Proceedings of the Harvard Medical School Faculty Council, November 18, 2015

Dean Flier called on John Hedley-Whyte, the David S. Sheridan Professor of Anaesthesia and Respiratory Therapy, to read the Memorial Minute on John R. Pappenheimer.

John Richard Pappenheimer was the youngest of the three children born to Alwin Max Pappenheimer, Sr., distinguished pathologist of the College of Physicians and Surgeons at Columbia University and Beatrice (Leo) Pappenheimer. John R. Pappenheimer was granted his B.S. degree from Harvard College in 1936: he followed his sister Anne and his elder brother Alwin Max, Jr. Anne (later Forbes), went on to become Clinical Professor in Medicine based at the Massachusetts General. Together with Fuller Albright, Nan (Anne) produced "Classic Endocrinology,” which made the treatment of many diseases routine. Elder brother Alwin Max, Jr. was to become Professor of Biochemistry at the College.

John started serious academic research at the Marine Biological Laboratories at Woods Hole. F.J. W. Roughton recruited John to Sir Joseph Barcroft's Department of Physiology at Cambridge. While doing the Cambridge Natural Science Tripos, John worked on the thermodynamic efficiency of urine formation. This work required the development of spectrophotometric methods for determining oxygen saturation in flowing blood. When war came to Britain in 1939, John at Clare teamed with Glen A. Millikan of Trinity to develop ear oximeter and oxygen equipment for military aircraft. Lord Adrian had asked Millikan, his tutee, to help the Royal Air Force develop a reliable breathing apparatus to prevent loss of consciousness during high altitude dog fights. The oximeter was integrated into the pilot's mask and was clamped to the ear: a major factor in eventual Allied air supremacy.

John Pappenheimer received his Cambridge Ph.D. in 1940. Of this stage of his career Pappenheimer later wrote, "I was fortunate to take the Natural Science Tripos in full-time physiology. One lecture each day followed by reading, reading and more reading ... But we came to know the classical literature of three languages, leading up to the then frontiers in almost all sectors of physiology. I have been everlastingly grateful for this period of intensive study. It provided a framework for subsequent research and teaching and made possible the enjoyment of continued reading in fields outside one's own narrow research interests."

From 1940 to 1942 John Pappenheimer worked in physiology at the College of Physicians and Surgeons of Columbia University. From 1942 to 1945 John resumed his work with Millikan not at Cambridge but at the University of Pennsylvania. In 1946, at the end of this critical World War II work on assessing human oxygenation in unpressurized combat aircraft, John was called back to Harvard.

In Landis's Physiology Department, John Pappenheimer resumed his studies begun at Cambridge on edema formation. In John's own words, "the theory of restricted diffusion, molecular sieving and osmotic transients", soon followed, and with it the understanding that diffusion permeability differs from flow permeability, and their ratio is directly related to the aqueous channels through the membrane. By 1951 Pappenheimer and colleagues "Were able to characterize the passive permeability of muscle capillaries in terms of the molecular dimensions of permanent molecules, on the one hand, and the dimensions of aqueous channels through capillary walls, on the other." This general theory stands to this day. Pappenheimer was elected to the National Academy of Sciences in 1965 and call to the George Higginson Professorship followed.

Almost every day, John Pappenheimer bicycled from Fayerweather Street, across Brattle Street and along the Charles River to the Medical School. As a result, he was called upon to open the Paul Dudley White Bikeway along the Charles. This he did with aplomb followed by several hundred bicycling Cliffies. John Pappenheimer reckoned that cycling upright on his old fashioned bicycle, Cambridge-Clare 1940s style, he could pass all but the college crews destined for Henley or the Olympics. Traffic along Storrow Drive engaged Pappenheimer s interest. On arrival at the Medical School he would recount the amount of gasoline that had been squandered by the idling vehicles. A particular joy was the jamming of trucks under the bridges since this increased the diesel and gasoline score. From these calculations, Pappenheimer used to announce the mileage that a DC-3 could cover with the same amount of fuel. The fuel consumption of all types of World War II planes was known to him from his work with Millikan.

John Pappenheimer recalled that, "Half-way between the Cottage Farm Bridge and the Medical School there is a park and here a little path leads to Mason's Pond. The pond is surrounded by willow trees which hide completely the nearby buildings. On high pressure days, when deadlines seem impossible to meet. . .I dismount at Mason's Pond to spend a few sane moments watching the ducklings swim behind their mothers ... "

On his return from the Medical School after a difficult day Pappenheimer was wont to say that it was nice to return to Brattle Street and relatively intellectual order. Late in John Pappenheimer's career he worked at the Concord Station of the University. John claimed that the steep uphill bicycle travail was worth every pedal. On the downhill bicycle ride he often carried surplus emu eggs to cook as sole dinner nutrient. Dogs were invited to dine at the Pappenheimers'. Sherry was served in the living room and an emu omelet in the kitchen. John cracked the top of the egg with one of his old rotary hand drills, the egg in a big bowl to stabilize it and the drill at the perfect point on the top of the huge green egg. After dinner the health of the emu was assured and its muscle physiology discussed.

John recounted of his return to the roots of Emerson and Thoreau and to Harvard's Estabrook Woods was spiritually uplifting. Working next to the Concord site of the College (October 5, 1775-June 11, 1776) during the American Revolution made him suggest to everyone that they read the three volumes of George Otto Trevelyan's epic account. The decision of the President and Fellows to preserve the Estabrook Woods in their Thoreauvian state in perpetuity pleased John Pappenheimer immensely.

John Pappenheimer's work on the measurement of oxygen tensions in urine and flowing blood during and after World War II led to refusal by the U.S. Patent Office to issue a patent to investigators from the University of California and the University of Copenhagen. Pappenheimer was said to be the prior inventor. After this judgment John Pappenheimer was urged to pick up the patents for oxygen and carbon dioxide electrodes which require the accurate measurement of 10-15 volts. "Gentlemen do not take out patents," he declared, at least not those that drive up the cost of patient care. Later, when at the urging of Harvard he was issued patents for Sleep Promoting Factor (1982), Sleep Inducing Agents (1987) and Somnogenic Compositions and Methods of Use (1987), he assigned them in their entirety to the President and Fellows of Harvard College.

In 2003 John Pappenheimer published in the Journal of Physiology that capillaries of jejunal villi can absorb nutrients at rates several times higher than capillaries in other tissues. His studies detected that increase of villus capillary blood flow and permeability-surface area product are essential components of absorptive mechanisms. This jejunal absorption is significantly impaired by general anaesthesia.

John R. Pappenheimer was Visiting Professor at Cambridge based at Churchill College, and in 1975-76 he held the Eastman Professorship, "to be filled ... by senior American Scholars of the highest distinction" at Oxford. All three distinguished Pappenheimer siblings served Harvard with distinction and humanity. Their international friendships and the summoning of F.J. W. Roughton led to Roughton's help in the establishment of the blood gas laboratories at the Anaesthesia Laboratory of the Harvard Medical School at the Massachusetts General Hospital. Rarely if ever has any University been blessed with three such delightful and erudite siblings. John Pappenheimer was survived by his wife of fifty-eight years, Helena (Palmer) and their four children.

Respectfully submitted,

John Hedley-Whyte, Chairperson

The Lord Grabiner of Aldwych in the City of Westminster

Morris J. Kamovsky

Sharon Bushnell Sears

Flier thanked Hedley-Whyte and noted that the memorial minute will become a permanent part of the Faculty Council records.

Next, Flier commented on his announcement to step down as Dean of the Faculty of Medicine as of July 3, 2016.  He expressed appreciation for the outpouring of accolades from across the faculty.

Flier then discussed the meeting agenda. Several months ago, he asked the Conflict of Interest and Commitment (COI) Committee (standing committee) to conduct a review of the HMS policy and, through that process, develop recommendations for improvements. He invited Robert Mayer, standing committee chair, and Gretchen Brodnicki and Jennifer Ryan to present such recommendations to the Faculty Council.

Brodnicki provided a brief history of the HMS Policy on Conflict of Interest and the 2015 HMS COI policy review.  She discussed the basic two tenants in research under review—the research support and clinical research rules. In January 2015, Flier charged the standing committee to review these two rules after faculty and others voiced questions and issues with the current policy. Feedback was solicited throughout the process via email, surveys and meetings.  The standing committee also heard testimony from members of the HMS community and advisors, considered peer institution policies and approaches, and conducted literature review of bias in research.

Mayer discussed the current wording of the research support rule:

“Faculty may not accept sponsored research support from any business in which they, and/or members of their family, hold an equity financial interest.

  • $30,000 de minimis if business is publicly traded.
  • $0 de minimis if business privately held.”

Mayer explained that sponsored research is defined as money, personnel, certain proprietary materials or technology, and other compensation from outside sources that support basic research.  It also includes gifts that are made solely for the support of the faculty member’s research or that of the faculty member’s laboratory.

Next, he reported that the standing committee found a variety of opinions and a general consensus that the rule-based approach prohibited consideration of any flexibility or certain conflicts that may, in fact, be managed with appropriate safeguards as well as restricted certain opportunities for trainees.  With overwhelming support in the HMS community for revising the rule to allow consideration of the facts and circumstances of each particular situation, the committee’s interim recommendation would be to propose:

1. For equity in privately held companies:

  • Faculty are presumed to be prohibited from receiving sponsored research support, but a faculty member may file a petition for consideration to rebut this presumption with the standing committee and the COI committees at their own affiliated institutions.
    • Criteria for approval of petition are
      • compelling circumstances that potential benefits of the proposed sponsored research will outweigh the potential risks of conflict from the financial interest and
      • reasonable safeguards can be implemented to manage the potential conflict.

2.  For equity in publicly traded companies:

  • A faculty member who holds equity in a publicly traded business will not be prohibited from receiving sponsored research support from that business unless the faculty member owns equity valued at more than 1 percent of the total equity of that business at which point the faculty member may petition the standing committee for approval consistent with the process described above.

The proposed review process would include the following steps:

  • Investigator submits petition to affiliated institution or HMS (if Quad-based).
    • HMS will refer to affiliated institution if received centrally.
  • COI office at investigator’s primary institution collaborates with investigator to learn more information as well as work with its committee for initial review.
  • COI office submits form to standing committee for evaluation and recommendation.
    • Review process will be blinded.
  • If approved, COI office develops and implements COI management plan.

Following their report, Mayer and Brodnicki entertained questions. After discussion, Flier asked for and received approval from the council (all present in favor, none opposed) to approve the recommendations as presented.

Flier then introduced Robert Troug, director of the Center for Bioethics. He remarked that the new Center for Bioethics serves as a platform for leaders in the community to address rapidly evolving ethical questions about the ever-shifting terrain of biomedicine.  The School’s commitment to bioethics was underscored when the Division of Medical Ethics became the independent Center for Bioethics last year.

Troug gave a brief history of ethics at HMS. In 1988, Dean Daniel Tosteson created the Division of Medical Ethics within the Department of Social Medicine and appointed Lynn Peterson as the first director.  In 1997, Allan Brandt was appointed director, and under his leadership, it developed a close integration with the affiliated hospitals.  In 2004, Daniel Brock was appointed director with Troug as the assistant director and established the required course in medical ethics. In 2014, Brock retired and the Center for Bioethics was created.

Truog commented that the center aims to teach ethics to medical students across the four-year curriculum, to support and strengthen the ethics program at HMS

teaching hospitals and affiliated facilities, to prepare the next generation of practitioners and leaders in bioethics and address contemporary ethical issues in the biosciences and health care that are emerging all the time, and to  engage the public in understanding and addressing ethical aspects of health care and new biotechnologies.  The center’s educational initiatives include the Medical Ethics and Professionalism course; the Patient-Doctor curriculum, the Master of Bioethics degree, a fellowship in bioethics, two endowed lectureships and public ethics symposia.

Following his presentation, Troug entertained questions.