MPNforum Magazine

Damn it, Schafer, why don’t you find out?

by Zhenya Senyak

In a path that saw him alter the trajectory of his medical scientific career path multiple times, Dr. Andrew Schafer is now firmly at the top of our medical MPN research and clinical worlds.  But what a long, strange trip it’s been.  One abrupt command may have helped set the direction.

First, a little background.  Andy Schafer always knew he would be a doctor. In the beginning, it was a firm but hazy objective.

By an extraordinary stroke of luck, as an undergraduate, he worked with Dr. Charles Gainor  at Northeastern “a full professor, an established microbiologist in the department of biology,  a wonderful person, very formal and stiff until you got to know him,  intimidating … interested in bacterial genetics. He spent unbelievable amounts of time with me, actually a one on one tutorial that went on for three years.I got to do lots of hands on crude work looking for answers. I would take afternoons off and work in the lab through the night. This was about a decade after the structure of DNA was discovered.”

“Dr. Gainor basically assigned me a series of lectures…based on a book and articles he assigned me to read.  We were learning and the field was exploding. And then after studying materials for about an hour I’d do an experiment, basically research … absolutely from scratch. Neither one of us had any experience. We had no technicians,  we did it all: autoclave, preparing reagents, it was remarkable.

“I had a girlfriend at the time who would become my wife, a college student a few blocks away. She would actually come stay with me at the lab. This was fundamental research really basic research. We understood it would be applicable  but didn’t have a sophisticated understanding of how it would be applicable.     Applying researchto human care is translational research.”

 Translate findings from the bench to clinical applications of patient care.

In the Northeastern experience were several threads that would dominate  Andy Schafer’s career:  the need to find a good mentor, the need to mentor young scientists and physicians, to find answers to fundamental biological questions, to rely on hands-on research, and, perhaps mostly, the need to offer the highest level of patient care by wedding the research bench with the clinical bedside.

His medical school experience didn’t get off to a pretty start.  He knew he was going to be a doctor. It’s all he ever thought  of doing in life. But when he applied to medical school he was in for a shock.  His first letter of rejection came from the University of Colorado. They didn’t reject his application. They rejected his pre application, indicating he need not apply.

Eventually he was interviewed at a prestigious medical school by a  renowned former Chief of Neurology. “He asked me why I was commuting to college from home. I tried politely to say I couldn’t afford residence fees but he just kept lecturing me about all the things I’d miss. Coming from family wealth and privilege himself, he seemed completely incapable of understanding why I couldn’t afford to live on campus. I was mesmerized. This man was a jerk of breathtaking proportions and what Northeastern had offered me was different from the pedigree his university could offer… and would turn out to be far more valuable.  Northeastern offered me the companionship of fellow students and taught me resilience and a little bit of courage

“I ended up going to the University of Pennsylvania Medical School and in short order the idea of research had receded from my mind. Med school is very tough. I was beginning to forget my days with Charles Gaynor.”

Then in the fourth year of medical school something amazing happened.

“It was another one of those epiphanies…aha moments. In my fourth  year at Penn I decided on internal medicine. My first elective was a clinical rotation in hematology. The attending physician was Dr. Frank Gardner, about 6’7″, He had a really strong booming baritone voice, wore bow tie, and was very accomplished and intimidating.

“The first day on that service med students are asked to participate in hematological consultations.  Take histories.. present to attending.  First patient I saw was a young man with sickle cell anemia. What struck me while working him up was he had been in an out of hospitals half his life.

“Dr. Gardner with an entourage of fellows and residents and students would converge and insist the medical student present the case without notice at the Nursing station. I presented my findings and at the end he said, ‘So do you have any questions about this patient?’

“Why is he in and out of this hospital?  Why is he plagued with so many infections.?”

A long silence.

Gardner looked down at me and with his loudest voice, so I was sure everyone on the ward must have heard him, yelled, ‘Well damn it Schafer, why don’t you find out?’

“What do you mean?”

“Go into a laboratory and figure it out?”

“That,” said Schafer,” was the Aha moment that took me back to the lab. Later that day, Dr. Gardner spent several hours introducing me to the workings of a medical research lab.   I looked at the patient’s blood, developed some hypotheses, set up an experiment and isolated the problem to an abnormality in the function of leukocytes in sickle cell anemia.

“To be able to take care of a patient, ask questions and then take that into the laboratory and try to figure it out. This is translational research going the other way ..this is Bedside to Bench instead of bench to bedside. I was immediately captivated by the possibility of helping patients by taking questions about them — for which there were no good answers — directly into a research lab to try to find answers.”

The Lattice

His official biography following medical school is what Schafer himself terms “climbing the lattice career path.” A little straight up, a little side to side.

On his way to the top he’s been a teacher, bench scientist, physician, author, mentor, administrator. “Climbing the lattice career path means taking time here and there to drop out, try something new, come on back in and work like hell to get back up to speed, and follow your passion every step of the way.”

In his case, every step of the way has been extraordinary.  After his University of Pennysilvania medical degree he completed his residency at the University of Chicago and then went on to a fellowship at Brigham Hospital where his passion for MPNs was ignited.

Dr. Robert Handin

His mentor, Dr. Robert Handin, was chief of hematology at the Brigham and a specialist in platelets.   It’s there that Schafer produced his NEJM paper, Deficiency of platelet lipoxygenase activity in myeloproliferative disorders.

After serving at Brigham and as an associate professor of medicine at Harvard for 13 years, Schafer abruptly shifted gears and took a position as Chief of Medicine at the VA Medical Center in Houston.

The VA has its own medical system, its own research funding  and in many respects is its own medical world. The job Andy Schafer took on was daunting. The Houston VA is the largest in the system and yet its fund-raising results – essential to fund research – were near the bottom of the associated system hospitals.”

How did that career shift happen?

“That’s very interesting,” said Schafer.  ” Doing administrative work was never in the blueprint of my life.  But I had some experience at the Brigham being Acting Chief of Hematology when the chief was on sabbatical  and I kind of liked a lot of things I was doing.   Of course I didn’t like the drudgery of budget development or personnel  conficts. . .but I really enjoyed helping to mentor young people …getting involved with their careers.  So I thought maybe I should be doing this more as a permanent kind of thing.

“So I took that job and things went very well.  I recruited several young physician-scientsits, cultivated an environment where medical research became a major priority and within five years the Houston VA became number one in the country in research funding.  At that point I was asked to become chairman of the department of medicine at Baylor so that took me out of the VA mostly although I kept some patients there.”

In 2002, Schafer was back at the University of Pennsylvania this time as professor of medicine and chairman of the department. Five years later he moved East to fill a similar role at Weill Cornell Medical College and serve as physician-in-chief of New York Presbyterian Hospital.

As crammed as this high level lattice movement was, it’s only part of the story. Along the way Schafer continued research and publishing  — over 200 articles in hematology plus editing five books. He was founding editor of Hematology, the popular ASH newsletter, and is co-editor of the Cecil Textbook of Medicine.  He was elected president of the American Society of Hematology.  One publishing activity, his The Vanishing Physician-Scientist (2009) sets out his concerns over the growing division between exploding scientific findings and actual clinical practice.

The MPN Research Foundation

In many ways the MPN Research Foundation and Dr. Andrew Schafer are a perfect match.

Robert Rosen, CEO, MPNRF

The Foundation’s focus on basic MPN research, on bringing scientific findings into the clinical arena, and encouraging young scientists through grants, requests for proposals and mentoring complement Schafer’s core concerns as a physicians/scientist.

For the past five or six years, Andy Schafer has been chairman of the Foundation’s Scientific Advisory Committee. This is the group responsible for reviewing hundreds of applications and supervising the extensive vetting process that has resulted in the Foundation providing >$10 million in MPN research funding.

“It’s really very exciting,” says Schafer.  At study section meetings several board members and patients sit in as we review grants, 12 or 14 people all expertss in the MPNs, lots of electricity in the room..

“This kind of research walks a  fine line between what we call high yield low impact research, research where we  know what the answer is going to be as it gets ready for trial versus the kind of high impact,  high risk  research funded by the Foundation, like (Robert) Kraloivics’  work on the CALR (calreticulin) mutation. Or Shaoguang Li’s  research into the Alox5 inhibitor.

“The Foundation catalyzes discoveries, addressing the most refractory, most challenging MPN issues.  We’ve always taught fibrosis is irreversible but there never has been any good attempt to understand the nut we have to crack.  The MPN Research Foundation took the lead on that the past two or three years, focused on MF grants.

“What I wanted to do was reach out to top notch researchers worldwide  in related areas, develop a much broader baseof scientific expertise to attack the fundamental problem of fibrosis. The Foundation has done that and research is beginning to address the issue of fibrosis.  We don’t have any idea what’s causing this. We have some clues but it’s too complicated. We need to take lessons from other diseases, not blood diseases, where’s there’s fibrosis and see what we can learn.”

Mentoring, enabling

“The Foundation tends to underestimate the impact of its funded grants.  They ‘re  too close. I urged them  to take a more ambitious view take credit for their work.   When Bob (Robert Rosen, CEO)  and I were talking  he almost seemed discouraged that the Foundation wasn’t doing a lot.  I summarized all the grants, wrote that report up and showed him that the Foundation has been part of every significant MPN scientific development in the past decade.

“Shaoguang received a Foundation grant for novel research on the Alox5 gene targeting the downstream pathway of the JAK2 mutation. https://mpnforum.com/4800-2/  His continued work on an Alox5 inhibitor brought the work close to immediate clinical trial. But Shaoguang as a PhD didn’t have close clinical collaborators necessary to go the next step.

“Bob and I talked about it.  Part of my job is to take people who have been funded and help them bring their research forward. ….I connected Shaoguang with Dr. Ron Hoffman who had core resources to look at MPN stem cells and collaborate in clinical trial. (Hoffman, at Mt. Sinai, supported by a Foundation grant, is the recipient of an NCI research grant.)

The newest MPN institution —  and perhaps the most ambitious challenge for Dr. Andrew Schafer —  is the new MPN Silver Center. =

The Silver Center

The Richard T. Silver, M.D. Myeloproliferative Neoplasm Center at Weill Cornell,  established with a $3.7 million gift from the Cancer Research & Treatment Fund, is a multi-disciplinary research and treatment facility.  The Silver Center may be the culmination of Schafer’s lifelong work to bring bench and bed, clinicians and researchers, together to bear down on the myeloproliferative neoplasms.

CR&T, several decades after its founding by Dr. Richard Silver, has contributed over $13 million toward cancer research, education, and endowments.

Dr. Richard Silver Weill-Cornell

Although an effective philanthropic source for funding  general cancer research, Silver’s own intensive pioneering work in MPN research,  clinical care, and publication led the Board to fund the MPN Center as a  startup gift to Weil Cornell.

” Our common vision for the Center is clear.  We see the  Silver Center as a place to bring together MPN patient care and research. These are interdependent and inseparable missions that feed each other. We can’t honestly provide outstanding patient care without doing outstanding research.  And to do that we need synergistic relationships.

“The idea is to get researchers doing MPN research and clinicians caring for MPN patients together…get them to communicate and  build a cohesive seamless clinical enterprise.

“And this is based on  our own experience.  We can’t simply focus on the MPN disease. We have to focus on all the problems and issues that MPN patients have that aren’t hematologic. That means assembling a  stable team, specialists working with us who can also treat the complications, cardiologists, vascular surgeons, obstetricians to handle high risk pregnancies and special needs, dermatologists, etc.  We’re assembling a multi-specialty team to work on comprehensive care. The needs are great. MPNs are not nearly as rare as we thought.”
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