September 2015 - The Pharmacologist

the

A Publication by The American Society for Pharmacology and Experimental Therapeutics

Pharmacologist Vol. 57 • Number 3 • September 2015

Inside: EB2016 Preliminary Program Awards Deadline Postdoctoral Survey Results

The Early Days of L-Dopa

134 The Pharmacologist is published and distributed by the American Society for Pharmacology and Experimental Therapeutics.

Contents...

135 Message from the President 137 EB2016 Meeting Highlights Story: Sleepy Sickness, Oliver Sacks, 144 Feature and the Early Days of L-DOPA 155 Science Policy News 160 Education News 166 Journal News 168 Membership News 173 Members in the News 175 Division News News 176 Chapter

179 Meetings & Congresses

THE PHARMACOLOGIST PRODUCTION TEAM Prateeksha Nagar Suzie Thompson Rich Dodenhoff Catherine L. Fry, PhD Judith A. Siuciak, PhD COUNCIL President Kenneth E. Thummel, PhD President-Elect David R. Sibley, PhD Past President Annette E. Fleckenstein, MD, PhD Secretary/Treasurer Dennis C. Marshall, MD Secretary/Treasurer-Elect Charles P. France, PhD Past Secretary/Treasurer Paul A. Insel, PhD Councilors Wayne Backes, PhD John D. Schuetz, PhD Margaret E. Gnegy, PhD Chair, Board of Publications Trustees Mary E. Vore, PhD Chair, Program Committee Scott Waldman, MD, PhD FASEB Board Representative Brian M. Cox, PhD Executive Officer Judith A. Siuciak, PhD The Pharmacologist (ISSN 0031-7004) is published quarterly in March, June, September, and December by the American Society for Pharmacology and Experimental Therapeutics, 9650 Rockville Pike, Bethesda, MD 20814-3995. Annual subscription rates: $20.00 for ASPET members; $45.00 for U.S. nonmembers and institutions; $70.00 for nonmembers and institutions outside the U.S. Single copy: $20.00. Copyright Š 2015 by the American Society for Pharmacology and Experimental Therapeutics Inc. All rights reserved.

Periodicals postage paid at Bethesda, MD. GST number for Canadian subscribers: BN:13489 2330 RT. ASPET assumes no responsibility for the statements and opinions advanced by contributors to The Pharmacologist.

Postmaster: Send address changes to: The Pharmacologist, ASPET, 9650 Rockville Pike, Bethesda, MD 20814-3995.

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Message from

The President Dear ASPET Members, It is a great privilege and honor to serve you as the 84th President of the American Society for Pharmacology and Experimental Therapeutics. When considering the incredible scope of research, educational, and public service activities being pursued by the membership of ASPET, I am awed to find myself in this leadership role. Like many of you, I suspect, I operated for many years within a relatively small world of like-minded colleagues pursuing research and education in a narrow sub-discipline of pharmacology (drug metabolism and disposition, in my case). I crept out for the annual EB meeting and thoroughly enjoyed my time there, with the opportunity to get immersed in a greater diversity of scholarly thought, but largely constrained daily activities to my niche, my real world – the one that pays the bills. That has changed, and I firmly believe for the better. In this day and age of competing interests for limited resources and reduced attention spans of government leaders, it is absolutely essential that we as a society function as a collective, a well-tuned machine, with a common vision and an unwavering will in order to achieve our mission of transforming discoveries into therapies. During the next 12 months, I invite you to join me in this exciting collective endeavor.

At the outset of my tenure, I want to thank ASPET’s Past-President Annette Fleckenstein, Executive Officer Judy Siuciak, the entire ASPET office staff, as well as departing and remaining Council members for their tireless and outstanding service to our organization. Just a few highlights of their accomplishments from the past year include implementation of the first round of BIG IDEAS, with an investment of resources in three educational initiatives that should foster new and a more diverse membership in the society and expand the career horizons of our youngest members. This is part of a broader initiative from the society leadership to grow membership and ensure the relevance of our discipline in the prevention and treatment of human disease. In addition, the number of ASPET divisions expanded, with creation of a Division for Cancer Pharmacology that will be led by Susan Cole (Chair) and Kip Guy (Secretary/Treasurer). The new division is expected to be highly popular, addressing an unmet intellectual need of our current membership, and brings the opportunity to attract new members to ASPET who are seeking kindred spirits and a rich environment for the exchange of research and educational advances in the development and use of drugs to treat and prevent cancer. In the past year, our society leadership oversaw the highly successful launch of the David Lehr Award and Reynold Spector Award in Clinical Pharmacology at the 2015 EB meeting in Boston. These add to a rich array of what are now fully-endowed award opportunities that recognize the scholarly accomplishments of our members, and others, working in the field of pharmacology. Finally, I want to extend my sincere thanks to Annette, Judy, Rich Dodenhoff, Mary Vore and the rest of the Board of Publications Trustees for ably representing the society during the recent public discourse on reproducibility of scientific results. Working with directors at NIH and the leadership of other scientific journals, including our sister pharmacology societies, they directly addressed this critically important issue and developed a serious, realistic implementation plan for ASPET journals that should enhance the quality of work published in our journals and assure the public that their support of biomedical research is well placed.

Looking forward to the next year, I am delighted to tell you about some new initiatives and changes to ASPET operations that should improve your experience when engaging in society activities and increase our visibility within the US government and biomedical science community. First and foremost, the ASPET office has recruited two new staff members: Susanna Aguirre, as Manager of Government Affairs and Science Policy, and Carla Burns, as Program Coordinator. Susanna will be leading efforts to further develop our science policy and government affairs programs, including highly successful initiatives such as the ASPET Washington Fellows program begun by her predecessor Jim

September 2015 • The Pharmacologist

136 Bernstein, and to increase the visibility and impact of ASPET within the government organizations and associated enterprises that are critical to our membership and their scientific and educational activities. Carla will be a liaison to all of the society divisions and importantly will be providing staff support for our expanding educational and mentoring initiatives. In addition to these important personnel changes, following the recommendations of an Awards task force and with approval of Council, we are implementing a new electronic portal for submitting ASPET award nominations, as well as the submission of abstracts for presentation at EB and application for trainee travel awards. We expect that this will be a more user-friendly platform than what existed in the past, that it will help ensure that opportunities to apply are not missed, and that it will greatly facilitate the review process by ASPET members who provide that invaluable service to the society.

Council also voted to expand the eligibility for general travel awards to include undergraduates, beyond the limited number that attend EB as part of the SURF program. They join graduate students and postdoctoral fellows in what will now be a unified “Young Scientists” travel award competition. These trainees represent the very best and brightest young minds and must be encouraged to attend EB, where we can engage them in a variety of scientific, educational, and social activities, planting the seeds for a lifetime of membership in ASPET and a career in pharmacology. While the number of undergraduate awards planned for EB2016 will be relatively modest (approximately 25), this can be increased in future years if the expected demand is realized. As part of ongoing efforts to develop future leaders in pharmacology, we are pleased to announce a new Young Scientists Committee that will build on the wonderful momentum of the Graduate Student/Postdoc Colloquium at EB2015. This committee initiated and led by ASPET postdoctoral members, will provide greater visibility to the needs of these members and to their ideas for a more enriching experience that promotes, once again, a life-long career in pharmacology and association with ASPET. As briefly described above, it is my goal for the next year to expand and enhance the ways in which the society leadership can serve its membership. But I also call upon you to consider your involvement in the society and how you can support ASPET’s mission and its fiscal health. With this in mind, I want to encourage you to publish your most impactful and exciting research in the ASPET peer-reviewed journals – Molecular Pharmacology, Journal of Pharmacology and Experimental Therapeutics, Drug Metabolism and Disposition, Pharmacological Reviews and Pharmacology Research & Perspectives. There will always be pressure on you to publish in journals with the highest impact factors, but consider that by our collective action we can change that publication mindset and ensure that ASPET journals remain the ultimate source for transformative pharmacological research discoveries. There is an added benefit to the society: the revenue generated by subscriptions to our journals constitutes a critical source of funding for society operations. This revenue allows us to keep membership fees low, to enhance the quality of service provided to our members; and to nurture future members and leaders of our society and the discipline of pharmacology. Publishing in ASPET journals is in our best interest.

Finally, as my predecessors have said so eloquently in the past, the door to ASPET leadership is always open and I welcome your feedback and suggestions that can help us better serve you, the members, who are the heart and soul of our society.

With the very best regards,

Kenneth E. Thummel

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ASPET Annual Meeting at EB2016

Meeting Highlights The 2016 Annual Meeting of the American Society for Pharmacology and Experimental Therapeutics will be held in conjunction with the Experimental Biology 2016 meeting in San Diego. The meeting will be held at the San Diego Convention Center from April 2 – 6, 2016. ASPET’s program will include a wide variety of scientific symposia from invited speakers in addition to award lectures, division sessions, education and career development sessions, a student and postdoctoral poster competition, and numerous mixers and networking events.

The annual meeting can help you learn about the latest developments in your field to push your research forward. Not only will your participation help you gain scientific information, but it will also bring you in contact with others from your scientific community who can advise you on any research issues and

career concerns. Save the date to attend the ASPET Annual Meeting at EB2016. We look forward to your participation and abstract submissions.

Exciting Meeting Events • Presentation of scientific achievement awards and travel awards • Opening reception and celebration of award recipients • Keynote lectures by award winners • Student-Postdoc poster competition • Student-Postdoc mixer • Nightly division mixers • Early morning networking walk • Poolside closing reception • New! ASPET members lounge • The Shop ASPET store open in ASPET booth #1802

2016 Lecture Highlights

Jean Rossier, MD, PhD

Rita J. Valentino, PhD

Joan Heller Brown, PhD

Since 2012, Dr. Rossier has worked at Hôpital Sainte Anne in Paris on translational research on imaging the brain in action.

He will present the Julius Axelrod Award in Pharmacology Lecture: Therapies of Brain Diseases, Past, Present and Future.

Dr. Valentino is a professor and director of the Division for Stress Neurobiology in the Departments of Anesthesiology and Critical Care Medicine at Children’s Hospital of Philadelphia and the University of Pennsylvania. She will deliver the Ray Fuller Lecture in the Neurosciences: Sex Biased Stress Signaling.

Dr. Brown is a distinguished professor and chair of the Department of Pharmacology at the University of California, San Diego.

She will present a special Invited Lecture: RhoA in Focus: Pathways from GPCRs to Disease.

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The ASPET 2016 Annual Meeting Website The 2016 ASPET Annual Meeting website has a simple user-friendly interface and easy navigation customized for a rich, informative user experience. Visit the microsite at www.aspet.org/EB2016 to access information on the meeting program, abstracts, speakers, special events, sponsorship opportunities, and more!

Important Dates

Thursday, November 5, 2015..........Abstract Submission Deadline Tuesday, February 23, 2016.............Discounted Housing Deadline Tuesday, March 1, 2016.....................Discounted Registration Deadline April 2 – 6, 2016.................................EB2016 in San Diego Saturday, April 2, 2016......................ASPET Annual Business Meeting

ASPET Travel Awards to Experimental Biology Application Deadline: Friday, December 11, 2015 Undergraduate students, graduate students, and postdoctoral fellows are invited to apply for a travel award to help defray the costs of registration, travel, and housing to attend the ASPET Annual Meeting at EB2016. Travel awards are only open to ASPET members and you must also submit an abstract to EB2016 in an ASPET topic category by the EB deadline of November 5, 2015.

For more information and to apply for a travel award, please visit: www.aspet.org/awards/travel

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ASPET Best Presentation Awards Application Deadline: Monday, November 23, 2015 Best presentation awards are presented by ASPET’s divisions for abstracts that have been submitted by postdoctoral fellows, graduate students, and undergraduates attending the ASPET Annual Meeting at Experimental Biology 2016. These awards are only open to ASPET members and you must also submit an abstract to EB2016 in an ASPET topic category by the EB deadline of November 5, 2015.

Selected finalists may be asked to present their research at the best poster competition on Sunday evening, April 3, 2016 or at a division oral session.

For more information and to apply for a best presentation award, please visit: www.aspet.org/ awards/best-presentation/

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Preliminary Program For additional program details and highlights, visit: www.aspet.org/eb2016.

Lectures

Symposia

John J. Abel Award in Pharmacology Lecture Keynote to be announced in January

ASPET Presidential Symposium: Precision Medicine in Anti-Cancer Pharmacology Chairs: Kenneth Thummel and Susan Cole

Julius Axelrod Award in Pharmacology Lecture Therapies of Brain Diseases, Past, Present and Future Keynote: Jean Rossier Goodman and Gilman Award in Receptor Pharmacology Lecture Keynote to be announced in January Ray Fuller Lecture in the Neurosciences Sex Biased Stress Signaling Keynote: Rita J. Valentino Invited Lecture: RhoA in Focus: Pathways from GPCRs of Disease Keynote: Joan Heller Brown Bernard B. Brodie Award in Drug Metabolism Lecture Keynote to be announced in January P.B. Dews Lifetime Achievement Award for Research in Behavioral Pharmacology Lecture Keynote to be announced in January

Julius Axelrod Symposium: New Vistas on Drug and Gene Therapies of Cognitive Deficits in Down Syndrome, Autism, Leucodystrophies and Alzheimer’s Disease Chair: Jean Rossier ASPET Journal Symposium: Hear it from the Editors: Navigating the Course through Journal Submission and Publication Chairs: Mary Vore and Edward Morgan Ray Fuller Symposium: Sex Differences in Biology: Challenges and Opportunities for Drug Development Chair: Rita J. Valentino Undergraduate Research: Cultivating the Next Generation of Researchers through SURF and Beyond Chairs: Catherine Fry and Catherine Davis and Lauren Aleksunes

Paul M. Vanhoutte Distinguished Lectureship in Vascular Pharmacology Keynote to be announced in January

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Division for Behavioral Pharmacology Beyond Traditional Assessments of Pain: Implications for Drug Discovery of Novel Pain Therapeutics Chairs: Carol A. Paronis and Harshini Neelakantan Keep Calm and Target Peptides: Modulation of StressRelated Behaviors by Neuropeptide Systems Chairs: Stewart Clark and Valentina Sabino Nicotinic Agonist/Antagonist Drug Development: Implications for Treatment of Neurodegenerative and Addictive Disorders Chairs: Annette Fleckenstein and Maryka Quik Quantitative Pharmacological Analysis of In Vivo Data and its Implications in CNS Drug Discovery Chairs: Jun-Xu Li and Lisa Gerak

Division for Cardiovascular Pharmacology Invited Lecture: RhoA in Focus: Pathways from GPCRs to Disease (Joan Heller Brown) Symposium: GPCR and RhoA as Mediators of Disease Co-sponsored with the Division for Molecular Pharmacology Chairs: Rick Neubig and Shigeki Miyamoto Novel Platelet Therapies: Attacking Them from the Inside and Out Chair: Marvin T. Nieman Sex Differences in Cardiovascular and Renal Pharmacology Chairs: Sarah H. Lindsey and Eman Gohar Novel Targets for Treatment of Cardiometabolic Diseases Chairs: Jun Ren and Sreejayan Nair Cardiovascular Pharmacology Division Trainee Showcase Applications accepted through 11/23/2015. Abstract submission to EB2016 using the online ASPET Awards Portal is required.

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Division for Cancer Pharmacology Cancer Stem Cells as Pharmacological Targets Chairs: J. Silvio Gutkind and Tannishtha Reya Chronopharmacology in Cancer: Does Time Really Matter?

Chair: Shobhan Gaddameedhi Translating MicroRNA Cancer Biology to Therapy Chairs: Aiming Yu and Andreas G. Bader

Division for Drug Discovery and Development The Biology and Translational Potential of Hydrogen Sulfide: One Person’s Trash is Another Person’s Treasure Chairs: John L. Wallace and Andreas Papapetropoulos Emerging Roles for the Ubiquitin-Proteasome System in Therapeutics Chairs: Benita Sjogren and Henry L. Paulson Current Trends in Antibody Drug Conjugates: From Discovery to the Clinic Co-sponsored with the Division for Drug Metabolism Chairs: Tim Esbenshade and Larry C. Wienkers Role of Chemical Biology in Drug Design and Discovery Chairs: John S. Lazo and Craig Beeson

Division for Drug Metabolism Current Trends in Antibody Drug Conjugates: From Discovery to the Clinic Co-sponsored with the Division for Drug Discovery and Development Chairs: Tim Esbenshade and Larry C. Wienkers Dose Selection Using Physiologically Based Modeling Chair: Jan Wahlstrom Substrate Modulation of Organic Anion and Cation Transporters Chairs: Bruno Hagenbuch and Jed Lampe

141 Drugs of Abuse and Antiretrovirals: Interactions and Toxicities Chairs: Santosh Kumar and Kelly Jordan-Sciutto

Central Mechanisms Contributing to Novel Antidepressant Efficacy Chair: Dan Lodge

James Gillette Award and Platform Session Applications accepted through 11/23/2015. Abstract submission to EB2016 using the online ASPET Awards Portal is required.

Division for Neuropharmacology Postdoctoral Scientist Award Finalists Applications accepted through 11/23/2015. Abstract submission to EB2016 using the online ASPET Awards Portal is required.

Division for Molecular Pharmacology Invited Lecture: RhoA in Focus: Pathways from GPCRs to Disease (Joan Heller Brown) Symposium: GPCR and RhoA as Mediators of Disease Co-sponsored with the Division for Cardiovascular Pharmacology Chairs: Rick Neubig and Shigeki Miyamoto From Ligands to Signaling: Recent Advances in Adhesion GPCR Pharmacology and Biology Chairs: Xianhua Piao and Randy A. Hall Wnt Signaling: From Disease Mechanisms to Therapeutic Interventions Chairs: Reinoud Gosens and W. Matthijs Blankesteijn Intracellular GPCR and Lipid Signaling Chairs: Adriano Marchese and Alan Smrcka Abstract submission to EB2016 using the online ASPET Awards Portal is required.

Division for Molecular Pharmacology Postdoctoral Scientist Award Finalists Applications accepted through 11/23/2015. Abstract submission to EB2016 using the online ASPET Awards Portal is required.

Division for Neuropharmacology New Twists on Neurotransmitter Transport: Unraveling Novel Therapeutic Targets for Addiction and Psychiatric Disorders Chairs: Lynette C. Daws and Harald H. Sitte Cannabinoid Signaling in Pain and Addiction: Translating Preclinical Basic Research to the Clinic Chairs: Daniel Morgan and Josee Guindon

Division for Pharmacology Education Meet the New POPS – They’ll Flip Your Teaching Chairs: Mark A. Simmons and Robert Theobald A Pharmacokinetics Primer: From Equations to Application Chair: Reza Mehvar Teaching Institute: Developing Mentees Using IDPs Chair: Kelly Karpa Securing NIH Intramural Fellowships to Enhance Your Pharmacology Training Chairs: Janet Clark and Margarita Valencia

Division for Translational and Clinical Pharmacology Newly Recognized GPCRs in Health, Disease and as Therapeutic Targets Chairs: Ross Corriden and Paul A. Insel Drug Transporter Protein Quantification by LC-MS/ MS for In Vitro to In Vivo Extrapolation (IVIVE) and Prediction of Interindividual Variability of Transporter-Mediated Drug Disposition Chairs: Bhagwat Prasad and Yurong Lai Pharmacometabolomics Enabling Tools for Systems Pharmacology and Precision Medicine Chairs: Rima Kaddurah-Daouk and Richard Weinshilboum Young Investigator Awards Platform Session Applications accepted through 11/23/2015. Abstract submission to EB2016 using the online ASPET Awards Portal is required.

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Division for Toxicology Patient-Specific Stem Cells as Models for GeneDisease, Drug, and Environment Interactions Chair: Jason Richardson Advances in Toxicogenetics of Metals Chairs: Jonghan Kim and Timothy Maher Modulation of BSEP and MDR3 in Drug-Induced Liver Injury (DILI) Chairs: Kan He and David Rodrigues

Fortuitous Protein Modification in Disease Pathogenesis and Treatment Chair: Serrine Lau

Mentoring and Career Development Committee Graduate Student – Postdoctoral Colloquium Saturday, April 2, 2016, 2:45 pm – 5:15 pm

Give a Day of Service at EB2016 Sponsored by ASPET and the Academic Drug Discovery Consortium Thursday, April 7, 2016 8:00 am – 9:00 pm This one-day colloquium sponsored by ASPET and the Academic Drug Discovery Consortium will include a full day of lectures, platform sessions, case studies, panel discussions, and scientific posters. It will explore drug discovery in academia, in particular, biological therapies, small-molecule success stories, and rare and neglected diseases.

Poster presenters for the colloquium will be selected from those submitted to EB2016 by November 5 specifically to the colloquium topic category (#3061-ASPET).

This is a satellite meeting to EB2016. Registration will be separate from your EB badge. Visit www.aspet.org/EB2016/Drug_Discovery_ Colloquium/ for more details.

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Since 2009, attendees at the EB meeting have given a day of volunteer service in the local communities (Boston, New Orleans, Washington DC, and San Diego).

Volunteer activities have ranged from home construction, to painting, cleaning, stocking, food preparation, and service. ASPET will again sponsor a volunteer opportunity at EB2016 in San Diego. For the third time we will spend the day at St. Vincent de Paul Village, doing whatever we can to help the dedicated people at Father Joe’s Villages provide assistance to San Diegans. If you plan to join us, please contact Charles P. France at france@ uthscsa.edu or 210-567-6969 at your earliest convenience. Further details will follow to those who express an interest in volunteering.

See Ne y xt ou Yea r!

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2016 San Diego April 2 – 6

Abstract Deadline: Thursday, November 5, 2015

Annual Meetings of:

American Society for Investigative Pathology

American Society for Nutrition

American Society for Pharmacology and Experimental Therapeutics

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Sleepy Sickness, Oliver Sacks, and the Early Days of L-DOPA Rebecca J. Anderson, PhD

© Luigi Novi / Wikimedia Commons

Neurologist and writer Oliver Sacks (July 9, 1933 - August 30, 2015) at the 2009 Brooklyn Book Festival

As this issue of The Pharmacologist was going to press, Oliver Sacks, neurologist, author, and the subject of this article, passed away. Dr. Sacks died on August 30th, 2015 at his home in Manhattan. He was 82 years old.

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Even before HIPAA, clinicians always concealed the identity of patients described in their published reports and monographs to ensure patient privacy. But Oliver Sacks told tales so fascinating – and so fantastic – that a reviewer once wrote, “This is an amazing book, the more so since Sacks is talking about non-existent patients in a nonexistent hospital and a non-existent disease” (1).

Yet, the patients and hospital did exist. And so did the disease.

Like his fellow neurologists, Sacks cared for patients with Parkinson’s disease, and he had seen impressive results after administering L-DOPA. However, he published cases of a different sort. The “nonexistent” patients suffered from encephalitis lethargica, an increasingly rare disorder that caused

145 complex nervous system deficits, including severe Parkinsonian symptoms. Sacks claimed his patients responded intensely to L-DOPA but in unusual and unpredictable ways, including adverse reactions neurologists had never seen in patients with ordinary Parkinson’s disease.

Acute Encephalitis Lethargica In the winter of 1916–1917, a new illness suddenly appeared in Europe and subsequently spread to become a worldwide epidemic. The signs and symptoms were so varied that no two cases were exactly alike and were so strange that physicians initially ascribed various names to it: epidemic delirium, epidemic disseminated sclerosis, acute dementia, epidemic stupor, epidemic lethargic encephalitis, bulbar paralysis, hysteron-epilepsy, or just “an obscure disease with cerebral symptoms” (2).

Despite the variations from one patient to another, a “classic triad” of symptoms soon emerged: fever, somnolence, and eye signs. The abnormal eye signs took many forms, including double-vision, squint, ptosis, and pupil irregularities. The most characteristic sign was oculogyric crisis. Abruptly and without warning, the eyes would be forced downward, upward, or to either side, in a sudden involuntary attack. The patient’s gaze would be fixed in that direction for several minutes before switching to another direction. These oculogyric crises would recur weekly, monthly, or at irregular intervals.

Somnolence, from which the disease eventually took its name, differed from normal sleep. Although patients appeared to be asleep, they reported that they were aware of everything that was going on around them but could not rouse themselves. They would “fall asleep” while sitting or standing, and even while walking or during meals. Their breathing pattern simulated normal sleep, including snoring. But if they were aroused by calling or shaking, they immediately “woke up,” fully oriented and conscious (3).

The lethargy typically lasted from days to a few weeks. In some cases, it lasted for months, progressing to a deeper and sometimes comatose state from which recovery was unlikely (3).

In Vienna, Constantin von Economo meticulously documented these puzzling cases and autopsied the brains of the lethargic patients who died. The curious constellation of signs, symptoms, and postmortem pathology did not fit any previously established neurological disease. To distinguish it from other forms

In the Public Domain

Constantin von Economo (August 21, 1876 – October 21, 1931)

of encephalitis (such as meningitis, polio, or rabies), some physicians called it epidemic encephalitis.

Von Ecomono named it encephalitis lethargica, which became the official clinical designation, but the general public and lay press called it “the sleepy sickness” (not to be confused with sleeping sickness, the African parasite-born, endemic disease, trypanosomiasis).

Sleepy sickness was something of a misnomer.

Although most patients were lethargic, some paradoxically exhibited intense catatonic excitement and uncontrollable impulses (4). These patients were unable to sleep and showed ceaseless movement. In the worst cases, their frenzied state of mind and body led to total exhaustion, which proved fatal within 10 to 14 days (2).

In children especially, the main characteristic of encephalitis lethargica was a profound emotional instability. They showed impulsive, tic-like, hyperactive states, including abrupt changes in personality and sudden tantrums, rages, and destructive outbursts (2).

Respiratory tics (hiccups, yawning, dry cough, sneezing, etc.) and other respiratory anomalies (hyperventilation, sighing, breath-holding, noisy expiration, etc.) were also common in the acute phase of sleepy sickness (2, 5, 6).

The number, type, and sequence of symptoms varied widely. In fact, sleepy sickness patients September 2015 • The Pharmacologist

146 exhibited a “maze of contradictory phenomena almost impossible to read anything like a rational order of events” (4). Besides the symptoms already mentioned, sleepy sickness patients sometimes exhibited paralysis, chorea, convulsions, head and limb pain, giddiness, delirium, and mania (4). Altogether, von Economo enumerated more than 500 distinct forms or varieties of these (2).

The brain pathology was consistent with the clinical profile. Pathologists saw vascular congestion leading to thrombosis, infarction, and hemorrhage in all parts of the brain. The grey matter was primarily affected, largely in the pons, basal ganglia, midbrain, and most of all, the cranial nerve nuclei, especially cranial nerve III (3, 6).

Between 1917 and 1930, an estimated five million patients suffered from sleepy sickness Despite the limited technology of the 1920s, clinicians were convinced, based on their observations of thousands of patients, that sleepy sickness was caused by a virus (4, 6, 7). But, it was comparatively nonvirulent. Even in enclosed environments such as hospitals, asylums, military barracks, and within households, person-to-person transmission rarely occurred (3, 6). The era’s most talented researchers tried but could not isolate and identify the virus. Only recently have investigators obtained evidence suggesting that it belonged to the genus Enterovirus (9).

People from 10 to 35 years of age were most at risk (3, 6). Between 1917 and 1930, an estimated five million patients suffered from sleepy sickness, and 20-40% of them died, either from a coma that could not be reversed or from a hyperactive insomnia that could not be calmed by sedation (2, 3, 5, 6). However, the sleepy sickness epidemic was largely overshadowed by the chaos surrounding World War I and the concurrent influenza pandemic of 1919. Except for the physicians who were managing afflicted patients and the communities that were hardest hit, sleepy sickness received little notice.

The sleepy sickness epidemic ended in the late 1920s, and only a trickle of new cases have been reported since 1930 (9). Of those who survived the acute stage of sleepy sickness, some exhibited “residual troubles” that seemed to disappear over

The Pharmacologist • September 2015

time. Other patients continued to show clinical abnormalities, and some got worse (5).

Interestingly, some patients were not definitively diagnosed with encephalitis lethargica until months, years, or even decades later. In these cases, the initial “sleepy” symptoms were mild and dismissed as a minor complaint. About 30% of the patients who were diagnosed retrospectively had medical histories that contained no record of an initial illness resembling the symptoms of sleepy sickness (3).

Despite the baffling mixture, variability, or perhaps total absence of initial symptoms, the sequelae of sleepy sickness were unambiguous and permitted a definitive diagnosis (4, 6). Those characteristic sequelae also emerged, eventually, in the patients who had seemingly made a complete recovery from their initial sleepy sickness; after months or years of productive life, they became gravely disabled. As one physician commented in 1927, “The distressing result is that we never know when the patient is cured. (5).

Post-encephalitic Parkinsonism The clinical sequelae of sleepy sickness were called “post-encephalitic symptoms.” Post-encephalitic patients, as they came to be called, exhibited a progressive syndrome consisting of both neurological and psychiatric abnormalities. No other disorder has been shown to produce these symptoms in the same manner (3).

At the onset of this post-encephalitic stage, many patients exhibited movements that were unexpected, playful, and abnormally fast. This actually gave them a distinct advantage in sports requiring speed and agility (2). However, motor function slowly deteriorated to a Parkinsonian-like syndrome, which was the most common disability and was often called post-encephalitic Parkinsonism (5). Features typically included loss of automatic or synergistic movements, slight rigidity of all muscles, loss of equilibrium, and a running or shuffling gait (6). The face was especially affected, with a mask-like expression, slightly open mouth, staring eyes, infrequent blinking, and quivering eyelids (5).

However, the post-encephalitic syndrome was distinctly different from ordinary Parkinson’s disease.

Unlike the “pill-rolling” movement in ordinary Parkinsonian patients, the tremor of post-encephalitic patients was coarse (6). Their “explosive” bursts of involuntary movement were aggravated by emotional distress and largely disappeared during

147 sleep (2, 5). Other common features included greasy skin, excessive sweating, drooling, attacks of hyperventilation, and – occasionally – excessive weight gain (4).

Despite the onset of movement abnormalities, patients often continued to work, though with difficulty, for a considerable time. Gradually, movement and speech became slower and less animated.

Physical exertion and mental exercise aggravated the sensation of weakness, and ultimately the patients gave up the struggle, preferring to lie in bed or sit in a chair doing nothing. Rest did little to restore the patient, and insomnia was often a serious complication. The persistent fatigue was both physical and mental, and the worries of patients with family responsibilities contributed to feelings of depression, fearfulness, and irritability (5).

Many post-encephalitic patients spent years in state institutions and psychiatric hospitals, misdiagnosed as schizophrenic Almost as common as the movement disorders, and frequently co-existing with them, were a wide range of psychotic-like abnormalities. The psychotic attacks would last a few minutes or hours and then disappear as suddenly as they came (2). Like the motor weakness, the psychotic outbursts were greatly influenced by suggestion, emotional problems, and other external events. Many post-encephalitic patients spent years in state institutions and psychiatric hospitals, misdiagnosed as schizophrenic (2). But they were not schizophrenic. Nearly half of the postencephalitic patients suffered extraordinary crises consisting of simultaneous neurologic and psychiatric abnormalities: Parkinson-like movement, catatonia, tics, obsessions, and hallucinations, among many other things (2).

Some survivors of sleepy sickness – despite their movement abnormalities and other problems – led active and independent lives. But most of them developed catatonia, melancholia, immobility, frigidity, and apathy, a unique kind of “sleep” that would become characteristic of their clinical condition for many decades (2). They looked like living statues – totally motionless for hours, days, weeks, or years on end. Their symptoms drove them to isolation

and a timeless state, but they retained their higher brain functions of intelligence, memory, imagination, judgment, and humor (2).

A sudden event (such as fire alarms, dinner gongs, or the unexpected arrival of friends) might catch their attention and arouse them, momentarily, from their motionless, statuesque state. Shifts from immobility to motor activity were very characteristic of postencephalitic patients, but these flashes of mental alertness were rare (2). Mostly, their thoughts and feelings were fixed at the point in time when their long “sleep” had closed in on them. They could not react or relate. Their minds remained perfectly clear and unclouded, but it was as though their brains had been put on hold (1, 2).

Unable to work or care for themselves and difficult to look after, these patients were frequently abandoned by their families and friends. They were put away in chronic care hospitals, nursing homes, lunatic asylums, or special colonies. There they stayed, almost totally forgotten for decades, and there they died by the hundreds of thousands (2).

Autopsies showed brain abnormalities similar to patients with ordinary Parkinson’s disease (6).

Catastrophic damage to the substantia nigra was the hallmark of the post-encephalitic brain: an almost total loss of neurons and pigment and replacement by a pale glial scar (6, 8). There was also calcification and hyaline degeneration of the blood vessels, most notably in the corpus striatum (6). Neurofibrillary tangles were noted in the substantia nigra, coeruleus, hippocampus, parahippocampus, and amygdala (6). In some patients, the loss of grey matter extended to the spinal cord, particularly the anterior horns; the cortex was usually spared. And, in general, the white matter was spared (8).

After 1935, the medical literature on sleepy sickness came to an abrupt end. Few attending physicians took an academic interest in postencephalitic patients, and over time there were fewer of them to study (2). New cases rarely emerged, and the disease was all but forgotten. Consequently, the more profound forms of encephalitis lethargica and its long-term outcomes were not documented in medical journals (1, 2).

Renewed Interest During the 1920s and 1930s, hospitals around the world had been built or converted to accommodate and care for the influx of post-encephalitic patients.

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148 One of them was Beth Abraham Hospital, which opened in 1920 in the Bronx, New York (1).

When Oliver Sacks arrived in the fall of 1966, a year out of his neurology residency, Beth Abraham’s population of sleepy sickness survivors had dwindled to about 80 patients. Fortunately for Sacks, it was perhaps the largest such group remaining in the United States (1, 2). The post-encephalitic patients were scattered in various wards among the hospital’s 500 residents, who suffered from a variety of degenerative neurologic diseases, including motor neuron disease (ALS), syringomyelia, Charcot-MarieTooth disease, Parkinson’s disease, strokes, brain tumors, and senile dementia (1).

Sacks was well suited to the task before him: an unconventional physician who had always taken the road less traveled. When he was only 12, his schoolmaster had accurately predicted, “Sacks will go far, if he does not go too far” (1).

During his medical school training at Oxford University, he read the entire 12 volumes of his personal copy of the Oxford English Dictionary, along with first edition books by Johnson, Gibbon, Pope, and Darwin in the Queen’s College library. The newly minted physician moved to the United States in 1961, feeling that “there were too many Dr. Sackses in London” (1). (His parents, two brothers, an uncle, and three first cousins were all British physicians.)

Sacks completed his internship and neurology residency in California while also breaking the California state squat-weightlifting record (600 pounds). On weekends, he shed his white coat for black leather and rode his motorcycle to the Grand Canyon, 1,000 miles round-trip. On Monday mornings, he reported “bright and fresh” for neurology rounds (1).

In September 1965, Sacks moved to New York to begin his fellowship in neurochemistry and neuropathology at Albert Einstein College of Medicine. He aspired to be a “real” bench scientist, but he lacked the temperament and manual skills for laboratory work. His recreational drug use, begun during his residency in California, had ramped up to huge doses of amphetamines every day and, unable to sleep, huge doses of the hypnotic, chloral hydrate, every night (1). Laboratory mistakes were, perhaps, inevitable. His bosses pulled him aside and in the kindest manner possible advised, “Why don’t you go and see patients – you’ll do less harm” (1).

In October 1966, Sacks reported to Beth

The Pharmacologist • September 2015

Abraham Hospital, and indeed he “felt better,” not only because he enjoyed seeing patients but also because he had ended his self-administered drug experiments (1). Sacks was intrigued by the postencephalitic patients. They defied the prevailing view that neurologic and psychiatric disorders were distinct. He was also surprised that most of the post-encephalitic patients, although now in their 50s or 60s, looked half their actual age. Their consciousness had been suspended at the point when the disease locked and imprisoned parts of their brains, and somehow, their suspended animation had also suspended the aging process.

“It was my first encounter with disease of a depth I had never seen, read of, or heard of, before” (2).

He sifted through the patients’ original charts from the 1920s and 1930s to confirm that they were survivors of the sleepy sickness epidemic.

Chronically institutionalized, they were profoundly isolated, and many had no contact with anyone but the nursing staff (2). Sacks arranged to have the post-encephalitic patients moved into a single ward, hoping that this environment might foster a community atmosphere. Over the next few years, through intensive observation, Sacks got to know each of them not only as patients but as people (1).

L-DOPA Changes Everything Casimir Funk, a Polish chemist working in London, first synthesized L-3,4dihydroxyphenylalanine in 1912 (10). The amino acid was of interest as a probable precursor of epinephrine, but the name was unwieldy.

Bruno Bloch at the Basel County Hospital in In the Public Domain Switzerland coined DOPA, Casimir Funk (February 23, an acronym derived from 1884 – November 19, 1967) the chemical’s German name, Dioxyphenylalanin.

Scientists subsequently adopted Bloch’s acronym, despite its mildly scatological meaning in Polish (10).

In the 1950s, investigators found unusually rich concentrations of dopamine in the extrapyramidal system, especially the striatum, and Arvid Carlsson proposed that dopamine was involved with the

149 control of motor function (10, 11). In Montreal, André Barbeau showed that urinary excretion of dopamine was significantly lower in patients with Parkinson’s disease (12). In parallel in Vienna, Oleh Hornykiewicz and coworkers reported that patients who died of Parkinson’s disease had virtually no dopamine in the striatum and subnormal amounts in the substantia nigra and pallidum (13). The dopamine losses were more prominent in post-encephalitic patients than in patients with ordinary Parkinson’s disease (12, 13).

Dopamine replacement was a reasonable therapeutic strategy. Barbeau and Hornykiewicz, working independently but frequently communicating, conducted the first clinical trials in 1961. Because dopamine does not cross the blood-brain barrier, they administered L-DOPA, the active enantiomeric precursor of dopamine.

Barbeau reported that L-DOPA rapidly reduced the rigidity of Parkinson’s disease, but the effect lasted only three hours. Similarly, Hornykiewicz observed that L-DOPA reduced the akinesia of Parkinson’s disease in a dose-dependent manner (13). Soon afterward, many other centers conducted similar clinical trials and confirmed the ameliorative effect of L-DOPA (10, 13).

They looked like living statues— totally motionless for hours, days, weeks, or years on end Other agents had been used with limited success to treat Parkinson’s disease: anticholinergics, antihistamines, apomorphine, and amantadine. Those treatments had been discovered empirically, whereas the clinical introduction of L-DOPA represented a successful example of translational research. Basic research on the central and sympathetic nervous systems had led directly to L-DOPA, the first rational therapy for Parkinson’s disease (10).

Unfortunately, the pharmacologic effect of L-DOPA was short-lived, and follow-up clinical studies disputed its value as a therapeutic agent. At Brookhaven National Laboratory in New York, George Cotzias applied the ancient axiom, “if some is good, more is better.” He sought “to saturate (and keep saturating) the enzyme, DOPA decarboxylase, which generates dopamine from L-DOPA in the brain” (14). Cotzias escalated the daily dose of L-DOPA until he achieved a lasting response – at doses that were up to a thousand times larger than those previously used.

Other neurologists soon adopted Cotzias’s doseescalation procedure and confirmed his findings (10).

In the Public Domain

The L-dopa molecule

To suppress the gastrointestinal and cardiovascular effects of excess peripheral dopamine, L-DOPA is often combined with Carbidopa, a peripheral decarboxylase inhibitor. The L-DOPA/Carbidopa combination remains the standard of care and most effective treatment for ordinary Parkinson’s disease.

Cotzias published his findings in February 1967, and the impact was immediate (2). Patients who had been facing only misery and increasing Parkinsonian disability were suddenly given hope that they might be transformed by this new drug (1).

Awakening At Beth Abraham, Sacks read Cotzias’s paper and a half-dozen other clinical reports with great interest, but he hesitated giving L-DOPA to his patients. Their post-encephalitic syndromes were far more complex than ordinary Parkinson’s disease, and they had been institutionalized far longer. “I did not know what might happen” (2). Some of his patients had been violently impulsive and hyperkinetic in the early stages of their illness – before becoming enveloped in their Parkinson-like cocoon – and he worried that L-DOPA might unmask or exacerbate those psychomotor abnormalities (1, 2). He overcame his reluctance in the summer of 1968 when an especially fierce heat wave claimed the lives of some of his patients. “The need to do something became even clearer and stronger” (2).

Sacks and Beth Abraham Hospital applied to the Food and Drug Administration to use L-DOPA, which was still an experimental drug. In March 1969, he

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150 began a 90-day double-blind, placebo-controlled trial with six post-encephalitic patients. Within a few weeks, L-DOPA produced “clear and spectacular” responses, and he could infer from the precise 50% failure rate the three patients who had received placebo (1, 2).

With such convincing results, Sacks felt he could not justify continuing the clinical trial. He abandoned the placebo treatment and offered L-DOPA to any patient who wanted to try it (1). He also abandoned the 90-day limit of L-DOPA treatment. “This would have been like stopping the very air that they breathed” (2).

By contrast, the post-encephalitic patients exhibited a profound and rapid awakening. Once the dose escalation of L-DOPA reached a certain threshold, the patient snapped to life As Sacks expanded treatment through the summer of 1969, nearly all of his patients exhibited an astonishing, festive “awakening.” Suddenly, the ward of silent, stationary post-encephalitic patients was electric with excitement (2). After living for decades in a state of suspended memory, perception, and consciousness, the patients came back to life, fully conscious. Patients who had been mute for 40 years were talking. Patients who had spent their days motionless in their chairs now stood up and walked without effort. Their muscles functioned with full strength on their command – not the slow recovery so typical of a limb weakened by being immobilized in a plaster cast.

Most remarkably, their intellectual and emotional faculties returned, but in a sort of time-warp. They spoke of events and people from the time that their post-encephalitic symptoms had enclosed them, as if those people were still alive and those events had just happened. Even their colloquial speech and mannerisms reflected the 1920s and 1930s, but they were not disoriented or unaware of the intervening years. As one patient explained (after decades of silence), “I can give you the date of Pearl Harbor; I can give you the date of Kennedy’s assassination. I’ve registered it all – but none of it seems real. I know I’m 64, but I feel I’m 21” (2).

Sacks asked his patients to keep personal diaries.

Their entries confirmed that their higher brain functions had remained intact, but for decades they had been

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unable to connect with the world around them.

The FDA wanted Sacks to document these results on standard case report forms, but the responses to L-DOPA were so complex in both neurological and human terms that the standard forms “could not begin to accommodate the reality of what I was witnessing” (1). He kept detailed notes and started carrying a tape recorder, camera, and Super 8 movie camera “because I knew that what I was seeing might never be seen again” (1).

Some of the patients slept much of the day and were wide awake at night. That meant that he, too, needed to keep a 24-hour schedule. He volunteered to be the hospital’s “permanent” on-call physician for all 500 patients at Beth Abraham but spent much of his time in the post-encephalitic patient ward (1).

In addition, the hospital staff (neurologists, psychologists, social workers, physiotherapists, speech therapists, and music therapists) were in constant communication, talking to each other excitedly, phoning each other on weekends and at night, and discussing the unprecedented events unfolding before them (1, 2).

Virtually all patients with ordinary Parkinson’s disease show some sort of awakening when given L-DOPA. They improve gradually over days, reaching a plateau in about two weeks. By contrast, the postencephalitic patients exhibited a profound and rapid awakening. Once the dose escalation of L-DOPA reached a certain threshold, the patient snapped to life.

Patients with the severest disease awakened almost instantaneously (2). In addition, the post-encephalitic patients were much more sensitive to L-DOPA and were awakened with a fraction of the dose required for patients with ordinary Parkinson’s disease (2).

Patients with ordinary Parkinson’s disease are usually in excellent behavioral health, apart from their Parkinsonian symptoms, which may be mild. Their response to L-DOPA consists chiefly of a reduction or apparent abolition of the Parkinsonism. By contrast, the post-encephalitic patients suffered from a large number of disabilities. L-DOPA caused a profound reduction in both the Parkinsonian symptoms and the patients’ innumerable other problems, such as torsionspasms, involuntary writhing, chorea, tics, catatonia, depression, apathy, and torpor – some of which were not thought to be mediated by dopamine or amenable to L-DOPA (2).

L-DOPA also reversed the post-encephalic patients’ feelings of being cut off and withdrawn from the

151 world. They became intensely interested and amazed at everything around them as if they were children again or released from prison (2). In the words of one patient, “I feel so contented, like I’m at home at last after a long hard journey. Just as warm and peaceful as a cat by the fire” (2).

Unfortunately, the beneficial effects of L-DOPA, which had returned the post-encephalitic patients to near-normal mental and physical functioning, lasted only a few weeks or in some patients, only days. Then, things became much more complicated.

Tribulation

By August 1969, almost all of the post-encephalitic patients ran into trouble. Some developed an extreme sensitivity to L-DOPA, and Sacks had to severely cut back the dose. He stopped treating some patients completely, inserting a “drug holiday” for weeks or months, and then reintroduced L-DOPA. Some of these patients did better after the drug holiday, but others reacted differently – and adversely – to the drug each time he re-administered it. He tried carefully titrating the dose to optimize efficacy, without success.

“There seemed to be, with many patients, nothing between too much L-DOPA and too little” (1).

In addition, the patients’ responses grew more complicated, splitting into numerous and more bizarre abnormalities: new phenomena (chorea, tics), overexcitement (restlessness, mania), and fluctuations that rapidly developed into sudden and catastrophic oscillations (2).

Patients became increasingly excited, going from impatience and restlessness to a state of mania and frenzy. Then, they suddenly crashed into a deep depression – worse than their pre-DOPA state (2).

Once these oscillating episodes emerged, their severity could sometimes be softened by increasing L-DOPA, sometimes by decreasing L-DOPA, and sometimes by neither (2). Patients would shuttle between the “up” and “down” states almost instantly, spending less and less time in an “in-between” state. Sacks called these sudden oscillations a “yo-yo effect” (1).

Sacks was dismayed by the extreme sensitivity to L-DOPA, the sudden unpredictable responses, the rapid development of oscillations, and finally, the absolute impossibility of matching dose and effect (2).

“The ‘system’ now seemed to have a dynamic of its own” (2).

Despite the bizarre reactions caused by L-DOPA, stopping treatment was sometimes not an option.

Withdrawing the drug plunged some patients immediately into a stupor and life-threatening coma.

The drug caused disturbing effects, but without it, they would die.

These phenomena, in 1969, had not been seen by other clinicians. Patients with ordinary Parkinson’s disease typically showed a long period of therapeutic benefit with L-DOPA and the side effects, when they came, were usually mild. The post-encephalitic patients, on the other hand, appeared much more prone to early and severe adverse reactions (2).

Sacks knew he “had been given the rarest of opportunities; I knew that I had something important to say” (1). In September 1970, he sent a letter to JAMA, describing his observations in 60 patients who had been maintained on L-DOPA for a year (15).

Half were post-encephalitic patients and half had ordinary Parkinson’s disease. Nearly all of them had done well at first, but almost all of them, sooner or later, developed complex, sometimes bizarre, and unpredictable adverse reactions (1).

In December, several clinicians responded to Sacks in letters to JAMA. They had treated hundreds of Parkinsonian patients with L-DOPA and questioned his findings. One correspondent said that even if Sacks’s observations were real, he should not publish, because it would “negatively impact the atmosphere of optimism” that surrounded the introduction of L-DOPA (1).

Sacks had shaken conventional wisdom about the dose-response relationship. “The effects of L-DOPA should have been straightforward – but weren’t. They were straightforward at first and then something happened” (2). Convincing his colleagues would require more comprehensive evidence. He wrote a detailed clinical report – full of statistics, figures, tables, and graphs – and sent it to Brain, the oldest and most respected journal of neurology. The paper was rejected (1).

Sacks’s findings could not be easily conveyed in a medical journal report. Encephalitis lethargica was a complex disorder, and the post-encephalitic patients’ responses to L-DOPA were unpredictable and unreproducible. To describe the phenomena faithfully, Sacks turned to writing detailed, individual patient narratives. He compiled 20 of these case studies in a book, Awakenings, which was published in June 1973 (2).

The book was largely ignored by the medical community, but several documentary film producers

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Biosketch:

Rebecca J. Anderson holds a bachelor’s in chemistry from Coe College and earned her doctorate in pharmacology from Georgetown University. She has 25 years of experience in pharmaceutical research and development and now works as a technical writer. Her most recent book is Nevirapine and the Quest to End Pediatric AIDS. Email rebeccanderson@msn. com.

In the next issue of The Pharmacologist…

Dr. Anderson will tell us a story about the birth of modern cancer chemotherapy. Don’t miss the exciting December 2015 issue.

approached Sacks. He hesitated. A documentary would expose his patients’ identities, which he had diligently concealed in Awakenings. But when asked, they said, “Go ahead; film us. Let us speak for ourselves” (1).

In October 1973, a film crew from Yorkshire Television arrived at Beth Abraham to interview the patients. In moving descriptions, they looked back on their illness and described how they were now living their lives after having been cut off from the world for so many years (1). The filmmakers supplemented the interviews with some of Sacks’s Super 8 footage, showing the patients before treatment and their awakenings in 1969 after receiving L-DOPA. The documentary, also entitled Awakenings, was broadcast in England in 1974, the only documentary account of a forgotten epidemic and how the patients’ lives were transformed, for a while, by a new drug (1).

The Yorkshire documentary was subsequently shown at a psychiatry conference (1). Neurologists who had been skeptical of Sacks’s clinical observations saw, many for the first time, the dizzying array of bizarre reactions in postencephalitic patients who had received L-DOPA treatment (2).

After L-DOPA’s approval by the FDA in 1970, experience with the drug expanded to millions of patients, and a greater understanding of the complex responses to L-DOPA gradually emerged.

Sacks’s patients had been harbingers of the complicated pharmacological response induced by long-term L-DOPA administration. Despite the greater magnitude of the post-encephalitic patients’ reactions to L-DOPA, the breadth and types of those reactions – both short term and long term – were the same in patients with ordinary Parkinson’s disease (2). The adverse reactions simply took longer to develop and were usually milder in patients with ordinary Parkinson’s disease (1).

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The sudden oscillations, extraordinary “sensitization” to L-DOPA, and wide array of extrapyramidal effects were being reported by everyone. The yo-yo effect described by Sacks became a textbook sign of long-term L-DOPA therapy: the on/off phenomenon. Although dosing remains constant, patients rapidly fluctuate between an “off” state in which they receive no therapeutic benefit to being “on” in which they benefit from L-DOPA but may also exhibit disturbing motor abnormalities.

In 1977, Sacks partnered with P. C. Carolan to study the electrical brain activity of his post-encephalitic patients under a variety of conditions, with and without L-DOPA treatment (16). Untreated patients, during their trance-like state, generated EEGs with exceedingly slow and irregular brain activity, similar to patients who are in a stupor. After taking L-DOPA (or other anti-Parkinsonian drugs), their EEGs suddenly shifted to faster, better organized, and more rhythmical activity at the instant they become alert and animated. With continued drug use, as the patients became increasingly frenzied, the EEG showed repeated bursts of highvoltage paroxysmal activity (2).

Accommodation Some post-encephalitic patients never achieved a satisfactory therapeutic benefit and were forced either to cease taking L-DOPA altogether or, because of the possibility of a life-threatening coma, to accept a very miserable compromise.

They were maintained on a constant or periodic schedule of L-DOPA, tolerating tics and other dyskinesias as the price for a marginally alert and functional state (2).

Fortunately, some post-encephalitic patients, as well as the majority of patients with ordinary Parkinson’s disease, eventually achieved a satisfactory net benefit from L-DOPA. In these patients, L-DOPA efficacy gradually diminished, but the patients reached a sort of steady state.

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This stable response resulted from a compromise dosage that permitted a fairly satisfactory level of functioning, in between a full therapeutic response and serious adverse reactions. The patients were much better than their pre-DOPA state, but “they are no longer very well or very ill” (2).

Successful treatment of the post-encephalitic patients depended on comprehensive medical care, of which L-DOPA was only one component. They required adequate rest (12 hours or more) and needed to avoid stress. The therapeutic power of music allowed many of them an ease of movement that was not otherwise possible. Patients who were able to re-establish personal relationships enjoyed the best outcomes. Caring family members helped them restore a connection to the world around them (2).

With advancing age, the post-encephalitic patients developed a highly specific impairment in speech and motor function, but they retained their intellect, good humor, and interest in life (2). They survived “by being uncomplaining, undaunted, and finally laughing; not succumbing to nihilism or despair, but maintaining an inexplicable affirmation of life” (2).

After 1974, Sacks’s clinical interests broadened, but he continued to monitor his post-encephalitic patients at Beth Abraham and elsewhere. Perhaps no other physician had observed and cared for more post-encephalitic patients, nor observed the effects of L-DOPA for so long (2). In 1990, Columbia Pictures released a movie, also entitled Awakenings, starring Robin Williams as a fictional neurologist based on Sacks and Robert De Niro as one of his patients.

In 2008, Oliver Sacks was named Commander of the Order of the British Empire by Queen Elizabeth II. Although he gave up his motorcycle, he continued to swim daily and frequently trekked mountain trails. As Stephen Jay Gould wrote in a poem about his friend: “Oliver Sacks / Still lives life to the max” (1).

In addition to sleepy sickness, Sacks wrote compelling patient narratives on migraine, Tourette’s syndrome, hallucinations, autism, and other neurological conditions. But Awakenings remains his signature work. “I cannot think back on this time without profound emotion,” he said, “– it was the most significant and extraordinary in my life, no less than in the lives of our patients” (2).

References 1. Sacks O (2015) On the Move: A Life. Knopf, New York.

2. Sacks O (1990) Awakenings. Vintage, New York.

3. Foley P B (2009) Encephalitis lethargica and the influenza virus. II. The influenza pandemic of 1918/19 and encephalitis lethargica: epidemiology and symptoms. J Neural Transm 116(10):1295-1308.

4. McKenzie I (1927) Discussion on epidemic encephalitis. I. Epidemiological considerations. Brit Med J 2(3481):532-524.

5. Riddoch G (1927) Discussion on epidemic encephalitis. III. Chronic encephalitis. Brit Med J 2(3481):537-539.

6. Dourmashkin R R (1997) What caused the 1918-30 epidemic of encephalitis lethargica? J Royal Soc Med 90:515-520.

7. Greenfield J G (1927) Discussion on epidemic encephalitis.

II. The pathology of epidemic encephalitis. Brit Med J 2(3481):535-537.

8. Foley P B (2009) Encephalitis lethargica and the influenza virus. III. The influenza pandemic of 1918/19 and encephalitis lethargica: neuropathology and discussion. J Neural Transm 116(10):1309-1321.

9. Dourmashkin R R, Dunn G, Castano V, and McCall S A (2012) Evidence for an enterovirus as the cause of encephalitis lethargica. BMC Infect Dis 12:136.

10. Sourkes T L and Gauthier S (1983) Levodopa and dopamine agonists in the treatment of Parkinson’s disease, in Discoveries in Pharmacology: Psycho- and Neuro-pharmacology (Parnham MJ and Bruinvels J eds) pp 249-267, Elsevier, New York.

11. Carlsson A (1959) The occurrence, distribution and physiological role of catecholamines in the nervous system.

Pharmacol Rev 11:490-493.

12. Barbeau A, Murphy GF, and Sourkes TL (1961) Excretion of dopamine in diseases of basal ganglia. Science 133:1706-1707.

13. Hornykiewicz O (1966) Dopamine (3-hydroxytyramine) and brain function. Pharmacol Rev 18:925-964.

14. Cotzias GC (1969) Metabolic modification of some neurologic disorders. JAMA 210(7):1255-1262.

15. Sacks OW, Messeloff CR, and Schwartz WF (1970) Long-term effects of levodopa in the severely disabled patient. JAMA 213(13):2270.

16. Sacks OW and Carolan PC (1979) EEG findings in postencephalitic and Tourettic patients. Proc Annual Meeting, Metropolitan EEG Society, New York.

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Science Policy

It’s beginning to look a lot like…2013!

Despite efforts to return to “regular order” for FY2015, appropriators are once again facing the reality of having to rely on a “continuing resolution” (CR) to keep government agencies running this fall. When Congress returns from summer recess on September 8th, there will be just 3 ½ weeks and 12 legislative days to complete the appropriations process. This is even more unfortunate, given that it is the first time in six years that both chambers’ appropriations committees have approved all twelve spending bills. Despite the momentum generated from this progress, the full House has passed only six bills and the Senate has yet to bring any to the floor.

Now the priority has shifted to keeping the government from

another shutdown, with little chance of completing the appropriations process by October 1st. Congress will have to pass a short-term CR to keep the government running while they negotiate either a sequestration relief deal or the terms of a yearlong CR. Speaker Boehner, confronting the realities of the legislative calendar, has conceded that a CR is on the horizon to avert a government shutdown, saying, “It’s pretty clear, given the number of days we’re going to be here in September, that we’re going to need a CR of some kind.” How long that CR would run, or what form it will take is very much unclear.

Things are at a standstill on the Senate side as well, with Democrats promising to filibuster every spending bill in a bid to force negotiations over

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strict spending caps and Republicans refusing to come to the bargaining table. With at least a shortterm CR all but inevitable at the end of September, lawmakers will then be faced with one of two outcomes: an omnibus appropriations bill or yet another long-term CR. A successful CR will require the cooperation of Speaker Boehner’s caucus and many are weary as they recall the revolt in 2013 led by Senator Ted Cruz that foiled plans to pass a short-term, clean CR and resulted in a three-week government shutdown. House HAC Chairman Hal Rogers has insisted that he does not want a full year CR and reports indicate that leadership may be leaning toward a short-term CR that goes until December but no details have been released.

With at least a short-term CR all but inevitable at the end of September, lawmakers will then be faced with one of two outcomes: an omnibus appropriations bill or yet another long-term CR. The 2016 primary season will likely add an additional strain to the negotiations process as lawmakers typically move further left or right respectively; if a CR is extended into the election

year, hot-button issues are sure to be used as political footballs, further complicating the process.

A new budget agreement to lift the $1.017 trillion spending cap set under sequestration will be a critical first step for lawmakers. Some Democrats have suggested amenability to an agreement like the deal struck in 2013 by Rep. Paul Ryan (R-WI) and Sen. Patty Murray (D-WA) that eased sequestration for two years and set spending levels across the government. To that end, several Democratic lawmakers have been strategically pushing a variety of proposals and amendments in the markups with the intention of addressing them in future budget talks. Senator Jeff Merkley (D-OR), for example, recently offered an amendment that would have added $890 million to a $20.5 billion Agriculture and Food and Drug Administration (FDA) funding bill and said openly that the measure was intentionally structured to be part of a new budget deal. All of the proposals from Senate Democrats to increase funding explicitly say the money cannot be made available until a bipartisan budget act is signed into law.

While the current state of affairs may render them moot, the House and Senate approval of their respective FY2016 Labor, Health and Human Services (LHHS) spending bills cannot be overlooked:

House Appropriations Advances First Labor-HHS Funding Bill in Six Years In a 30-21 vote following a nearly seven hour markup, appropriators advanced a $153 billion bill funding Labor, HHS, Education and other related services (LHHS) for the next fiscal year. This marks the first time in six years the full committee has advanced a funding measure for these departments, which would receive $3.7 billion less than current funding levels and $14.6 billion less than President Obama’s request for FY2016.

However, the bill provides a total $31.2 billion for

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NIH; $1.1 billion above the FY2015 enacted level and $100 million above the President’s budget request. Additional HHS funding included $7 billion for the Centers for Disease Control and Prevention (CDC), up $140 million from FY2015.

Notable cuts in the measure included: • $7 billion in funding for the Center for Medicare and Medicaid Innovation • $100 million from the Patient-Centered Outcomes Research Institute (PCORI)

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The bill would also eliminate funding for the Agency for Healthcare Research and Quality (AHRQ), a $440 million unit that supports research designed to identify best clinical practices that improve patient quality and safety. Supporters of this measure have asserted that eliminating AHRQ would cut costs and allow for limited funds to go to areas with seemingly greater impact, like the National Institutes of Health, (set to receive a $1.1 billion increase). A motion by Representative Lucille Roybal-Allard (D-CA) to restore the funding failed by a voice vote.

Senate Appropriators Adopt LHHS Bill The Senate Appropriations Committee approved the LHHS bill by a vote of 16-14 with all Democrats opposed. NIH received $32 billion, an increase of $2 billion (5.6 percent) above FY2015 (and equal to FASEB’s recommendation, which ASPET supported). The $32 billion total meets the specific funding requests for the Precision Medicine and Combatting Antibiotic Resistance Initiatives outlined in the administration’s FY2016 NIH budget request and increases support for the Institutional Development Award program by nearly $27 million above the current funding level. Senate LHHS Subcommittee Chairman Roy Blunt (R-MO) noted that the $2 billion increase for NIH was the largest provided since 2003.

The proposed funding will support the following NIH initiatives: • $200 million for Precision Medicine • $350 million increase for the National Institute on Aging, the lead Institute researching Alzheimer’s disease • $135 million, an increase of $70 million, for the BRAIN Initiative to map the human brain • $461 million, an increase of $100 million, to Combat Antibiotic Resistance • $300 million, an increase of $26.7 million, for the Institutional Development Award There are several items of interest in the report language, including a significant expansion of data to be collected in the NIH’s existing database on research spending by disease and condition, and a provision requiring each Institute and Center

(I/C) Director to adopt a policy for reviewing and approving every grant that is funded.

The report also features statements on conflict of interest, research prioritization, reproducibility, young researchers, protection of human subjects and non-human primate research, as well as language criticizing NIH for requesting new initiatives each year without asking for proper longterm funding to support them. Additional language is included expressing support for the Maximizing Investigators Research Award (MIRA) and Capstone grant proposal. Finally, the Committee requested that the NIH FY2017 budget justification provide updates on dozens of initiatives and projects currently underway at the agency.

The $32 billion total meets the specific funding requests for the Precision Medicine and Combatting Antibiotic Resistance Initiatives outlined in the administration’s FY2016 NIH budget request and increases support for the Institutional Development Award program by nearly $27 million above the current funding level.

The report introduction states that “the Committee recommendation reflects the challenges inherent in achieving deficit reduction solely through reductions in discretionary spending.” It also notes that funding for biomedical research was a priority in the bill, including support for Alzheimer’s research and the precision medicine initiative in the FY2016 NIH budget request.

No Guarantees It’s not clear if the White House will agree to a continuing resolution with the priorities demanded

by House Republicans such as additional military spending and less domestic. Also unclear is the likelihood of Republicans considering a straight CR that simply continues all programs at their current

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levels. The GOP turmoil in the Senate, combined with the Democratic unity against appropriations bills and the division between House and Senate Republicans, makes a shutdown impossible to eliminate as an outcome. Budget Tracker has reported that Democrats will start negotiations by pushing for a two-year sequestration relief deal to get through the 2016 election. With GOP leaders showing little interest in early negotiations, they may be vying for a high stakes winter showdown to tackle spending and the debt ceiling together.

Debt Ceiling While the fiscal focus right now is on a deal to replace sequestration and keep the government running, Congress will have to face the debt ceiling early in the fiscal year. All indications point toward a messy battle as we can surely expect Republicans to make demands for concessions on the debt ceiling and President Obama and Democrats to hold firm on refusal to negotiate raising the limit. This will be pivotal for the GOP as it will mark Republicans’ first reckoning with the debt limit since they took full control of Congress.

The GOP turmoil in the Senate, combined with the Democratic unity against appropriations bills and the division between House and Senate Republicans, makes a shutdown impossible to eliminate as an outcome.

On March 16th, the government hit the current borrowing limit of $18.1 trillion and the Treasury Department has been forced to use so-called “extraordinary measures” (essentially moving money between accounts) to allow the government to continue operating without going into default. This is only a short-term solution; the agency has not provided a hard deadline by which Congress must act. Budget forecasters have suggested that unless Congress acts to raise the $18.1 trillion debt limit, the Treasury could run short of funds for the first time to pay obligations by November or December.

House Passes 21st Century Cures Legislation Despite roadblocks in the appropriations process, House Energy and Commerce Committee Chairman Fred Upton (R-MI) and ranking member Diana DeGette (D-CO) achieved a major victory with the passage of the 21st Century Cures Act (HR 6) by an overwhelmingly bipartisan vote of 34477. The legislation, which ASPET has supported since its introduction last year, authorizes funding increases for NIH of $1.5 billion annually over three years. It also establishes a new “NIH Innovation Fund” to provide $8.75 billion in mandatory funding ($1.75 billion per year) for biomedical research from FY2016 to FY2020. The additional

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money from the Innovation Fund is intended to supplement regular NIH appropriations.

Another key provision would allow the FDA to grant early market approval to a drug with breakthrough designation based on its early-stage testing for safety and effectiveness. Medicaldevice makers would also be able to apply for breakthrough designation for products that treat conditions where no alternative exists or that significantly improve on approved therapies.

Passage of the bill came after a coalition of research advocacy groups, including ASPET, engaged in an aggressive campaign that

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defeated an amendment from Representative David Brat (R-VA) and four of his colleagues.

The Brat amendment proposed shifting the NIH Innovation Fund from mandatory to discretionary funding. This would place further pressure on the discretionary budget and jeopardize the chances NIH would ever receive the additional money

because appropriators would still be limited by the Budget Control Act (BCA) caps. ASPET joined FASEB in the advocacy effort and sent a letter to all members of the House urging them to vote “no” on the Brat amendment.

Now attention shifts to passage in the Senate; stay tuned to ASPET for updates in this space.

Looking Ahead Back in July, the White House Office of Science and Technology Policy (OSTP) Director John Holdren, PhD, sent a memo to all federal departments outlining the science and technology priorities for the Administration’s last budget cycle. The OSTP, in partnership with the Office of Management and Budget (OMB), advises the President on the Federal Research and Development (R&D) budget and shaping R&D priorities across those federal agencies that have significant portfolios in science and technology, as well as the coordination of interagency research initiatives. The OSTP is charged with assisting in the development and implementation of sound

science and technology policies that reflect Administration priorities toward important national policy goals.

The memo encourages agencies to focus on investments in the life sciences and to prioritize programs that support fundamental biological discovery research that could generate unexpected, high-impact scientific and technological advances in health, energy, and food security. Other priority areas mentioned in the OSTP memo include “improving interoperability of health records, addressing privacy concerns, and launching research that will enable discoveries derived from Big Data.”

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Education News 2015 AAMC-CFAS Meeting in Review The Association of American Medical Colleges Council of Faculty and Academic Societies (AAMCCFAS) was established to facilitate communication and engagement between the AAMC and medical school faculty and member academic societies. CFAS meetings allow faculty representatives to identify, communicate, and advise the AAMC on critical issues facing medical schools and academic societies and to educate faculty representatives on ways to affect change at their institutions to help strengthen the core missions of academic medicine.

Joe Blumer (Medical University of South Carolina) represented ASPET at the Spring 2015 AAMC-CFAS meeting held in San Diego March 5-7, 2015. Nearly 200 of 366 total AAMC-CFAS representatives of 70 academic societies and 140 medical schools and teaching hospitals attended, including fellow pharmacologists Kurt Varner (LSUHSC), Gary Rankin (Marshall University), Kent Vrana (Penn State) and Amy Wilson-Delfosse (Case Western). Discussion topics and programming were diverse, but emphasis was placed on faculty resiliency, the evolution and future of medical education, the economics of academic medicine, NIH funding of biomedical research, the life cycle of faculty members, and career development.

The first plenary session addressed the issue of faculty burnout and resiliency in academic medical centers (AMCs). Burnout is typically defined by prolonged, work-related stress resulting in a loss of physical, emotional, and mental energy. Kimberly Gerhart (University of Arizona) pointed out that such work-related stress can lead to detachment, loss of satisfaction and sense of accomplishment, and ineffective teaching. A potential solution is to change the culture of academic medicine to improve

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lifestyles among faculty with reduced stress and decreased demands on time.

Participants also discussed the current duration of medical education, not only with respect to curriculum consolidation but also in regard to student debt.

A plenary session on the future of medical education introduced several important transformations currently affecting medical education.

Amy Wilson-Delfosse (Case Western) addressed the role of basic science in undergraduate medical education, including: the value of basic science in helping physicians make nonroutine, difficult decisions for patients; that understanding the molecular mechanisms of diseases and drug action is one of the primary factors that distinguishes physicians from other health care professionals; and that a strong basic science background provides value for the safest care of patients. Dr. Wilson-Delfosse pointed out that instead of overwhelming students with information, educators should focus on helping students find and evaluate data and to teach those basic sciences that allow future clinicians to justify medical decisions. Instead of remaining in silos, Dr. Wilson-Delfosse encouraged discussions between basic science and clinical faculty to identify which basic science material is most appropriate to allow future clinicians to interpret clinical findings. To this end, the common Flexnerian approach to medical education, which separates learning basic science and

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clinical medicine, is being revised at many schools to include earlier exposure to clinical care and later exposure to basic science. Case Western, for example, is implementing a small-group, case-based approach to integrate basic science into the third and fourth (clinical) years of medical school. Participants also discussed the current duration of medical education, not only with respect to curriculum consolidation but also in regard to student debt. One possibility piloted at other institutions includes combining the fourth year of medical school with the first year of residency.

Another approach consolidates the first two years into 12–15 months.

With respect to the political climate and the future of governmental support for biomedical research, the AAMC leadership, including AAMC President Darrell Kirch and AAMC Chief Public Policy Officer Atul Grover, stressed the importance of research literacy among the public and political leaders, with a need for a positive public image of research, NIH funding, and biomedical science. Biomedical science should not be regarded as a “fee for service,” a view held by some in Congress that once money is given, some type of tangible “deliverable” is expected at the end of the funding period. Rather, research funding should be seen as an investment in foundational discoveries that provide a platform for future breakthroughs, and as scientists we should engage in a dialogue with the public (including public servants) about the process and nature of discovery, including the role of NIH funding. Claire Pomroy, president of the Lasker Foundation, stressed that academic medicine and research are a powerful and important public good, and that academic medicine must work with the public as partners to make the greatest impact on the patients and public we serve.

Dr. Lawrence Tabak, principal deputy director of the NIH, discussed the role of the NIH in funding AMCs. He stated that the NIH has had a “contract” with AMCs for many years of funding applications based on scientific merit, providing a significant amount of money to offset faculty salaries with limited expectations for how AMCs use nonindividual research project grant funds to support infrastructure.

He then posed several questions. Should the NIH continue this current model, or should it broaden its distribution to investigators and/or institutions?

Should the NIH and AMC community renegotiate

this “contract” to help catalyze right-sizing of the biomedical research force? Dr. Tabak said that the NIH should optimize funding policies and mechanisms to enhance longer-term stability for researchers, including the areas of salary support, award length, and the number of grants per investigator and/or institution (e.g., the new MIRA/R35 mechanism offered

by NIGMS). In addition, there should be a realignment of NIH funding to core facilities to maximize efficiency and research output, incentivizing the hiring of new tenure-track faculty and perhaps creating an “emeritus award” for investigators making the transition to the next phase of their careers.

A breakout session was held to discuss NIH funding of biomedical research and how to address the current funding crisis. Participants discussed the recent FASEB report “Sustaining Discovery in Biological and Biomedical Sciences” (www.faseb. org/Portals/2/PDFs/opa/2015/Sustaining%20 Discovery%20Report%20Final.pdf) regarding possible solutions for current funding issues. Discussion topics included strategies for maintaining support for current programs, facilitating early career PIs in critical transitions, and educating policy makers and the public regarding the benefits of basic science research (the phrase “discovery science” was proposed as an alternative descriptor). In addition to the topics mentioned above, AAMC-CFAS seeks to address the changing roles and responsibilities of faculty at AMCs and the different models that AMCs are adopting as part of these changes. These points and others will be discussion topics at upcoming meetings, and AAMC-CFAS is encouraging more communication between faculty and the AAMC, including more small-group interaction, so that more voices are heard during these meetings. As one of your AAMC-CFAS representatives, I welcome any comments and suggestions you may have (blumerjb@ musc.edu).

Joe Blumer Medical University of South Carolina

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Postdoc Member Survey Suggests Strategies for Supporting Young Scientists Recent national reports on the status and career outcomes of postdoctoral researchers have highlighted a number of issues with the current training paradigms for young scientists.

Over the past 15 years, there have been dramatic increases in both the number of individuals pursuing postdoctoral training and the cumulative time spent as a trainee. While these issues affect all scientists, they disproportionately impact life scientists, who compose 65% of those serving in postdoctoral positions. As the number of postdoctoral life scientists continues to expand, career trajectories are rapidly shifting away from the historical trend of obtaining independent research or faculty positions. Approximately one-third of life sciences Ph.D. recipients ultimately move into jobs unrelated to research.2 Those who do obtain academic positions face a rapidly declining number of tenuretrack opportunities and are more likely to serve in contingent or adjunct roles with little job security.

Other commonly cited concerns include low and stagnant wages for postdoctoral researchers and an increasing reliance on external funding to support trainees.1 Despite the expanding numbers of postdocs, surprisingly little is known about them. Their titles, responsibilities, and compensation levels can vary widely across institutions. At many institutions, they lack adequate mentoring, recognition, and benefits.1 In general, their career outcomes are not tracked in the same manner as graduate students, if they are tracked at all. Owing to the wide variation in their job titles, employment status, and funding mechanisms, there are currently only rough estimates of the number of postdocs in the U.S. In a recent report, the National Academy of Sciences issued a call to action that encouraged professional societies to contribute to what is known about postdoctoral researchers.1 In light of this recommendation, ASPET invited its

postdoctoral members to take a survey in June and July 2015. The response rate for the survey was 24% (56 out of 234 active postdoctoral members). What follows are some highlights of the findings. We hope that the survey data will allow us to better support our own postdoctoral members while contributing to the knowledge base about this crucial group of young scientists.

1 National Academy of Sciences (2014) The postdoctoral experience revisited. Committee to Review the State of Postdoctoral Experience in Scientists and Engineers; Committee on Science, Engineering, and Public Policy, Policy and Global Affairs, National Academy of Sciences, National Academy of Engineering, Institute of Medicine. The National Academies Press, Washington, DC. 2 National Institutes of Health (2012) Biomedical research workforce working group report. Bethesda, MD.

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The majority of respondents are serving as postdocs at academic institutions, although employers reflect a range of organizations, including the pharmaceutical industry, federal agencies, and hospitals.

While most respondents are called “postdoctoral fellows” by their employers, some diversity in job titles is apparent, mirroring that found by national reports.

Respondents to the survey were mainly new postdocs, with one or two years spent in postdoctoral positions.

When asked if they participate in the leadership of any ASPET divisions or committees, the large majority of respondents said “no.” Free-response comments suggested that this is mainly due to either a lack of opportunities or a lack of awareness about possible service. Notably, nearly one-third of the respondents indicated that they were seeking nonresearch positions, which parallels national data on career trajectories.2 Leadership opportunities such as service on committees may be even more desirable to those who are building nonacademic resumes.

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To What Extent Would the Following Contribute to Your Professional Development? not at all

somewhat

a moderate amount

a substantial amount

not sure or no opinion

Career fair at the Annual Meeting

7% 4

14% 8

36% 20

43% 24

0% 0

Availability of statistics about salaries within your discipline

5% 3

34% 19

25% 14

36% 20

0% 0

Availability of statistics about career paths within your discipline

4% 2

13% 7

30% 17

52% 29

2% 1

Availability of information about job market trends within your discipline

0% 0

16% 9

34% 19

48% 27

2% 1

Availability of mentors outside your institution/organization

0% 0

9% 5

20% 11

66% 37

5% 3

Greater opportunities to speak and/ or organize events at conferences

0% 0

9% 5

34% 19

50% 28

7% 4

Respondents were asked to rate the usefulness of a variety of professional development activities.

While all were seen as potentially useful, increased access to mentors was identified as a significant need.

Free-response comments also suggested workshops on grant writing, CV writing, conflict resolution, salary negotiation, and interview skills.

The views expressed in the survey largely mirror those from a recent symposium called the Future of Research, organized by and for postdoctoral scientists on the future of the biomedical research enterprise. Symposium participants called for greater transparency about postdoc outcomes, improved advocacy and connectivity, and suggested strategies for incentivizing effective mentoring.3 Through member-led initiatives, ASPET is beginning to address some of these issues. The BIG IDEA project “From senior mentor to highly skilled career coach: A novel approach to breaking the diversity roadblock” will match mid- to late-career scientists with cohorts of junior scientists to guide them in their career development. The newly established Young Scientists committee aims to provide and increase postdoc

3

representation in existing ASPET committees and to enhance the trainee experience at the ASPET Annual Meeting at EB. Survey respondents suggested a variety of ways to better integrate them at the ASPET Annual Meeting, and these will be shared with the Young Scientists committee as well as with other relevant committees (e.g., the Mentoring and Career Development committee). We thank those who shared their views in the survey, and look forward to expanding ASPET’s role in developing the talent of our postdoctoral members.

McDowell GS, Gunsalus KTW, MacKellar DC, et al. (2015) Shaping the future of research: a perspective from junior scientists. F1000Research, 3:291.

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Update on the BIG IDEAS I Initiative Pharmacology Industry Internships for PhD Students (PIIPS) Submitted by ASPET members Kathryn Meier, Joan Heller Brown, Mike Jarvis, Jim Barrett, Jeff Herz, and Jeff Jasper, with advice from Glenn Prestwich

In 2014, ASPET announced its BIG IDEAS initiative, a unique opportunity for members to propose a project that would directly benefit ASPET’s membership. The three projects selected for the initial round of funding are now in development, and each one addresses an educational need that will ultimately serve the broader community of ASPET members as well as the discipline of pharmacology. What follows are brief highlights of the current status of each of the projects.

Enhancing Undergraduate Engagement in ASPET at EB Meetings Submitted by Carol L. Beck, Catherine M. Davis, and the Division for Pharmacology Education

The goal of this project is to increase undergraduate engagement in ASPET in general, and specifically at the ASPET Annual Meeting at Experimental Biology.

ASPET is now working to add new undergraduate travel and best presentation awards to its offerings, and an undergraduate networking luncheon is under development for EB2016.

This program provides a unique funding opportunity for PhD students to obtain internship experiences in industrial settings by encouraging partnerships between academia and industry. A PIIPS steering committee has been established and has been working on developing the program guidelines, application process, review criteria, and other program details. The launch of the program is anticipated later this year.

From Senior Mentor to Highly Skilled Career Coach: A Novel Approach to Breaking the Diversity Roadblock Submitted by Lynn Wecker, the Mentoring and Career Development Committee, and the Division for Pharmacology Education

The ASPET Mentoring Network proposed by this project follows a mentoring model that will match mid- to late-career scientists with cohorts of young scientists to help guide them in their development and career advancement. The first year-long cohort will begin during EB2016 with in-person activities and be followed by virtual interactions throughout the year.

The Mentoring and Career Development Committee is currently working to finalize the first group of coaches and is developing the application process for mentees.

They are also working with ASPET staff to plan related events at EB2016.

ASPET Big Ideas II Initiative After the tremendous success of the BIG IDEAS I initiative, the ASPET council announced the second cycle of the initiative at the annual business meeting in March 2015. Once again, we are asking members to put forward their best ideas for projects. Submit your initial proposal to Judy Siuciak at jsiuciak@aspet.org no later than Monday, September 28, 2015. For more information, visit: www.aspet.org/ASPET_Big_Ideas_II/

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Journal News New DMD Editorial Advisory Board Member Dr. Donald Mercante, Emory University School of Medicine, joined the Drug Metabolism and Disposition Editorial Advisory Board in June. Dr. Eddie Morgan and the other members of ASPET’s Board of Publications Trustees welcome him to the journal and are grateful for his service.

Image Forensics Added to ASPET’s Journals Since July 20, 2015, figures in manuscripts considered for acceptance in ASPET’s four wholly owned journals have been examined for evidence of manipulation. Although certain modifications of primary data are often needed for clarity and/or brevity, image manipulation for deceptive purposes, to unfairly enhance or eliminate or otherwise obscure data, are grounds for rejection and may constitute misconduct. Inappropriate image manipulation will result in rejection of the manuscript. Suspected misconduct may be reported to the authors’ institution(s) and funder(s).

Revised figures submitted after acceptance also undergo image forensics.

The section on figures in each journal’s Instructions to Authors provides information about image manipulation. Authors should carefully read and follow these requirements prior to submission. The Office of Research Integrity’s “Guidelines for Best Practices in Image Processing” at 1.usa.gov/1EyhKVe provides additional information.

The implementation of image forensics supports ASPET’s commitment to high standards of scientific rigor and the Society’s support for the National Institutes of Health Principles and Guidelines for Reporting Preclinical Research (see 1.usa. gov/1x8pOe9). That support was first expressed in an announcement from ASPET’s Board of Publications

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Trustees published in the July issue of each of the Society’s four wholly owned journals and in the last issue of The Pharmacologist.

Author Beware…

From time to time, concerned members notify the ASPET journals department that they have been solicited to submit to a new publication with a name similar to one of ASPET’s journals. They are typically author-fee-based open-access online-only predatory journals from little known publishers. In some cases, a predatory journal simply copies the name of an established, reputable journal. Predatory publishers and their journals have been the topic of multiple posts on The Scholarly Kitchen blog from the Society for Scholarly Publishing (scholarlykitchen.sspnet.org/), articles in The Chronicle of Higher Education, and commentaries in Nature, Science, BMJ, and other research journals.

ASPET staff members have been asked what we can do to stop these journals. Unfortunately, the answer is nothing. Journal titles cannot be copyrighted, and trademark protection applies only to the graphic presentation of a title and not the words (think of the consequences of trademarking “science,” “nature,” and “cell”). There are legitimate, well regarded journals with titles similar to ASPET’s, some of which have been published for many years.

What we can do is educate authors. Although this problem has been around for a few years, authors continue to be tricked into submitting to these journals not infrequently. The burden lies on authors (and readers) to discern legitimate journals from the rest.

Check before submitting!

A useful resource is Beall’s List: Potential, possible, or probably predatory scholarly open-access publishers available at scholarlyoa.com/publishers/ that is compiled and maintained by Jeffrey Beall, a librarian at the University of Colorado Denver. In addition, there are signs to look for:

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•D oes the journal have an editor and an editorial board, and do you recognize any of the people on the board? A journal with a title similar to JPET’s was recently brought to our attention. It has no editor and no editorial board but is gladly accepting submissions. If you know anyone on the editorial board, contact that person to ask about the journal. Predatory journals have been known to list respected researchers on their boards without those researchers even knowing they are listed. This is a case when Googling your name isn’t necessarily an exercise in vanity – are you on an editorial board without your knowledge?

• I s the journal indexed? MEDLINE/PubMed and Thompson Reuters thoroughly screen the journals they index. It can take years for a new journal to be included, so also check PubMed Central if the title is not indexed by PubMed or Web of Science. PMC screens journals but adds new titles faster than the others (our own Pharmacology Research & Perspectives is a case in point).

• L ast, who is the publisher? New, legitimate publishing companies do come into being. If it is a name you do not recognize, Google it to find out more. I enjoy looking at the “contact us” page of predatory publishers.

One lists 16 contact people, 5 of whom share the same telephone extension. That seems a little odd. Some have a full name, some have no last name, some only an initial – not something you would expect from a legitimate company. Digging into the publisher’s and the journal’s website can be informative.

If things were not bad enough with predatory journals, some of the people who produce them are moving into predatory conferences. One lists a “World Congress of Pharmacology” alternatively

called “Pharmacology 2015” – conference names used by IUPHAR and the British Pharmacological Society, respectively. Potential submitters and registrants beware!

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Membership News Dr. E. Leong Way Celebrates 100th Birthday Dr. E. Leong Way, known as “Eddie” to those who love and work with him, celebrated his 100th birthday in San Francisco on July 9, 2015. Many former students, postdocs, faculty from the Department of Pharmacology in the UCSF School of Medicine, colleagues, and friends from around the United Professional Event Photography by States came to help Eddie Frank Jang Dr. E. Leong Way celebrate by holding a Chinese banquet. Friends included his current golf partners and his ballroom dancing partners! Dr. E. L. Way was President of ASPET in 1976, and received the 1992 Torald Sollman Award in Pharmacology. He was also awarded the 1979 Nathan B. Eddy Memorial

Award for outstanding research in drug dependency.

Honored by both the East and the West, in 1978 he received the Gold Medal and Cultural Citation from the Ministry of Education in China.

Professional Event Photography by Frank Jang

Eddie with faculty and staff

ASPET Commemorates the Following Members for Their 50 Years with the Society Thomas C. Westfall, PhD Richard H. Adamson, PhD Thomas R. Tephly, MD, PhD Harold H. Wolf, PhD Jane H. Chin, PhD Marvin E. Rosenthale, PhD Frederick F. Cowan, PhD Donald C. Kvam, PhD Lincoln T. Potter, MD Joseph R. Davis, MD, PhD Salvatore J. Mule, PhD Alan C. Sartorelli, PhD Larry Stein, PhD

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Herbert Weissbach, PhD Roger A. Yeary, DVM Peter K. Gessner, PhD Oakley S. Ray, PhD Joseph R. Bertino, MD Jay N. Cohn, MD Stanley Deutsch, MD, PhD Edwin I. Goldenthal, PhD Plinio Prioreschi, MD, PhD Abel M. Dominguez, PhD Angelo R. Furgiuele, PhD Karl L. Gabriel, PhD, VMD Velayudhan Nair, PhD, DSc

Arnold Schwartz, PhD Philip A. Khairallah, MD Franklin J. Rosenberg, PhD Philip F. Hirsch, PhD I. A. Michaelson, PhD Jiro Nakano, MD, PhD Arthur J. Weiss, MD Joseph H. Gans, PhD, VMD Thomas C. Hall, MD Melville W. Osborne, PhD Herbert Wells, DMD Stanley E. Gitlow, MD Arthur Jeske, PhD

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A Tribute to Dr. Frances Kathleen Oldham (1914-2015) Dr. Frances Oldham Kelsey, the physician and pharmacologist who played a critical role in preventing the distribution of the drug thalidomide in the US, passed away on August 7th, 2015 at 101 years of age.

Dr. Kelsey was a member of ASPET since 1942.

Dr. Kelsey was born in British Columbia in 1914. She received her BSc in 1934 and MSc in 1935 from McGill University. She subsequently moved to the United States to the University of Chicago, earning her PhD in pharmacology in 1938 and her MD in 1950. While in graduate school, Kelsey participated in studies identifying diethylene glycol as the toxic agent in the elixir of sulfanilamide that killed 107 people in 1937.

She taught at both the University of Chicago and the University of South Dakota and also practiced medicine in Vermillion, South Dakota.

In 1960, she took a position as medical officer at the Food and Drug Administration and moved to Washington, DC. She later became chief of the Division of New Drugs, director of the Division of Scientific Investigations, and deputy for Scientific and Medical Affairs, Office of Compliance. She remained at the FDA until her retirement at the age of 90.

Dr. Kelsey’s first assignment at the FDA was to review an application for the use of thalidomide, which had already been used throughout Europe and Great Britain as an anti-nausea drug to treat morning sickness. After noting a number of concerns with the application, she requested additional information and ultimately blocked approval of the drug in the United States. However, by late 1961, evidence was growing that thalidomide was causing serious birth defects in other parts of the world. Thalidomide was taken off the market in 1962, but not before approximately 10,000 children had been impacted.

On August 7, 1962, President John F. Kennedy awarded Frances Kelsey the highest honor given to a

civilian in the United States, the President’s Award for Distinguished Federal Civilian Service. She was the second woman to ever receive the award. In 2010, the FDA established a Dr. Frances O. Kelsey Award for Excellence and Courage in Protecting Public Health, which is given annually to an FDA staff member.

More information about Dr. Frances Oldham Kelsey can be found here in an article about her published in Molecular Interventions.

Frances Kathleen Oldham Kelsey received the President’s Award for Distinguished Federal Civilian Service from President John F. Kennedy in 1962

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New Members REGULAR MEMBERS Carlos Barajas-Lopez IPICYT, Mexico Farhat Batool Univ of Nottingham, UK Bhaskar U. Bhattacharya Cancer Science Inst of Singapore Chun Cheng Andy Chen Lake Erie College of Osteopathic Medicine Alan Davis Pharmedicor Laurent A. Decosterd Univ Hospital and Univ of Lausanne, Switzerland Vanja Duric Des Moines Univ Jane E. Ishmael Oregon State Univ Mohita Kumar Ferring Pharmaceuticals Robert Lukowski Univ of Tuebingen, Germany Gary A. Piazza Univ of South Alabama Mitchell Cancer Inst.

Dominique Schols Rega Inst for Medical Research, Belgium Amit K. Tiwari Univ of Toledo Adam L. VanWert Wilkes UnivKarthick Vishwanathan, AstraZeneca Pharmaceuticals Bradley K. Wong Tonn and Wong DMPK Solutions LLC

POSTDOCTORAL MEMBERS Fatima Z. Alshbool Western Univ of Health Sciences Andy R. Eugene MN Patrycja Kleczkowska Medical Univ of Warsaw, Poland Valerie F. Miller National Institutes of Health Johnathan P. Neiswinger National Institutes of Health Kruti Patel Univ of Massachusetts Dartmouth Iuliana Popescu Univ of Kentucky Coll of Med The Pharmacologist • September 2015

PS Shantanu Rao Univ of Tennessee Health Science Center Tahmineh Tabrizian SUNY Stony Brook

AFFILIATE MEMBERS Francis Rainer B. Atanacio Food and Nutrition Res Inst, Phillipines Johnny L. Barr USA ISR Jennifer L. Cubeta The Univ of Arizona Ritika Kurian Thomas L. McCormick Coventry Diagnostics Tod L. Steinfeld Reset Therapeutics

GRADUATE STUDENT MEMBERS Gisella Campanelli Long Island Univ Shannon A. Coghlan Ernest Mario School of Pharmacy, Rutgers Univ Sabrina C. Fechtner Washington State Univ Mayuresh S. Garud SVKM’s NMIMS Shobhaben Pratapbhai Patel Sch of Pharmacy and Techn Mgmt, India Maciej Gonek Virginia Commonwealth Univ Juliet D. Gotthardt Rutgers Univ Amber L. Guidry Univ of Alabama at Birmingham Ashley M. Hopkins Univ of South Australia Asti Jackson Virginia Commonwealth Univ Joanna C. Jacob Virginia Commonwealth Univ Oluwafemi E. Kale Babcock Univ, Nigeria Miki Katuwal The Univ of Kansas Medical Center Gayatri Mamidanna Univ of Memphis

Muhammad A. Musa Usmanu Danfodiyo Univ, Nigeria Michael Ohene-Nyako Rush Univ Medical Center Annie M. Racine Univ of Wisconsin-Madison Alejandro N. Rondon MCPHS Univ Fatima O. Saeed Univ of Cincinnati Ekundayo S. Samuel University of Ibadan, Nigeria Justin D. Schumacher Rutgers Univ Santu K. Singha Univ of Mississippi Zachary E. Tibbs Univ of Alabama at Birmingham Julia Tobacyk Univ of Arkansas for Medical Sciences Justin K. Tomblin Marshall Univ

UNDERGRADUATE MEMBERS Kevin M. Adams Vanderbilt Univ Stephanie O. Agba Franklin College Eda Algur Harvard College Mudassir S. Ali Univ of Illinois Urbana-Champaign Kristin Allan The College of Wooster Roseanna Amrit Univ at Buffalo Yiran An Univ of Pittsburgh Jason M. Arne Case Western Reserve Univ Nathan G. Arnett Pennsylvania State Univ Tiara D. Askew Bowie State Univ Sainath Asokan Univ of North Carolina - Chapel Hill Aaron A. Bickert Medical College of Wisconsin Alejandro R. Botas Rice Univ

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Member-Get-A-Member Campaign After the success of last year’s campaign, ASPET will be launching the Member-Get-A-Member campaign this September! Any current active member who recommends a new regular, affiliate, or postdoctoral member will receive a complimentary ASPET t-shirt. In addition, any current member who recommends a new member join ASPET (including new graduate student and undergraduate members) will receive entry in the raffle for the Grand Prize, a $100 American Express gift card!

Speak with your students, professional contacts, and other interested individuals and let them know

Elise M. Bowler Univ of IL at Chicago Edward G. Brauer Michigan State Univ Kiera J. Broussard Xavier Univ of Louisiana Veronica M. Campbell Texas A&M Univ - Corpus Christi Dorsin Chang Univ of Pittsburgh Sonam Chodon Rutgers Univ Randall B. Clapp Gannon Univ Bridget G. Condon Loyola Univ Emma K. Dallon Washington State Univ Tayyeb Din Nhu Y T. Doan Pomona College Christian L. Dohring Univ at Buffalo Kevin N. Eddy Rutgers Univ Michael A. Epp Baker Univ Abdelrahman A. Ewis Rutgers Univ - Ernest Mario School of Pharmacy Chelesa T. Fearce Spelman College Rachel M. Felger Trinity Univ Katherine R. Ferrick Southwestern Univ

about the exciting benefits of ASPET membership. Helping to grow the ASPET membership ensures the strength of the organization and allows us to continue to offer our many benefits and explore new ways to help grow the field of pharmacology and experimental therapeutics. For more details, visit: www.aspet.org/ membership/member-get-a-member/

Courtney L. Fisher Michigan State Univ Kailey M. Fogo Univ of Arkansas for Med Sci Eric Franklin Univ of Rochester Anne E. Freeman Univ of Texas Health Science Center Daniel M. Frey Milwaukee School of Engineering Claire A. Gianakas Carnegie Mellon Univ HyunJung Go Rutgers Univ Delfina P. Gonzalez Pomona College Patrice Groomes Brown Univ Shivani Gupta Rutgers Univ Ernest Mario School of Pharmacy Patrick C. Gurley Univ of Arkansas for Medical Sciences Ronald J. Harris Livingstone College Nathaniel J. Hayes Medical College of Wisconsin Kionna L. Henderson Univ of Arkansas at Pine Bluff Kevlyn M. Holmes Louisiana State Univ Health Sciences Amy Huang Rutgers Univ Rachel D. Hutchison Univ of Arkansas at Little Rock

Brittany M. Jack Rockhurst Univ Sinthia Jahan Univ of Arkansas at Little Rock Jennifer R. Jensen Univ of North Carolina Arianna J. Kee Rutgers Univ Willa G. Kerkhoff Oberlin College Junga Kim Rutgers Univ Holly E. Kraus Wheeling Jesuit Univ Minseo Kwak Rutgers Univ Jasmine Kyung Univ of California, San Diego Caitlin E. Labay Univ of Texas Health Science Center, San Antonio Sharmaine A. Lee Stritch School of Medicine: Loyola Univ Chicago JongWon Lee Rutgers Univ Rebecca Lee Cornell Univ Sophie L. Lewandowski Univ of Virginia School of Medicine Diana H. Mansour Univ of Pittsburgh Emily E. Marra Univ at Buffalo Kaitlin E. Marrison Michigan State Univ September 2015 • The Pharmacologist

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Brian P. McHugh University of Rhode Island Ian M. McVinney Hendrix College Vivek Medepalli Univ of California, San Diego Sarah L. Metcalfe St. Bonaventure Univ Kendrique A. Morgan Tougaloo College Michael Mudrak Rutgers Univ Brendan F. Mullan Michigan State Univ Lailun Nahar Univ of Rochester Rachan V. Narala Ivy D. Ngo Gordon College Jessica M. Noll Manchester Univ Ishmael L. Ochir Univ of Illinois Daniella I. Olan Rutgers Univ Kayla L. O’Sullivan Washington State Univ College of Pharmacy Hope Pan Vanderbilt Univ Rohan J. Peer Case Western Reserve Univ Morgan S. Phillips McGill Univ, Montreal Matthew J. Purcell Northern Illinois Univ

Christopher V. Radcliffe West Virginia Univ Ashley L. Rand Oral Roberts Univ David T. Reich Brown University Lindsay L. Robinson The College of Wooster Jasper N. Rubin-Sigler Emory Univ Matthew M. Rusgis Univ of Missouri, Columbia Isaac Sappington Washington State Univ Kendall J. Schick Concordia Univ Regina D. Schnegelberger Northwest Missouri State Univ Zaheera Shabbir Binghamton Univ Harsh Shah Univ of Florida Li Ching Sheng Rutgers Univ Byron S. Sigel Grinnell College Kara L. Smith Miami Univ Calvin G. Snyder Univ of North Carolina – Chapel Hill Alexander C. Stoudt Washington State Univ Gabriel D. Tallent Univ of Michigan Kevin A. Tam Univ of Illinois College of Pharmacy

Amr M. Tawfik Rutgers Univ Kristian E. Teichert Northeastern Univ Daniel L. Theisen The Univ of Kansas Raghav Tripathi Case Western Reserve Univ Kalu E. Udensi Stony Brook Emma Vargas Gordon College Randy E. Verduguez Univ of Dayton Kaliana M. Veros Univ at Buffalo Maria J. Vides Pomona College Laura A. Vinck Graceland Univ Eric J. West Lafayette College Stephen D. Williams Norfolk State Univ Andrew P. Wodrich Univ of Miami Keegan B. Wolter Michigan State Univ Hanan Yacoub Univ of Illinois at Chicago Haoyue Zhou Rutgers, State Univ of New Jersey Wenyi Zhu Rutgers Univ

2015 Membership Renewal In Sympathy G. Alan Robison Frances Kathleen Oldham Kelsey Heather Hostetler

It’s time to renew your membership! Be sure to watch your email for your 2016 Dues Notice later this month. 2016 is going to be a great year for ASPET members with the annual meeting taking place in San Diego this April, continued growth of the education department, and further exploration of the BIG IDEAS II Initiative. We hope you continue your membership and take advantage of all of the many benefits ASPET membership has to offer.

Thank you for your valued support of ASPET!

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Members in the News Achievements, Awards, Promotions, and Scientific Breakthroughs

Dr. Bradley McConnell University of Houston

Dr. Bradley McConnell of the University of Houston, Texas Medical Center, received a National Institutes of Health/NHLBI R15 Academic Research Career Enhancement Award to study the biophysical, cellular, and physiological properties of A-kinase anchoring proteins (AKAP) scaffolding protein network dynamics using molecular-defined mutants to integrate structure-function relationships, local sub-cellular signaling, and co-complex regulation associated with cardiac cell signaling.

Dr. McConnell along with his team will investigate the effect of human mAKAP mutations on the modification of protein-protein interaction binding kinetics and its role as an interaction network to regulate second messenger dynamics. McConnell said that “Characterization of mAKAP scaffolding protein-protein interactions will improve our understanding for this central regulator of kinase, phosphodiesterase, and phosphatase cardiac intracellular signaling.”

As a new principal investigator of an R15 award, Dr. McConnell

has already spearheaded a mini symposium at the University of Houston titled “Opportunities in Science, Technology, Engineering and Mathematics (STEM): An Introduction of Health Sciences to High School Students” this past June. The mini symposium hosted several local area high school students and the primary goal was to expose them to a variety of activities including basic science research presentations by faculty and students, laboratory demonstrations, and a campus tour.

In recognition of his recent success in receiving a grant, along with his longstanding devotion to integrate education and research while supporting outreach and service, and creating opportunities for students, he was recently recognized by the University of Houston and the College of Pharmacy with a 2015 Certificate of Achievement for Excellence in Service.

Dr. McConnell has been a member of ASPET since 2013. He is a member of the Division for Cardiovascular Pharmacology.

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Dr. Charles Antzelevitch Lankenau Institute for Medical Research

Main Line Health has named Charles Antzelevitch, PhD, FACC, FAHA, FHRS, executive director of the cardiovascular research program at Lankenau Institute for Medical Research and director of research at Lankenau Heart Institute. Dr. Antzelevitch is an internationally recognized expert in cardiac electrophysiology and arrhythmia syndromes. In his new role at Main Line Health, he will assemble a cardiovascular research team of clinical investigators and basic scientists to advance understanding of the underlying mechanisms of cardiac arrhythmias and to translate these discoveries into novel approaches to therapy.

Dr. Antzelevitch joins Main Line Health after more than 31 years as executive director, director of research, and Gordon K. Moe scholar (endowed chair in experimental cardiology) at the Masonic Medical

Research Laboratory in Utica, NY. He also holds an academic appointment as professor of pharmacology at SUNY Upstate Medical University in Syracuse, NY. Since the start of his scientific career, Dr. Antzelevitch has been awarded more than $24 million in research grants. Together with his research colleagues, Dr. Antzelevitch discovered and characterized the physiological basis for how lifethreatening arrhythmias begin.

Dr. Antzelevitch’s contributions to the scientific literature on cardiac arrhythmias include nearly 500 original articles and book chapters and 6 edited reference texts. His achievements have been widely recognized, with many professional honors.

Dr. Antzelevitch has been a member of ASPET since 2013. He is a member of the Division for Cardiovascular Pharmacology.

Share Your Career Achievements with ASPET Membership Is there something exciting happening in your career that is worth sharing with other ASPET members? Let us put the word out! Submit a brief 150-word summary of your recent career achievements, awards, promotions, and scientific breakthroughs for inclusion in the members in the news segment of The Pharmacologist.

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Division News Division for Translational & Clinical Pharmacology The Division for Translational & Clinical Pharmacology (TCP) is delighted to begin hosting the Ray Fuller Lecture and Symposium beginning with the ASPET Annual Meeting at EB2018. This will serve as our flagship venue for recognizing bench-to-bedsideto-bench research at the Experimental Biology meeting.

More information about how the division will be soliciting nominations and selecting an awardee for the inaugural TCP Ray Fuller Lecture and Symposium will be available in the future.

As part of our commitment to provide resources and opportunities for showcasing and mentoring junior faculty and trainees, we are developing three key initiatives: 1) Following the inaugural and highly successful Meet the Experts Luncheon at EB2015, we will hold a similar event at EB2016 with a few twists that will enable our members to meet an even greater diversity of experts in translational and clinical pharmacology.

2) We are launching Career Development Site Visits with travel and lodging support for trainees seeking to

get a glimpse of science in an environment outside of their current lab. Options for these 2–3 day site visits will be announced soon; trainees will then be invited to submit a letter of intent that will be followed by a more complete application. The selected candidates will be announced at the TCP business meeting at EB2016.

3) We will also provide travel support for a Junior Faculty Showcase to enable our early-career investigators to highlight their work presented at EB2016.

More updates will follow for each of these exciting initiatives.

Are you interested in learning more about membership or serving on the Executive Committee?

The secretary/treasurer position is currently open for nominations. Please contact Pam Hornby at phornby@ its.jnj.com or Ben Green at ben.green@ars.usda.gov.

Update on the Division Website Redesign Project As part of our continuing efforts to improve the user experience on all of ASPET’s web properties, the ASPET marketing and communications team proposed a website redesign initiative for all ten division websites at the division communication officer’s meeting held during EB2015 in Boston this year.

The revisions of the division websites include achieving consistency in branding and layout, improving navigation, updating content as it relates to each division, and linking the sites to ASPET’s social media channels along with the the division LinkedIn group pages.

We are happy to report that the redesign project commenced in a timely manner earlier this summer

and is making good progress. After incorporating all redesign changes, we hope to set a new standard in terms of how the ASPET division websites are viewed and utilized as hubs of divisional information not only by current and new Society members but also nonmembers interested in learning more about the specific disciplines within pharmacology that the divisions represent.

Stay tuned for an announcement as we gear up to roll out the new changes on all ten division websites later this year.

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Chapter News 2015 NYPS Annual Meeting in Review (formerly known as UNYPS) The fourth annual NYPS meeting highlighting “G-Protein Coupled Receptor Signaling Systems in Health and Disease” held at the University of Rochester on Tuesday, May 19, 2015 was a great success! There were nearly a hundred attendees including students, faculty, and industry scientists representing Albany College of Pharmacy and Health Sciences, Cornell University, D’Youville College School of Pharmacy, SUNY College at Brockport, Roswell Park Cancer Institute, SUNY Upstate Medical University, University at Buffalo, University of Rochester, and industry research organizations.

Dr. J. Silvio Gutkind, chief of the Oral and Pharyngeal Cancer Branch of the NIDCR and soon to be of the UC San Diego Moores Cancer Center, delivered the keynote address entitled “G-Protein Coupled Receptor Signaling Circuitries and Cancer.”

Dr. Gutkind described how activation of the PI3K/Akt/ mTOR-signaling axis is NYPS keynote speaker one of the most frequent J. Silvio Gutkind events in cancer and alterations in these and other specific signaling pathways may drive remarkable expansion of the stem cell compartments and rapid carcinoma formation. Additional invited thematic speakers were Xianhua Piao MD, PhD of Harvard Medical

The Pharmacologist • September 2015

Center and the Boston Children’s Hospital and Peter A. Friedman, PhD of the University of Pittsburgh, School of Medicine. Dr. Piao spoke of her research on the adhesion G-protein coupled receptor GPR56 and its role in neurodevelopment, particularly in oligodendrocyte precursor cell (OPC) proliferation and myelination. Dr. Friedman spoke of his research on the mechanisms of parathyroid hormone receptor (PTHR) action and how specific ligands can promote either receptor recycling or ubiquitinationdownregulation.

Presidential Graduate Student Symposium speakers included six advanced graduate students from regional universities and research institutes: Shannon Clough of the University at Buffalo, Jesi Lee Anne To of the University of Rochester, Forrest Wright of SUNY Upstate Medical University, Walter Knight of the University of Rochester, Kirstie Cummings of the University at Buffalo, and Bharti Patel of the University of Rochester. Early Career Scientist talks were made Dr. Jianwen Que of the University of Rochester and Dr. Jun-Xu Li of the University at Buffalo.

Outgoing president Gregory G. Tall of Rochester gave final remarks and welcomed the new president Paul J. Kammermeier, also of Rochester. Further details can be found at https://www.aspet.org/NYPS/.

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2015 GLC Annual Meeting in Review

Poster session at the 2015 GLC Annual Meeting

In June 2015, the Great Lakes Chapter of the American Society for Pharmacology and Experimental Therapeutics (GLC-ASPET) hosted its annual meeting to foster interactions among pharmacologists in the Great Lakes region and to provide a forum for graduate students and post-doctoral fellows to present their research.

The annual meeting had a very interesting program, including the scientific symposium on “Epigenetics and Human Disease: From Etiology to New Therapeutics” that featured nationally and internationally recognized researchers in epigenetics and human disease research.

John Christman, MD, director of the Critical Care Signature Program, chief of the Section of Pulmonary, Allergy, Critical Care and Sleep Medicine, The Ohio State University Wexner Medical Center, discussed in his talk “Epigenetic Regulation of Macrophage Gene Expression in ARDS Associated with Severe Sepsis” novel molecular pathways by which macrophages contribute to the pathogenesis and recovery of ARDS. His recent data indicate that the macrophage inflammatory phenotype is regulated, at least in part, through epigenetic mechanisms. He addressed the pivotal role for macrophages in the generation and recovery phase of ARDS and several mechanisms of

epigenetic regulation of macrophage gene expression as a major determinant of the macrophage inflammatory phenotype.

Ali Shilatifard, PhD, chairman, Department of Biochemistry and Molecular Genetics, Northwestern University, Feinberg School of Medicine, discussed in his talk “Enhancer Malfunction in Cancer” some recent studies on the identification of factors that function in the regulation of the chromatin state and the activities of enhancers during development.

Tao Pan, PhD, professor, Department of Biochemistry and Molecular Biology, The University of Chicago, discussed in his presentation “Dynamic RNA Modifications in the Regulation of Gene Expression” the N6-methyladenosine (m6A) modification in mammalian mRNA/lncRNA and its role in regulating mRNA abundance, alternative splicing, and nucleocytoplasmic translocation with a particular emphasis on how m6A regulates the access of mRNA/lncRNA binding proteins to their target sites.

William N. Pappano, PhD, senior group leader at AbbVie, Greater Chicago Area presented in his talk “Targeting Histone Methyltransferases in Cancer” some new studies to generate several small molecule chemical probes against a number of methyltransferases and explore the biology and druggability of these targets in vitro and in vivo.

Jindan Yu, MD, PhD, associate professor of Medicine-Hematology/Oncology, Northwestern University Feinberg School of Medicine, discussed in her talk “IncRNA Regulation of Androgen Receptor Signaling and Prostate Cancer” how key transcription factors as well as epigenetic regulators, such as lncRNAs, in prostate cancer promote disease progression through altering the androgen receptor transcriptional program.

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Meetings & Congresses September 2015 Amer. Physiological Soc. 14th Ann. Conf. on Endothelin www.the-aps.org/et-14 Sept. 2–5, Savannah, GA 2015 DIA/FDA Oligonucleotide-based Therapeutic Conf. bit.ly/16NZaOM Sept. 9–11, Washington DC 67th Clin. Endocrinology Update www.endocrine.org/ceu Sept. 10–12, Miami, FL North Amer. Artery 5th Ann. Mtg. www.naartery.org Sept. 11–12, Chicago, IL Eurotox: 51st Cong. of the Europ. Socs. of Toxicol. www.eurotox2015.com Sept. 13–16, Porto, Portugal 21st Scientific Symp. of the Austrian Pharmacological Soc. www.bps.ac.uk/meetings/14844de2424 Sept. 16–18, Graz, Austria The Mobile Genome: Genetic & Physiological Impacts of Transposable Elements bit.ly/1DIHbDq Sept. 16–19, Heidelberg, Germany Int’l Soc. for Eye Res. XXII Biennial Mtg. www.iserbiennialmeeting.org Sept. 26–30, Tokyo, Japan Amer. College of Clin. Pharmacology Ann. Mtg. accp1.org/2015_meetings_welcome.shtml Sept. 27–29, San Francisco, CA 15th Ann. Mtg. of Safety Pharmacology Soc. www.safetypharmacology.org/ annualmeetings.asp Sept. 28–Oct. 1, Prague, Czech Republic

October 2015 2015 Amer. Soc. of Human Genetics www.ashg.org/2015meeting/index.shtml Oct. 6–10, Baltimore, MD

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2015 IPA Int’l Cong. www.ipa-online.org/wordpress/event/2015international-congress-berlin Oct. 13–16, Berlin, Germany 25th Neuropharmacology Conf. 2015 www.neuropharmacology-conference. elsevier.com Oct. 15–16, Chicago, IL Advances in Breast Cancer Res. www.aacr.org/Meetings/Pages/ MeetingDetail.aspx?EventItemID=49#.

VWTTrWdFCUk Oct. 17–20, Bellevue, WA Soc. for Neuroscience: Neuroscience 2015 www.sfn.org/annual-meeting/ neuroscience-2015 Oct. 17–21, Chicago, IL 20th North Amer. ISSX Mtg. www.issx.org/BlankCustom. asp?page=20NAISSXInvite Oct. 18–22, Orlando, FL Int’l Soc. for Applied Cardiovascular Biology & NAVBO www.navbo.org/events/vb2015 Oct. 18–22, Hyannis, MA 2015 Soc. of Forensic Toxicologists Ann. Mtg. www.soft-tox.org/meeting Oct. 19–23, Atlanta, GA 4th AACR Int’l Conf. on Frontiers in Basic Cancer Res. www.aacr.org/Meetings/Pages/ MeetingDetail.aspx?EventItemID=59#.

VWTTdmdFCUk Oct. 23–26, Philadelphia, PA 2015 SACNAS Nat‘l Conf. www.sacnas.org/events/national-conf Oct. 29–31, Washington, DC

November 2015 Pharma Middle East 2015 middleeast.pharmaceuticalconferences.com Nov. 2–4, Dubai, UAE Amer. Soc. of Nephrology: Kidney Week 2015 www.asn-online.org/education/kidneyweek Nov. 3–8, San Diego, CA

AACR-NCI-EORTC Int’l Conf. on Molecular Targets & Cancer Therapeutics www.aacr.org/Meetings/Pages/ MeetingDetail.aspx?EventItemID=59#.

VWTTdmdFCUk Nov. 5–9, Boston, MA Translational Cancer Res. for Basic Scientists Workshop www.aacr.org/Meetings/Pages/ MeetingDetail.aspx?EventItemID=67#.

VWXQL2dFCUk Nov. 8–13, Boston, MA 63rd Amer. Soc. of Cytopathology Ann. Scientific Mtg. www.cytopathologymeeting.org/2015 Nov. 13–16, Chicago, IL 8th AACR Conf. on the Science of Cancer Health Disparities in Racial/Ethnic Minorities & the Medically Underserved www.aacr.org/Meetings/Pages/ MeetingDetail.aspx?EventItemID=68#.

VWXSeGdFCUk Nov. 13–16, Atlanta, GA Cardiovascular, Renal & Metabolic Diseases: Physiology & Gender www.the-aps.org/mm/Conferences/APSConferences/2015-Conferences/Physiologyand-Gender Nov. 17–20, Hyannis, MA Developmental Biology & Cancer www.aacr.org/Meetings/Pages/ MeetingDetail.aspx?EventItemID=67#.

VWXQL2dFCUk Nov. 30–Dec. 3, Boston, MA

December 2015 EORTC-NCI-EMA-AACR Int’l Conf. on Innovation & Biomarkers in Cancer Drug Development www.aacr.org/Meetings/Pages/ MeetingDetail.aspx?EventItemID=71#.

VWXS6mdFCUk Dec. 3–4, Brussels, Belgium 54th Ann. Mtg. of the Amer. Coll. of Neuropsychopharmacology www.acnp.org/annualmeeting/default.aspx Dec. 6–10, Hollywood, FL

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San Antonio Breast Cancer Symp. www.sabcs.org Dec. 8–12, San Antonio, TX 2015 Ann. Mtg. of the Amer. Soc. of Cell Biology www.ascb.org/2015meeting Dec. 12–16, San Diego, CA 2015 British Pharmacological Soc. Mtg. www.bps.ac.uk/meetings/Pharmacology2015 Dec. 15–17, London, UK

January 2016 Systems Immunology: From Molecular Networks to Human Biology www.keystonesymposia.org/ index.cfm?e=web.Meeting.

Program&meetingid=1431 January 10–14, Big Sky, MT Cytokine JAK-STAT Signaling in Immunity & Disease www.keystonesymposia.org/ index.cfm?e=web.Meeting.

Program&meetingid=1372 January 10–14, Steamboat Springs, CO Metabolism, Transcription & Disease www.keystonesymposia.org/ index.cfm?e=web.Meeting.

Program&meetingid=1390 January 10–14, 2016, Snowbird, UT Molecular & Cellular Basis of Growth & Regeneration www.keystonesymposia.org/ index.cfm?e=web.Meeting.

Program&meetingid=1385 January 10–14, 2016, Breckenridge, CO Nuclear Receptors: Full Throttle www.keystonesymposia.org/ index.cfm?e=web.Meeting.

Program&meetingid=1389 January 10–14, Snowbird, UT Axons: From Cell Biology to Pathology www.keystonesymposia.org/ index.cfm?e=web.Meeting.

Program&meetingid=1422 January 24–27, Santa Fe, NM Biology of Down Syndrome: Impacts Across the Biomedical Spectrum www.keystonesymposia.org/ index.cfm?e=web.Meeting.

Program&meetingid=1426 January 24–27, Santa Fe, NM Cancer Immunotherapy: Immunity and Immunosuppression Meet Targeted Therapies www.keystonesymposia.org/ index.cfm?e=web.Meeting.

Program&meetingid=1377 January 24–28, Vancouver, BC, Canada

Drug Discovery for Parasitic Diseases www.keystonesymposia.org/ index.cfm?e=web.Meeting.

Program&meetingid=1416 January 24–28, 2016, Tahoe City, CA

Stromal Cells in Immunity www.keystonesymposia.org/ index.cfm?e=web.Meeting.

Program&meetingid=1405 February 7–11, Keystone, CO

Purinergic Signaling www.keystonesymposia.org/ index.cfm?e=web.Meeting.

Program&meetingid=1371 January 24–28, Vancouver, BC, Canada

ACNS Ann. Mtg. www.acns.org/meetings/annual-meetingand-courses/2016 February 10–14, Orlando, FL

Small RNA Silencing: Little Guides, Big Biology www.keystonesymposia.org/ index.cfm?e=web.Meeting.

Program&meetingid=1396 January 24–28, Keystone, CO Traumatic Brain Injury: Clinical, Pathological & Translational Mechanisms www.keystonesymposia.org/ index.cfm?e=web.Meeting.

Program&meetingid=1424 January 24–27, Santa Fe, NM Cell Biology and Immunology of Persistent Infection www.keystonesymposia.org/ index.cfm?e=web.Meeting.

Program&meetingid=1409 January 31–February 4, Banff, AB, Canada Ligand Recognition & Molecular Gating www.grc.org/programs.aspx?id=12689 January 31–February 5, Lucca (Barga), Italy Neurological Disorders of Intracellular Trafficking www.keystonesymposia.org/ index.cfm?e=web.Meeting.

Program&meetingid=1384 January 31–February 4, Keystone, CO

February 2016 Alcohol & the Nervous System www.grc.org/programs.aspx?id=16702 February 7–12, Galveston, TX The Cancer Genome www.keystonesymposia.org/ index.cfm?e=web.Meeting.

Program&meetingid=1374 February 7–11, Banff, AB, Canada Fibrosis: From Basic Mechanisms to Targeted Therapies www.keystonesymposia.org/ index.cfm?e=web.Meeting.

Program&meetingid=1407 February 7–11, Keystone, CO Genomics & Personalized Medicine www.keystonesymposia.org/ index.cfm?e=web.Meeting.

Program&meetingid=1394 February 7–11, Banff, AB, Canada

Plasminogen Activation & Extracellular Proteolysis (GRS) www.grc.org/programs.aspx?id=14484 February 13–14, Ventura, CA Plasminogen Activation & Extracellular Proteolysis www.grc.org/programs.aspx?id=12243 February 14–19, Ventura, CA Thalamocortical Interactions www.grc.org/programs.aspx?id=17257 February 14–19, Ventura, CA Obesity & Adipose Tissue Biology www.keystonesymposia.org/ index.cfm?e=web.Meeting.

Program&meetingid=1429 February 15–19, Banff, AB, Canada Angiotensin (GRS) www.grc.org/programs.aspx?id=15143 February 20–21, Lucca (Barga), Italy Angiotensin www.grc.org/programs.aspx?id=13998 February 21–26, Lucca (Barga), Italy Enhancer Malfunction in Cancer joint with the meeting on Noncoding RNAs in Health and Disease www.keystonesymposia.org/ index.cfm?e=Web.Meeting.

Program&Meetingid=1392 February 21–24, 2016, Santa Fe, NM Immunometabolism in Immune Function & Inflammatory Disease www.keystonesymposia.org/ index.cfm?e=web.Meeting.

Program&meetingid=1400 February 21–25, Banff, AB, Canada G Protein-Coupled Receptors: Structure, Signaling & Drug Discovery www.keystonesymposia.org/16B3 February 21–25, 2016, Keystone, CO New Frontiers in Understanding Tumor Metabolism joint with the meeting on Immunometabolism in Immune Function and Inflammatory Disease (Q8) www.keystonesymposia.org/ index.cfm?e=web.Meeting.

Program&meetingid=1375 February 21–25, Banff, AB, Canada

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Noncoding RNAs in Health & Disease www.keystonesymposia.org/ index.cfm?e=web.Meeting.

Program&meetingid=1395 February 21–24, Santa Fe, NM

T Follicular Helper Cells & Germinal Centers www.keystonesymposia.org/ index.cfm?e=web.Meeting.

Program&meetingid=1401 February 26–March 1, Monterey, CA

Peptides, Chemistry & Biology of (GRS) www.grc.org/programs.aspx?id=15395 February 20–21, Ventura, CA

Basal Ganglia (GRS) www.grc.org/programs.aspx?id=17132 February 27–28, Ventura, CA

Peptides, Chemistry & Biology of Crossing Barriers by Peptide Science for Health and Wellness www.grc.org/programs.aspx?id=11886 February 21–26, Ventura, CA

Basal Ganglia www.grc.org/programs.aspx?id=16708 February 28–March 4, Ventura, CA

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Immunity in Skin Development, Homeostasis & Disease www.keystonesymposia.org/ index.cfm?e=web.Meeting.

Program&meetingid=1406 February 28–March 2, Tahoe City, CA Tuberculosis Co-Morbidities & Immunopathogenesis www.keystonesymposia.org/ index.cfm?e=web.Meeting.

Program&meetingid=1411 February 28–March 3, Keystone, CO

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ASPET BIG IDEAS II Do you have a BIG IDEA for ASPET? Submit your proposal today!

Due to the tremendous success of the last BIG IDEAS Initiative, ASPET is once again asking members to put forward their best ideas for projects. The requirements for these projects are that they:  Have broad appeal to ASPET membership  Have long term positive impact on the discipline of pharmacology or on ASPET membership  Are creative and transformative for ASPET  Invest in the future of ASPET Subm Submit bm your proposal by September S ep pt 28, 2015!

For more information and to submit your BIG IDEA vi visit:

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ASPET Member-Get-A-Member Participate Today!

Participate in the ASPET Member-Get-A-Member program, get a free ASPET t-shirt, and be entered into a raffle to win a $100 American Express Gift Card!

Get Started Today!  Tell a friend, colleague or student about the benefits of ASPET membership.  Encourage them to fill out an application form online at: www.aspet.org  Tell the applicant that they must enter your name in the “Sponsor Name/Email” field on the application form.

By helping us recruit new members, you will be contributing to the growth and sustainability of ASPET. A growing ASPET means great recognition for the field of pharmacology, more resources and support for our members, and a louder voice with policy makers.

*T-shirts will be given to participants who recruit paying members (not students). T-shirt sizes are subject to availability and will be given out on a first come, first served basis.

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 Tell the applicant that they must enter the marketing code “MGM” in the field that asks, “Where did you hear about ASPET?”  Once they are approved for membership and their dues payment has been made, you will receive credit for your recruitment efforts.

For more information about this program, visit www.aspet.org/membership/member-get-a-member or contact the membership department at membership@aspet.org or call (301) 634-7060.