April 8 - 15, 1999
![[Features]](/standard/image/headers/features_header.gif)
How to get ahead in science
The future of neurology lies in a room full of Tupperware in Belmont
by Alicia Potter
At 12:30 P.M. in Grand Junction, Colorado, a 70-year-old man dies. His family immediately places a phone call: 1-800-BRAINBANK. Less than 24 hours later, the man's brain, packed in a cardboard box, arrives at a three-story brick building in Belmont.
The building is the Mailman Research Center at McLean Hospital, and the box is headed for a suite of offices on the second and third floors. This is the Harvard Brain Tissue Resource Center, which staffers -- and everyone else associated with the center -- simply call the Brain Bank. It is the world's largest clearinghouse of donated brain tissue. Brains arrive here, on average, once a day; like most of them, today's shipment from Colorado is nestled inside an ice-packed Styrofoam cooler, in a white plastic container, in two clear bags tied with a red twist tie.
At the Brain Bank, this is what's known as a "fresh one." It glistens. Slick with cerebral spinal fluid and blood, this pinky-beige hunk of braided tissue looks, ironically, like something out of a joke shop. Its lacing of blood vessels is a disconcertingly deep blue, and, though it weighs about the same as a cantaloupe -- two and a half pounds -- the organ appears too big to fit inside a human head. It feels firm, cold, slippery; it smells faintly of blood.
The Brain Bank is one-stop shopping for the neuroscientist, a nonprofit whose mission is to collect posthumously donated brains from around the country, dissect them, then distribute the tissue to researchers studying neurological disorders. It specializes in three categories of organs: healthy "normal" brains; brains with neurodegenerative disorders such as Alzheimer's, Parkinson's, and Huntington's diseases; and brains affected by mental illnesses, specifically schizophrenia and bipolar disorder.
"The reason you need human brain tissue to study these disorders is that they are uniquely human," says Stephen Vincent, a neuroscientist and associate director of the Brain Bank. "Animal models are useful only to an extent. These disorders are ours and ours alone."
Progress in the field has been remarkable over the past decade. The medical world has seen exponential gains in knowledge about the biology of mental illness, many of which are directly linked to Brain Bank tissue. More and more scientists are flocking to the field, upping the demand not just for brains with schizophrenia and bipolar disorder but for neurologically normal specimens, too.
"The brain is biology's last, vast frontier," says Francine Benes, the Brain Bank's director. "And within brain studies, those aspects of the brain that give rise to thinking and feeling, cognitive function, and our ability to reason really constitute the final mystery of biological science."
The enthusiastic pursuit of these mysteries puts considerable pressure on the Brain Bank, which must now hustle to feed the scientific phenomenon it helped to create.
It's not an easy job. For one thing, the nondegenerated brains science wants most are the hardest to come by. And beyond that, getting people to part with their brains is like, well, getting people to part with their brains. Given the fact that the brain is the very source of our individuality, the psychological issues around brain donation are formidable. They're even more deeply entrenched for the mentally ill and their families, who have witnessed firsthand the brain's potential as a source for torment and tragedy. In these cases, the resistance to donation is daunting, the situations delicate.
To meet the challenge, the Brain Bank is launching a big publicity push to keep the organs coming. How it's going about this, though, is hardly conventional: armed with collateral materials, brain-shaped tchotchkes, and a singing spokesperson, the Brain Bank is embarking on perhaps the most morbid public-relations effort ever. The Brain Bank doesn't just want to change your mind; it wants to collect it, too.
The Brain Bank is already eerily good at its job. From its sunny offices, it "harvests" about 350 brains a year and ships up to 7000 tissue samples to a hundred labs around the globe. Its collection -- 22 shelves of gray fillets floating in formaldehyde-filled Rubbermaid containers -- totals about 4000 brains.
Amid the hushed halls and friendly atmosphere, you might not guess that brain banking is stressful work. Several times a week, Stephen Vincent is paged, sometimes in the wee hours of the morning, to help a family make the arrangements for delivery of a deceased loved one's brain. Time is crucial: to prevent any major deterioration or changes in brain chemicals that could affect research, a brain must be shipped within 24 hours of death.
"It's difficult to wake up and call someone I've never spoken to before, in some other part of the country, and talk to them about the recent death of their family member," says Vincent. "Often they'll call us just as grandma gave her last breath, and they're in the room with her."
But unlike traditional organ donation, where you might already have your preference printed on your driver's license, brain donation isn't something most people pre-register for (though it is an option for anyone over 18). In most cases, the legal next of kin is the one who makes the decision to donate.
From there, Vincent contacts whoever is handling the body -- be it a hospital, medical examiner's office, or funeral home -- to arrange for a pathologist or laboratory assistant to remove the brain. For brains within a three-hour drive of Boston, the Brain Bank uses its own lab assistant, who collects them for $300 each.
Brain removal is a pretty straightforward -- albeit cringe-inducing -- task. The pathologist makes an incision at the back of the head, from the top of one ear to the other; lifts up a flap of skin to access the skull; then uses a special saw to cut through the bone. Once the top of the skull is removed, the brain is visible and easily released. The pathologist takes the organ out, replaces the top of the skull, brings down the skin flap, sews in some sutures, and combs the hair neatly into place.
"You can't even tell," says Vincent.
Not only is brain removal surprisingly easy, but transportation of the brain to the Brain Bank is, too. The Brain Bank employs its own courier, who specializes in transporting organs for research or transplantation. And when the Brain Bank knows ahead of time that someone will be dying shortly, it even provides its own shipping materials.
The days when brains arrive are, of course, red-letter ones at the Brain Bank. "We get pretty jacked up," says Vincent.
The brain that travels 2268 miles from Colorado is an Alzheimer's case. It waits on a cork dissection board, oozing a rosy puddle, as research technician Alex Elliott slips into a lab coat and snaps on surgical gloves.
"It's a nice one," says Vincent, eyeing the brain's plump cerebellum, its cute, cinnamon-heart-like pituitary gland. "Go to it."
Elliott begins the dissection. He grades the brain on a scale of zero to four in terms of its overall degenerative appearance -- color, firmness, consistency -- and marks his impressions on a record sheet. He then bisects the organ with one slice of a 12-inch blade; it halves as easily as a soft round of bread.
From here, the brain's right hemisphere goes into a formaldehyde-like fixative; later, the Brain Bank's neuropathologist will study it for definitive signs of Alzheimer's (the disease can be diagnosed for certain only on a postmortem brain). When he has completed the examination, the family and their physician will receive a report of his findings.
Next, Elliott begins carving the rest of the brain as if it were a very tender, very fragile roast. The slices, about a quarter- to a half-inch thick, are the spongy consistency of tofu. With a spatula, Elliott places them onto a digital-imaging board to be photographed for the Brain Bank's Web page (http://www.brainbank.mclean.org:8080/), all the while recording notes on his data sheet, which by now is spattered with blood.
"This is the best part of the job," he says, slicing into the occipital lobe. "Every time I look at a brain I wonder how it works."
Elliott then cuts about 18 smaller pieces from the most-requested areas of the brain, including the sea horse-shaped hippocampus, which is responsible for memory and learning. Next he freezes the slivers of the brain with liquid nitrogen and places them in baggies for storage in a freezer, set at a frosty -180° Celsius. Later in the week, when the pathologist's report comes in, the brain's dissected right hemisphere will join row upon row of specimens in the Fixed Tissue Room.
In just 40 minutes, the gentleman from Grand Junction's mind -- 70 years of memories, ideas, and emotions -- has become brain No. 4508.
In 1978, Harvard endocrinologist Edward Bird founded the Brain Bank as a means of procuring fresh brains for his research on Huntington's disease. It started small, collecting fewer than a dozen brains a year, most of them with Huntington's. (Brain research being very sparing with its tissue use, some of those early brains are actively studied to this day.)
Since then, some 100 brain banks have sprung up around the country, most of them small collections specializing in a particular disorder. Only four such centers are federally funded; the Brain Bank was the first and is by far the largest, most active, and most broadly stocked.
The relationship between brain banks and the direction of neuroscience research has always been symbiotic. At this point, whether the Brain Bank is responding to or creating a need for such specific types of tissue is hard to tell. But one thing is clear: progress in neuroscience is directly dependent on the ability of the Brain Bank to provide not just brains, but the right kind of brains.
It's certainly no coincidence that the neuroscience area that's seen the most advances in the past decade -- the neurodegenerative diseases -- is also the one with the most brain tissue available for study. Nearly a third of all incoming brains are Alzheimer's brains; another 20 percent are Huntington's brains.
With treatments, and even cures, for neurodegenerative diseases well under way, the Brain Bank is now hoping to provide the same kind of tissue supply for mental-illness researchers, specifically those studying schizophrenia and bipolar disorder. Such research has already undergone tremendous growth in the past decade as new scientists enter the field, new technologies emerge, and new cultural attitudes accept biology -- not bad parenting -- as the root of these disorders.
Nowhere is the shifting of the Brain Bank's focus more evident than in McLean Hospital's appointment of Francine Benes as director (she succeeded Bird, the founder, who retired three years ago). Benes is also the director of McLean's Laboratory for Structural Neuroscience, which she established to study the neurobiological basis for schizophrenia. Not surprisingly, given her background, one of her goals for the Brain Bank is to surpass its typical intake of 25 mentally ill brains a year.
"For schizophrenia research to be able to make the progress that has been made in the study of other brain disorders, we need to have numbers equivalent to theirs," says Benes, who estimates that mental-illness research lags about 15 years behind that on the neurodegenerative diseases.
The catch is that degenerated brains -- brains affected by Alzheimer's, Huntington's, and so on -- are simply much easier to come by. According to Vincent, the reason is that the medically aware baby boomers are quite open to donating the brains of parents and grandparents afflicted with these disorders. "The diseases are hitting the baby boomers both emotionally and financially," explains Vincent. "They're thinking, `Gee whiz, I certainly don't want this to happen to me.' " Consequently, he says, these families are more likely to do what it takes -- brain donation included -- to help scientists find the cause of the disease and, perhaps eventually, a cure or treatment.
Finding nondegenerated brains -- and, specifically, mentally ill brains -- is a trickier mission. The Brain Bank's current publicity push is aimed largely at building awareness among the families of mentally ill people (see "A Mind Is a Terrible Thing to Waste," right). Benes points out that postmortem brain tissue is instrumental in determining the genetic links of mental illness, identifying abnormal cell and neurotransmitter activity, and examining the role of prenatal trauma and overall stress in the development of schizophrenia.
Last year, Katie and Gene (who asked that their last names not be used) were in the audience of an Alliance for the Mentally Ill meeting outside of Boston where Jill Bolte Taylor, the "singin' scientist," performed. A few months later, their 26-year-old son, who had schizophrenia, committed suicide. A mind is a terrible thing to waste
"For some reason I can't recall," Katie says, "I looked at Gene and thought, 'We should contact the Brain Bank.' " Her younger son pulled up the Brain Bank's Web page, and the family made the call.
"The next couple of days were pure chaos for us," says Katie. "The donation was the only thing we did that made utter sense."
However silly Taylor's shtick may be, Katie admits that it got her thinking; in fact, she believes she never would have gone through with a brain donation if someone had simply suggested it to her after her son had died.
"If you can laugh about an organ," says Katie, "it becomes just another organ. You have a heart. You have a liver. You have a brain."
Katie and Gene are even discussing donating their own brains to the Brain Bank. For researchers, this is a critical decision: to study the genetic links of mental illness, you need not only the brains of the mentally ill, but also those of their closest relatives.
It seems the Brain Bank's message has gotten through. Says Gene, "The brain is no different from any other part of the body."
And, she adds, this is only the beginning.
What's next, Benes says, "is completely dependent upon the willingness of the public to donate."
To fathom just what an uphill battle Benes faces, one needs only to consider the words of research technician Alex Elliott when asked if he'll donate his brain to science: "Hell, no! I'm going out with whatever I came in with."
The entire organ-donation business is used to such reactions. According to the most recent study of organ donation, a 1993 Gallup poll, only about 37 percent of Americans report that they are very likely to donate an organ at all -- and, by all accounts, the brain is low on that list. Says Melissa Christie, a hospital donation coordinator for the New England Eye and Tissue Transplant Bank, "Families feel it's morbid to take organs and tissues from a loved one. They want that person buried in one piece."
Further complicating matters for the Brain Bank is that donation for research doesn't have the altruistic appeal of donation for a transplant. For many, giving a brain doesn't count as giving "the gift of life." "With transplantation, the organ is going to another human being," says Christie. "It's living in someone. Research means just cutting it up."
And then there's the obvious reason for passing up brain donation, as summed up by Larry Sussman, clinical manager of the New England Organ Bank: "Cutting open a head is much more disturbing than an abdomen."
But what the resistance to brain donation really comes down to is this: unlike such tidy machines as the liver, the corneas, and the lungs, the brain is personal. For centuries, we've believed it to be sacred, the very seat of the soul.
"The heart or the kidneys don't have a particular personality associated with them," says Vincent. "They're almost abstract. But the brain . . . that's where Aunt Betty lived."
On top of these attitudes toward the brain, the families of the mentally ill have their own set of reservations about brain donation that make their contribution, while particularly valuable, particularly elusive as well. According to Vincent, these families are often angry at the medical community and bewildered by a disease that strikes in the prime of life (schizophrenia and bipolar disorder usually appear anywhere from the young-adult years to the mid-30s). The mentally ill endure so much despair when they're living, their relatives feel -- why literally uproot their minds when dead?
In addition, the circumstances around the deaths of mentally ill people are many times not conducive to brain donation: they die alone or in particularly shocking and tragic ways. "People with these disorders often die young," says Vincent. "Because of accidents, because of suicide, because of drug overdoses, because of unusual circumstances."
He adds, "It's a different kind of heartbreak."
And the brain, clearly, is a different kind of organ. That's what the Brain Bank has decided in putting together its unusual marketing campaign to reach the mentally ill and their families.
Subtlety, it seems, has fallen by the wayside, and the solemn intonations you might expect have given way to a pitch that feels, at first, almost goofy. Vincent wears a wristwatch imprinted with a brain and the Brain Bank's toll-free number; he hands out magnets with little brains on them and the slogan "From Knowledge Will Come a Cure." At his desk, he squeezes a brain-shaped stress reliever; he intends to emblazon these with the toll-free number and distribute them to "particularly helpful" pathologists and medical personnel. Try that with a liver.
"Humor helps cut through some of the tension," says Vincent. "I find that even with us here dealing with this on a daily basis, you really never get used to it. Dealing with human body parts, particularly the brain, evokes a natural tension."
The Brain Bank does rely on more-typical marketing tactics -- an attractive Web page, a new newsletter, several donation-registration brochures, a booth at the annual Society for Neuroscience conference -- but it has found that its most effective efforts are the most lighthearted.
Jill Bolte Taylor, the former associate director of the Brain Bank and an accomplished schizophrenia researcher, is now its national spokesperson. For a little more than a year, she has been on the road to about 15 cities across the country making presentations about brain donation to family support groups, such as local Alliances for the Mentally Ill. She also attends major conferences, such as that of National Alliance for the Mentally Ill.
Oh, and she sings.
Taylor calls herself the Brain Bank's "Singin' Scientist." With her guitar and her cowgirl twang, the Indiana-based neuroscientist teaches audiences about the importance of brain research, then warbles a few rounds of brain songs. There are three on her set list right now: "I'm a Brain Banker," "Advocates for Humanity," and a rap number called the Dendrite Dance. ("Doin' the dendrite dance! Stimulate me!")
Taylor laughs. "Some people have to hear about brain donation five or six times before they stop freaking out," she says.
Much of Taylor's knowledge about the brain comes not just from the lab but from her own life. Taylor's brother was diagnosed as schizophrenic when he was 24 years old. Two years ago, at age 37, she suffered a stroke when a golf-ball-size blood clot blocked the language center of her brain. She lost all ability to communicate. After an operation and therapy, Taylor has recovered her speech; however, she has permanently lost the ability to calculate numbers.
Taylor is shrewd about the fact that she is a living, breathing example of the resilience of the brain and the effects of brain research. "This stroke's been a great thing!" she says.
One day soon, she hopes to write a book about her experiences. But Taylor doesn't see the memoir as simply a chance to share her story: as with everything she does, it seems she regards it as a chance to get more brains, both those of the mentally ill and those of the neurologically normal. It's the Brain Bank's big chance, she explains, to infiltrate the mainstream. Already, she's seen the number of donations from the mentally ill jump from five brains a year to the current 25.
"I go for the big numbers," says Taylor, who hopes to harvest 100 mentally disordered brains a year. "Shoot, I told [Dr. Benes] my goal in life is to have more brain tissue than she knows what to do with."
Taylor's ability to do that will have ripple effects in neurobiology. A steady supply of brains, says Vincent, means a steady supply of scientists gravitating to the field. That means better research in the long run -- but for now, it means a continuing struggle in that building in Belmont.
"We find that if we drop off our effort in the area of mental-illness collection at any point," says Stephen Vincent, "the number of brains very quickly and dramatically drops off."
If they can keep the numbers up, this year Benes and her lab staff will begin to study the extent of the role heredity plays in the onset of schizophrenia and bipolar disorder. The study, if it's successful, may give new credence to the argument that genetics outweigh environmental factors in the development of these diseases -- and thus help change the way mental illness is studied.
Down the road, the Brain Bank's outreach to the families of the mentally ill could influence brain donation for other disorders, including major depression, obsessive-compulsive disorder, and panic and anxiety disorders. Currently, very little tissue for studying these afflictions is available.
"This is a precious, precious commodity that's not easy to come by," says Laura Lee Hall, director of research for the National Alliance for the Mentally Ill. "The fact that so much tissue has already been gathered and distributed already speaks to how important a resource it is. At this point, there's really no other way of understanding these disorders; the fundamental treatment advances are going to come from this type of biology."
Ultimately, increasing the flow of normal brains will be key to advancing neuroscience's general understanding of not just how the brain breaks down, but also how it works in the first place. Despite centuries of inquiry, our ability to think, feel, and create remains a mystery.
"A tremendous void exists in our overall knowledge of how the brain works," says Stephen Vincent. "As much progress as there's been, there are still unanswered questions. Then there are those questions we haven't even asked, because we don't know enough now to ask them."
He understands that the brains won't start pouring in overnight; getting people to embrace brain donation will take some time. Still, he's confident that the packages will arrive.
"We always get our brain," he says.
Alicia Potter can be reached at apotter@tiac.net.
Copyright © 1999 The Phoenix Media/Communications Group. All rights reserved.
