The Brain Doctor

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for members of the alumni association of the UNIVERSITY OF NEBRASKA–LINCOLN

SUMMER 2007

THE BR AIN DOCTOR Nancy (Coover) Andreasen’s, B.A. ’58; Ph.D. ’63

“The brain is the most important organ in our bodies.

It’s the source of our identity, the source of everything we are – but it is also vulnerable to diseases, just like all the other organs in our body.”

Nancy Andreasen 30 summer2007

THE BR AIN DOCTOR Nancy Andreasen’s Breakthrough Research Changed The Way Modern Science Understands Schizophrenia

By Tom Nugent

A turning point in the history of psychiatric research began on a summer afternoon back in 1984, at the moment when Nancy Andreasen (B.A. ’58; Ph.D. ’63) stretched out on the couch of a Magnetic Resonance Scanner in the Department of Radiology at the University of Iowa.

“All set, Nancy?”

“I’m ready when you are” she replied.

After many years of relentless preparatory work using other technologies, Andreasen’s quest to hone in more precisely on the cause of schizophrenia with a powerful new tool was about to begin.

“Okay,” said the technician in the white lab coat, “I’m going to slide you inside the scanner, Nancy. It’s a little noisy, so don’t be surprised.”

“No problem,” she said.

The motorized couch slowly moved her entire body into the tightly confined space of the scanner. Feeling a bit claustrophobic as she looked at the ceiling only a few inches above her face, she closed her eyes and concentrated on remaining as still as possible.

The giant scanner began to rumble and groan. Shaped like an enormous, beige-painted doughnut, it rattled loudly for a few seconds, then subsided into a high-pitched whining punctuated by occasional thumping-and-bumping sounds.

During the next 60 minutes, she lay motionless inside the doughnut – which generated a magnetic field around her head 100,000 times stronger that the magnetic field produced by the earth, lining up the protons in her brain so that a very highresolution, three-dimensional image of it could be created.

It was an experience the current Andrew H. Woods Chair of Psychiatry and director of the Mental Health Clinical Research Center at the University of Iowa would never forget.

Dr. Nancy Andreasen, the former undergraduate and English Lit Ph.D. student at UNL (where her maiden name had been Nancy

Coover), became her own “first human guinea pig” so that she could learn firsthand about the powerful new MRI technology now used everywhere to help diagnose patients with cancer, spinal injuries and other ailments. Her goal was to be the first person to apply this technology to the study of mental illnesses so that she could better understand how they arise in the brain.

Because it can generate crystal-clear, cross-sectional images in any plane, and with increasingly thin slices (half a millimeter or less), this revolutionary medical tool allows its operators to study human tissues, organs and bones in enormous detail, and with the kind of sharply focused precision that had only been dreamed of in the past.

For Andreasen, who earned an M.D. at the University of Iowa after nailing down her English Ph.D. at UNL and publishing a pivotal book about the work of the famed 17th-century English poet John Donne, undergoing the MRI brain-scan 23 years ago was a way to take the first steps toward pioneering a method that would revolutionize research in her chosen medical field of psychiatry. She could foresee this tool turning psychiatric research into a major discipline in the brain sciences, more technically known as neuroscience.

But Andreasen hadn’t come to the basement lab on this summer day merely to satisfy her curiosity about the workings of the university’s brand-new MRI scanner. Far from it. After experiencing the new procedure first, herself, she would lead 38 mental patients who had been diagnosed with schizophrenia through the clattering MRI machine, en route to obtaining the scientific data she needed for an important medical discovery.

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Sexism In The Groves Of Academe?

Here’s How One Woman Fought Back

Before she became a nationally renowned psychiatrist and the author of 560 scientific papers on various aspects of mental illness, the hard-charging Nancy Andreasen was a brilliant Ph.D. student in the liberal arts at UNL. Eager and idealistic, the youthful UNL grad student had decided to go after a doctoral degree in English literature because she dreamed of “changing the world” by “helping to shape the minds” of students who would “go forth” from her classroom to fight for truth, justice and liberty for all.

Things didn’t quite work out as she’d planned, however.

Although Andreasen did manage to earn her UNL Ph.D. in English, she soon discovered that women faced a steep uphill climb in the 1960s, if they wanted to become highly regarded scholars who published in the nation’s top literary journals.

“As a graduate student at UNL,” she recalls, “I learned early on that if I submitted an article on (the 17th-century English poet) John Donne or William Shakespeare to a literary journal under the name ‘Nancy Andreasen,’ it would be turned down. Let’s face it: The male editors at the prestigious journals weren’t about to publish an article by someone named ‘Nancy,’ no matter how good it was.”

What to do? Determined as always to overcome every obstacle, the wily grad student came up with the perfect solution: Trickery.

“In those days, there was a world-class John Donne scholar named H.J.C. Grierson,” Andreasen remembers with a delighted chuckle, “and he was published everywhere. So you know what I did?

“I changed my authorship, and I started submitting my articles under the name ‘N.J.C. Andreasen.’ Those are my actual initials, so I wasn’t deceiving anyone. And it worked like a charm. As ‘N.J.C.Andreasen,’ I was able to publish three different articles on Renaissance literature, before I even got my Ph.D.” Even better, the budding English Lit scholar was also able to expand her UNL dissertation on Donne into an acclaimed critical re-evaluation of the poet: “John Donne: Conservative Revolutionary” (Princeton University Press, 1967). It was the first of 15 books that Andreasen would eventually publish ... although the other 14 were written about psychiatry and mental illness, after she switched careers and became an M.D. psychiatrist in 1970.

“All during my early years, I had to fight for things because of my gender,” she says with a cheerful laugh. “My father was a wonderful man, but I wish he’d taken me hunting once or twice, like he used to take my brother John. I had to fight for several years, just to get a baseball glove.

“But I really wanted one and I did fight. At four-foot eleven and 98 pounds, I learned early that I would often have to battle for the things I wanted, and after awhile, I think I got pretty good at it.”

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Her remarkable breakthrough: For the first time in the history of medicine, thanks to the noisy MRI scanner, Andreasen published a research study in which an investigator “quantitatively” measured the key frontal lobe areas (the centers of memory, language and problem-solving) of the brains of a group of living people with the severe mental illness of schizophrenia. (Previously such precise measurements of the brain could only be done after death, using post mortem tissue). Andreasen had just launched a paradigmshifting field in psychiatry and neuroscience: in vivo anatomic neuroimaging. That study of 38 patients, published by the American Medical Association’s authoritative Archives of General Psychiatry (“Structural Abnormalities in the Frontal System in Schizophrenia: A Magnetic Resonance Imaging Study,” 1986, http://archpsyc. ama-assn.org/cgi/content/abstract/43/2/136), was the first to show that the frontal lobes of patients with schizophrenia were smaller and less developed than those of non-schizophrenics.

The implications of Andreasen’s groundbreaking study were significant, to say the least. For the first time since science had begun to study schizophrenia – a devastatingly painful and disruptive mental illness that affects nearly one percent of the U.S. population, or about 2.5 million Americans – it was now evident, based on her 1986 MRI study, that schizophrenia was a “developmental” rather than a “degenerative” disease.

In other words: Unlike mental illnesses such as Alzheimer’s, which usually occur after a patient has reached physical maturity and then grow progressively worse over time, schizophrenia appears to begin early in life during childhood or adolescence – as the crucially important frontal lobes of the brain develop.

Andreasen’s breakthrough study triggered a wide-ranging “paradigm shift” in science’s understanding of the causes of schizophrenia, according to many health researchers. Before that, most psychiatrists had assumed that the disease was degenerative, and that it could occur at any time in a patient’s life span, after being triggered by causes that appeared to be highly complex.

While some leading researchers believed that the agonizingly painful mental illness was caused by flawed genes, others insisted it was primarily the result of psychological trauma earlier in the patient’s life. Still others contended that the disease was caused by invading viruses or other pathogens that attacked sensitive brain tissues.

But Andreasen’s dramatic study helped to change all that. Based on the frontal lobe measurements that she had obtained with the MRI scanner, patients with schizophrenia were actually suffering from a “structural abnormality” that had occurred during the early development of their brains. Instead of seeing them as “insane” or “demented” or “crazy,” it was now possible to think of them simply as human beings who were struggling with a physical ailment that happened to be located in their brains.

“We now know that mental illnesses arise from the brain,” Andreasen will tell you, when you ask her to describe the bottomline significance of her research, for which she received the National Medal of Science from President Bill Clinton in 2000.

“The brain is the most important organ in our bodies. It’s the source of our identity, the source of everything we are – but it is also vulnerable to diseases, just like all the other organs in our body.

“I hope my lasting contribution to psychiatry will be that I quantified the fact that schizophrenia is a brain disease. Mental illnesses should be understood as diseases, and they should be placed on the same level as illnesses like diabetes or cancer. And from this point on, patients who have diseases such as schizophrenia should no longer be stigmatized, or thought of as ‘crazy.’

“Nor should they be treated as if they were somehow suffering from a mental or spiritual defect. Mental illness is a terribly painful experience, and my life’s work has been dedicated to trying to heal and protect human beings who’ve had the misfortune to develop such illnesses as depression, bi-polar disease and schizophrenia.”

PASSIONATELY INTERESTED IN WINE, ART ... AND R ACCOONS Spend an afternoon with Nancy Andreasen at her simply but elegantly furnished condominium on the outskirts of Iowa City, and you’ll find yourself in the presence of a high-octane thinker who seems to fiercely enjoy every aspect of her extraordinary life.

This globetrotting neuroscientist and author of 560 scientific papers and 15 books says she simply doesn’t have time to get old – because she’s far too busy doing psychiatric research, collecting art (she’s got two Calder drawings on the wall and a Picasso print in the kitchen), gardening in her own backyard, and also tracking down the dozens of rare French vintages that she stacks on shelves in her 1,500-bottle wine cellar.

A tiny but athletic-looking woman with a commanding physical presence, Andreasen grew up as the “mighty mite tomboy” daughter of a U.S. Army officer, John Coover, who moved his growing family all around the country for more than a decade before finally settling down in Lincoln during Nancy’s high school days.

“I was always the smartest kid in class during high school,” she recalled with a laugh, during a recent interview over a cup of steaming cinnamon tea, “but I certainly don’t take any credit for that, because I think it was mostly a matter of genetics. My Uncle Harry Coover was a brilliant chemical engineer – he invented Super Glue – and another close relative, J.E. Coover, wound up as a pioneering psychologist out at Stanford. And Robert Coover, the novelist? He’s a cousin. So I guess I got my genes from a pretty creative bunch of people, and that was hardly my doing was it?”

Andreasen arrived on the UNL campus in the fall of 1955.

During a lightning-fast undergrad career (she graduated in only three years), she decided to major in English and become a scholar who would write books on Renaissance literature, while also helping to “shape young minds in the classroom.”

“I think I was really lucky to study at Nebraska when I did,” she explained, while describing how she wound up with a “triple major” in English, history and philosophy, “because I got to take classes with some terrific professors who were totally committed to helping students learn and grow. My passions in those days were the French Revolution and European history, along with Renaissance poetry, and I wound up studying that stuff with some great teachers like (English professor) Robert Knoll and (former history professor) Bob Koehl.

“These guys were great teachers inside the classroom and great friends outside the classroom. To this day, I feel like I owe them a debt – because of the way they constantly encouraged me to challenge myself. Really, they gave me the intellectual foundation on which I built the rest of my life.”

Still only 19 years old when she graduated with her B.A. from UNL, Andreasen spent a year studying the liberal arts at Harvard, before winning a coveted Fulbright Fellowship that allowed her to attend Oxford University in England for a year. Having by then married a recently graduated dental student, George Andreasen, ’59, ’63, (the father of her two now-adult daughters, Susan and Robin), she wound up following him back to UNL so that he could study orthodontics there.

By then, of course, the peripatetic Andreasen had also decided that she wanted to spend her life as a Renaissance Lit professor ... and so she plunged into several years of intense study for her Ph.D., which she received in 1963. But her life took a totally unexpected turn the next year, when she was a young English prof at the nearby University of Iowa. After the birth of her first child, Susan, she nearly died from a postpartum infection ... and suddenly began to have doubts about the importance of writing endless scholarly articles and books about English literature.

“I’d written this book about John Donne,” she said with a wry grimace, remembering those early struggles, “and I nearly died giving birth. I was in the hospital for 10 days, and I wound up asking myself: Okay, I wrote the Donne book – but what is it going to do to change things? Nothing! How is it going to help people deal with the very real problems they will face in their very real lives?

“Those were some very tough questions, and I couldn’t seem to answer them. And so I finally decided: ‘Okay, penicillin saved my life, after I developed postpartum sepsis, so let me see if I can find something in medicine that might help me save some other lives.’

“For me, everything changed during that hospital stay. All at once, I realized that I wanted to go to medical school. And that was a huge challenge, because my husband later became ill and eventually died of multiple myeloma (a bone marrow cancer), and I wound up spending much of my early medical career as a single mother of two little girls.”

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What They’re Saying About National Medal of Science Winner Nancy Andreasen ...

Former President Bill Clinton (during National Medal Presentation): “Nancy Andreasen is known for her discovery of the relationship between manic-depressive illness and creativity. She was also one of the first scientists to demonstrate brain abnormalities in people with schizophrenia and mood disorders.”

Jean Robillard, M.D., dean of the University of Iowa Carver College of Medicine: “Nancy is a dedicated researcher and educator at all levels of medical training. She’s also a champion for women in science and has been an exceptional mentor to women pursuing scientific careers. And she’s made major contributions to the general public’s understanding of mental illness and how the brain works.”

Torsten N. Wiesel, M.D., Nobel Laureate in Physiology or Medicine, 1981: “Nancy Andreasen makes an excellent case ... for the ways in which the new and promising methods of genetics and brain imaging are being used to further our understanding of both the normal and diseased brain.”

Steven Gabbe, M.D., dean of the Vanderbilt University School of Medicine (after announcing that she had won the $25,000 Vanderbilt Prize for 2006): “Dr. Andreasen’s active support of the careers of other scientists – particularly women investigators – is especially noteworthy.”

E. Fuller Torrey, M.D., psychiatrist and former special assistant to the director of the National Institute of Mental Health: “Dr. Andreasen’s lucid and comprehensive book (“The Broken Brain: The Biological Revolution in Psychiatry”) should be enthusiastically welcomed by patients and the families of patients with severe psychotic disorders. It puts up-to-date knowledge into the hands of consumers; such knowledge becomes power.”

Terry Gwinn, retired U.S Army officer and Vietnam helicoptor pilot (Distinguished Flying Cross) and also husband of Nancy Andreasen: “She’s a bulldog, and when she decides to go after something, you better not get in her way. But she’s also one of the kindest and most compassionate people I’ve ever met. She’s been fighting the good fight for the mentally ill in this country for many years, and I deeply admire her for that.”

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Describing herself as a “risk-taker” whose “orientation was never to be safe,” Andreasen recalled premedical studies and medical school at the University of Iowa (she got her M.D. in 1970) as a “wonderfully challenging and thrilling time. I absolutely loved physics and biochemistry, and I even enjoyed taking the advanced math classes that I hadn’t really been prepared for.”

She paused for a moment, and her eyes lit up in a joyful smile.

“That’s the thing about me – I really enjoy learning about everything. We’ve got a couple of raccoons that come around our backdoor every night, looking for the peanuts we leave out for them ... and now I find that I’ve become passionately interested in raccoons. Can you believe it? There’s just so much out there to learn about, and I enjoy digging into every bit of it.”

What followed Nancy Andreasen’s graduation from U-Iowa Medical School in 1970 was an extraordinary career in which she has achieved half a dozen breakthroughs in the field of psychiatric research – while also writing endless books and articles and teaching psychiatry and research methodology to hundreds of medical students. Best known today for her pioneering neuroimaging studies of schizophrenia and manic-depressive disorder, Andreasen also distinguished herself by developing the first scales for measuring the intensity of both positive (psychotic) and negative (emotional and cognitive) symptoms in schizophrenia.

And while serving as the longtime editor-in-chief of The American Journal of Psychiatry, she also found time to provide expert advice and counsel to the key U.S. task force that wrote the standard DSM-III and DSM-IV medical manuals used everywhere today in the diagnosis and treatment of mental illness. And then there were also the 15 books she wrote ... several of which (including “The Broken Brain” and “Brave New Brain”) eventually became bestselling consumer guides to mental illness that are still in print and readily available today.

So where does Nancy Andreasen go from here? After her long and storied career, she could retire anytime she wants to, and then settle into the pleasant, easygoing lifestyle of the backyard gardener who spends her days puttering among the begonias and the dahlias, while slowly composing her memoirs.

No thanks, says Nancy Andreasen.

“Listen, I figure I’ve got at least 10 or 15 more years of hard work in me, and maybe more” growled the compassionate bulldog, as our lengthy interview finally came to an end. “These days, I’m more fascinated than ever by the workings of the human brain, and I’m especially excited about opportunities that we have to combine genomics and neuroimaging in order to really understand how brain dysfunctions in mental illness are caused and can perhaps be cured. I’m also excited about a new project I’m doing to understand how the brains of creative people work by using MR technology.

“This world of ours is full of fascinating things to study, and I feel fortunate that I remain eternally curious and have been given the opportunities to study them.”