Saturday, September 15, 2012

Life Went On Around Her, Redefining Care by Bridging a Divide -

In 1988, when Anne Fadiman met Lia Lee, then 5, for the first time, she wrote down her impressions in four spare lines that now read like found poetry:

barefoot mother gently rocking silent child

diaper, sweater, strings around wrist

like a baby, but she's so big

mother kisses and strokes her

The story of Lia, the severely brain-damaged daughter of Hmong refugees who had resettled in California, became the subject of Ms. Fadiman's first book, "The Spirit Catches You and You Fall Down," published in 1997.

Its title is the English translation of the condition known as qaug dab peg (pronounced "kow da pay"), the Hmong term for epilepsy, from which Lia had suffered since infancy.

In traditional Hmong belief, qaug dab peg, like many illnesses, is spiritual in origin, caused when the soul becomes separated from the body. A traditional cure might entail visits from a shaman, who would attempt to reunite body and soul.

A work of narrative nonfiction, Ms. Fadiman's book is a cautionary tale about the cultural chasm between Lia's family, with its generations-old animist beliefs, and her rationalist American doctors.

"In some sense, I was trying to provide a way of controlling her seizures with Western methods and Western medicines," said Dr. Neil Ernst, who with his wife, Dr. Peggy Philp, was one of the pediatricians who treated Lia early on. "And in some sense, the Lees were giving up control of their child to a system that they didn't understand."

That cultural divide — despite the best intentions of both sides, Ms. Fadiman wrote — may have brought about Lia's condition, a consequence of a catastrophic seizure when she was 4.

Over the years, whenever Ms. Fadiman lectured about the book, readers would press a single question on her before any other: "Is Lia still alive?"

Lia Lee died in Sacramento on Aug. 31. (Her death was not widely reported outside California.) The immediate cause was pneumonia, Ms. Fadiman said. But Lia's underlying medical issues were more complex still, for she had lived the last 26 of her 30 years in a persistent vegetative state. Today, most people in that condition die within three to five years.

Acclaimed by reviewers, "The Spirit Catches You and You Fall Down" won a National Book Critics Circle Award. It has sold almost 900,000 copies, according to its publisher, Farrar, Straus & Giroux, and remains widely assigned in medical schools and in university classes in social work, anthropology, journalism and other fields.

As a result, Lia's story, as few other narratives have done, has had a significant effect on the ways in which American medicine is practiced across cultures, and on the training of doctors.

"A lot of people in medicine were talking about that book for a very long time after it was published," Sherwin B. Nuland, the physician and National Book Award-winning author, said on Wednesday. He added:

"There's a big difference between what we call 'disease' and what we call 'illness.' A disease is a pathological entity; an illness is the effect of the disease on the patient's entire way of life. And suddenly you read a book like this and you say to yourself, 'Oh, my God; what have I been doing?' "

A labor of eight years, "The Spirit Catches You and You Fall Down" is also the story of the immense benefits of tradition, which can furnish, Ms. Fadiman makes clear, a level of familial devotion less often seen among modern Americans. Lia spent her entire life at home, assiduously cared for by her family, and it was this devotion, Ms. Fadiman came to feel, that kept her alive for so long.

"She was never shunted to the periphery," Ms. Fadiman, the daughter of the author and television personality Clifton Fadiman and the journalist Annalee Jacoby Fadiman, said on Wednesday. "I remember her most in her mother's arms. Family life went on around her and in some ways revolved around her."

The 14th of 15 children born to her mother, Foua Yang, and her father, Nao Kao Lee, Lia Lee was born on July 19, 1982, in Merced, Calif. — the first of her parents' children born in the United States, and the first born in a hospital. She was plump, porcelain-skinned, lively and beautiful.

The Lees had arrived in the United States two years earlier with their seven living children, a blanket, a mortar and pestle and little else. They had been farmers in their native Laos; three of their children died there when they were very young.

During the Vietnam War, many Hmong were recruited by the United States to fight the North Vietnamese in Laos; after Laos fell to the Communists in 1975, 150,000 Hmong, in fear of their lives, fled the country. The Lees were among them.

It took the family until 1980 to reach the United States. Along the way they endured a perilous odyssey that included an attempt to flee their village before being forced back at gunpoint by Vietnamese soldiers, and a later attempt, culminating in a 26-day walk to Thailand, where they spent a year in refugee camps. During these five years, three more of their children died.

In the United States, the Lees eventually settled in a modest apartment in Merced, about 120 miles southeast of San Francisco. By the time Ms. Fadiman met them, Merced's population was one-sixth Hmong.

Lia had her first seizure when she was about 3 months old. At Merced Community Medical Center, a resident misdiagnosed her condition. Communication was impossible: the Lees spoke no English, and the hospital had no Hmong interpreter.

"My parents weren't able to convey exactly that she was having seizures," Lia's sister Mai, now 32, said in an interview on Wednesday. "The word 'seizure' didn't come out. To them, they saw it as her soul being tampered with by something of a different realm."

Lia's seizures continued; epilepsy was eventually diagnosed and anti-seizure medication prescribed. But to her parents, qaug dab peg was literally a mixed blessing: on the one hand, Lia's soul had been taken from her and she needed it back; on the other, her condition portended spiritual giftedness, something many traditional cultures ascribe to epilepsy. Perhaps, the Lees believed, Lia was destined to become a shaman herself.

The Lees did not always give Lia her medication, Ms. Fadiman wrote, because they did not want to interfere with qaug dab peg entirely.

To encourage her soul's return, her parents gave her herbs and amulets. She was sometimes visited by a Hmong shaman, who performed a ritual that included chanting, beating a gong and sacrificing a chicken or pig. (The strings around Lia's wrist noted by Ms. Fadiman are used in Hmong tradition to help protect people from malevolent spirits.)

All this baffled Lia's doctors. "I felt that I was trying to penetrate a very dense wall — a cultural wall — and didn't have the tools to do it," Dr. Ernst said.

The seizures worsened; by the time Lia was 4 ½, she had made more than 100 outpatient visits to medical facilities and been admitted to the hospital 17 times. When she was not quite 3, in frustration at what he viewed as her parents' refusal to administer her medication, Dr. Ernst had Lia legally removed from the family home.

She spent a year in foster care — a time, Ms. Fadiman reported, of great trauma for Lia and great bitterness for her family — before being returned to her parents. (In recent years, Dr. Ernst and Mai Lee said, there has been a rapprochement between Lia's family and her doctors.)

In 1986, when Lia was 4, she suffered a grand mal seizure that lasted nearly two hours before doctors were able to bring it under control. At some point, amid the many procedures her condition required that day, an infection set in. She went into septic shock, and her organs began to fail.

By the time she was stabilized, Lia had lost higher brain function. Her doctors expected her to die.

She did not die. She could breathe and whimper but could not speak; she was capable of little voluntary movement but could still feel pain. It was unclear how much she could see or hear.

Lia no longer had seizures, because she now had vastly reduced electrical activity in her cerebral cortex, the brain's outermost layer. She grew only slightly, as is typical of children with severe brain damage: by the age of 30, she was 4 feet 7 inches and weighed 47 pounds.

For 26 years, her days varied little: her parents bathed her, fed her, flexed her stiffened limbs, kissed, caressed and tenderly talked to her. There were visits to doctors in Merced and later in Sacramento, where the family moved in 1996. There were periodic visits from a shaman, intended not so much to cure Lia as to ease her suffering.

"Everything that my parents had done for her is all manual labor," Mai Lee said on Wednesday. "Carrying her from place to place, transporting her to appointments here and there, it was all done manually. They did that for a very long time."

Nao Kao Lee, Lia's father, died in 2003. Besides her mother, Foua Yang, and her sister Mai, her survivors include a brother, Cheng, and six other sisters, Chong, Zoua, May, Yer, True and Pang.

In Merced and far beyond, Lia's legacy is pervasive. In 1996, largely in response to her case, Healthy House, a social-service agency that facilitates medical care for Merced County's non-English-speaking residents, was founded in Merced, the county seat. Among its services is an interpreter training program, which provides medical interpreters in a half-dozen languages, including Hmong.

At Mercy Medical Center Merced, the current incarnation of Merced Community Medical Center, Hmong shamans are now allowed to visit patients and practice a limited number of their traditional arts. (Animal sacrifice is excluded.)

"The Spirit Catches You and You Fall Down," continuously in print and released this year in an updated edition, has extended Lia's reach to a new generation of doctors. At the Yale School of Medicine, for instance, the incoming class is required to read it — a tradition that was begun a dozen years ago, well before Ms. Fadiman herself began teaching at Yale, where she is the Francis writer in residence.

And as hospital wards across the country become ever more diverse, seasoned doctors, too, have found there is much to be learned from Lia's story. Among them is Dr. Nuland, the son of Jewish immigrants from Eastern Europe, who received his medical training in New Haven in the 1950s.

"Most wards were filled with Italians, Irish and Jews," he said, recalling those years. "We had an occasional Gypsy, an occasional Chinese person and some Hispanics, and we would walk among them with our lordly presence. You'd learn a couple of words of Italian, a couple of words of whatever, and you'd use them with patients and think you were being very clever."

He added: "In our day, the whole thing was to assimilate, to look and act like a WASP. We could have provided so much comfort to patients who looked like our parents. And we just didn't."

Friday, September 14, 2012

How To Buy a Daughter: Choosing the sex of your baby has become a multimillion-dollar industry - Slate Magazine

Megan Simpson always expected that she would be a mother to a daughter.
She had grown up in a family of four sisters. She liked sewing, baking, and doing hair and makeup. She hoped one day to share these interests with a little girl whom she could dress in pink.
Simpson, a labor and delivery nurse at a hospital north of Toronto, was surprised when her first child, born in 2002, was a boy. That's okay, she thought. The next one will be a girl.
Except it wasn't. Two years later, she gave birth to another boy.
Desperate for a baby girl, Simpson and her husband drove four hours to a fertility clinic in Michigan. Gender selection is illegal in Canada, which is why the couple turned to the United States. They paid $800 for a procedure that sorts sperm based on the assumption that sperm carrying a Y chromosome swim faster in a protein solution than sperm with an X chromosome do.
Simpson was inseminated with the slower sperm that same day. Fifteen weeks later, she asked a colleague at the hospital to sneak in an after-hours ultrasound. The results felt like a brick landing on her stomach: another boy. 
"I lay in bed and cried for weeks," said Simpson, now 36, whose name has been changed to protect her privacy. She took a job in the operating room so she would no longer have to work with women who were giving birth to girls.
Simpson and her husband talked about getting an abortion, but she decided to continue with the pregnancy. In the meantime, she looked for a way to absolutely guarantee that her next child would be the daughter she had always dreamed about. She discovered an online community of women just like her, confiding deep-seated feelings of depression over giving birth to boys. The Web forums mentioned a technique offered in the United States that would guarantee her next baby would be a girl. It would cost tens of thousands of dollars, money Simpson and her husband did not have. Simpson waited until her third son was born. Then she began to make some phone calls.
The conventional wisdom has always been this: Given a choice, couples would prefer sons. That has certainly been the case in places like China and India, where couples have used pregnancy screening to abort female fetuses. But in the United States, a different kind of sex selection is taking place: Mothers like Simpson are using expensive reproductive procedures so they can select girls.
Just over a decade ago, some doctors saw the potential profits that could be made from women like Simpson—an untapped market of young, fertile mothers. These doctors trolled online forums, offering counseling and services. They coined the phrase "family balancing" to make sex selection more palatable. They marketed their clinics by giving away free promotional DVDs and setting up slick websites.
These fertility doctors have turned a procedure originally designed to prevent genetic diseases into a luxury purchase akin to plastic surgery. Gender selection now rakes in revenues of at least $100 million every year. The average cost of a gender selection procedure at high-profile clinics is about $18,000, and an estimated 4,000 to 6,000 procedures are performed every year. Fertility doctors foresee an explosion in sex-selection procedures on the horizon, as couples become accustomed to the idea that they can pay to beget children of the gender they prefer.
Inside a fourth-floor office suite off a palm-tree-lined street in Encino, Calif., in an embryology lab, two men wearing maroon scrubs peer into high-tech microscopes. The men are fertilizing human eggs with sperm samples collected earlier that day. After fertilization and three days of incubation, an embryologist uses a laser to cut a hole through an embryo's protective membrane and then picks out one of the eight cells. Fluorescent dyes allow the embryologist to see the chromosomes and determine whether the embryo is carrying the larger XX pair of chromosomes or the tinier XY. The remaining seven cells will go on to develop normally if the embryo is chosen and implanted in a client's uterus.
The lab is part of the Fertility Institutes, a clinic set up by Jeffrey Steinberg, one of the most prominent gender selection doctors in the United States. In his spacious, oak-paneled office down the hall, Steinberg is surrounded by photos of his own naturally conceived children. His clinic is the world leader for this gender selection technique, known as preimplantation genetic diagnosis (PGD). "We're by far number one. Number two is not even a close second," he said.
The United States is one of the few countries in the world that still legally allows PGD for prenatal sex selection. The procedure was designed in the early 1990s to screen embryos for chromosome-linked diseases. It is illegal for use for nonmedical reasons in Canada, the U.K., and Australia.
Steinberg's gender-selection patients are typically around 30 years old, educated, married, middle to upper class. They also typically have a couple of children already, unlike the women in his waiting room undergoing in vitro fertilization and hoping to conceive any child at all.
Statistics on gender selection are sparse. A 2006 survey by Johns Hopkins University found that 42 percent of fertility clinics offered PGD for gender selection. But that was half a decade ago, before many clinics undertook aggressive online marketing campaigns to drive the demand.
Gender selection is the primary business at Steinberg's Fertility Institutes, with nurses casually asking couples in the waiting room whether they, too, are interested in selecting the gender of their baby. Business quadrupled when Steinberg started advertising PGD for gender selection.
Steinberg said he never intended to make gender selection his niche. But then the ethics committee of the American Society for Reproductive Medicine, a nonprofit organization that attempts to set standards in the industry, came out against prenatal sex selection for nonmedical reasons in 1994. The group said the practice would promote gender discrimination and was an inappropriate use of medical resources. That made Steinberg angry.
"I took it on as a challenge," he said. "The fact that they didn't like it, and the fact that I saw nothing wrong with it, made me more aggressive."
He advertised in Indian-American and Chinese-American newspapers. Local groups accused him of stoking cultural biases for boys in those communities, and his ads were pulled by the publishers. 
In 2009, Steinberg came under a worldwide media firestorm when he announced on his website that couples could also choose their baby's eye and hair color, in addition to gender. He revoked the offer after receiving a letter from the Vatican. Steinberg seems to enjoy the attention, whether good or bad. After all, the publicity only helps bring in more patients to his clinics.
Many women who undergo PGD for gender selection discovered the procedure in online forums. Reading the posts on these forums is like entering another world. Users adorn their avatars with pink and princess imagery. They talk about their desperation to have daughters. They share notes on the process of going through PGD, recounting in detail their own experiences: blood-test results, drug effects, in vitro cycles.
Daniel Potter, the medical director of the Huntington Reproductive Center, has written more than 1,000 posts for and answered forum members' questions about the procedure and its costs. He arranged in-person and phone consultations with forum members, including Megan Simpson. In 2011, he even started a personal website where he calls himself the "gender selection expert."
From posting on message boards to using Twitter, Facebook, and YouTube, fertility doctors have appropriated 21st-century marketing methods to bring a 21st -century technology to the masses. Competition is stiff for search-friendly domain names for clinic websites and sponsored Google search ads. For example, there's, not to be confused with There's also and, all websites maintained by fertility clinics promoting PGD. These sites are filled with glossy stock photos of happy families, polished YouTube videos of doctors making their pitch, and patient testimonials in numerous languages.
In May 2008, Simpson and her husband traveled to California to undergo PGD at the Laguna Hills branch of the Huntington Reproductive Center. There, she met up with some of the women she had made friends with online. "We went shopping and picked out girly clothes and dreamed of the day we could have a baby to wear them," Simpson recalled.
Three days after arriving in California, Simpson underwent egg retrieval surgery. Eighteen eggs were retrieved; of these, 11 were mature and were fertilized.
Her husband left after the surgery to return home and take care of their three boys. After resting for five days, Simpson returned to the clinic for her embryo transfer.
She was met with devastating news: all of her embryos were found to be chromosomally abnormal. None were useable.
"I cried. And cried some more," recalled Simpson. "All that money, the drugs, the travel, time off work. The money."
Despite the financial and emotional setbacks, she wanted to try PGD again, soon. Three months later, she was back in Laguna Hills. She had taken out $15,000 on a line of credit to pay for the second attempt.
She went through the whole process again. This time, the embryos were good to go. An ultrasound was used to guide a catheter containing the embryos into her uterus. Six days later, Simpson took a pregnancy test. It was positive.
When she was 15 weeks pregnant, she asked a friend at work to once again sneak her into an after-hours ultrasound. Simpson was anxious, haunted by the memory of her last ultrasound.
But this time, it was different. She was pregnant with a girl.
After nearly four years and $40,000, Simpson's dreams of being a "girl-mommy" were finally going to come true.
Simpson gave birth to her daughter during a home delivery in her bathtub in 2009. "The moment she was born, I asked if it was still a girl," she recalled.
Simpson had to work six days a week right up until the delivery and months afterward to repay the loan she took. 
"My husband and I stared at our daughter for that first year. She was worth every cent. Better than a new car, or a kitchen reno."
Much of the evidence that Americans preferentially choose girls is anecdotal, as no larger body tracks gender selection procedures. But data from Google show that "how to have a girl" is searched three times as often in the United States as "how to have a boy." Many fertility doctors say that girls are the goal for 80 percent of gender selection patients. A study published in 2009 by the online journal Reproductive Biomedicine Online found Caucasian-Americans preferentially select females through PGD 70 percent of the time. Those of Indian or Chinese descent largely chose boys.
So where does this preference come from? And with the sex-selection rhetoric in the United States centered around "family balancing," a feel-good term that implies couples are rationally planning their families, is it still sexist to choose for girls?
For Jennifer Merrill Thompson, the reasons were simple. "I'm not into sports. I'm not into violent games. I'm not into a lot of things boys represent and boys do," she said. Thompson is the author of Chasing the Gender Dream, a self-published book that documents her use of gender-selection technology to conceive her daughter.
Interviews with several women from the forums at and yielded the same stories: a yearning for female bonding. Relationships with their own mothers that defined what kind of mother they wanted to be to a daughter. A desire to engage in stereotypical female activities that they thought would be impossible with a baby boy.
The American Society for Reproductive Medicine says it's concerned that gender selection is leading otherwise healthy women to undergo unnecessary medical procedures, and that fertility doctors might turn their attention away from treating infertility to pursue a more lucrative specialty. And the group points out the possible psychological harm to children born through gender selection. They fear these children would be pressured to live up to the stereotypes of the gender that was picked out and paid for by their parents.
"It's high-tech eugenics," said Marcy Darnovsky, director of the Center for Genetics and Society, a Berkeley, Calif. nonprofit focused on reproductive technologies. "If you're going through the trouble and expense to select a child of a certain sex, you're encouraging gender stereotypes that are damaging to women and girls. …What if you get a girl who wants to play basketball? You can't send her back."
Despite the objections from some medical ethicists, it seems that gender selection, like many aspects of fertility medicine, will remain legal and unregulated in the United States.

America’s Health Worker Mismatch -

DESPITE high unemployment, there is one bright spot in the economy: while nearly all other sectors shrank during the recession, jobs in health care increased by more than 1.2 million, with most paying salaries of over $60,000. And demand for those workers will keep improving: the Affordable Care Act will add 32 million people to insurance rolls over the next several years, while the aging of America will drive the need for health care for decades to come.

But for American health workers, this is hardly good news. Despite a labor shortage, our crowded medical professional schools are turning away hundreds of thousands of qualified applicants; to fill the gap, we are importing tens of thousands of foreign workers. Today about 12 percent of the health work force is foreign-born and trained, including a quarter of all physicians.

That's bad for American workers, but even worse for the foreign workers' home countries, including some of the world's poorest and sickest, which could use these professionals at home.

The blame lies primarily with the woeful state of schools in the health professions. Despite increased demand for their graduates, they have done little to expand their output.

Even worse, although the cost of higher education increased faster than inflation for the past two decades, the per graduate cost of health professional education has increased even faster: over the past 20 years, public medical school tuitions have increased 312 percent.

State regulators also artificially limit the number of health professionals we can train by effectively requiring that students be trained almost exclusively in teaching hospitals, even though most go on to work in clinics or community hospitals. Not only does this limit the number of people who can be educated, but the resulting increases in tuition and length of training reduce the number of students from poor and underserved communities who apply to health professional schools in the first place.

Then there's the phenomenon of credential creep: in fields like audiology, physical therapy and optometry, a therapist who once needed a master's degree must now have a doctorate to get a license, which means more years of school, higher attrition rates, higher debt, higher wage demands and fewer workers from underserved and low-income areas. The same licensing system actually favors foreign-trained health workers, who, for various reasons, do not have to meet these degree requirements.

It's no surprise, then, that the response to this self-made labor shortage has been to recruit inexpensive workers from abroad, including the 57 poor countries defined by the World Health Organization as having significant shortages of their own. Among them is India, America's largest source of foreign-trained doctors. A special visa program has made hiring these workers even easier.

A Gates Foundation study recently showed that immigration, with the United States as the most common destination, was siphoning off the largest number of African medical professionals.

The Global Health Workforce Alliance estimates that a billion people alive today will die without ever seeing a health care worker. Meanwhile, the W.H.O. estimates that below a threshold of 2.3 doctors, nurses and midwives per 1,000 people, countries are unable to provide even the most basic health services.

Multiple studies, even when controlled for poverty, show that access to health workers is directly related to mortality and health outcomes. A meta-analysis of 13 studies of developing countries showed that newborns who live more than three miles from a staffed health facility are almost twice as likely to die than infants who live closer to one. Health workers in developing countries don't just provide clinical care — they also manage their countries' health and disaster response systems, as well as nutrition and sanitation programs, all of which crumble in their absence.

There are other casualties, closer to home. Every study that has examined how to incentivize health workers to move to underserved areas has shown that training people from these communities is the most cost-effective approach. But because we've essentially given up on recruiting from underserved places in the United States, we've made their chronic lack of health workers much worse. Some 54 million people live in the 5,700 parts of the country defined as "health professional shortage areas," the communities with the worst health statistics and the worst unemployment.

In response, schools should be required to pay attention to cost effectiveness and train more workers with their existing budgets. Federal money could go toward helping these schools expand.

Meanwhile, the Departments of Education and Health and Human Services, which essentially let the health professions regulate their schools, could mandate that all new licensing requirements be justified with cost-effectiveness data; they could also require schools to communicate with employers to gauge the numbers and skills of workers needed.

It is irrational and immoral to recruit health workers from countries where one in five children die before their fifth birthday when we could be recruiting and training workers domestically. Doing so would help our economy, global public health and the 314 million Americans who rely on our medical system to provide high-quality, affordable care.

Kate Tulenko, the senior director of health system innovation at IntraHealth International, is the author of "Insourced: How Importing Jobs Impacts the Healthcare Crisis Here and Abroad."

Thursday, September 13, 2012

The Mouse Trap: The dangers of using one lab animal to study every disease - Slate Magazine

Mark Mattson knows a lot about mice and rats. He's fed them; he's bred them; he's cut their heads open with a scalpel. Over a brilliant 25-year career in neuroscience—one that's made him a Laboratory Chief at the National Institute on Aging, a professor of neuroscience at Johns Hopkins, a consultant to Alzheimer's nonprofits, and a leading scholar of degenerative brain conditions—Mattson has completed more than 500 original, peer-reviewed studies, using something on the order of 20,000 laboratory rodents. He's investigated the progression and prevention of age-related diseases in rats and mice of every kind: black ones and brown ones; agoutis and albinos; juveniles and adults; males and females. Still, he never quite noticed howfat they were—how bloated and sedentary and sickly—until a Tuesday afternoon in February 2007. That's the day it occurred to him, while giving a lecture at Emory University in Atlanta, that his animals were nothing less (and nothing more) than lazy little butterballs. His animals and everyone else's, too.
Mattson was lecturing on a research program that he'd been conducting since 1995, on whether a strict diet can help ward off brain damage and disease. He'd generated some dramatic data to back up the theory: If you put a rat on a limited feeding schedule—depriving it of food every other day—and then blocked off one of its cerebral arteries to induce a stroke, its brain damage would be greatly reduced. The same held for mice that had been engineered to develop something like Parkinson's disease: Take away their food, and their brains stayed healthier.
How would these findings apply to humans, asked someone in the audience. Should people skip meals, too? At 5-foot-7 and 125 pounds, Mattson looks like a meal-skipper, and he is one. Instead of having breakfast or lunch, he takes all his food over a period of a few hours each evening—a bowl of steamed cabbage, a bit of salmon, maybe some yogurt. It's not unlike the regime that appears to protect his lab animals from cancer, stroke, and neurodegenerative disease. "Why do we eat three meals a day?" he asks me over the phone, not waiting for an answer. "From my research, it's more like a social thing than something with a basis in our biology."
But Mattson wasn't so quick to prescribe his stern feeding schedule to the crowd in Atlanta. He had faith in his research on diet and the brain but was beginning to realize that it suffered from a major complication. It might well be the case that a mouse can be starved into good health—that a deprived and skinny brain is more robust than one that's well-fed. But there was another way to look at the data. Maybe it's not that limiting a mouse's food intake makes it healthy, he thought; it could be that not limiting a mouse's food makes it sick. Mattson's control animals—the rodents that were supposed to yield a normal response to stroke and Parkinson's—might have been overweight, and that would mean his baseline data were skewed.
"I began to realize that the 'control' animals used for research studies throughout the world are couch potatoes," he tells me. It's been shown that mice living under standard laboratory conditions eat more and grow bigger than their country cousins. At the National Institute on Aging, as at every major research center, the animals are grouped in plastic cages the size of large shoeboxes, topped with a wire lid and a food hopper that's never empty of pellets. This form of husbandry, known as ad libitum feeding, is cheap and convenient since animal technicians need only check the hoppers from time to time to make sure they haven't run dry. Without toys or exercise wheels to distract them, the mice are left with nothing to do but eat and sleep—and then eat some more.
That such a lifestyle would make rodents unhealthy, and thus of limited use for research, may seem obvious, but the problem appears to be so flagrant and widespread that few scientists bother to consider it. Ad libitum feeding and lack of exercise are industry-standard for the massive rodent-breeding factories that ship out millions of lab mice and rats every year and fuel a $1.1-billion global business in living reagents for medical research. When Mattson made that point in Atlanta, and suggested that the control animals used in labs were sedentary and overweight as a rule, several in the audience gasped. His implication was clear: The basic tool of biomedicine—and its workhorse in the production of new drugs and other treatments—had been transformed into a shoddy, industrial product. Researchers in the United States and abroad were drawing the bulk of their conclusions about the nature of human disease—and about Nature itself—from an organism that's as divorced from its natural state as feedlot cattle or oven-stuffer chickens.
Mattson isn't much of a doomsayer in conversation. "I realized that this information should be communicated more widely," he says without inflection, of that tumultuous afternoon in Atlanta. In 2010, he co-authored a more extensive, but still measured, analysis of the problem for the Proceedings of the National Academy of Sciences. The paper, titled " 'Control' laboratory rodents are metabolically morbid: Why it matters," laid out the case for how a rodent obesity epidemic might be affecting human health.
Standard lab rats and lab mice are insulin-resistant, hypertensive, and short-lived, he and his co-authors explained. Having unlimited access to food makes the animals prone to cancer, type-2 diabetes, and renal failure; it alters their gene expression in substantial ways; and it leads to cognitive decline. And there's reason to believe that ragged and rundown rodents will respond differently—abnormally, even—to experimental drugs.
Mattson has seen this problem in his own field of research. Twenty years ago, scientists started to develop some new ways to prevent brain damage after a stroke. A neurotransmitter called glutamate had been identified as a toxin for affected nerve cells, and a number of drug companies started working on ways to block its effects. The new medicines were tested in rats and mice with great success—but what worked in rodents failed in people. After a series of time-consuming and expensive clinical trials, the glutamate-blockers were declared a bust: They offered no benefit to human stroke patients.
Now Mattson has an idea for why the drugs didn't pan out: All the original test-animals were chubby. If there's something about the brain of an obese, sedentary rodent that amplifies the effects of a glutamate-blocker, that would explain why the drugs worked for a population of lab animals but not in the more diverse set of human patients. This past June, he published apaper confirming the hunch: When he put his test mice on a diet before administering the glutamate-blockers, the drugs' magical effects all but disappeared.
Many promising treatments could be failing for the same reason, Mattson argues, and other trials should be re-examined—but that's unlikely to happen anytime soon. "It comes down to money and resources," he says. "There's some fraction of studies that may have been compromised by [these] issues, but there's no way to know unless one does the experiment with the proper controls."
That's the drawback of the modern lab mouse. It's cheap, efficient, and highly standardized—all of which qualities have made it the favorite tool of large-scale biomedical research. But as Mattson points out, there's a danger to taking so much of our knowledge straight from the animal assembly line. The inbred, factory-farmed rodents in use today—raised by the millions in germ-free barrier rooms, overfed and understimulated and in some cases pumped through with antibiotics—may be placing unseen constraints on what we know and learn.
"This is important for scientists," says Mattson, "but they don't think about it at all."
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