daily for another month, then lowered again to 1,000 micrograms weekly. Sublingual B12 or B12 patches, or even B12 lollipops, can be helpful for people who require a supplement but cannot swallow pills.
Others at risk of developing a B12 deficiency include heavy drinkers (alcohol diminishes B12 absorption), those who have had stomach surgery for weight loss or ulcers, and people who take aminosalicylic acid (for inflammatory bowel disease or tuberculosis) or thediabetes drug metformin (sold as Glucophage and other brands). Patients who take the anticonvulsants phenytoin, phenobarbital or primidone are also at risk.
Large doses of folic acid can mask a B12 deficiency and cause permanent neurological damage if normal levels of B12 are not maintained. Supplements of potassium impair B12 absorption in some people.
Although a B12 deficiency can raise blood levels of the amino acid homocysteine, a risk factor for heart disease and stroke, supplements of B12 have not reduced cardiovascular risk.
And while high homocysteine levels are linked to Alzheimer’s disease and dementia, lowering them with B12 supplements has not been shown to improve cognitive function. However, in one study, among women with a poor dietary intake of B12, supplements of the vitamin significantly slowed the rate of cognitive decline.

Depression Defies the Rush to Find an Evolutionary Upside

In certain quarters of academia, it’s all the rage these days to view human behavior through the lens of evolutionary biology. What survival advantages, researchers ask, may lie hidden in our actions, even in our pathologies?

Depression has come in for particular scrutiny. Some evolutionarypsychologists think this painful and often disabling disease conceals something positive. Most of us who treat patients vehemently disagree.
Consider a patient I saw not long ago, a 30-year-old woman whose husband had had an affair and left her. Within several weeks, she became despondent and socially isolated. She developed insomnia and started to ruminate constantly about what she might have done wrong.
An evolutionary psychologist might posit that my patient’s response has a certain logic. After all, she broke off her normal routine, isolated herself and tried to understand her abandonment and plan for the future. You might see a survival advantage in the ability of depressed people like her to rigidly and obsessively fix their attention on one problem, tuning out just about everything and everyone else around them.
Certain studies might seem to support this perspective. Paul W. Andrews, a psychologist at Virginia Commonwealth University, reported that normal subjects get sadder while trying to solve a demanding spatial pattern recognition test, suggesting that something about sadness might improve analytical reasoning.
In a similar vein, Joseph P. Forgas, a psychologist at the University of New South Wales in Australia, found that sad subjects were better judges of deception than happy ones. After subjects were shown a video intended to induce a happy or a sad mood, Dr. Forgas had them view deceptive or truthful interviews with people who denied committing a theft.Subjects in a sad mood were more skeptical and more accurate in detecting deceptive communication, while subjects in a positive mood were far more trusting and gullible.
Findings like these may suggest some benefits to sadness, but lately they have been generalized to patients with full-blown depression. For example, Dr. Andrews and Dr. J. Anderson Thomson Jr., a psychiatrist at the University of Virginia, have proposed that the rumination of depressives is an adaptive strategy to solve a painful problem. Clinicians, on the other hand, continue to maintain that the grim outlook of depressives is evidence that their thought process is distorted and erroneous. It must be fixed, not embraced.
There is strong evidence from neuropsychological and brain imaging studies that clinical depression is linked with various types of memory impairments in all age groups and at all levels of depressive severity. Challenging and changing the dysfunctional thoughts of depression are the exact aims of cognitive-behavioral therapy, one of the most empirically validated and popular forms of psychotherapy.
So who’s right about depression, the evolutionary biologists or the clinicians?
To start, the subjects in the above studies were normal controls whose moods were manipulated to be transiently sad. They do not really resemble people with clinical depression, whose condition can last months or even years.
Indeed, as Dr. Forgas said by e-mail, “I never worked with depressives, and I do not think that the experiments we have done looking at mood effects on cognitive processes in normal populations experiencing minor, everyday mood differences can be readily generalized to depressive cognition.”
Under close scrutiny, the case for depression’s adaptive benefits has problems — big ones. For one thing, the ruminative thinking of depression is often not particularly effective in solving problems. As another patient of mine once said: “I would think the same things over and over and could never decide what to do. It’s not a creative way of thinking.”
More critically, depression can arise without any psychosocial stressor at all, which makes it hard to argue that depression is a response to a difficult situation or problem. Dr. David J. Kupfer, a psychiatrist at the University of Pittsburgh, has found that a major life stressor almost always precedes a first episode of depression, but that episodes recur with milder stressors, or even none at all.
If depression conferred a problem-solving benefit, it should not become a chronic or autonomous condition — which it is for about half the patients.
According to the World Health Organization, depression is the leading cause of disability and the fourth leading contributor to the global burden of disease, projected to reach second place by 2020. There is also strong evidence that it is an independent risk factor for heart disease, and several studies show that prolonged depression is associated with selective and possibly permanent damage to the hippocampus, a region of the brain critical to memory and learning.
Add the fact that 2 percent to 12 percent of depressed people eventually commit suicide, and the “advantages” of depression suddenly don’t look so good.
Why, then, does the notion persist that depression confers special insights and benefits?
I got a clue recently from one depressed patient. He was an educated and articulate young man, unhappy because the world was such an awful place, he said. Because he had so many other symptoms of depression — insomnia, fatigue, low libido and poor self-esteem — I told him that he was clinically depressed and that his Hobbesian worldview was probably a result of depression, not its cause.
He scoffed, but he was willing to try a course of cognitive-behavioral therapy and antidepressant medication, if only to feel better. Months later, when he had recovered, I asked him again about his worldview.
The world was just as dire, he said, but he felt better. Still, he speculated wistfully that his newfound cheerfulness was not his authentic self, which he described as brooding and creative.
This cuts to the heart of why depression is increasingly romanticized. What is natural, the thinking goes, is best. If we are designed to suffer depression in response to life’s ills, there must be a good reason for it, and we should allow it to take its painful and natural course.
But unlike ordinary sadness, the natural course of depression can be devastating and lethal. And while sadness is useful, clinical depression signals a failure to adapt to stress or loss, because it impairs a person’s ability to solve the very dilemmas that triggered it.
Even if depression is “natural” and evolved from an emotional state that might once have given us some advantage, that doesn’t make it any more desirable than other maladies. Nature offers us cancer, infections and heart disease, which we happily avoid and do our best to treat. Depression is no different.

Cracking Open the Scientific Process


The New England Journal of Medicine marks its 200th anniversary this year with a timeline celebrating the scientific advances first described in its pages: the stethoscope (1816), the use of ether foranesthesia (1846), and disinfecting hands and instruments before surgery (1867), among others.
For centuries, this is how science has operated — through research done in private, then submitted to science and medical journals to be reviewed by peers and published for the benefit of other researchers and the public at large. But to many scientists, the longevity of that process is nothing to celebrate.
The system is hidebound, expensive and elitist, they say. Peer review can take months, journal subscriptions can be prohibitively costly, and a handful of gatekeepers limit the flow of information. It is an ideal system for sharing knowledge, said the quantum physicist Michael Nielsen, only “if you’re stuck with 17th-century technology.”
Dr. Nielsen and other advocates for “open science” say science can accomplish much more, much faster, in an environment of friction-free collaboration over the Internet. And despite a host of obstacles, including the skepticism of many established scientists, their ideas are gaining traction.
Open-access archives and journals like arXiv and thePublic Library of Science (PLoS) have sprung up in recent years. GalaxyZoo, a citizen-science site, has classified millions of objects in space, discovering characteristics that have led to a raft of scientific papers.
On the collaborative blog MathOverflow, mathematicians earn reputation points for contributing to solutions; in another math experiment dubbed the Polymath Project, mathematicians commenting on the Fields medalistTimothy Gower’s blog in 2009 found a new proof for a particularly complicated theorem in just six weeks.
And a social networking site called ResearchGate — where scientists can answer one another’s questions, share papers and find collaborators — is rapidly gaining popularity.
Editors of traditional journals say open science sounds good, in theory. In practice, “the scientific community itself is quite conservative,” said Maxine Clarke, executive editor of the commercial journal Nature, who added that the traditional published paper is still viewed as “a unit to award grants or assess jobs and tenure.”
Dr. Nielsen, 38, who left a successful science career to write “Reinventing Discovery: The New Era of Networked Science,” agreed that scientists have been “very inhibited and slow to adopt a lot of online tools.” But he added that open science was coalescing into “a bit of a movement.”
On Thursday, 450 bloggers, journalists, students, scientists, librarians and programmers will converge on North Carolina State University (and thousands more will join in online) for the sixth annual ScienceOnline conference. Science is moving to a collaborative model, said Bora Zivkovic, a chronobiology blogger who is a founder of the conference, “because it works better in the current ecosystem, in the Web-connected world.”
Indeed, he said, scientists who attend the conference should not be seen as competing with one another. “Lindsay Lohan is our competitor,” he continued. “We have to get her off the screen and get science there instead.”
Facebook for Scientists?
“I want to make science more open. I want to change this,” said Ijad Madisch, 31, the Harvard-trained virologist and computer scientist behind ResearchGate, the social networking site for scientists.
Started in 2008 with few features, it was reshaped with feedback from scientists. Its membership has mushroomed to more than 1.3 million, Dr. Madisch said, and it has attracted several million dollars inventure capital from some of the original investors of Twitter, eBay and Facebook.
A year ago, ResearchGate had 12 employees. Now it has 70 and is hiring. The company, based in Berlin, is modeled after Silicon Valley startups. Lunch, drinks and fruit are free, and every employee owns part of the company.
The Web site is a sort of mash-up of Facebook, Twitter and LinkedIn, with profile pages, comments, groups, job listings, and “like” and “follow” buttons (but without baby photos, cat videos and thinly veiled self-praise). Only scientists are invited to pose and answer questions — a rule that should not be hard to enforce, with discussion threads about topics like polymerase chain reactions that only a scientist could love.
Scientists populate their ResearchGate profiles with their real names, professional details and publications — data that the site uses to suggest connections with other members. Users can create public or private discussion groups, and share papers and lecture materials. ResearchGate is also developing a “reputation score” to reward members for online contributions.
ResearchGate offers a simple yet effective end run around restrictive journal access with its “self-archiving repository.” Since most journals allow scientists to link to their submitted papers on their own Web sites, Dr. Madisch encourages his users to do so on their ResearchGate profiles. In addition to housing 350,000 papers (and counting), the platform provides a way to search 40 million abstracts and papers from other science databases.
In 2011, ResearchGate reports, 1,620,849 connections were made, 12,342 questions answered and 842,179 publications shared. Greg Phelan, chairman of the chemistry department at the State University of New York, Cortland, used it to find new collaborators, get expert advice and read journal articles not available through his small university. Now he spends up to two hours a day, five days a week, on the site.
Dr. Rajiv Gupta, a radiology instructor who supervised Dr. Madisch at Harvard and was one of ResearchGate’s first investors, called it “a great site for serious research and research collaboration,” adding that he hoped it would never be contaminated “with pop culture and chit-chat.”
Dr. Gupta called Dr. Madisch the “quintessential networking guy — if there’s a Bill Clinton of the science world, it would be him.”
The Paper Trade
Dr. Sönke H. Bartling, a researcher at the German Cancer Research Center who is editing a book on “Science 2.0,” wrote that for scientists to move away from what is currently “a highly integrated and controlled process,” a new system for assessing the value of research is needed. If open access is to be achieved through blogs, what good is it, he asked, “if one does not get reputation and money from them?”
Changing the status quo — opening data, papers, research ideas and partial solutions to anyone and everyone — is still far more idea than reality. As the established journals argue, they provide a critical service that does not come cheap.
“I would love for it to be free,” said Alan Leshner, executive publisher of the journalScience, but “we have to cover the costs.” Those costs hover around $40 million a year to produce his nonprofit flagship journal, with its more than 25 editors and writers, sales and production staff, and offices in North America, Europe and Asia, not to mention print and distribution expenses. (Like other media organizations, Science has responded to the decline in advertising revenue by enhancing its Web offerings, and most of its growth comes from online subscriptions.)
Similarly, Nature employs a large editorial staff to manage the peer-review process and to select and polish “startling and new” papers for publication, said Dr. Clarke, its editor. And it costs money to screen for plagiarism and spot-check data “to make sure they haven’t been manipulated.”
Peer-reviewed open-access journals, like Nature Communications and PLoS One, charge their authors publication fees — $5,000 and $1,350, respectively — to defray their more modest expenses.
The largest journal publisher, Elsevier, whose products include The Lancet, Cell and the subscription-based online archive ScienceDirect, has drawn considerable criticism from open-access advocates and librarians, who are especially incensed by its support for theResearch Works Act, introduced in Congress last month, which seeks to protect publishers’ rights by effectively restricting access to research papers and data.
In an Op-Ed article in The New York Times last week, Michael B. Eisen, a molecular biologist at the University of California, Berkeley, and a founder of the Public Library of Science, wrote that if the bill passes, “taxpayers who already paid for the research would have to pay again to read the results.”
In an e-mail interview, Alicia Wise, director of universal access at Elsevier, wrote that “professional curation and preservation of data is, like professional publishing, neither easy nor inexpensive.” And Tom Reller, a spokesman for Elsevier, commented on Dr. Eisen’s blog, “Government mandates that require private-sector information products to be made freely available undermine the industry’s ability to recoup these investments.”
Mr. Zivkovic, the ScienceOnline co-founder and a blog editor for Scientific American, which is owned by Nature, was somewhat sympathetic to the big journals’ plight. “They have shareholders,” he said. “They have to move the ship slowly.”
Still, he added: “Nature is not digging in. They know it’s happening. They’re preparing for it.”
Science 2.0
Scott Aaronson, a quantum computing theorist at the Massachusetts Institute of Technology, has refused to conduct peer review for or submit papers to commercial journals. “I got tired of giving free labor,” he said, to “these very rich for-profit companies.”
Dr. Aaronson is also an active member of online science communities like MathOverflow, where he has earned enough reputation points to edit others’ posts. “We’re not talking about new technologies that have to be invented,” he said. “Things are moving in that direction. Journals seem noticeably less important than 10 years ago.”
Dr. Leshner, the publisher of Science, agrees that things are moving. “Will the model of science magazines be the same 10 years from now? I highly doubt it,” he said. “I believe in evolution.
“When a better system comes into being that has quality and trustability, it will happen. That’s how science progresses, by doing scientific experiments. We should be doing that with scientific publishing as well.”
Matt Cohler, the former vice president of product management at Facebook who now represents Benchmark Capital on ResearchGate’s board, sees a vast untapped market in online science.
“It’s one of the last areas on the Internet where there really isn’t anything yet that addresses core needs for this group of people,” he said, adding that “trillions” are spent each year on global scientific research. Investors are betting that a successful site catering to scientists could shave at least a sliver off that enormous pie.
Dr. Madisch, of ResearchGate, acknowledged that he might never reach many of the established scientists for whom social networking can seem like a foreign language or a waste of time. But wait, he said, until younger scientists weaned on social media and open-source collaboration start running their own labs.
“If you said years ago, ‘One day you will be on Facebook sharing all your photos and personal information with people,’ they wouldn’t believe you,” he said. “We’re just at the beginning. The change is coming.”

A Drug That Wakes the Near Dead

The moment she saw him, Judy Cox knew her son was dead. It was an October morning in 2008, and she had just stepped out the door to run an errand when she found him lying faceup in the driveway, ghost white, covered in purple splotches. He wasn’t breathing, and when she couldn’t revive him, she ran screaming into the house where her husband, Wayne, was still asleep. “Chris is dead,” she cried. “Call 911!”



Wayne jumped out of bed and raced down to the driveway, where he knelt over his son’s limp frame and tried frantically to elicit a breath or a heartbeat. As he pumped Chris’s chest and scooped out the vomit that had collected in his mouth, Judy ran to the kitchen and steadied herself long enough to call for an ambulance.
Chris was 26. He had not been well. An A.T.V. accident the previous August left him with debilitating back pain that physical therapy did nothing to alleviate. His doctor had recently prescribed Oxycontin. His parents learned later that he had taken too much.
By the time the ambulance arrived, Chris’s heart had been still for at least 15 minutes. It took the paramedics another 15 to get it pumping again; even then, doctors had little hope he would survive. Brain cells begin dying off just five minutes after blood stops delivering oxygen. After 30 minutes, there is likely to be more dead tissue than living.
Nonetheless, the emergency-room staff members at the local hospital did their best. They hooked Chris up to a tangle of tubes and machines and injected him with drugs to stabilize his heart rate. Wayne and Judy watched helplessly from the hallway. After four hours, a doctor finally summoned them to a secluded corridor.
Chris was in a coma, the doctor said, and in all likelihood had suffered severe, irreversible brain damage. He was breathing only with the help of a ventilator and would probably have a series of heart attacks in the night.
“First they asked us to let them pull the plug,” Judy recalled one recent afternoon, as we sat in the living room of the Coxes’ house in a Memphis suburb. “Then they tried getting us to sign a do-not-resuscitate order.” Without one, the doctor explained, hospital staff would be forced to revive Chris each time he started slipping away, which could mean cracking his ribs and shocking him with electricity. Even if they managed to keep his body alive, what was left of his brain would surely die in the days ahead.
Wayne and Judy refused to sign. “This is not some dog we’re talking about putting down,” Wayne shouted. “This is our son.” Chris still lived with his parents. He was a good kid, a joker, but bashful, especially around girls. He liked playing basketball and fishing in the pond near his house. He was planning to take over the family repo business when Wayne retired in a few years. Before the A.T.V. accident, he’d never given them much trouble at all. He deserved every chance the hospital could give him.
The heart attacks never came. Four days later, Chris woke up.
It was not the awakening of Hollywood movies in which the patient comes to, just as he was, speaking full sentences and completely mobile. Three years later, Chris still cannot talk. Although he breathes on his own, his lungs battle a steady barrage of infections; a feeding tube provides all his sustenance, and his muscles have contracted into short, twisted knots. He can move only the slightest bit — his fingers and eyelids twitch, but his arms and legs remain mostly immobile — and his neck is not quite strong enough to hold up his head, which leans against a crescent-shaped support around his wheelchair headrest.
Still, Wayne and Judy say that his cognition is improving. On good days, they say, he can respond to basic commands — blink his eyes for yes, wiggle his finger for no, give a thumbs up when asked. Doctors agree that Chris has progressed beyond a vegetative state, to a hazy realm known as minimal consciousness. What that means — what it says about his experience of the world around him or his prospects for further recovery — is something they are still trying to figure out.
Convinced that the son they know and love is still “in there,” Chris’s parents have spent the past three years searching for a way to bring him back out. So far, their best hope has come from an unlikely source: Ambien. A growing body of case reports suggests that the popular sleep aid can have a profound — and paradoxical — effect on patients like Chris. Rather than put them to sleep, both Ambien and its generic twin, zolpidem, appear to awaken at least some of them. The early reports were so pronounced that until recently, doctors had a hard time believing them. Only now, more than a decade after the initial discovery, are they taking a closer look.
The first report of a zolpidem awakening came from South Africa, in 1999. A patient named Louis Viljoen, who, three years before, was declared vegetative after he was hit by a truck, had taken to clawing at his mattress during the night. Thinking he was suffering from insomnia, his family doctor suggested zolpidem to help him sleep. But 20 minutes after his mother ground the tablet up and fed it to him through a straw, Viljoen began to stir. His eyes, which normally wandered the room, vacant and unfocused, flickered with the light of consciousness. And then he began to talk (his first words were “Hello, Mummy”), and move (he could control his limbs and facial muscles). A few hours later he became unresponsive. But the next day, and for many days after that, zolpidem revived him, a few hours at a time.
Here was a case worthy of Hollywood: three years was well past the point at which doctors would expect any sort of spontaneous recovery. Viljoen awoke with the ability to speak in complete sentences. Not only did he recognize his mother, but he also recognized the voices of people who had spoken to him only when he was apparently vegetative. He remembered nothing of the mysterious realm he kept receding back into. When doctors asked him what it was like to slip away, he said he felt no changes at all. But he could recall conversations from the previous day’s awakening, along with bits and pieces of his former life: his favorite rugby team, specific matches he attended, players that he rooted for and against. As time passed, his cognition improved. He could laugh at jokes, and his awakenings stretched from a few hours to entire days. Eventually, he no longer needed zolpidem.
In the years that followed, a steady trickle of similar reports emerged — some from doctors who tried zolpidem after hearing about the Viljoen case, others from those who discovered its benefits accidentally, as Viljoen’s doctor had. The drug did not work for everyone, and even when it did, its effects typically wore off after an hour or two. But for a lucky few, those effects were profound. People who seemed vegetative for years were waking up.
There are roughly 200,000 patients in the United States trapped in the borderlands between consciousness and oblivion. Until recently, most doctors believed that recovering from this condition was not possible. Vegetative states were considered permanent after three months if the injury was caused by oxygen deprivation, or one year if it was caused by blunt trauma. And since minimally conscious patients did not fare much better than those who were vegetative, most doctors did not bother to draw the distinction.
But in the past decade, a series of developments have coalesced into a far more complicated picture than previously imagined. In 2003, an Arkansas man named Terry Wallis emerged, after 19 years, from a minimally conscious state. Neuroimaging suggested that his brain had essentially reconfigured itself — surviving neurons bypassed dead ones and forged new connections to one another. In a 2007 Nature paper, Nicholas Schiff, a neurologist from Weill Cornell Medical College, and his colleagues showed that deep brain stimulation — surgically implanting a “brain pacemaker” that sends electrical impulses to specific regions of the brain — can help some severely injured patients recover the ability to speak and eat, years after the injury. And just this month, Adrian Owen, a British neuroscientist, reported in the journal The Lancet that the brains of some patients who seemed vegetative responded to basic commands: their bodies didn’t move, but distinct patterns of neuronal firing were detected on EEG scans when these patients were told to make a fist (which triggered one region of the premotor cortex) or wiggle their toes (which triggered another).
This year, scientists at Moss Rehabilitation Research Institute and at the University of Pennsylvania, both in the Philadelphia area, began the first large-scale clinical study of zolpidem as a treatment for disorders of consciousness. (Amantadine, a drug used to treat Parkinson’s disease, and the anti-anxiety medication Ativan also show promise in increasing awareness in minimally conscious patients.) So far, the evidence suggests that less than 10 percent of brain-injured patients will experience the drug’s paradoxical effects, and that among those, only a few will respond as profoundly as Viljoen did. For families like the Coxes, such odds provide a tortured kind of hope. For doctors, they bring questions. Why does a sleeping pill induce awareness in some patients but not others? And what can these bizarre awakenings tell us about the brain’s ability to heal?
Two weeks after Chris first emerged from the coma, he began tracking objects with his eyes. At one month, he could follow simple commands. “His friends would come in the room, and there’d be two or three on each side of the bed,” Judy recalled. “And eventually, when they’d say, ‘Look at Jim,’ or ‘Look at Bob,’ he’d fix his eyes on the right guy.” Wayne and Judy asked for a follow-up M.R.I., but their neurologist said it would be pointless. Chris’s behaviors were entirely reflexive, he said; they were produced by his brainstem, which regulates basic functions like breathing and body temperature, not by his cortex, the region responsible for higher-order thinking. That Chris’s friends and family saw him following commands was proof of their denial, not of Chris’s recovery.
“Every couple days, the doc would stop in the doorway and shout Chris’s name to see if Chris responded,” Judy said. “But he wouldn’t come in the room and look at Chris up close. So one day, I practically grabbed his arm and dragged him into the room, over to Chris’s bed.” She told Chris to blink his eyes. He did. Then she made the doctor walk across the room and told Chris to keep his eyes on the doctor. He did. Finally, with the doctor standing across the room, eyes fixed on Chris, she asked Chris to give her a thumbs up. When he wiggled his thumb, just the tiniest bit, the doctor’s jaw dropped. Chris was not in a vegetative state after all. He was minimally conscious.
Still, there was little that the community hospital could do for him. It had neither the resources nor the expertise to tease out a prognosis or chart a course of therapy. The same was true of local nursing homes, which is where many patients like Chris end up.
So Wayne and Judy took over their son’s care, bringing him first to a premier brain-injury center in Atlanta (where Chris had a device implanted in his spine, which releases drugs to help with spasticity) and then to a clinic in Destin, Fla. (where he tried an experimental treatment known as hyperbaric oxygen therapy). They had just made their way back home to Tennessee when a friend told them about the Ambien paradox and the clinical trial in Philadelphia.
One hallmark of the minimally conscious state is a rapid fluctuation between levels of awareness. Spend 10 or 20 minutes with Chris Cox, and you might conclude that there is nothing going on upstairs. But spend a full hour, and at some point you’ll see his puppy-dog eyes come into focus. They will appear to search for one of his parents, or to settle quizzically on the new person in the room. Ask him to say something, and he’ll smack his lips frantically before leaning forward and tapping his feet in apparent frustration. You’ll swear that he is there with you and that only his physical infirmities (he cannot quite swallow or control his jaw) prevent him from describing the netherworld from which he has just emerged.
And then, a few minutes later, he’ll slip away again.
This fluidity makes diagnosis a challenge. “If a patient follows every command you give them, you know that,” says Dr. John Whyte, director of the Moss Institute and lead investigator on the zolpidem trial. “If a patient has never, ever followed a command, you know that too. But if you tell a patient to wiggle their finger, and they do it occasionally — which is the case for most of these folks — how do you figure out if that ‘occasionally’ means something or not?”
Whyte has spent his entire career trying to answer this question. His first job after his residency was at a facility with a large number of vegetative patients. While working there, he was struck by the amount of contention over diagnoses. For all their experience with this population, clinicians could not seem to agree on whether any given patient was actually conscious. Family members also argued, with one another and with staff, over the meaning of every wince, twitch and eye flutter.
It turned out that a lot of people — staff members included — were drawing their conclusions from pure coincidence. Whyte told me about one mother who insisted that her son would point down toward his feeding tube to indicate that fluid was leaking onto his stomach, causing irritation. “He did it while I was there,” Whyte says. “And she lifted his shirt and said: ‘See, doctor, there’s the liquid. He’s communicating with us.’ And I said: ‘How often do you look under there when he isn’t pointing like this? Never? Not even once?’ ” It was possible that the pointing corresponded to the leak, Whyte explained. But it was also possible that the leaking was constant and the pointing was random. There were countless other examples. “Behaviors would be exceptions if they happened at the wrong time, and evidence if they happened at the right time,” Whyte says.
To help eliminate this bias, Whyte developed what he calls the single-subject assessment, in which doctors design a set of tests specific to each patient’s idiosyncrasies to determine whether the patient is vegetative or minimally conscious. It is painstaking work, but the information it yields is significant. “Patients who achieve minimal consciousness early tend to have a better prognosis,” Whyte says. “And you can at least try to build a communication system with them, because you have a foundation to work from.”
With a reliable assessment method in place, he began searching for ways to build on that foundation. Then the curious Ambien awakenings caught his attention.
It’s not entirely surprising that Ambien would arouse instead of sedate. The pill has long been linked to reports of bizarre sleepwalking behavior (not to mention sleepeating, sleeptalking, even sleepdriving). Some scientists call this phenomenon “paradoxical excitation.” So far, none of the accepted determinants of prognosis — age, overall health, the nature of the initial injury or the extent of brain damage as determined by an M.R.I. — have proved useful in predicting which brain-injured patients will experience it and which won’t. To begin answering that question, Whyte says, you need to study both responders and nonresponders in an unmedicated state.
One morning this past March, I met Chris, Wayne and Judy at the University of Pennsylvania’s main hospital, where they had been flown in from Tennessee, at the study’s expense, so that Chris could be tested in an unmedicated state. From the corner of a small hospital room, we watched as Whyte’s research assistant, Andras Szeles, attached dozens of tiny electrodes to Chris’s face and scalp, then fitted him with a large headset. The electrodes would measure Chris’s brain activity as Szeles administered a series of cognitive tests.
For one test, Szeles placed a rubber glove on Chris’s right hand. A voice coming through the headset told Chris to either “squeeze glove” or “squeeze bare,” several times over. Chris did not seem to be responding at all, but Szeles explained that the electrodes would measure what the naked eye could not. “We’re not so interested in whether or not Chris can squeeze,” he said. “We just want to know if he’s trying to squeeze.” Different neurons fire when you move your left hand versus your right hand. They also fire if you imagine moving it, prepare to move it or start to move it but stop, all of which the electrodes would detect.
“The term ‘consciousness’ can be a real can of worms,” Szeles said. “There are degrees of awareness, and it’s not always clear what the threshold should be. What we’re really looking for here is evidence of comprehension and will.” If Chris understood the words “squeeze” and “glove,” knew that this very specific thing was being asked of him, and possessed, at the most basic level, the will to respond, a distinct pattern of brain waves would show up in the results.
After Whyte and his team have tested 80 patients, they will compare the results of zolpidem responders to those of nonresponders and look for clues that might help explain the difference — maybe a specific brain region that lights up unexpectedly, or a pattern of neuronal firing common to one group but not the other. Any such discovery could light a path not only through the labyrinths of Chris’s fractured mind but to a better understanding of consciousness itself.
Wayne and Judy have a more immediate question: they want to know their son’s long-term prognosis. Has he reached the pinnacle of his cognitive recovery? Or is it a launching pad from which greater heights might be reached?
“Once a patient progresses to minimal consciousness, we can’t predict what’s going to happen,” says Dr. Joseph J. Fins, chief of medical ethics at Weill Cornell Medical College and author of a coming book, “Rights Come to Mind: Brain Injury, Ethics and the Struggle for Consciousness.” Some patients have recovered full consciousness, but many more remain stuck in limbo. The only way to know the outcome is to give the patient time.
But offering time is a complex proposition. “Early on, when families have the option to pull the plug, it’s almost impossible to tell what the long-term prognosis will be,” says Dr. Soojin Park, a neurointensivist at the University of Pennsylvania Hospital, and an investigator on the zolpidem trial. “And then later, when we have the certainty — that this is as good as it’s going to get — that option is gone. Because by then, the patient is breathing on their own. There’s no more plug to pull.” At that point, families who want to end a loved one’s suffering must either have the feeding tube removed, or agree to let the next bacterial infection win out, unhindered by antibiotics. Many families find choosing these deaths much more difficult than turning off a ventilator. It’s an instinct reinforced by religious edicts that forbid the withholding of basic sustenance but allow, for example, unplugging artificial respirators.
It is not uncommon for doctors to assume the worst and advise family members to withdraw care early. They do so in part because they see their duty as helping loved ones face reality. But Fins argues that this is a cop-out. “It’s glossing over all the unknowns for the sake of a quicker, cleaner solution,” he says. “It’s wrong to be so uniformly fatalistic so early on, especially with all the data emerging about the prospects for later-stage recovery.”
According to several studies, about 40 percent of patients who have been declared vegetative are actually minimally conscious. Other studies have shown that a surprising number of vegetative and minimally conscious patients made huge strides toward recovery much later than conventional wisdom would predict.
Park says that more doctors are trying drug therapy on vegetative and minimally conscious patients, but for the most part, they are groping in the dark. “We still don’t understand which drugs should work on which patients, or at what dosage, or at what point in their recovery,” she says. “And that makes it tough for families to know when they should fight and when they should give up.”
There is also the matter of cost. Treating and monitoring patients like Chris — designing and performing single-subject assessments that can discern random twitches from deliberate behavior, managing the host of medical complications that can stymie brain recovery and continually evaluating progress — is significantly more expensive than placing them in nursing homes, where they receive basic care but have no access to brain-injury specialists. Proponents argue that the measures will save money in the long run — if the patient is able to go home, for instance. Still, it’s unclear whether even the most aggressive care will make much difference for many patients. “The payers need a better sense of what the likely outcome is for any given patient,” says Tom Smith, program director at Moss, “so that they can say with confidence which patients are likely to benefit from treatment, and how significant that benefit is likely to be. And I hate to sound this way, but then it’s basically: ‘Am I going to invest this amount of money to get this outcome? Is that worth it?’ And that is a tough, tough question to answer.”
When Chris first returned from the hospital, the Coxes’ house was flooded with well-wishers. A former teacher brought a quilt that Chris and his classmates made in grade school. Old girlfriends, acquaintances and childhood pals visited regularly. His high-school friends even held a fund-raiser to help pay for some of his therapy. But as time wore on, and it became clear that he would neither die nor fully recover, the guests dwindled. Besides Chris’s sister, Amber, who visits often, Wayne and Judy are now mostly on their own.
The couple surrendered their bedroom, which is on the ground floor of their split-level house, to Chris. They take turns sleeping there, on a small cot in the corner of the room, surrounded by medical equipment: a hospital bed with a queen-size air mattress that helps prevent bed sores, a special chair called a “sit-stand,” which can be cranked into an upright position and is supposed to help ease muscle contractions. A mechanical lift. A breathing machine.
Judy is especially keen to show me Chris’s latest gadget, a device called an Eyegaze, that looks a bit like an iPad, and which Chris is learning to use to communicate. She mounts it to a handlebar on Chris’s wheelchair. At first, Chris’s eyes move rapidly across several rows of icons — words with pictures, partial sentences like “I want” or “I like,” and cartoon images of friends and family members with their names in bold. Tracking his eyes, the computer reads: “Green. Brit. I want.” And then, “Brit–Brit–Brit–Brit–Brit.” Brit is his cousin. It’s unclear if he’s asking for her, or if his eyes are just not cooperating.
Judy puts the computer away. He still needs practice, she says. When they first tried it, in February, during outpatient rehab, the therapist asked Chris what color went with Valentine’s Day, and he was able to look at the “red” icon. But so far, “I want a drink,” is the only full sentence he has managed.
Each day begins with the same routine: Judy helps Chris up, forcing him to sit on the edge of the bed, without neck or back support, for several minutes. The goal is to strengthen his neck muscles so that one day he can hold his own head up. A nurse helps her bathe him and then lift him into his chair, so that he can be wheeled into the living room or taken outside. Three times a week, a van delivers mother and son to a rehab center, where a therapist works to stretch and stimulate Chris’s contracted muscles. And almost as often, either Wayne or Judy spends several hours on the phone, battling Chris’s insurance company, which they say has covered private nursing and weekly therapy but denied an extended stay at a brain-injury rehab center. The couple arrange their schedules so that their son is never without at least one parent.
The Coxes have surrounded themselves with a new group of friends — other parents with children like Chris. The families in this informal group share strategies and trade information on emerging research and experimental treatments. They also talk of weariness and isolation. “At the end of the day, you feel like you’re a thousand years old,” Judy says. “And you have no idea how you’re going to get up and do it all over again tomorrow.” Both Wayne and Judy admit to being frustrated by the slow pace of Chris’s progress. But he’s come this far; they can’t help hoping that he might come further still. “I know that some people, even people who loved Chris, think maybe he should have just died,” Wayne says. “But he didn’t die. He lived. And as long as he’s still breathing, we have to do the absolute best we can for him.”
The reports on zolpidem are still mixed. Viljoen and a few others have improved steadily over time; some of them are now fully conscious on their own, without medication. (Viljoen is confined to a wheelchair and has cognitive disabilities but has improved over the years.) But such improvement is rare. According to Whyte, most responders fall into one of two categories: those who can take zolpidem daily, with no appreciable loss of efficacy, and those for whom the “awakenings” wane with continued use. The latter type, he says, may be the most common.
With no way of knowing which type of responder Chris might be, the Coxes play it safe. They give Chris Ativan every day; it has a similar though less profound effect on his behavior. But zolpidem they hoard like pixie dust, giving it only on special occasions, when friends and family can be there.
They gave him some when I visited, so I could see how it works.
A few minutes after receiving the zolpidem, Chris opened his eyes and smiled. Judy sat on the bed, facing him. “Hey, buddy!” she said. “Can I have a kiss?” She leaned in, cheekward, but he turned his head up in what looked like a deliberate slight. “Chris!” she admonished, playfully. He smiled and grunted. He was teasing her. Just as she pulled away, he thrust forward and grazed her cheek with puckered lips. Confident that he was there with us, Judy took out a marker and some paper and wrote one command after another, each of which Chris followed: Stick out your tongue, give me five, give me a thumbs up. And then, “Show us your Elvis grin.” Chris curled his upper lip into a sneer. When Judy ran out of commands, Chris began smacking his lips and moving his tongue. “Talk to us, buddy,” Wayne said. “Say, ‘Mom,’ ” Judy said. After several moments, Chris managed a loud, slow “Maaaa.”