The Aging Revolutionary

Teresa L. Johnson, MSPH, RD
Woodbridge, Virginia

 

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I’m looking at a 1958 Associated Press photo. The timeworn, black-and-white image shows an enthusiastic young man seated in a chemistry lab, pipetting a solution into a beaker. Beneath the photo a caption reads, “Dr. Paul Talalay, 34, works in his laboratory at the University of Chicago. Dr. Talalay, described as a brilliant scientist, has received a lifetime grant of $587,344 from the American Cancer Society to further his work in the study of cancer.” At the time, it was the largest grant ever awarded by the organization, and a notable sum. Four years later, in 1962, The Saturday Evening Post highlighted Talalay’s career in a prescient article titled “People on the Way Up.”

Five decades later, it seems Talalay, now 93, is still on his way up: He and his colleagues recently identified a possible treatment for some of the behavioral symptoms associated with autism. It came from an unlikely source—broccoli.

“If you were to tell someone you were treating autism with broccoli [before the study] they would tell you to take a cold shower, and rightly so,” says Talalay. The idea formed a few years ago, and grew as he and his colleagues posed questions about the underlying cellular and metabolic problems associated with the disorder.

This is not the first time Talalay asked difficult questions or proffered radical, contrarian ideas. He started challenging norms about cancer in the 1940s, when he was in medical school at the University of Chicago, where his research focused on treating cancer, a disease all but considered inevitable. But mid-career Talalay shifted his aim toward preventing cancer, a revolutionary idea now widely considered possible.

That Talalay posed such an idea came as no surprise to Bert Vogelstein, a professor of oncology and pathology at Johns Hopkins University, who has known Talalay since the 1970s. “He can see into the future about what will be important in research before others,” Vogelstein says, “and he has the tenacity to hold onto that vision to try to realize it.”

I first met Talalay in 2011. I was in graduate school at the time studying nutrition, and I had a groupie-like obsession with his research. Although Talalay wasn’t precisely a household name for the layperson, he was practically an icon in the scientific world, his name nearly synonymous with broccoli. So it was with some surprise at our first meeting that I found him not eating the green vegetable for which he’s famous, but a cookie. “My diet is atrocious,” confessed a sheepish Talalay, “just ask my wife!”

It has been four years since that first meeting. While most days I would find Talalay in his fourth floor Johns Hopkins office, today he is recovering from recent surgery, so I’m meeting him at his home. A modest, mid-century brick structure with dove-gray trim, the house sits on a gently sloping wooded lot in suburban Baltimore. Talalay greets me at his front door wearing a nubby charcoal gray pullover, dark jersey knit pants, and navy house slippers, a stark contrast to his usual business attire and lab coat. Short and compactly built, he is shaped like a fireplug; a halo of white hair encircles his balding pate. He pecks me on the cheek. “Lovely to see you, my dear,” he says, dropping the r on the end of dear. The doctor’s sophisticated, yet gentle demeanor is simultaneously unnerving and reassuring: cast Paper Chase actor John Houseman as Marcus Welby, and you’ve got Paul Talalay.

The dropped r’s of Talalay’s Oxfordian English are end products of a circuitous upbringing that began in Germany. The child of Russian immigrants, 10-year-old Talalay and his family fled Nazi rule in 1933. Landing first in France, then Belgium, the family eventually settled in England. Talalay’s fortuitous arrival in the United States came in July 1940, just two months before the London Blitz. After earning an undergraduate degree in biophysics from Massachusetts Institute of Technology and a medical degree from Yale University, Talalay briefly served as a general surgeon at Massachusetts General Hospital. In 1963, after a successful research career at the University of Chicago, he became professor and director of the Department of Pharmacology at Johns Hopkins. Talalay stepped down from the directorship in 1974, but remained at Hopkins as the John Jacob Abel Distinguished Service Professor of Pharmacology and Molecular Sciences.

Talalay escorts me to a chair at his kitchen table. After a moment or two of small talk, he begins his dissertation, repeating almost verbatim the words he spoke in our first conversation. The breakthrough discovery of sulforaphane’s anti-cancer effects came in the early 1990s after handing a Ph.D. graduate student twenty dollars and sending him to Baltimore’s Northeast Market to buy a bunch of vegetables, Talalay says. When the student returned to the lab, they started looking for substances in the vegetables that switched on the cells’ protective mechanisms. Cruciferous vegetables, especially broccoli, are especially effective at increasing these mechanisms, and sulforaphane was identified as the responsible party. The rest was nutrition history, published in 1992 in a seminal paper in Proceedings of the National Academy of Sciences, and widely acclaimed in the media.

When Talalay finishes recounting his story, he produces various supporting documents, including a book, The Congressional Quarterly, in which excerpts of the landmark sulforaphane paper were presented to the United States Congress, and a list of all his scientific publications—nearly 280 in all. This is Talalay’s modus operandi: meticulous preparation.

Solomon Snyder, whom Talalay calls “Solly,” is a neuroscientist and psychiatrist at Hopkins. Snyder recalls his first meeting with Talalay in the 1960s. “He was unbelievably well organized, fastidious, and obsessive compulsive.” This last descriptor is interesting, coming from a psychiatrist. I ask if that’s his official diagnosis. Snyder laughs and reconsiders his words. “He likes things…elegant.”

That elegance is reflected in the way Talalay approaches and conducts science, and extends to how he communicates it. “He brings precision to everything,” says Tom Kensler, a professor of toxicology at Hopkins, “and there’s no slack, no slop, no shortcuts. His papers are art forms to read, beautifully written, very provocative—not just bland reports of observations or platitudes.”

A visitor to Talalay’s office likely will find a collage of notes, ideas, and chemical structures scribbled on his whiteboard in a sort of free-flow stream of ideas. Some wonder if he sleeps. “He’s indefatigable—he’s always ‘on’ in terms of the science, and he’s always thinking,” says Kensler. “He’ll come in the office and say, ‘Oh, Tom, I’ve been thinking.’ And he’ll produce a document or a page summary of guidance on how he thinks something should be done.”

Nearly twenty-five years have passed since the discovery of sulforaphane’s beneficial health effects, and the idea that fruits and vegetables can benefit human health is now well established in the scientific community. “Talalay’s research began a new era in nutritional research,” says Bernhard Juurlink, professor emeritus at University of Saskatchewan, “where we truly began to understand the mechanisms of Hippocrates’ dictum: ‘Let food be your medicine and medicine your food.’”

Countless scientists have since shown that sulforaphane might be effective in treating or preventing a litany of ills, including cardiovascular disease, diabetes, and neurodegenerative disease, and more than a decade of clinical trials with sulforaphane has yielded impressive results. So, when Hopkins autism experts Andrew Zimmerman and Kirby Smith started looking at sulforaphane as a potential treatment for autism, it seemed like a good match. Sulforaphane falls into the chemical category of “small molecules,” compounds that regulate key cellular processes. In autism, some of those processes fall short. Zimmerman and Smith considered several other small molecules to address the cellular deficits associated with autism, but none held the potential that sulforaphane did.

A brief phone call from Zimmerman was all it took to spark Talalay’s interest, who appeared at Zimmerman’s office the next day. “I’ll never forget it,” says Zimmerman. “He showed up with two armloads of big notebooks. I had to find a conference room for a table big enough to hold all the stuff!”

A four-year collaboration culminated in a study involving twenty-nine teenage boys and young men, ranging in age from 13 to 27, who had autism. Conducted in 2014 at the Lurie Center for Autism of the Massachusetts General Hospital for Children in Lexington, Massachusetts, the study gauged sulforaphane’s effects on the social and communication deficits associated with autism, two of the condition’s core features. The results were dramatic: the participants shook hands and made eye contact with their parents and caregivers—something many of them had never done before—after receiving sulforaphane supplements.

Given the extensive grounding of the sulforaphane research in cancer, Talalay’s move toward autism was not self-evident to many. But to those who have known and worked with Talalay, it was a classic example of his exacting science, unfailing foresight, and youthful moxie. And, whereas reaping the benefits of cancer research likely will take two or three lifetimes, the results with autism were more immediate and, for Talalay, more personally gratifying: his grandson has autism.

Kensler spent an hour with Talalay recently, hearing about his “next priorities in science.” High on his list: more clinical trials with sulforaphane and autism. Indeed, Talalay and his colleagues plan to study the effects of sulforaphane in young children—as young as three years old—who have autism.

Talalay’s friends and colleagues often ask him when he’ll retire, but he doesn’t have an answer for them. “You see, I haven’t found anything more interesting,” he says. “I’ve had a life full of interesting happenings. I’m a lucky boy.”

List of Sources

  1. In-person interview with Paul Talalay, MD, The Johns Hopkins University. 25 March 2015. paultalalay1@gmail.com Phone: 410-323-0871.
  2. Telephone interviews with Paul Talalay, MD, The Johns Hopkins University. Spring 2015. paultalalay1@gmail.com Phone: 410-323-0871.
  3. In-person interview with Tom Kensler, Ph.D., The Johns Hopkins Bloomberg School of Public Health. 7 April 2015. tkensle1@jhu.edu Phone: 410-955-1292.
  4. In-person interview with Donald Coffey, Ph.D., The Johns Hopkins University. 7 April 2015. dcoffey@jhmi.edu Phone: 410-955-2517.
  5. In-person interview with Solomon Snyder, MD, The Johns Hopkins University. 7 April 2015. ssnyder@jhmi.edu Phone: 410-955-3024.
  6. Telephone interview with Theresa Shapiro, MD, Ph.D., The Johns Hopkins University. 14 April 2015. tshapiro@jhmi.edu Phone: 410-955-1888.
  7. Telephone interview with Bert Vogelstein, Ph.D., The Johns Hopkins University. 13 April 2015. bertvog@gmail.com Phone: 410-955-8878.
  8. Telephone interview with Yeusheng Zhang, MD, Ph.D., Roswell Park Research Institute. 17 April 2015. Yeusheng.zhang@RoswellPark.org Phone: 716-845-3097.
  9. Telephone interview with Andrew Zimmerman, MD, University of Massachusetts. 23 April 2015. Andrew.Zimmerman@umassmemorial.org Phone: 508-856-3279.
  10. Telephone interview with Jed Fahey, ScD, The Johns Hopkins University. 30 April 2015. jfahey@jhmi.edu Phone: 410-614-2607.
  11. Skype interview with Albena Dinkova-Kostova, Ph.D., University of Aberdeen. 16 April 2015. a.dinkovakostova@dundee.ac.uk Phone: +44 (0) 1382 383386.
  12. Telephone interview with Paul Talalay, MD, The Johns Hopkins University. December 2011. ptalalay@jhmi.eduPhone: 443-287-9900.
  13. Talalay, Paul. “A fascination with enzymes: the journey not the arrival matters.” Journal of Biological Chemistry 280, no. 32 (2005): 28829-28847.
  14. Singh, Kanwaljit, Susan L. Connors, Eric A. Macklin, Kirby D. Smith, Jed W. Fahey, Paul Talalay, and Andrew W. Zimmerman. “Sulforaphane treatment of autism spectrum disorder (ASD).” Proceedings of the National Academy of Sciences 111, no. 43 (2014): 15550-15555.
  15. People on the Way Up. (1962). Saturday Evening Post, 235(10), 26-27.

Teresa Lynn Johnson is a freelance science writer and health communications consultant. Her work draws on elements of nutritional biochemistry, toxicology, and epidemiology, and she has written and lectured on a variety of topics including phytochemistry, ethnobotany, skeletal biology, vaccines, and cancer prevention. Ms. Johnson has a strong background in the biological sciences and public health, and she is credentialed as a registered dietitian. Currently, she is pursuing an advanced degree in science writing. This unique mix of education, training, and clinical experience provides her a wide-angle view that few of her contemporaries possess.