Excursions with Paul Greengard

Nobel laureate, an expert on the neuron’s “inner world,” returns to where the work began.

The visit of Paul Greengard, Ph.D., to Yale in May was a homecoming of sorts for the Nobel laureate.

Greengard, who gave the 15th annual Farr Lecture on Student Research Day, spent 15 years working in a lab on the third floor of Sterling Hall of Medicine’s B wing before moving to Rockefeller University in 1983.

“The work which formed the foundation for the Nobel Prize was all carried out here at Yale,” said Greengard, who shared the 2000 Nobel Prize in physiology or medicine for his research into how nerve cells in the brain communicate. In a joking aside, he added, “Don’t tell the president of Rockefeller I said that.”

Greengard said that when he started the work shortly after coming to Yale, “one of the things that our research was most interested in was to try to elucidate the mechanism by which neurotransmitters activate receptors.” One school of thought argued that electrical impulses drove communications among neurons. An opposing view held that neuronal communications were mediated by a chemical process. The chemical view eventually won out, and Greengard’s research led to his discovery of the role of phosphorylation in the mechanism of action of neurotransmitters.

While at Yale, he came close to making a serious error. In 1978 a young scientist wrote and asked for a position in his lab as a postdoc. “I wrote back and said no,” Greengard said. “It was probably the dumbest thing I had ever done.” Five days later Greengard had a visit from cell biology Chair George Palade, M.D., who had won the Nobel in 1974. “He came into my office and said, ‘You made a big mistake.’ He was God at that time. He told me how bad the mistake was, and I reversed my decision.”

The young postdoc was Pietro De Camilli, M.D., now a professor and former chair of cell biology himself, who introduced Greengard to a standing-room-only crowd in the auditorium of the Jane Ellen Hope Building. “He discovered the inner world of the neuron,” De Camilli said of his former mentor.

Greengard’s talk capped a day of poster and oral presentations by students. Five students made oral presentations and 65 had posters on the walls of the Hope Building. While slightly more than half of the posters described the results of laboratory work, the range of research questions was quite broad, delving into the basis of absolute pitch, conflicts of interest in medical research, the risk of injury to children in Pakistan and supports and barriers to the use of health care interpreters for patients with limited English.

The science behind AIDS and prevention

About 250 people attended AIDS Science Day at the School of Public Health on April 12 for discussions of a wide range of medical, preventive, social and political aspects of the disease. “In simple terms,” said public health Dean Michael Merson, “the pandemic now rivals in size and dimension the bubonic plague of the Middle Ages.” Three panels discussed sex, drugs and politics; therapeutic and preventive interventions; and risk factors among vulnerable populations. The 18 posters on display examined topics including the Tijuana sex industry, syringe access in Hartford and links between substance abuse and domestic violence.

Among the presenters was Shalini Kapoor, M.P.H. ’02, who received the student poster award for her research into the impact of AIDS on households in South Africa. (She also received the Dean’s Prize for Outstanding M.P.H. Thesis.) Kapoor found many of them overwhelmed by the loss of productive family members and an increase in the number of orphans. Many households in the KwaZulu Natal province, she said, were unaware of government assistance programs. She also observed obstacles to obtaining that assistance, missing birth certificates being high on the list. “Most children are in need of food, clothing, shoes, school uniforms, blankets and mattresses,” said Kapoor, who spent last summer in South Africa. “The information in this assessment is intended to assist in designing programs targeted to the needs of young orphans and their families.”

For budding scientists, the road ahead holds both promise and pitfalls

At a biotech job fair in February, a panelist on alternative careers offered a sobering statistic. “Only one in five of your peers is going to have their own lab,” Laurie Dempsey, Ph.D., told the crowd of graduate students and postdocs in the Harris Auditorium at the Child Study Center. The implication was clear. The other four would have to consider alternatives. Dempsey herself traded pipettes and Western blots for an editor’s green eyeshade at Nature Immunology.

And that is only one decision facing scientists, according to members of the two panels at this year’s Graduate Student Research Symposium. If they remain at the bench, will it be an academic or corporate lab? If the lure of the corporate world is stronger, should a scientist go for big pharma or an unknown biotech startup?

Two panels, which divided neatly along gender lines as it happened—men discussing traditional career paths, women considering alternatives—offered the advice and experience of scientists who have been out of school for a few years. Whether in traditional or unusual careers, all managed to keep their hand in science.

“I do a lot of writing, a lot of financial modeling, and I talk to investors constantly,” said Hailey Xuereb, Ph.D., who now does equities research in biotechnology at the financial giant Bear Stearns. Dempsey said she takes satisfaction in helping scientists communicate their work to a larger audience. “You have to write well and enjoy being challenged all the time,” she said.

Karen Mangasarian, Ph.D., spent five years as a postdoc before becoming a technical advisor at a law firm by day, while getting a law degree at night. Small biotech companies make up a large part of her client base. “You can help bring those companies from a middling company to something of substance,” she said.

All agreed that an M.B.A. is not essential to their careers. “It’s helpful, but you really learn once you’re on the job,” said Xuereb.

Students wishing to pursue more traditional careers were warned of the trade-offs inherent in choosing among established firms, startups and academic research.

“There are high risks involved and you have to determine whether it’s worth that risk,” said Timothy S. McConnell, Ph.D., who chose a startup—Rib-X Pharmaceuticals, founded in New Haven last July.

“There’s a big misconception out there that big companies equal stability and small companies equal instability,” said Vic Myer, Ph.D., a founding scientist at Akceli, a 12-person Cambridge, Mass., company that works on high-throughput, cell-based assays. Picking up on Myer’s thought, Mark R. Miglarese, Ph.D., a senior research scientist at Bayer, added, “A big company is probably not going to go down, but your research area might.”

And, the panel noted, working at small companies allows scientists to develop skills in other areas, such as business, marketing and public relations, while corporations offer another kind of flexibility. “In large companies there’s a fair bit of opportunity to move around, because big companies do a lot of different things,” said Miglarese.

Panel members also warned students about the difference between science in academia and in industry. Academic researchers have the luxury of pursuing projects for no other reason than that they find them interesting. “Let’s face it, these are money-making ventures,” Miglarese said of corporate research. “You’ve got to sell it. It’s got to make some sense for the company.”

Shalini Kapoor
Photograph:
John Curtis

A good year to be matching

Nationally, a record number of seniors make the grade; for two Yale students, it’s on to Hopkins and UCSF.

By 11:30 a.m. on March 21, students were gathering in the Marigolds dining hall to wait for the doors to the Harkness Lounge to open. As the crowd grew it was seized by the giddiness that often accompanies high anxiety. This was, of course, Match Day, and in a few minutes the 109 students, along with 14,227 others around the country, would open the letters that would determine the course of their medical careers.

Jordan Prutkin, one of the first to arrive, appeared sanguine. “I think I matched at one of my top three or four choices and I would be happy at any of them,” he said. “But talk to me in 25 minutes.” What Prutkin couldn’t know at that time was that he had good reason to be calm. Not only did he fare well but 2002 was the best year ever for medical school seniors, according to the National Resident Matching Program—94.1 percent matched, up from 93.7 percent last year.

The Office of Student Affairs tried to reduce the anxiety with a new system for getting the letters to their recipients. In years past Nancy R. Angoff, M.P.H. ’81, M.D. ’90, HS ’93, associate dean for student affairs, and Cynthia Andrien, M.S., assistant dean for student affairs, trekked through the milling crowd, smiles on their faces and letters in their hands, closeted themselves in the mail room, inserted letters in boxes, then opened the door to the waiting throng. No more.

“The anxiety was just too much, with some people trying to get into the mail room and others not being able to get out,” Angoff said.

This year the letters were divided into alphabetical groupings and were waiting at tables in the lounge. Students appeared to welcome the new system. “I thought it gave us enough space,” Anna Gibb Hallemeier said. “You hear screams, but it isn’t in your face.”

Indeed, screams and squeals of joy filled the room as students learned their fates.

Outside the lounge, Prutkin sat with his classmate Jennifer Wang, a good friend since they met at Yale College nine years ago. Prutkin is headed for Johns Hopkins Hospital—his first choice—and a residency in internal medicine. Wang’s match will take her to the University of California-San Francisco for general surgery.

“Since freshman year of college we’ve been friends,” Prutkin said. “Now we’re on opposite coasts.”

“I’ll be sure to call you at 11 p.m. my time,” Wang joked.

With 109 students involved, this year’s match was larger than usual—many of those in the Class of 2001 took a fifth year, while most of the students in the Class of 2002 finished their studies in four years. More than half the Yale students chose a generalist discipline: 26 percent went into internal medicine, another 6 percent chose internal medicine/primary, 6 percent opted for family practice and 14 percent chose some form of pediatrics.

The results of this year’s match at Yale appear below.

2002 residency placements for Yale medical students

The Office of Student Affairs has provided the following list, which outlines the results of the National Resident Matching Program for Yale’s medical graduates. Some names appear twice because the graduate is entering a one-year program before beginning a specialty residency. The transitional designation is a one-year program with three-month rotations in different specialties.

CALIFORNIA
Cedars-Sinai Medical Center, Los Angeles
Rupal Badani, pediatrics

Contra Costa Regional Medical Center, Martinez
Kinari Webb, family practice

Harbor-UCLA Medical Center, Los Angeles
Marc Davis, emergency medicine

Scripps Mercy Hospital, San Diego
Jeffrey Bush, transitional

Stanford University Programs
Shannon Sheu, dermatology, medicine
Scott Sutherland, pediatrics
Jeanne Tyan, emergency medicine
M. Reza Vagefi, medicine

University of California, Irvine
Kier Ecklund, orthopaedic surgery
Hung Nguyen, obstetrics and gynecology

University of California Medical Center, Los Angeles
Trac Duong, internal medicine
Amit Jha, internal medicine
Nara Shin, emergency medicine

University of California, San Diego
Jeffrey Bush, emergency medicine
University of California, San Francisco
Felix Adler, diagnostic radiology
Diana Bojorquez, pediatrics/primary
Jon Boone, psychiatry
Karen Kim, internal medicine/primary
Brian Lee, radiation oncology
Yee-Bun (Ben) Lui, internal medicine/primary
Kamyar Madani, internal medicine
Sarah Rettinger, internal medicine
M. Reza Vagefi, ophthalmology
Jennifer Wang, general surgery

VA Greater Los Angeles Health System
Nara Shin, medicine

COLORADO
University of Colorado School of Medicine, Denver
David Larson, pediatrics

CONNECTICUT
Greenwich Hospital
Brian Lee, medicine
Patricia Pahk, medicine

Hospital of Saint Raphael, New Haven
Michael Dutka, transitional
Scott Floyd, medicine
Joyce Oen-Hsiao, internal medicine
Marlyanne Pol-Rodriguez, medicine
Neesha Rodrigues, medicine

Middlesex Hospital Program, Middletown
F. Nikki Pinkerton, family practice

Norwalk Hospital
Afari Arash, medicine

Yale-New Haven Hospital
Hyacinth Browne, obstetrics and gynecology
Anita Chandrasena, internal medicine
Jen Chow, otolarnygology, surgery
Emmanuelle Clerisme, internal medicine/primary
Aaron Covey, orthopaedic surgery
Michelle Diu, internal medicine
Monique Grey, orthopaedic surgery
Anna Hallemeier, medicine/pediatrics
Heather Heimerdinger, psychiatry
Joshua Horenstein, internal medicine
Darnita Johnson-LaBorde, psychiatry
Vasanthi L. Narayan, internal medicine
Susan Lee, ophthalmology
Vivian Lombillo, medicine/primary
Louis Marotti Jr., neurosurgery, surgery
Leo Otake, plastic surgery
Patricia Pahk, ophthalmology
Andy Redmond, neurosurgery, surgery
Jennifer Sharp, internal medicine
Kiriaki Stylianopoulos, pediatrics
Bayan Takizawa, surgery, urology
Karen Tie, internal medicine

DISTRICT OF COLUMBIA
Georgetown University Hospital
James Castle, medicine

GEORGIA
Eisenhower Army Medical Center, Augusta
Jose Miranda, orthopaedic surgery

LOUISIANA
Tulane University, New Orleans
Roya Vakili, ophthalmology

MARYLAND
Johns Hopkins University, Baltimore
James Castle, neurology
Jordan Prutkin, internal medicine
Prashanth Vallabhajosyula, general surgery

MASSACHUSETTS
Beth Israel Deaconess Medical Center, Boston
Amy Herman, internal medicine

Brigham and Women’s Hospital, Boston
Sandeep Bansal, internal medicine
Wendy Garrett, internal medicine
Seth Goldbarg, internal medicine
Dawn Harris, internal medicine/primary
Julie Jaffe, internal medicine
Biren Modi, general surgery
Virginia (Jeanne) Triant, internal medicine

Brigham/Faulkner Hospital, Boston
Felix Adler, medicine
Andrew Norden, medicine
Michael Sherling, medicine
Michael Singer, medicine
Luke Yoon, medicine

Children’s Hospital of Boston
Amy Fahrenkopf, pediatrics
Melissa McKirdy, pediatrics

Harvard Combined Program, Boston
Michael Fehm, orthopaedic surgery
George Lui, medicine/pediatrics

Harvard Medical School
Andrew Norden, neurology

Joint Center for Radiation Therapy, Boston
Scott Floyd, radiation oncology

Massachusetts Eye and Ear Infirmary, Boston
Michael Singer, ophthalmology

Massachusetts General Hospital, Boston
Brooke Bailey, pediatrics
John Davis, internal medicine
Rebekah Gross, internal medicine/primary
Eric Hazen, pediatrics/psychiatry
Neesha Rodrigues, radiation oncology
Michael Sherling, dermatology
Karen Thomas, internal medicine
Luke Yoon, diagnostic radiology

Massachusetts General Hospital/McLean, Boston
Rocco Iannucci, psychiatry
Tufts-New England Medical Center, Boston
Daniel Hoit, neurosurgery

MICHIGAN
University of Michigan Hospitals, Ann Arbor
Elizabeth Bird, pediatrics
Nathan Siegel, emergency medicine
Deborah Smith, internal medicine

NEW YORK
Einstein/Montefiore Medical Center, Bronx
Monica Lopez, general surgery

Mount Sinai Hospital, New York
Stephen Krieger, neurology
Rashida N’Gouamba, obstetrics and gynecology

New York Presbyterian Hospital-Columbia
Premila Bhat, internal medicine
Nataki Douglas, obstetrics and gynecology
Kebba Jobarteh, pediatrics
Jeffrey Miller, psychiatry
Jacqueline Park, internal medicine
Marlyanne Pol-Rodriguez, dermatology

New York Presbyterian Hospital-Cornell
Charles Stowell, psychiatry

New York University School of Medicine, New York
Anita Karne, internal medicine/primary

St. Vincent’s Hospital, New York
Stephen Krieger, medicine
Susan Lee, transitional

South Nassau Community Hospital, Oceanside
Jennifer Hammerstein, family practice

SUNY Health Science Center-Brooklyn
Afari Arash, diagnostic radiology

Westchester Medical Center, Valhalla
Jennifer Kreshak, orthopaedic surgery

NORTH DAKOTA
University of North Dakota School of Medicine, Bismarck
Corey Martin, family practice

OREGON
Oregon Health Sciences University, Portland
Analene Pentopoulos, obstetrics and gynecology

PENNSYLVANIA
Children’s Hospital of Philadelphia
Naomi Balamuth, pediatrics

Hospital of the University of Pennsylvania, Philadelphia
Antony Chu, internal medicine
Kate Lally, internal medicine
Ingi Lee, internal medicine

Thomas Jefferson University, Philadelphia
Michael Dutka, diagnostic radiology

University Health Center of Pittsburgh
Hany Bedair, orthopaedic surgery
Karl Lozanne, neurosurgery, surgery

Washington Hospital, Washington
R. Griff Kelley Jr., family practice

RHODE ISLAND
Rhode Island Hospital/Brown University, Providence
Tara Lagu, internal medicine/primary
Steven Song, pediatrics

VIRGINIA
Medical College of Virginia, Richmond
Sandra Scott, emergency medicine

WASHINGTON
Tacoma Family Medicine Program
Rebecca Holmes, family practice

University of Washington Affiliated Hospitals, Seattle
Vivian Lombillo, dermatology

WISCONSIN
University of Wisconsin Hospital and Clinics, Madison
Frederick (Frecky) Lewis, anesthesiology


			Originally published in Yale Medicine, Summer 2002. Copyright © 2002 Yale University School of Medicine. All rights reserved.