The Pharmacologists September 2023 by ASPET

the

A Publication by The American Society for Pharmacology and Experimental Therapeutics

Pharmacologist Vol. 65 • Number 3 • September 2023

INSIDE

Pharmacology for Cats and Dogs

Leadership Profile: Ashim Malhotra ASPET 2024 Annual Meeting Washington Fellows Policy Briefs

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

Contents 1 Message from the President Profile: 2 Leadership Ashim Malhotra, ASPET IDEA Chair 4 ASPET 2024 Annual Meeting News 8 Feature Story: Veterinarian Pharmacology Policy News: 20 Science Washington Fellows Policy Briefs 33 Journals News 37 Membership News 42 Chapter News 43 Message to Subscribers

THE PHARMACOLOGIST PRODUCTION TEAM Catherine L. Fry, PhD Lynne Harris, MA, APR Dave Jackson, MBA, CAE Maria Pasho COUNCIL President Namandjé Bumpus, PhD President Elect Carol L. Beck, PhD Past President Michael F. Jarvis, PhD Secretary/Treasurer XinXin Ding, PhD Secretary/Treasurer Elect Pamela Janet Hornsby, PhD Past Secretary/Treasurer Kathryn A. Cunningham, PhD Councilors Amy C. Arnold, PhD Nina Isoherranen, PhD John R. Traynor, PhD Chair, Publications Committee Kenneth Tew, PhD Chair, Program Committee Carol Paronis, PhD FASEB Board Representative Jerry Madukwe, PhD Chair, IDEA Committee Ashim Malhotra Chair, Young Scientists Committee Dianicha Santana, PhD Executive Officer Dave Jackson, MBA, CAE The Pharmacologist (ISSN 0031-7004) is published quarterly in March, June, September, and December by the American Society for Pharmacology and Experimental Therapeutics, 1801 Rockville Pike, Suite 210, Rockville, MD 20852-1633. Annual subscription rates: $25.00 for ASPET members; $75.00 for U.S. nonmembers and institutions; $100.00 for nonmembers and institutions outside the U.S. Single copy: $25.00. Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics Inc. All rights reserved. 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, 1801 Rockville Pike, Suite 210, Rockville, MD 20852-1633.

Message from

The President Dear ASPET Members, I am excited to write my first message as president of ASPET. I feel fortunate to serve in this role with talented and dedicated staff, council members and membership. ASPET has been my professional home since I was a trainee. During my time in ASPET, I have served on the public affairs committee, awards committee, as an officer in the Division for Drug Metabolism and Disposition, as a councilor and now as president. Through these service opportunities, ASPET has nurtured my growth as both a pharmacologist and a member of our pharmacology community. A primary goal for me as president is to strengthen our sense of community and collaboration. As part of this goal, I aim to widen the circle of people who consider ASPET their professional home and who see an opportunity for themselves as future leaders of ASPET. We will continue to provide meaningful space and platforms for those early in their careers to showcase their work and to grow both professionally and scientifically. Additionally, volunteerism is key to ASPET and a strong partnership between our staff and members. We will continue to call for volunteers for various opportunities and encourage you to let us know how you would like to volunteer with ASPET. What a wonderful ASPET 2023 Annual Meeting we had in May! Many thanks to the ASPET staff for making it such a special experience for all of us. The venue was outstanding and unique, second only to the scholarly work presented at the meeting including sessions focused on science, policy, education and other topics. The breadth of symposia and commensurate discussions were unparalleled and I’m already excited for ASPET 2024. A particular highlight for me at ASPET 2023 was the innovative and reimagined approach taken to presenting the ASPET awards. The videos recognizing recipients were fantastic, and I greatly enjoyed the chance to chat with and learn from the panel of esteemed awardees in a special session. We are going to keep this momentum going! Please plan to join us for the ASPET 2024 meeting, which will bring new and exciting experiences. Among the many ASPET programs and initiatives, I want to bring special attention to recent efforts under way to expand our plans for Inclusion, Diversity, Equity and Accessibility (IDEA). ASPET has embarked on a partnership with Nova Collective to learn more about what our membership thinks about IDEA at ASPET and expectations moving forward. Thank you to all members who provided input during the initial survey phase as well as those participating in the focus groups to further explore members’ experiences. I also want to call attention to a few highlights of this month’s issue of The Pharmacologist. In addition to all of the ASPET updates you usually receive, new ASPET IDEA Chair Ashim Malhotra, PhD provides his background and views in our Leadership Profile column. Please note that this will be the last issue of the quarterly format of The Pharmacologist. In January 2024, we will begin issuing an electronic monthly version of the magazine. We hope you enjoy the new format and everything that comes with 2024! Sincerely,

Namandjé N. Bumpus, PhD ASPET President The Pharmacologist • September 2023

Leadership Profile A Conversation with ASPET IDEA Chair Ashim Malhotra, PharmBS, MS, PhD, FAPE Ashim Malhotra, PhD is currently ASPET’s Chair of the Inclusion, Diversity, Equity and Accessibility (IDEA). He is Assistant Dean of Academic Affairs and Accreditation, and a Professor at the California Northstate University. He is also Founding Senior Director of the university’s Institute of Teaching and Learning Excellence & Academic Affairs and Director of the University Interprofessional Education Program. Dr. Malhotra has been an ASPET member since 2015. He is a Fellow of the ASPET Academy of Pharmacology Education.

How did you get started in pharmacology? My academic journey is one of struggles and economic hardship. My professional identity as a scientist has been sculpted by international experiences, minoritized personal identity, and sometimes challenging access to top-notch programs due to a paucity of resources. Nevertheless, I feel fortunate that I earned a Bachelor of Pharmacy degree with a “gold medal” for academic achievement from the top-ranked pharmacy school in India due to government-subsidized education. I came to the United States for further studies in 2000. Around this time, monoclonal antibodies were being used for various molecular targeting techniques for the first time. I remember attending a seminar at the NYU School of Medicine, which was in proximity to my alma mater, St. John’s University. I was drawn to the colorful antibody-based microscopy images which

The Pharmacologist • September 2023

made me realize the power of the molecular revolution occurring in pharmacology at the time. I think the very next day, I changed my major from a Master of Cosmetic Sciences in pharmacy to degree pathways in Life Sciences which eventually led to a pharmacology-based PhD thesis. A lifetime commitment to pharmacology came during my postdoctoral career at the NYU School of Medicine under Dr. Michael Schlame, a renowned scholar in cardiolipin research.

How did you first get involved with ASPET? I have been a member of FASEB, ASBMB, and ASEPT for more than two decades! As a graduate student, I first presented work at the Experimental Biology meeting in 2003, 20 years ago! My academic journey and work in mitochondrial molecular pharmacology encouraged me to become an ASPET member. I was also the Chair of the Graduate Student Organization at my PhD program at St. John’s University and thus a representative from my college to ASPET in the early years. Another deeply impactful career-changing moment came from ASPET, when as a graduate student, I was selected for ASPET’s competitive podium presentations alongside prominent national scholars. I am grateful to ASPET for encouraging young scientists through this inclusive approach. This early national-level recognition galvanized my intent as a minority individual in the sciences to continue to conduct good science.

What do you want the ASPET membership to know about you and your ideas on how to move the organization forward during your term? I am a servant leader who is committed to inclusion, diversity, equity, and accessibility (IDEA) principles. Two decades of IDEA work in science education, policy, bench research, the scholarship of teaching and learning, assessment, accreditation, and organizational health and vitality have chiseled my personal and professional identity. My experience includes service as a national accreditor of US Doctor of Pharmacy programs, national Chair of the American Association of Colleges of Pharmacy’s (AACP) Global Education, leader of AACP’s international delegation to Cuba, and scholar and advocate for embedding service-learning medical, pharmacy, and dental medicine experiences for our most vulnerable BIPOC, migrant, unsheltered, and LGBTQIA+ communities. I am committed to working with ASPET, listening carefully for a needs assessment as occurring with the Nova initiative, followed by imbibing what we learn into enhancing an inclusive and positive organizational culture within ASPET. As Chair of the IDEA Committee and a member of the ASPET Council, I will foster collaborative approaches to build IDEA principles into the warp and weft of ASPET’s organizational framework. For this, working with the IDEA Committee, I will establish strategies, create programming, and support initiatives embedding IDEA into five initial focus areas of education, advocacy, industry pharmacology, scholarship, and organizational health and vitality.

What has been your proudest accomplishment in your career so far? I feel that the biggest achievement of my career has been the trust my colleagues, fellow scientists, senior university leadership, national organizations, and international partners have placed me in over the years. I am equally proud of the trust and affection I have received from my undergraduate, graduate, and professional degree program students in pharmacology in Doctor of Pharmacy and Doctor of Audiology programs. National recognition for junior faculty and postdoctoral fellows whom I have mentored, especially those from minority and/or

underrepresented backgrounds in pharmacology gives me a lot of satisfaction. For instance, I am most proud that my postdoctoral fellow, Dr. Adeleke Badejo, a Nigerian-Canadian, won first prize in the prestigious Dolores Schockley Poster Competition in 2017 at the ASPET meeting in Chicago. This is another shining example of ASPET’s longtime commitment to inclusion and diversity and encouraging young scientists from a minority background to make strides in pharmacology research. Of course, my induction by ASPET’s Division for Pharmacology Education as a Fellow of the Academy of Pharmacology Educators was a career milestone for recognition of a lifetime of service in pharmacology education, especially for underrepresented students.

What advice would you give young scientists who are just starting out in their careers? Stay “hungry” cultivates a deep and insatiable passion for your work and allow this “hunger” for excellence to drive all your decision-making. Listen carefully to perspectives different from your own and invest in building relationships. Work hard and strive to be the best but stay mentally and emotionally flexible throughout your career. Only those prepared for opportunities can make the most of them.

What do you want your legacy to be as the first Chair of the IDEA Committee for ASPET? As ASPET’s inaugural IDEA Chair, I want to enhance and foster positive organizational culture and ASPET’s organizational health and vitality. IDEA work can be challenging and should be approached with cultural, intellectual, and philosophical humility. I would like to foster sustainable and cooperative strategies that ensure that all pharmacologists regardless of race, ethnicity, gender, gender expression, sexual identity, US or international status, socio-economic status, or the field of practice within pharmacology feel welcome and supported at ASPET. I will strive to enhance visibility for minority and minoritized lived experiences, including for indigenous cultures in pharmacology to build a better, more aspirational future for all pharmacologists.

The Pharmacologist • September 2023

ASPET 2024 Annual Meeting News The ASPET Annual Meeting is the place to discover and to present the highest quality, innovative science in pharmacology and experimental therapeutics. The 2024 Annual Meeting will build on the success of our redesigned 2023 meeting that warmly welcomed more than 1,000 participants to our home for pharmacology.

2024 Highlights

Keynotes

Poster Presentations

Listen to inspirational insights from world-renowned experts, join thought-provoking discussions, and interact with keynotes and award winners.

Present your work to a robust and engaged crowd and receive valuable feedback. Discover young talent doing fascinating work in your field and adjacent to your field. Enjoy our evening poster receptions.

Concurrent Sessions Participate in a mix of shorter, faster-paced concurrent sessions that take a broad approach to pharmacology or dive deep into a divisional area. Hear from a diversity of voices representing scientific excellence and professional development.

The Pharmacologist • September 2023

Community Building Deepen valuable connections with old friends and colleagues as well as build new relationships with prospective scientific collaborators, mentors, trainees and employers in a wide range of pharmacologic research areas.

Location, Location, Location Less than four miles from the National Mall in Washington, D.C., and a half-mile from Ronald Reagan National Airport (DCA), the Hyatt Regency Crystal City is Arlington, Virginia’s largest meeting hotel. All sessions and posters will be held at the hotel. We’ll head off site for our opening event to explore the nation’s capital.

ASPET 2024 Important Dates September 29

February 8

Last day to submit a session proposal

Deepest registration discounts end

October 2

February 22

Last day to apply for the year-round 2024 Washington Fellows program

Last day to submit an abstract to be considered for a poster presentation

December 7

April 2024

Last day to submit an abstract to be considered for a speaking opportunity, travel award or poster award

Online VIP award lectures and division town halls

December 14

May 16-19 ASPET Annual Meeting in Arlington, Va.

Last day to apply for the ASPET Mentoring Network (orientation takes place at the Annual Meeting)

ATTENTION: PIs and faculty

Partner with ASPET

Encourage your students and postdocs to join ASPET now. With payment of their 2024 dues, the remainder of the 2023 dues year is free. This opens their access to apply for ASPET programs supporting young scientists such as annual meeting travel awards, poster awards, Mentoring Network, Washington Fellows and more!

Do you want to connect with more than 1,000 scientists at all career stages who are leading cutting-edge research in pharmacology and experimental therapeutics? We are seeking corporate, academic and government partners to join us in supporting our mission to accelerate the discovery of cures for disease. Contact partnerwithus@aspet.org.

The Pharmacologist • September 2023

Schedule at a Glance THURSDAY, MAY 16

FRIDAY, MAY 17

SATURDAY, MAY 18

SUNDAY, MAY 19

8:00 am

Breakfast Business Meeting

Keynote / General Session

9:00 am

Keynote / General Session

Concurrent sessions

Networking break

10:00 am

Networking break Early arrivals

11:00 am 12:00 pm

Optional Activities: Community service project Extra ticket tourist activities

Concurrent sessions Concurrent sessions Lunch break

Lunch break

1:00 pm 2:00 pm 3:00 pm

Concurrent sessions

Networking break

Concurrent sessions

Networking break

Poster Presentations and Reception

Opening General Session with Keynote

4:00 pm 5:00 pm 6:00 pm

Concurrent sessions

Closing Awards Luncheon

Optional Activities: (Extra tickets) ADDC/ASPET Academic Drug Discovery Colloqium (3pm Sun thru 5pm Mon) Tourist Activities

7:00 pm Welcome Event (off-site)

Why Present Your Research with ASPET? We welcome you and your latest research results for inclusion at the ASPET 2024 Annual Meeting. Share your work. ■ Receive feedback on your work ■ Present a scientific poster to a global audience ■ Publish your abstract in a special supplement to The Journal for Pharmacology and Experimental Therapeutics (JPET) ■ Contribute to the pharmacology community’s

The Pharmacologist • September 2023

collective knowledge with the discussion of successes and challenges

Advance your career. ■ Receive recognition for your scientific advances ■ Spark conversations with potential research collaborators and employers

■ Network with peers and international experts in your specialty ■ Be considered for speaking opportunities (if abstract received by Dec. 7)

Apply for financial assistance and prizes. ■ Apply for travel awards* ■ Compete for poster presentation awards* ■ Save at least $50 on abstract processing fees for presenting authors who are ASPET members Don’t miss your chance to be part of the outstanding ASPET program.

Submit your abstract by Thursday, December 7: ■ To be considered for speaking opportunities in sessions or poster presentations ■ To apply for student/postdoc travel awards *

■ To apply to take part in the student/postdoc poster award competition * ■ To receive early notice (Feb. 2) if accepted for an oral or poster presentation

Submit your abstract by Thursday, February 22: ■ To be considered for a poster presentation ■ To receive notification by March 22 if accepted * The presenting author must be an ASPET member in good standing for 2023 and 2024 in an eligible young scientist category. Be sure to renew your ASPET membership for 2024 or join now!

Did you know? ASPET members who are presenting authors save at least $50 on abstract submission fees.

ASPET Seeks Abstracts in These Research Areas ■ ■ ■ ■ ■ ■ ■ ■

Cancer Pharmacology Cardiovascular Pharmacology Cellular and Molecular Pharmacology Central Nervous System Pharmacology Behavioral Central Nervous System Pharmacology Neuropharmacology Drug Discovery and Development Drug Metabolism and Disposition Pharmacogenomics and Translational Pharmacology

■ Pharmacology Education ■ Toxicology ■ Other (including COVID-19, health disparities, science policy and other specialties) ATTENTION: Students, post-bacs and postdocs: You must be an active ASPET member for 2024 to be eligible for awards. Renew now to participate!

Opportunities for Young Scientists ASPET is dedicated to helping early-career scientists showcase their research, expand their scientific experience and make connections with pharmacology experts. The ASPET 2024 Annual Meeting will provide many opportunities for early-career scientists, including undergraduates, post-baccalaureate students, graduate students and postdoctoral scientists. ■ Travel Awards with free registration and up to 4 hotel nights complimentary ■ Poster Competition with cash prizes

■ Oral Competitions with cash prizes ■ Oral Presentations in platform sessions, showcases, and the datablitz ■ Peer Mentoring match-ups ■ Mentoring Network (year-round program with orientation at annual meeting) ■ Washington Fellows program in government and science policy ■ Career Development sessions geared to young scientists ■ Career Display Tables to learn about university programs and job prospects

The Pharmacologist • September 2023

Pharmacology for Cats and Dogs By Rebecca J. Anderson, PhD For a long while, Fluffy had not been feeling quite herself. The 15-year-old calico was tired, frequently irritable and just didn’t want to play. Fluffy suffered from chronic kidney disease, and like many older cats with kidney disease, her blood pressure was too high. The family’s veterinarian was concerned because hypertension often accelerates kidney deterioration, leading to kidney failure. He invited Fluffy’s owners to have her participate in an experimental study, which was testing a new antihypertensive treatment for cats.

The Pharmacologist • September 2023

Comparative Pharmacology There are about 1,600 drugs specifically labeled for veterinary use, compared to about 20,000 drugs approved for people (1). In fact, for many animal species, there are diseases and conditions for which no suitable veterinary drug is available. Veterinarians, like physicians, may legally prescribe human drugs for conditions (and species) not approved by the Food and Drug Administration (FDA). In the veterinary community, off-label prescriptions are called “extra label” use (1, 2).

Developing a new animal drug follows a similar process as that for human pharmaceuticals, and the FDA requires the same level and amount of data for approval. But animal healthcare companies face challenges and complications that do not occur with human pharmaceuticals (2). Animal species (and breeds) vary in size, behavior, metabolism, and lifespan. Those factors largely account for the differences in pharmacokinetics and toxicity profiles. Drug assessment, particularly regarding side effects, is further complicated because animals cannot directly communicate with investigators (2). For these reasons, the FDA requires that a veterinary drug label must include species-specific dosing instructions, and the label may also impose restrictions that are not part of a human drug label (2). The review and approval process is handled by the FDA’s Center for Veterinary Medicine. The agency evaluates and regulates new drugs for seven “major” species (cats, dogs, horses, cattle, pigs, chickens, and turkeys), as well as all “minor” species, including fish, ferrets, goats, sheep, birds, rabbits, guinea pigs, reptiles, zoo animals, wildlife, and bees, among others (1, 2). Because of the species differences and other variables not present in human pharmacology, the cornerstone of veterinary medicine is “comparative pharmacology.” That is, the systematic study of how different species (and breeds) handle and respond to a drug.

Fluffy Steps Up Telmisartan (Micardis) is a non-peptide angiotensin II receptor blocker and was already approved by the FDA to treat people with hypertension. So, the purpose of Fluffy’s clinical trial was to confirm that the appropriate dose adjustments had been made for optimal treatment of cats. Considerable data had already been collected from preclinical animal studies that had been conducted to support the original human drug approval of telmisartan. Only two additional issues needed to be addressed.

https://twitter.com/US_FDA/status/1429050070243192839?lang=en

The basic principles of drug action are identical across veterinary and human pharmacology (2). But estimating the optimal dosing regimen for an animal using a human drug is often little more than guesswork. Each animal species (and breed) may respond with different pharmacokinetics, pharmacodynamics, and adverse effects.

U.S. FDA Tweet on Ivermectin

The FDA requires data from one well-controlled trial showing that the drug works in the “target animal species” (1). Often, such as in this case, the trial is a field study, which evaluates how the drug performs when the animal is in its normal environment (that is, under “field” conditions). Fluffy’s owners agreed to enroll her in the study. She was one of 221 cats in the placebo-controlled, double-blind trial (3). Her owners were taught how to administer the drug solution, which Fluffy slurped daily at home. Fortunately, Fluffy was in the group receiving telmisartan, and after four weeks of treatment, her blood pressure dropped significantly to near-normal. The investigators continued to follow Fluffy for six months. Each day, she took a maintenance dose of telmisartan, and her blood pressure remained under control (3). During development of telmisartan for human use, much of the adverse effect data and specialized safety test results had already been compiled from laboratory animals (mainly rodents and dogs), as well as from people. The only remaining requirement to get regulatory approval of veterinary telmisartan was data showing that the drug was safe in cats (4).

The Pharmacologist • September 2023

10 Typically for a target species safety study, a small number of healthy animals are used, so that investigators can easily identify species-specific side effects and establish the safety margin (1). The study must be conducted under Good Laboratory Practices, and the standard study design recommended by the FDA is extremely detailed and specific. Drug companies rarely deviate from it (4, 5). Assessment of drug safety is based on observations of animal behavior, blood tests, and necropsy, pathology, and histopathology of tissues and organs (1). The target animal safety study for telmisartan was conducted in healthy, normotensive cats. After 6 months of dosing, the cats exhibited no troublesome side effects, and the data were also used to establish the safety margin of telmisartan in cats. In 2018, the FDA approved veterinary telmisartan (Semintra). In doing so, telmisartan became the only angiotensin receptor blocker approved for first-line treatment of hypertension in cats.

the practice is legal. Veterinary drugs are often manufactured in highly concentrated form to accommodate large animals, and the likelihood of overdosing people is a serious concern (6). For example, ivermectin was approved in 1981 as a veterinary medicine. It is widely used to treat worms and other parasites in livestock (6). Subsequently, ivermectin (Stromectol) was approved to treat river blindness, a parasitic infection that is prevalent in Africa. The standard treatment to protect people from acquiring river blindness is a 3- to 12-mg dose given once per year. The average ivermectin dose in cattle is 80-160 mg. So, people are more likely to overdose by taking the veterinary formulation. Ivermectin’s overdose effects include nausea, vomiting, diarrhea, seizures, coma, and sometimes death.

Prescription veterinary drugs, like telmisartan, can be dispensed or prescribed only by a licensed veterinarian. If a drug label’s directions are clear enough for lay people to administer the drug safely and appropriately to the animal, the FDA can permit the drug to be available over the counter (1).

During the COVID-19 pandemic, off-label use of veterinary ivermectin garnered some media attention, but there was never any data showing it was effective for treating or preventing COVID-19. Concerned about the public’s health, FDA officials posted a nowfamous tweet: “You are not a horse. You are not a cow. Seriously, y’all. Stop it….Using ivermectin to treat COVID-19 can be dangerous and even lethal” (7).

But Not Vice Versa

Encouraging New Animal Drugs

Physicians are discouraged from prescribing veterinary drugs for human use, even though

About 70% of American households own pets, totaling nearly 280 million, including 65 million cats and 85 million dogs (2, 8). Pets have close interactions with their owners, and they are increasingly treated like members of the family. Some are comfort or service animals and provide an important wellness function for people. Consequently, many pets receive a high level of medical care, which increasingly resembles human healthcare (9). https://clinicaltrials.vetmed.ucdavis.edu/

Veterinary clinical trials at UC Davis

The Pharmacologist • September 2023

Despite the increased demand for veterinary drugs, the animal healthcare industry has had little incentive to invest in new drug development (2). HealthforAnimals reported that in 2015, it took 6.5 years and $22.5 million to bring a new veterinary drug to market (8). The

11 https://ccr.cancer.gov/comparative-oncology-program/ consortium#:~:text=The%20Comparative%20 Oncology%20Trials%20Consortium,cancer%20to%20 assess%20novel%20therapies.

NCI Comparative Oncology Trials Consortium (COTC) profit margin on those drugs remains far less than the profitability of a new human pharmaceutical (2). To reduce the financial burden on animal healthcare companies, the FDA’s regulatory requirements were amended. Greater flexibility is now permitted in the types of “adequate, well-controlled” trials that are required to establish efficacy and safety. Also, three or five years of patent exclusivity after market approval (depending on certain criteria) has been added to offset the time required to develop a new veterinary drug. Finally, the FDA adopted a phased review process, which created efficiencies for the reviewers, shortened the regulatory review time, and increased the likelihood that the veterinary drug will be approved (2).

New Drugs for Animals Among the companies that have taken advantage of these incentives is Pfizer Animal Health, which recently developed maropitant specifically for veterinary use. Maropitant is a selective neurokinin-1 receptor inhibitor. It binds to receptors in the chemoreceptor trigger zone and the medullary vomiting center, which receive inputs from the many neurological pathways that trigger vomiting. Because of this central mechanism of action, researchers hoped that maropitant would block a broad range of nauseous and emetic stimuli (10).

In a series of studies in laboratory-bred dogs and placebo-controlled field trials with pet dogs, Pfizersponsored investigators showed that, indeed, maropitant had broad efficacy. It prevented vomiting induced by chemotherapy, viral diseases, food and toxin ingestion, intestinal inflammation, opiates, and motion sickness. The results also showed that maropitant prevented vomiting as effectively as, or better than, the commercially available antiemetics (2, 10, 11). Likewise, the target animal safety studies in dogs showed that maropitant is safer than the other antiemetic drugs used in veterinary medicine. Although neurokinin-1 receptors are involved in a wide range of physiological and behavioral responses, the low doses of maropitant used to control vomiting do not cause adverse effects associated with those other physiological functions (2). In 2007, the FDA approved maropitant (Cerenia) as a veterinary prescription drug to manage vomiting in dogs (10). Pfizer Animal Health then sponsored another series of studies in cats. Under both laboratory conditions and in field trials with pet cats, maropitant was effective in preventing vomiting induced by various noxious stimuli, including motion sickness (2, 12). The target animal safety studies showed, like dogs, that there was a wide margin of safety between the effective

The Pharmacologist • September 2023

https://www.cancer.gov/news-events/cancer-currents-blog/2019/ comparative-oncology-dogs-cancer-clinical-trials

NCI Comparative Oncology Program dose and the appearance of adverse effects in cats (12). Based on these data, FDA approved maropitant for cats in 2012. The comparative pharmacology results from these studies reinforced the view that animal clinical trials must be species-specific. Maropitant has a higher oral bioavailability and a longer half-life in cats than in dogs (2). Consequently, the drug label for cats specifies a dose that is one-half the dose listed on the label for dogs.

Helping Human Drug Development Small pharmaceutical companies often lack development resources and sometimes turn to veterinarians to assist with preliminary efficacy testing of their drug candidates before launching clinical trials in people. Investigators at veterinary schools are especially helpful when the target disease or medical condition cannot be easily simulated in the laboratory. For example, Plex Pharmaceuticals in San Diego, Calif., recently received Small Business Innovation Research grants from the U.S. National Eye Institute to test their novel anti-cataract compounds (13). The protein, alpha-Acrystallin, is a major component of the eye lens and helps to maintain its transparency. Damage or aging can cause aggregation of this protein, and protein aggregation in the lens leads to the formation of cataracts (13). The Plex lead compound, CAP4196, had produced promising results in treating other protein aggregation diseases. The Plex researchers developed a topical eye drop formulation, and they wanted to confirm its efficacy in animals with cataracts before beginning human clinical trials.

The Pharmacologist • September 2023

Age-related cataracts are a major health problem in dogs. By age 13, almost 80% of dogs develop cataracts (14). Surgery is the only remedy currently available. Plex partnered with researchers at the Univ. of California, Davis, School of Veterinary Medicine to test the CAP4196 formulation. The UC Davis veterinarians are recruiting 24 pet dogs for the trial. Each dog must be at least eight years old and have age-related cataracts. The randomized, placebo-controlled study will follow CAP4196 treatment at two different doses for 9 months (14). The Plex researchers hope that the data from the UC Davis trial, along with other preclinical and regulatoryrequired studies, will be sufficient to gain FDA clearance to start Phase I clinical trials of CAP4196 in patients with cataracts (13).

Repurposing a Drug Sometimes, investigational drugs intended for people are redirected to veterinary medicine. For example, when Gilead Sciences decided to discontinue its human clinical trials of rabacfosadine, the small biotech firm, VetDC, acquired the veterinary rights to the drug (15). In 2019, VetDC licensed the compound to Elanco Animal Health, a global leader in animal healthcare products, for further development and commercialization (16). Rabacfosadine is a nucleotide analog that preferentially targets lymphoid cells and causes cell death by inhibiting DNA polymerases. One-quarter of all dogs will be diagnosed with cancer in their lifetime, and lymphoma is one of the most common types of cancer seen by veterinarians (15, 16). The efficacy of rabacfosadine in dogs was established in a masked, randomized, placebo-controlled clinical trial (16). Researchers at several veterinary schools recruited 158 pet dogs of various breeds. Each dog had been diagnosed with multicentric lymphoma. For the dog to be included in the trial, researchers needed to be able to externally measure at least one peripheral lymph node tumor (16). Every three weeks, the owners brought their pets to the clinic for a 30-minute intravenous infusion of rabacfosadine (or placebo solution), for a total of five doses over 15 weeks (16). Complete or partial responses were observed in 73% of the rabacfosadine-treated dogs. The compound was not

13 only more effective, but also required less frequent dosing than human cancer drugs, which are the only alternatives for dogs with lymphoma (15). The target animal safety assessment was based on three studies using healthy beagles. Because of their demeanor and uniform size, beagles are specifically bred for laboratory studies and toxicology testing. Rabacfosadine was well-tolerated at the doses used for cancer treatment. In 2021, the FDA gave full approval of rabacfosadine (Tanovea) as a prescription drug for the treatment of lymphoma in dogs. In so doing, rabacfosadine became one of the most comprehensively studied treatment options for dogs with lymphoma (16).

Veterinary Pharmacology Research Pharmacologists at veterinary schools conduct a wide range of research, from comparative pharmacology studies to experimental therapeutics. Sometimes, their basic research findings serve as the starting point for development of a new veterinary drug by an animal health company or a new treatment option for practicing veterinarians. In some cases, those discoveries are also leveraged to improve human therapeutics. For example, veterinarians at Cummings School of Veterinary Medicine (Tufts Univ.) discovered genes in dogs that are biomarkers for canine compulsive disorder. These genes correlate with an increased incidence of stereotypical behaviors such as tail chasing (9). In one series of studies, the Tufts researchers collaborated with colleagues at Harvard, MIT, and the Univ. of Massachusetts Medical School to search for behavior-associated genes in Doberman pinschers. Up to 30% of Dobermans display compulsive behaviors such as incessant licking of flanks or sucking on blankets (17). In Dobermans that exhibited compulsive behavior, the researchers found a mutation in CDH2, a gene on chromosome seven. This canine gene codes for the same protein that is coded by a corresponding gene on chromosome 18 in humans. Mutations of chromosome 18 are associated with various human psychiatric disorders (17). Researchers in China found this same gene, CDH2, was associated with the compulsive circling behavior in Belgian Malinois. Interestingly, German shepherds,

a breed similar to Malinois, are also known to circle compulsively (17). CDH2 is involved with the development of glutamate receptors, and dysfunction of glutamate neurotransmission has been associated with obsessive compulsive disorder (OCD) symptoms in humans (18). With this in mind, Nicholas Dodman and colleagues at Tufts found that memantine, an Alzheimer’s drug that blocks brain glutamate, significantly reduced the compulsive behaviors of dogs (17). Michael Jenike at McLean Hospital in Belmont, Mass., followed up with a pilot study in 44 OCD patients who had not responded to SSRIs, the standard-of-care treatment for OCD (17). Half of the OCD patients were given memantine, and the other half received standard cognitive behavioral therapy. Only the memantinetreated patients exhibited significant decreases in their OCD symptoms (19). Subsequent clinical trials confirmed the efficacy of memantine, and Tufts patented memantine as a new treatment for OCD (17). Until now, investigational psychiatric drugs that showed impressive efficacy in animal models have often failed in patients with psychiatric disorders. Because of this lack of predictive correlation, the pharmaceutical industry has reduced research and development of new psychiatric drugs over the past 50 years (20). The results from the Tufts genomic studies in dogs and the therapeutic efficacy of memantine in both dogs and patients demonstrate the value of canine compulsive disorder as a valid model of OCD in people (9). It also suggests that a genomics approach may lead to better and more predictive animal models of the complicated neural networks associated with psychiatric disorders (20).

"The cornerstone of veterinary medicine is “comparative pharmacology,” that is, the systematic study of how different species (and breeds) handle and respond to a drug." The Pharmacologist • September 2023

Innovative Therapeutics In addition to genomic and other basic science studies, researchers at veterinary schools also explore innovative therapeutic regimens for animals. For example, veterinary researchers are investigating new drug combinations for osteosarcoma (bone cancer). Large, long-legged dog breeds are especially prone to develop osteosarcoma, an aggressive and malignant form of cancer that affects more than 10,000 dogs in the U.S. each year (21). The annual incidence of bone cancer in people is much less: about 1,000 cases, mostly children and young adults (21). Because of the small number of human cases, conducting clinical trials in people with osteosarcoma is challenging, and there is little incentive to fund those trials (22). Consequently, no new drugs or treatment regimens for osteosarcoma have been

"Investigators at veterinary schools are especially helpful when the target disease cannot be easily simulated in the laboratory." developed in over 35 years. On the other hand, the high incidence of osteosarcoma in dogs offers an opportunity to accelerate this research and drug testing (22, 23). Jellybean, a two-year-old Labrador-retriever mixed breed was diagnosed with bone cancer in her hind leg (23). The standard treatment is amputation followed by four rounds of chemotherapy with carboplatin. But despite amputation and chemotherapy, metastases to various organs occur in ~90% of dogs (23).

own immune system can be activated to recognize and kill osteosarcoma cells. Combining drugs that activate the immune system in complementary ways could potentiate their cancer-killing effect. In November 2020, Jellybean’s owners enrolled her in a clinical trial at Tufts Univ. School of Veterinary Medicine (23). They signed an Informed Consent Form and were trained to administer the drugs. Every day, they stuffed three pills in Jellybean’s favorite chickenflavored treats. By Christmas, Jellybean’s tumors had begun to shrink, and they haven’t come back. Now five years old, Jellybean walks with ease, as if she had never had metastatic cancer (23). The drug combo that Jellybean received was toceranib (Palladia), losartan, and ladarixin. Toceranib is a tyrosine kinase receptor inhibitor approved for treating dog tumors. It directly kills tumor cells. Toceranib is also an angiogenesis inhibitor and decreases the blood supply to the tumor. Losartan is an angiotensin II receptor blocker approved to treat hypertension. But at a tenfold higher dose, it also blocks the recruitment of immune cells that stimulate tumor growth (23, 24). Ladarixin is an experimental (unapproved) inhibitor of IL-8 receptors. It inhibits the recruitment of neutrophils. The complementary mechanisms of these three drugs enhance the immune system’s ability to target and kill tumor cells. The response of Jellybean and other dogs to the three-drug regimen was encouraging. But delaying treatment until after amputation and completion of chemotherapy permitted residual tumor cells to become drug-resistant and metastasize (23).

Jellybean’s case was typical. After undergoing amputation and chemotherapy, her cancer quickly spread to her lungs. A dog’s average survival time is about two months after metastases are detected (23). But Jellybean had another treatment option.

The Tufts researchers thought that the drug combo would work even better if treatment began earlier (23). In a follow-up study, which is ongoing, the researchers administer the toceranib-losartan-ladarixin regimen prior to amputation. At this early stage, any residual tumor cells are assumed to be more vulnerable to attack by immune cells. Hopefully, the drug combo will prevent the cancer from spreading to the lungs and other organs.

Evidence has accumulated from both laboratory studies and human clinical trials that an individual’s

In parallel with this trial, academic researchers at Children’s Hospital Colorado launched a Phase I

The Pharmacologist • September 2023

Pet Clinical Trials

https://www.vet.upenn.edu/veterinary-hospitals/ryan-veterinary-hospital/ services/comprehensive-cancer-care/cancer-care-clinical-trials

clinical trial (NCT03900793). This ongoing dose-escalation study is recruiting 41 children and young adults who suffer from resistant or recurrent osteosarcoma. The patients are receiving losartan and sunitinib (Sutent), a tyrosine kinase inhibitor that has been approved for human use and is analogous to the veterinary-approved toceranib.

melanoma) share features with human cancers (23, 25). Those animal tumors not only look the same as human tumors microscopically, but also mutations in the same genes often drive emergence and spread of the cancer (22). Given those similarities, it is perhaps not surprising that pet and human cancers seem to respond to treatments in similar ways (23).

As these examples suggest, Cancer trials in pets also provide researchers now recognize that pet data that have fewer uncontrolled dogs and cats have advantages variables that might interfere over lab-raised animals for Veterinary clinical trials at with interpreting drug efficacy. assessing human drugs. Pets are University of Pennsylvania Cancer patients typically must exposed to much of the same fail the standard of care (often environment as humans. They chemotherapy) before enrolling. Also, because it is share the same homes, consume the same water considered unethical to give a cancer patient only and foods, and are exposed to a number of the same an experimental drug (that might not work), they are hazards (21-23, 25). usually given the best-known effective treatment, in Because of their high level of medical care, the pets’ detailed medical records are often available (25). Unlike humans, there are fewer medical confidentiality concerns (e.g., HIPAA regulations), making data sharing easier (22). Cats are 90% genetically identical to humans, and dogs are 95% identical. Not surprisingly, similar genetics and a similar living environment make pets and their owners vulnerable to many of the same health risks (26). Like humans, cats and dogs naturally acquire diseases, such as obesity, diabetes, heart disease, and cancer (23, 26). Laboratory rodents, on the other hand, must be manipulated to induce a disease condition, and they have proven to be less reliable in predicting human responses to drug treatment (22, 23). For example, only 15% of cancer drug candidates survive to Phase III after successful preclinical testing in laboratory animals. Only half of the cancer drugs in Phase III trials will be approved for clinical use, giving an overall success rate of less than 8% (20). Researchers now know that many naturally occurring cancers that affect dogs and cats (including osteosarcoma, breast and prostate cancers, nonHodgkin’s lymphoma, head and neck cancer, and

combination with the experimental drug (22). By contrast, pets can enroll in an animal clinical trial without having their immune system already compromised by earlier (failed) treatments and without an accompanying standard-of-care drug. This makes the efficacy data easier to interpret. Over the past decade, great progress has been made in accumulating comparative genomic data, fostering collaboration between veterinarians and oncologists, and attracting funding for pet clinical trials.

The Comparative Oncology Program About four million dogs in the U.S. are diagnosed with cancer every year, and this large pool of pets promises to speed development of cancer treatments that will benefit both them and their owners (21). This approach is called comparative oncology (25). In 2003, the U.S. National Cancer Institute (NCI) launched the Comparative Oncology Program. Under the Program, NCI works collaboratively with academic researchers at 20 veterinary schools in the U.S. and 2 in Canada to study the biology of a variety of cancers and to assess novel treatments (25). The Program is now funded under the White House’s Cancer Moonshot Initiative and oversees dozens of pet clinical trials (21, 22).

The Pharmacologist • September 2023

https://www.tuftsyourdog.com/doghealthandmedicine/better-canine-cancer-treatments-on-the-horizon/

Veterinary clinical trials at Tufts University NCI and the participating academic veterinary clinics collaborate to design and implement these pet clinical trials, which closely mimic the procedures that are used to recruit, enroll, and treat people in a clinical trial. To participate, the pets must meet strict enrollment criteria. Their owners must sign an Informed Consent Form and follow the protocol procedures stipulated for their pet. Board-certified veterinary oncologists at the veterinary schools are responsible for conducting the trial and monitoring the pets’ health (25). The results from these cutting-edge trials give researchers valuable information on investigational drug pharmacokinetics, pharmacodynamics, dose strength, dosing schedule, biomarkers, toxicity, and various histology endpoints. This comparative oncology information is then used to design additional trials to establish the compounds’ efficacy and safety. Those results will hopefully benefit both animals and people with cancer (25).

polysaccharide that was derived from oats. BG34-200 dramatically increases the level of immune factors (i.e., gamma-interferon and TNF-alpha) at the tumor site. In addition, the compound mobilizes tumor-reactive T cells systemically (27). Unlike many chemotherapy drugs, BG34-200 can be prepared in both oral and injectable formulations. In laboratory mice that have been manipulated to express advanced melanoma, BG34-200 significantly inhibited tumor growth and improved survival (28). These results suggested that immunotherapy with BG34200 might be an effective alternative for patients with advanced melanoma, that is, melanomas that have failed to respond to current standard-of-care treatments (28). To confirm the compound’s efficacy and provide greater justification for human clinical trials, the NCI Comparative Oncology Program is sponsoring a study at the Univ. of Pennsylvania: “Pilot assessment of BG34-200 in spontaneous canine cancers” (COTC029). Up to 10 dogs weighing more than 15 kg are being recruited for the trial. Each dog must be diagnosed with an initial or recurrent solid tumor larger than 2 cm. This pilot study will evaluate the safety of BG34-200, as well as its ability to stimulate the dogs’ immune system, to recognize cancer cells and attack them. In addition to malignant melanoma, the study will also explore the compound’s efficacy against other tumor types, such as mammary tumors, soft tissue sarcoma, and osteosarcoma. Each week during the six- to seven-week treatment period, pet owners will bring their dogs to the Univ. of Pennsylvania clinic, where veterinary oncologists will measure the tumor size and assess drug-related side effects.

Cutting-Edge Trials

Recognizing the great promise of immunotherapy drugs to treat cancer, NCI established a network of five veterinary schools in 2017 to conduct clinical trials specifically of cancer immunotherapy drugs in pet dogs (29). In 2022, five additional academic sites were added. Currently, the cutting-edge immunotherapy treatments being investigated at these ten sites include drug combinations to treat dogs with lymphoma, osteosarcoma, and hemangiosarcoma (29).

For example, investigators at Case Western Reserve Univ. discovered BG34-200, a 200-k Dalton glucose

To ensure the quality and accessibility of data from each dog trial conducted by this network, the School

The Pharmacologist • September 2023

17 of Veterinary Medicine at the Univ. of Pennsylvania was designated as the Data Coordinating Center. The Center compiles data from all of the participating veterinary academic sites, ensures consistency in data collection across sites, harmonizes and integrates the data, and enables researchers to identify important common signals. This aggregated and high-quality data will allow both veterinarians and physicians to make evidence-based decisions when selecting treatment plans for their cancer patients (29).

Pet Prominence The first wave of veterinary schools in the U.S. arose in the 1860s at land grant colleges (30). Because the curriculum emphasized agriculture, engineering, and the “practical arts,” the land grant colleges were located in predominantly rural agricultural areas. Consequently, veterinary students at these schools had little exposure to the centers of medical education, which were largely contained within universities in urban areas (30). The main focus of veterinary education, practice, and research in the land grant colleges was related to the health and well-being of livestock and horses (31). Veterinary students consisted mainly of farm-reared boys, because of their intimate knowledge of farm animals (30). Companion animals were not considered a priority for either veterinary education or research (31). Farm experience was the dominant admissions criterion, and there was a strong bias against admitting veterinary students from urban areas (30). At some veterinary schools, applicants had to validate their farm proficiency by harnessing work horses, backing two-wheeled wagons with a tractor, and placing milking machines on cows (32). Given this situation, few women were admitted to veterinary schools in the 19th and early 20th centuries (32). The emergence and evolution of veterinary pharmacology paralleled changes in society and attitudes toward animals (6). In the mid-20th century, veterinary medicine shifted from a predominantly large animal practice to increasing consideration of companion animals. As pets became more integral family members, their health became a greater concern, and pet owners were more willing to invest in pet care (6, 31).

"Pet dog and cat tumors not only look the same as human tumors microscopically, but also mutations in the same genes often drive emergence and spread of the cancer. "

In 2022, spending on veterinary care reached $35 billion (9, 33). Much of this is spent on prescription and over-the-counter drugs (9). The median lifetime drug expenditures for a dog are $5,154 and for a cat are $5,325 (8). Increased pet owner demands encouraged more veterinarians to specialize in companion animal care, which in turn, drove veterinary college faculties to, slowly but steadily, increase coursework on small animal medicine (31). At the same time, thanks to the passage of Title IX in 1972, the barriers to acceptance of women students into veterinary schools were relaxed (31). The number of female veterinary students increased dramatically, and this trend continued over the following decades. By 2000, the gender ratio of veterinary students settled at ~80% women and 20% men. As a result, over half of practicing veterinarians are now women (31). Many of those women are drawn to veterinary positions in pet hospitals or group veterinary practices in urban areas, both of which cater mainly to cats and dogs. Large animal veterinary medicine is still needed, and those veterinarians must comply with special regulations regarding drugs prescribed for foodproducing animals, such as cattle and chickens, and performance animals, such as racehorses. But that’s another story.

The Pharmacologist • September 2023

References 1.

Food and Drug Administration (August 14, 2020) From an idea to the marketplace: the journey of an animal drug through the approval process; available from: https://www.fda.gov/animal-veterinary/animal-healthliteracy/idea-marketplace-journey-animal-drug-throughapproval-process. 2. Riviere JE and Papich MG, eds. (2018) Veterinary Pharmacology and Therapeutics, Tenth Edition. Wiley Blackwell, New York. 3. Coleman AE, Brown SA, Traas AM, Bryson L, Zimmering T, and Zimmerman A (2019) Safety and efficacy of orally administered telmisartan for the treatment of systemic hypertension in cats: Results of a double-blind, placebocontrolled, randomized clinical trial. J Vet Intern Med 33: 478-488. 4. FDA Guidance for Industry #104 (July 10, 2001) Content and format of effectiveness and target animal safety technical sections and final study reports for submission to the division of therapeutic drugs for non-food animals; available from: https://www.fda.gov/regulatoryinformation/search-fda-guidance-documents/cvmgfi-104-content-and-format-effectiveness-and-targetanimal-safety-technical-sections-and-final. 5. Wolford S, personal communication, May 8, 2023. 6. Lees P, Fink-Gremmels J, and Toutain PL (2013) Veterinary pharmacology: history, current status, and future projects. J Vet Pharmacol Ther 36(2): 105-115. 7. FDA Tweet (August 21, 2021); available from: https:// twitter.com/US_FDA/status/1429050070243192839. 8. Animal Health Institute. Approval and regulation of animal medicines; available from: https://ahi.org/ approval-and-regulation-of-animal-medicines/#toggleid-4. 9. Eaton H (July 27, 2017) 3 Major pet medications developed with animal testing. Foundation for Biomedical Research; available from: https://fbresearch. org/3-major-pet-medications-developed-animal-testing. 10. Food and Drug Administration (March 1, 2007) New animal drugs: maropitant Federal Register 72(40): 92429243. 11. Vail DM, Rodabaugh HS, Conder GA, Boucher JF and Mathur S (2007) Efficacy of injectable maropitant (Cerenia) in a randomized clinical trial for prevention and treatment of cisplatin-induced emesis in dogs presented as veterinary patients. Vet Comp Oncol 5(1): 38-46. 12. Hickman MA, Cox SR, Mahabir S, Miskell C, Lin J, Bunger A, and McCall RB (2008) Safety, pharmacokinetics and use of the novel NK-1 receptor antagonist maropitant (Cerenia) for the prevention of emesis and motion sickness in cats. J Vet Pharmacol Ther 31(2): 220-229.

The Pharmacologist • September 2023

13. Watson WH (July 8, 2020) Plex Pharmaceuticals awarded $1.6 million in grant funding from NIH to advance eye drop therapy for cataracts; available from: https://www.biospace.com/article/releases/plexpharmaceuticals-awarded-1-6-million-in-grant-fundingfrom-nih-to-advance-eye-drop-therapy-for-cataracts/. 14. UC Davis (2023) Investigation of CAP4196 in dogs with age-related cataracts; available from: https:// studypages.com/s/investigation-of-cap4196-in-dogswith-age-related-cataracts-144797/?ref=gallery. 15. Dashiell N and Maciejewski E (January 30, 2020) Animal research still helps animals, too! Foundation for Biomedical Research; available from: https://fbresearch. org/animal-research-still-helps-animals-too. 16. Morehouse S (July 19, 2021) Tanovea (rabacfosadine for injection) receives full FDA approval as first treatment for lymphoma in dogs: Elanco acquires product from VedDC, Inc.; available from: https://www.elanco.com/enus/news/tanovea. 17. Rajewski G (November 20, 2015) Tracing the roots of OCD in pets and people. Tufts now; available from: https://now.tufts.edu/2015/11/20/tracing-roots-ocd-petsand-people. 18. Dodman NH, Ginns EI, Shuster L, Moon-Fanelli AA, Galdzicka M, Zheng J, Ruhe AL, and Neff MW (2016) Genomic risk for severe canine compulsive disorder, a dog model of human OCD. Intern J Appl Res Vet Med 14(1): 1-18. 19. Stewart SE, Jenike EA, Hezel DM, Stack DE, Dodman NH, Shuster L, and Jenike MA (2010) A single-blinded case-control study of memantine in severe obsessivecompulsive disorder. J Clin Psychopharm 30(1): 34-39. 20. Tseng G, Ma T, and Zou J (July-August 2023) Of mouse models and humans. American Scientist 111(4): 213-215. 21. CBS (November 27, 2022) Dogs may hold key to treating cancer in humans. CBS 60 Minutes; available from: https://www.cbsnews.com/news/dogscomparative-oncology-60-minutes-2022-11-27/. 22. Jones S (June 20, 2023) Dog cancer research advances pursue of drugs for humans and canines. Washington Post; available from: https://www.washingtonpost.com/ wellness/2023/06/19/dog-cancer-trials-drugs-humantreatment/. 23. Weiss S (May 11, 2023) Your dog is a secret weapon in the fight against cancer. Wired; available from: https:// www.wired.com/story/dog-cancer-treatments/. 24. Regan DP, Chow L, Das S, Haines L, Palmer E, Kurihara JN, Coy JW, Mathias A, Thamm DH, Gustafson DL, and Dow SW (2022) Losartan blocks osteosarcoma-elicited monocyte recruitment, and combined with the kinase inhibitor, toceranib, exerts significant clinical benefit in canine metastatic osteosarcoma. Clin Cancer Res 28(4): 662-676.

25. National Cancer Institute: Comparative Oncology Program; available from: https://ccr.cancer.gov/ comparative-oncology-program. 26. Konkel L (September 25, 2012) Pets share owners’ diseases. Scientific American; available from: https:// www.scientificamerican.com/article/pets-share-ownersdiseases/. 27. Cheung N-KV (March 24, 2009) Cancer treatment using beta-(1-3)-(1-4)-glucan. US Patent 7,507,724 B2. 28. Roche V, Sandoval Vi, Senders Z, Lyons J, Wolford C, and Zhang M (2022) BG34-200 immunotherapy of advanced melanoma [COTC029]. Cancers (Basel) 14(23): 5911. 29. Baillie KU (October 18, 2022) NIH-funded canine immunotherapy data center charts a path toward transformative therapies. Penn Today; available from: https://penntoday.upenn.edu/news/nih-funded-canineimmunotherapy-data-center-charts-path-towardtransformative-therapies. 30. Smith DF (2010) 150th anniversary of veterinary education and the veterinary profession in North America. J Vet Med Ed 37(4): 317-327. 31. Smith DF (2013) Lessons of history in veterinary medicine. J Vet Med Ed 40(1): 2-11. 32. 32. Smith DF (2011) 150th anniversary of veterinary education and the veterinary profession in North America, part 2, 1940-1970. J Vet Med Ed 38(1): 84-99. 33. American Pet Products Association (2023) Pet industry market size, trends & ownership statistics; available from: https://www.americanpetproducts.org/news/ News-Public-Relations/pet-industry-market-size-trendsownership-statistics.

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 feature Goodman and Gilman’s World War II.

Don't miss the January issue.

The Pharmacologist • September 2023

Science Policy News The 2023 ASPET Washington Fellows have authored policy briefs as part of their experience in the Washington Fellows Program. A policy brief is a summary of information with recommendations that highlights a policy problem and helps readers understand, and likely make decisions about, government policies. The fellows were asked to write a brief on any policy area that interests them. This final activity for the 2023 Fellows Program provided an opportunity for participants to implement what they learned from the program that included advocacy and policy writing. Their briefs also provide writing samples they can use in the future. This section includes policy briefs from eight of the fellows.

The Rapid Rise of Dietary Supplement Consumption: A Case for Increased Efforts Towards Regulation and Safety Research Caitlin J. Risener, M.S., PhD Candidate Emory University, Molecular and Systems Pharmacology

What are Dietary and Herbal Supplements? Dietary supplements are defined by congress in the Dietary Supplement Health and Education Act (DSHEA) of 1994 as products that are taken orally (as a capsule, tablet, powder, or liquid), intend to supplement the diet, include one or more dietary ingredient (i.e., vitamins, minerals, herbs or other botanicals, amino acids, enzymes, tissues from organs or glands, or extracts of these). Herbal supplements (also referred to as “botanicals”) are a subset of dietary supplements that contain one or more herbs.

Rapid Market Growth of Dietary and Herbal Supplements Dietary and herbal supplement sales are multi-billiondollar industries steadily increasing over the last decade in the United States. Experts estimate that the overall sales of dietary supplement market ($33.7 billion as of 2020) will increase by 4% by 2025. Herbal supplement sales in 2011 totaled $5.302 billion, then increased nearly 140% to $12.350 billion by 2021. The COVID-19 pandemic contributed to a notable spike in sales for all dietary supplements

The Pharmacologist • September 2023

(7.5%), with a 17.3% increase in herbal supplement use from 2019 to 20206-8. These trends suggest that many U.S. residents placed trust in what they believed to be “natural” remedies during difficult times in public health.

“Natural” Does Not Necessarily Mean “Safer” Many dietary supplements are marketed based on potentially harmful understudied ingredients using overzealous claims not backed by scientific research. The lack of appropriate research funding towards safety and pre-market regulation for dietary supplements poses a risk to public health. Though sales of herbal supplements increased tremendously, the funding towards researching safety and efficacy of all dietary supplements remains inadequate with a steady average of $262.7 million from 2012-2022. In 2020, $318 million of government funds were devoted to dietary supplement research, which was only 0.94% of the revenue brought into the U.S. market from dietary supplement sales. While the United States Food and Drug Administration (FDA) regulates medical products under the U.S. Department of Human and Health Service, many consumers are unaware that the FDA does not

approve dietary supplements for safety and efficacy before they are sold to consumers. However, the FDA does investigate concerns regarding a product’s compliance with laws and regulations after entering the marketplace as described under the DSHEA.

Dietary Supplement Misinformation on Social Media Social media provides fast and easy to digest information to consumers, but the rise of health-related misinformation on various platforms (such as TikTok) is concerning. While many posts are well meaning, there are also financial incentives for some content creators promoting their own storefront or programs to sell potentially harmful “natural” alternatives for weight loss supplements, sexual stimulants, and products to reverse or prevent liver disease. Examples include: Berberine falsely promoted as a “natural” alternative to Ozempic for weight loss “100% Herbal Viagra” found to be adulterated with the FDA-approved active synthetic molecule in Viagra Avenir Nutrition “Liver Shield” – a dietary supplement that claims to cleanse and support the liver

The Future of Dietary Supplement Research and Regulation: In March 2023, the FDA announced in its budget request of $7.2 Billion for the 2024 Fiscal Year, highlighting numerous ways funds will be invested into dietary supplement safety and efficacy efforts, as well as modernizing the DSHEA. These changes would expand the transparency of dietary supplements in the marketplace, while also clarifying the FDA’s authority. In addition to the FDA, many dietary supplements are funded by The Office of Dietary Supplements (ODS) and the National Center for Complementary and Integrative Health (NCCIH). The ODS is the branch of the National Institute of Health (NIH) responsible for strengthening the

research and public education efforts regarding dietary supplements as a result of the DSHEA. The ODS budget for FY2022 was $27.9 million to largely support research. Many of its projects were co-funded with various agencies to promote further research on safety for dietary supplements, with the area of botanicals as the largest co-funded area (50%) in FY2022. The NCCIH is a branch of the NIH focused on strengthening the scientific information available regarding the usefulness and safety of complementary and integrative approaches. The FY2023 budget was $170.3 million, with a large focus on dietary supplement research. The NCCIH issued multiple notices from 2020-2023 highlighting funding opportunities for programs such as Centers for Advancing Research on Botanicals and Other Natural Products (CARBON) Program, Botanical Dietary Supplement Research Centers (BDSRC), and Center of Excellence for Natural Product Drug Interaction Research.

Consumer Resources: ■ To better inform consumers, the FDA released the Dietary Supplement Ingredient Directory in March 2023. This resource allows the public to access all current information for ingredients listed in dietary supplements and will eventually serve as a tool to alert consumers of unlawfully marketed ingredients and other advisories. ■ The FDA publishes Warning Letters – Health Fraud for consumers to cross-check their dietary supplements for all fraud including adulterated products and any unapproved or unsubstantiated claims. ■ Independent of government regulation, there are two not-for-profit groups, U.S. Pharmacopeial Convention (USP) and NSF International (NSF) that analyze dietary supplements to verify the product is unadulterated, uncontaminated, and potent. Additionally, these groups will audit the manufacturing facilities. Labdoor is a for-profit option that teams up with FDA-certified laboratories for chemical analysis of dietary supplements.

The Pharmacologist • September 2023

Diversity in STEM Stanley Cheatham, PhD Candidate Virginia Commonwealth University Diversity in science, technology, engineering, and mathematics (STEM) is not just an idea we should strive for—it’s a necessary element for true innovation and the continued advancement of our global society. The interplay of diverse perspectives fosters fresh ideas, spurs creative solutions, and bridges the gap between science and society. Despite this reality, STEM fields continue to struggle with inclusivity and representation, particularly concerning individuals from historically marginalized communities. The need for increased diversity is also not just limited to those who work in the field, but in the experiments and studies done. It is critical that we also emphasize the importance of diversity as it relates to conducting and applying data generated from clinical trials at a population level. The ability to have a diverse workforce that may be able to understand and more effectively advocate for their communities has myriad of benefits for all. The reasons behind the underrepresentation are complex and multifaceted, encompassing systemic barriers that include socioeconomic disparities, lack of social capital, inadequate access to quality education, and persisting biases in the academic and professional world. It is our responsibility as a society to break down these barriers and create a more inclusive environment that celebrates diversity and equal opportunity. One of the primary challenges to be addressed is the “pipeline problem.” Many underrepresented groups have insufficient access to quality education from an early age, setting the stage for ongoing disparities within these communities. This could be mitigated by policies and initiatives that provide equitable access to after-school programming, more robust resources for STEM education at the local level, and mentoring programs to guide these students.

The Pharmacologist • September 2023

Additionally, we need to address biases that are pervasive in our institutions of higher education. Whether overt or implicit, biases can impact hiring, promotion, funding, and recognition in STEM fields, posing considerable obstacles to those who lack the social capital to achieve at a high level. Implementing comprehensive training, prioritizing blind reviews in hiring and grant allocation, and creating systems of accountability can help to rectify these issues. Inclusion is not simply about representation—it is about creating an environment where all voices are valued and heard. This means not only bringing diverse individuals into the room but also ensuring they are given the opportunity to lead and shape the future of STEM. To do so, we must invest in mentorship and leadership development programs, fostering a culture that celebrates unique insights and ideas. We must also not overlook the importance of intersectionality in our conversations about diversity. Individuals can be simultaneously part of multiple underrepresented groups, and these overlapping identities can compound experiences of exclusion or bias. An intersectional approach is key to ensuring that our efforts to promote diversity are truly comprehensive and inclusive. Beyond the moral argument, diversity in STEM offers tangible benefits for innovation and problem-solving. Multiple studies have shown that diverse teams produce more creative solutions and are better at decision-making. In an increasingly global and interconnected world, the diverse experiences and perspectives in STEM are essential to tackling the complex challenges we face. However, achieving diversity in STEM is not the responsibility of a single individual, organization, or sector. It requires collective action from educators, policymakers, industry leaders, and communities. From systemic reforms in education and policy to changes in institutional culture and individual attitudes, we must all work towards a more inclusive future.

Biological Lab Hazard Risks in Politically Unstable Countries Rehab Alharbi, M.S., PhD Candidate Howard University

Summary Biological labs are essential for advancing scientific research, producing vaccinations, and improving public health. However, biological labs in unstable nations face several threats that can significantly affect lab workers, the local community, and global health safety. These hazards include accidental pathogens release, the stealing or misusing of biological materials, and intentional acts of bioterrorism. As a result, it is critical to implement policies and guides to protect biological labs and ensure the safety of lab staff and the public.

The problem Biological lab misuse raises substantial concerns about national security and increases the potential of biohazard occurrences following the takeover of biological labs in politically unstable countries. These risks seriously threaten the safety and security of lab workers and the public community, highlighting the critical need for effective measures to prevent and reduce such occurrences.

Policy highlights To avoid these potential risks, creating comprehensive risk assessments, providing extensive training and safety controls for lab staff, and implementing secure facility design and security protocols are necessary. International collaboration is essential in controlling these risks, and the World Health Organization (WHO), the United Nations (UN), and other international organizations and agencies should lead in providing professional support to countries that cannot manage these risks successfully. We can work together to guarantee that the seizing of biological labs in unstable nations proceeds appropriately and safely and that biohazard incidents are minimal.

Policy recommendations 1.

Risk assessment and management: Biological labs in unstable countries should conduct comprehensive

risk assessments to identify potential hazards and develop risk management plans. These plans should include safe handling and storage of biological materials, emergency response protocols, and ongoing monitoring and evaluation. 2. Design and security of biological labs: Biological labs must be constructed and designed accordingly to guarantee the safe and secure handling of biological materials. This includes using specialized ventilation systems, secure access controls, and physical barriers to prevent unauthorized entry. The facilities should also be regularly inspected and maintained to ensure continued safety and security. 3. Emergency response plan: Biological labs should have an emergency response strategy in place in case of any possible security breaches, disasters, or incidents of violence. 4. Training and awareness: All lab employees should be trained in safety precautions, rescue actions, and the proper handling of biological materials. Furthermore, public awareness programs should be conducted to educate the public about the importance of biological research, the risks involved in lab breaches, and the preventative strategies carried out. 5. International cooperation: Because biological threats are global in nature, it is important to encourage transparency in international cooperation and coordination communication to share best practices and experiences. The WHO, the UN, and other international organizations should lead this effort.

Conclusion Managing biohazard risks in labs in unstable countries is critical for public health and affects the continuing of advanced research. To avoid these risks and any future bioterrorism. It is important to conduct security precautions, and emergency response plans, provide comprehensive training and awareness programs, and international cooperation to help ensure these critical facilities’ safety and security.

The Pharmacologist • September 2023

From Patents to Patients: Rethinking Drug Patent Rights for a More Accessible Future Cuauhtemoc Ulises Gonzalez, PhD Candidate University of Texas MD Anderson Cancer Center at the UTHealth Houston

Mission ■ Reduce drug prices in the United States ■ Major Policy Recommendations to Congress 1. Remove the sole production rights obtained from a drug patent and allow generics to go through FDA approval sooner. 2. Ownership rights are maintained from a drug patent and generics must pay royalties to the drug patent owner for an extended duration longer than the current 20 years.

Introduction: Pharmaceutical patents The Patent Act of 1952 was signed into law by President Harry S. Truman to establish the provisions and principles surrounding patent rights in the United States. Since its establishment it has been amended to adopt a 20-year patent term from the initial 17-year patent term. In addition, to address concerns regarding access to affordable drugs and to continue fostering the innovation of drugs, the Drug Price Competition and Patent Term restoration Act of 1984 was enacted, also known as the Hatch-Waxman Act. While the 20-year term derives from the Patent Act, the Hatch-Waxman Act set up a pathway for generic drugs to be developed and introduced before the expiration of patents if they can prove the patents are invalid, unenforceable, or that the generic will not infringe on the patent. Lastly, the U.S. Food and Drug administration is the regulatory agency in charge of maintaining the safety, efficacy, and quality of drugs marketed in the United States.

has negatively impacted the people of United States as it limits access to healthcare for those in lower socioeconomic status. While high drug prices in the United States compared to other countries can be attributed to multiple complex factors, one factor that is rarely discussed is the large investment required to produce drugs. Pharmaceutical companies are invested in multiple drugs at a time as it is estimated that 0.1% of these drugs reach the counter, and it can take 10+ years for one drug to reach the counter due to the required FDA regulations that keep our drugs safe, effective, and high-quality. This leaves pharmaceutical companies with less than 10 years to recover their investment and profit to continue drug research and development, forcing companies to inflate their prices during their patent lifespan. This is in addition to the returns expected of investors. Pharmaceutical companies have also found ways to circumvent the 20-year lifespan of a drug by including patents surrounding the drug formulation, delivery, and equipment. This allows them to extend their patent and prevent generics from being produced and competing. Because competition allows drugs to be cheaper to the public due to cost and demand, action must be taken to tackle the issue of pharmaceutical companies needing to recoup their investments within a 10-year timeframe.

Proposal: Win-win for the public and drug companies. While the Hatch-Waxman Act aimed to address drug accessibility and promote the free market, it does not do this sufficiently. Therefore, I propose congress make policy changes on the patent system set for new drug development. To benefit U.S. citizens and pharmaceutical companies, the following aim must be met.

Current Challenges: Drug patents promote drug Reduce the cost of drugs while continuing to price hikes and obstruction of competition. incentivize drug development. Based on 2017 statistics, the United States sits at the top in pharmaceutical expenditure with $1220 price per capita when compared with the next four countries’ price per capita of $963, $838, $823, $806 which is 21%, 31%, 32%, 34% cheaper than that of U.S., respectively. This

The Pharmacologist • September 2023

To reduce the cost of drugs, generics must be allowed to initiate production earlier than allowed by the current patent system; therefore, the sole production rights generated by a patent must be removed, but rights to ownership should

be unaffected. Drug must be allowed to be produced as a generic by the time it is FDA approved. Generics will still have to comply with current FDA approvals. To keep pharmaceutical companies motivated to continue Research & Development programs, pharmaceutical companies will have appropriate royalties paid by generic drug producers for a longer lifespan than then currently set by patents but no longer than 50 years. This will allow pharmaceutical companies to continue to have profit and incentive for further drug development.

Limitations: Economic analysis Not enough studies have measured the lifespan use of an FDA approved drug before it is replaced by a newer drug or better treatment, therefore, it may be difficult to quantify the appropriate royalties. However, royalties should be calculated so pharmaceuticals can recover costs in 40 years after FDA approval and recalculated as more generics enter the market. This allows pharmaceuticals to spread the same profits which would be generated in 10 years to 40 years but reduce the cost to the public. However, the specific details of these proposals would require careful consideration and economic analysis by government officials.

Implementation: Reward successful drugs To initiate the new method and motivate pharmaceutical companies to transition,

pharmaceutical companies would be allowed to apply for small NIH funded grants for newly developed FDA approved drugs that aim to reimburse drug developers a small fraction of the cost and aid new research and development. In a sense, reward drug developers who have produced a novel FDA approved drug and have allowed generics to be produced immediately after FDA approval.

Conclusion In conclusion, the current pharmaceutical patent system, along with the Hatch-Waxman Act, have tried to balance drug accessibility and innovation. However, challenges remain in ensuring affordable drug prices and promoting market competition. I propose congress to make policy changes that address these challenges by allowing earlier production of generic drugs while still incentivizing drug development through longer royalty payments. These policy amendments, along with additional policy changes, have the potential to benefit both the public and pharmaceutical companies. Allowing pharmaceutical companies to be apply for small reimbursements by the NIH can further incentivize pharmaceutical companies to transition towards more affordable and accessible drugs. By addressing these issues, along with other issues in healthcare, we can foster a healthcare system that ensures access to affordable medications while encouraging innovation for the benefit of patients and society.

From Cells to Humans: Are We Too Eager to Eliminate Animals in Research? Donnell White, III, PhD Louisiana State University Health Sciences Centers New Orleans

Executive Summary On December 29, 2022, President Joe Biden signed the FDA Modernization Act 2.0 (S.5002) into law, removing the requirement that animal studies must be done to obtain a license for biological products, such as vaccines or pharmaceutical drugs. This poses an enormous risk to human health, as there is no standardization process for these alternative models, and they have yet to meet the needs that animals provide for screening of adverse

events. The overarching goal is to ensure these products are safe for human clinical trials while decreasing animal research use. I propose increasing funding to make more effective, innovative, and efficient alternative models, and raise awareness efforts to educate the general public and policymakers about the critical role that animals have and continue to play in saving millions of human lives.

Current Landscape of Pharmaceutical Testing and Public Perception of Animal Use in Science Animals have been used in biomedical science for hundreds of years. Specifically, mice and rats are

The Pharmacologist • September 2023

the most utilized subjects for studies investigating modernized vaccines and potential pharmaceutical candidates. Animals have been involved in scientific breakthroughs such as vaccine development, and the discovery of insulin, penicillin, cochlear implants, and inhalers. Even with the groundbreaking impact animal testing has had on human lives, animal research is a controversial and emotional topic for many. Recent statistics show that about half of the Western population favors animal testing, while the other half opposes it. Animal rights groups, such as People for the Ethical Treatment of Animals (PETA) and the Humane Society of the United States (HSUS), are dedicated to advocating for the complete opposition of animal research or demanding significant limitations when using animal models. The FDA Modernization 2.0 Act allows alternative models to be sufficient before testing in humans, bypassing animal experiments altogether. These alternatives, called New Approach Methodologies (NAMs), aim to limit animal use by utilizing cell-based models and artificial intelligence that mimic how an organ system might respond to a bioactive compound. Data collected from NAMs are combined to help understand possible interactions between different organ types. Although this may seem a great solution to a controversial issue, significant concerns remain: ■ Obtaining adequate data to derive a conclusion from a disjointed physiological system is challenging and, in many instances, impossible. ■ Comprehensive systemic and organismic-level biology cannot be studied using current alternative models. ■ Public misinformation surrounding animal research remains prevalent, leading to social and policy barriers that harm human health. Bypassing animal testing before human trials will cause detrimental harm to human health, as alternative models are not adequate substitutions at this time.

Approach 1: Increase the quality and standardization of alternative models. Animal testing limits unnecessary adverse events that may occur in human trials. Alternative models do not currently have the capabilities to understand how a pharmaceutical candidate might interact between organ systems in the human body. Thus, significant progress

The Pharmacologist • September 2023

must be made to create high-quality, standardized models that can provide adequate human-like physiological data in response to biological products. Standardized NAMs will decrease animal use in research as they can more efficiently streamline projects, resulting in only the most promising pharmaceutical candidates advancing to animal experiments.

Approach 2: Increase public awareness of animal treatment and care in research. Support from the general public is essential, as policymakers want to ensure they receive support from their constituents regarding the policies they vote for. With the current pharmaceutical landscape, it is vital that both the general public and government officials be better informed of the contributions animals make to scientific discovery and innovation to keep animal testing legal and required for biological products. Increasing awareness can help the general public understand the intense review processes before animal experiments to ensure they are cared for in the best way possible.

Recommendations for Policy Change Recommendations for Approach 1: Policymakers should devote a subset of NIH-funded grants to alternative model standardization and utility. ■ Every year, millions of dollars are spent on animal care and housing at academic institutions across the United States. Animal use in screening products can be minimized by aliquoting a subset of animal care grant funding to create better physiologically replicative NAMs. This action would ensure that only the most promising developments are used for animal experiments. ■ Educating investigators via NIH-funded workshops on NAMs’ usability and protocols will increase use and awareness among investigators, ensuring that valuable funding is not spent on unnecessary animal work when NAMs would meet similar screening needs. Recommendations for Approach 2: Public and policymakers’ perceptions of animal testing must become more positive to maintain adequate support and funding for animal research.

■ Implement an NIH-supported “Animal Research Awareness Day” for the public and policymakers, providing tours of animal research facilities and informational sessions about established organizations like the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) and Institutional Animal Care and Use Committees (IACUC). ■ Provide and advertise government funding for organizations that find animals long-term housing after experiments are complete, ensuring the continued care of these animals after the lab. This can be accomplished through partnerships with non-profit organizations that focus on animal care post-experiments. The initial connections and partnerships required for this initiative can be created through the annual Animal Research Awareness events. ■ A subset of the current animal care funding allotment should provide the resources and training for this approach. The organization and

execution of Animal Research Awareness Day should be tasked to the NIH’s Office of Laboratory Animal Welfare.

Conclusion The safety of future patients and clinical trial subjects should be the primary concern and goal of all researchers, scientists, and advocates. Ensuring the safety of both animals and humans can only be determined with comprehensive animal studies. Although both animal advocates and scientists aim to eliminate the need for animal testing eventually, it is doubtful and unrealistic that animal models will become irrelevant for many years. However, thanks to innovative technologies and forward-thinking scientists, alternative models can provide more data than previously, allowing for advanced screening before entering animal models, reducing costs and resources, and decreasing the use of animals when not necessary.

Maternal Vaping: A Safer Alternative or a Potential Threat to Next Generation Sabrina Rahman Archie Texas Tech University Health Sciences Center The widespread use of electronic cigarettes or vaping among young populations including pregnant women presents a serious public health concern. This policy brief covers the popularity of maternal vaping, explains the potential health consequences of maternal vaping on pediatric health, summarizes the current policy on e-cigarette use regulation and recommends the necessary steps required for policy development to protect the next generation.

What is Vaping? Vaping is the use of a battery-powered device, known as electronic cigarette or e-cigarette (e-cig), to inhale an aerosol derived from a heated liquid compound. It was introduced in the U.S. market in 2007 as a safer alternative to conventional tobacco smoke (TS) and has become extremely popular among all age groups and sexes. Apart from recreational purposes,

it is being used as a smoking cessation and tobacco replacement therapy.

Prevalence of Maternal Vaping E-cig use is increasingly prevalent among pregnant women, ranging between 5% and 15% of the surveyed pregnant population within the last five years. Several factors are responsible behind e-cig popularity among pregnant women, including usage out of curiosity or as a TS replacement therapy. In fact, sometimes pregnant women perceive e-cig as a safer alternative of TS and switch from tobacco smoke to e-cig during pregnancy.

Potential Health Consequences of Maternal Vaping The main ingredient in most of the e-cig products available in the U.S. market is nicotine at various concentrations. However, a vast array of other toxic chemicals including any number of approximately 7,000 flavoring agents, humectants, contaminants, (e.g. metals, formaldehyde, acrolein, and tobacco-specific

The Pharmacologist • September 2023

nitrosamines) as well as thousands of unknown chemicals are present in e-cig liquid. When e-cig was introduced in the U.S. market 15 years ago, there were limited preclinical and clinical studies to ensure the safety of e-cig in maternal and pediatric health. Since then, however, several studies have reported that maternal vaping may increase the risks of fetal health outcomes including but not limited to pre-term birth, reduced birth weight, cerebrovascular, respiratory, and cognitive dysfunction. These preclinical findings should raise concern among those who believe that the use of e-cig is less harmful than traditional tobacco cigarettes for pregnant smokers.

Current Policy on e-cig Use Regulation ■ Federal Regulation: The U.S. Food and Drug Administration (FDA) passed a rule in 2016 (effective from August 08, 2016) deeming that all tobacco products be brought under the purview of Federal Food, Drug, and Cosmetic Act; thus, authorized the FDA to regulate all tobacco products including e-cig to prevent a younger generation from becoming addicted to nicotine through e-cig products. ■ State Regulation: As of December 31, 2022, all 50 states have passed legislation prohibiting the sale of e-cig to underage persons, 33 states have passed legislation that requires a retail license to sell e-cig over the counter, 17 states have passed comprehensive smoke-free indoor air laws that includes e-cig and 30 states have passed legislation imposing a tax on e-cig.

Policy Recommendation on Maternal Vaping to Protect the Next Generation As of today, there is no legislative, regulatory or policy guidance for e-cig use during pregnancy. The following recommendations for e-cig use during pregnancy can be implemented based on maternal smoking regulations and current trend of maternal vaping. 1. Public Awareness: Develop comprehensive public awareness campaigns targeting both pregnant women and healthcare professionals to build awareness about the risks of maternal vaping and promote tobacco cessation resources. 2. Regulation on Labeling: Reinforce regulatory frameworks to warrant appropriate labeling for

The Pharmacologist • September 2023

e-cig products, including clear warnings about the potential health risks of maternal vaping on the product labeling. Education and Training: Educate and train the health care professionals on the risks of maternal vaping so that they can provide accurate information, counseling, and cessation support to pregnant women. Research and Surveillance: Invest in further preclinical and clinical research to elucidate the long-term health effects of maternal vaping on postnatal health and establish comprehensive surveillance systems to monitor trends and inform evidence-based interventions. Affordability: Reduce the affordability of disposable e-cig products by implementing taxation to disincentivize purchasing. Regulation on e-cig Advertisement: Implement stricter regulation on the advertisement and promotion of e-cig products on social media. Currently, the Advertising Standards Authority and Committee on Advertising Practice does not have rules for advertisement and promotion at point of sale, and this loophole needs to be addressed. Multi-Sectoral Collaboration: Collaborate among healthcare providers, public health agencies, researchers, policymakers, and advocacy groups to develop policy and implement comprehensive strategies to control maternal vaping. Industry Responsibility: Encourage e-cig manufacturers to prioritize public health by transparently disclosing ingredients, reducing nicotine content, and supporting evidence-based research on the safety of their products during pregnancy.

Conclusion Maternal vaping may pose potential risks for maternal and fetal/postnatal health. Hence, policy development for the regulation of maternal vaping is required to address this emerging public health concern. By implementing the recommended policy guidance, policymakers can raise awareness, promote research, provide support for pregnant women; thus, can help to reduce the prevalence of maternal vaping and protect the health of neonates as well as mothers.

Securing the Early Career Research Pipeline Paul Panipinto, PM, PhD Candidate Washington State University, College of Pharmacy and Pharmaceutical Science

Executive Summary Post-doctoral researchers have long been a critical component of U.S. biomedical research. Over the last two decades the job quality of these positions has degraded significantly, causing double digit decreases in the number of biomedical post-docs. The NIH has been unable to address this issue substantially leading to piecemeal attempts to address the problem by states. This has caused considerable disruption to academic budgets and workers. Comprehensive changes including a minimum pay scale, attaching the growth of future pay to fair market value and adequate funding by congress to enable this without harming U.S. research output are critical to restoring America’s early career biomedical research pipeline.

Critical Shortages of US Post-doctoral Researchers Between 2001 and 2021 the U.S. Post-doc rate – the rate at which newly minted PhDs enter a post-doctoral training position – for biological and biomedical sciences declined from 76% to 65%. This substantial drop is even more concerning given that every other field tracked by the National Science Foundation (NSF) demonstrated strong growth in the same 20-year period, with most showing double-digit increases. Anecdotal reports of difficulty finding people to fill post-doctoral positions, even for well-established and funded labs, have been relegated to the career sections of journals like Science and Nature with very little done to improve the issue. The White House and the National Institutes of Health (NIH) have begun to act by holding listening sessions to gather the opinions of stakeholders. However, as the COVID pandemic demonstrated, the security of our biomedical research pipeline is a critical issue that affects the sustainability of the U.S. health science system that the world depends on. As participation in these positions decline in the U.S., they will inevitably move to international

competitors, further hindering a field that has long set the standard for the world.

A Decade of Education Rewarded by Low Pay and Poor Working Conditions The two most common routes for biomedical PhDs have long been either moving to an academic postdoc at a research university or moving into the biomedical industry. Academic post-docs have for decades been the traditional position for those who receive a PhD and are intended provide further training to prepare PhD holders for a faculty position. Over the last two decades these positions have become more focused on producing science than producing faculty with only 9% of post-docs reporting working only their contracted hours and 61% reporting that they work more than six hours a week over their contract, often without compensation. Additionally, 55% of post-docs spend less than an hour a week with their faculty mentor, stymieing development and creating confusion about what the purpose of the position is2. A survey of top concerns by the National Postdoctoral Association found that 94.8% of postdocs thought their lives were negatively affected by their salary, 90.4% reported a lack of clarity about the pathway to their next position, 87.4% had an unclear definition of their current role, 86.6% were insecure about their job and 92.1% of international post-docs reported additional vulnerabilities due to their visa status. Together these data demonstrate that the professional state of some of our most highly skilled and educated workers is one of crisis.

Piecemeal Attempts and a Federal Solution As noted, the NIH has established working groups to provide potential solutions to this problem. The 21-member committee recently laid out a series of guiding principles that include increasing pay, encouraging employers to provide benefits and capping the length of post-doctoral appointments at the predicted cost of reducing the total number of post-docs supported by the NIH. These would be strong first steps, however, they are nearly identical to

The Pharmacologist • September 2023

the recommendations produced by the working group the NIH convened in 2012. Additionally, reducing the number of post-doctoral positions in the field will lead to a decrease in science produced – the same result we face. Alternatives have also proven problematic with California and Washington State legislatures codifying post-doctoral wages and allowing them to become overtime eligible. This approach has become problematic as faculty mentors – even those who support increased stipends and better working conditions – have found it difficult to reconcile their grant budgets to the new state requirements. This has led to severe responses including a brief strike by University of Washington post-docs. Solving the problems of poor working conditions and worse pay requires a concrete change in strategy from policymakers at the NIH and members of Congress. Lawmakers have tied the salary cap of NIH grant personnel to the Executive II level ($212,000) of the 2023 Executive Schedule Pay Table. This practice has been in place since 1990 with the most recent update in the Consolidated Appropriations Act, 2023. The median biomedical post-doc salary in 2022 was $52,685, much closer to NIH fellowship stipend levels which have become an anchor for compensation, and drastically below the U.S. median salary of $69,717. Outside of academia, the median salary for a biomedical industry post-doc is approximately $90,000. The piecemeal attempts to address this problem have exacerbated the problem by prolonging the crisis while not substantively providing a solution, though they were good faith attempts. Members of the Congress should set a compensation floor for early career researchers tied to executive pay

that acknowledges the critical research work of post-doctoral researchers. The NIH working group has warned that the negative effect of increasing compensation to stem the bleeding of our early career pipeline will lead to drastic cuts in the total number of early career NIH-funded research positions. This means that in addition to establishing a floor, lawmakers should also raise NIH funding to reflect these increases and prevent talented researchers working toward the success of the U.S. biomedical research system to leave either for better paying industry positions or seek a position outside of the United States. Spending additional money on anything – especially when Congress and the Executive are controlled by different parties can be a difficult prospect. Our national debt is near $33 trillion and the clamor for lower spending levels has steadily increased – so much so that once boring debt ceiling bills have become repetitive crises that have damaged the credit standing of the United States. Still, there have been bipartisan efforts for investment and reform in many similar areas such as support for the CHIPS Act of 2022, the National Science Foundation For the Future Act of 2021 and SASTA in 2019 largely because of the real and perceived benefits of investing in America’s research. The NIH must drastically raise wages and tie them annually to their industrial post-doc peer positions to encourage our most talented workers to fill these critical positions. Meanwhile, Congress must work to both fund this change, and mandate increases to the minimum stipends to avoid reducing the scientific output of our biomedical research institutions.

From Bars to Safe Spaces: Exploring Overdose Prevention Centers Elijah Ullman, PhD Candidate Emory University Amidst the ongoing opioid overdose crisis, it is imperative to envision a comprehensive framework for safe drug consumption; we must acknowledge that drug use has persisted throughout human

The Pharmacologist • September 2023

history for tens of thousands of years. Numerous factors contribute to individuals’ motivations behind drug use, and it is worth noting that lab animals will voluntarily self-administer drugs such as fentanyl. Opioid death overdose rates have increased five-fold between 1999 and 2017, coinciding with an increase in adulteration of the illicit drug supply with potent opioids such as fentanyl. Overdose prevention centers (OPCs), also known as supervised consumption

facilities (SCF), are facilities where persons can use drugs while monitored by health care personnel who provide sterile supplies (such as syringes), emergency care if an overdose occurs, primary medical care, and referrals to treatment or social services if needed. OPCs do not provide drugs to people but play a vital role in providing a safer alternative to public drug use. The United States implemented its first SCF in New York City in 2021. Bars can be considered as an existing model for SCFs - people can go to these facilities and consume their drug and are widespread throughout the world. The case for OPCs can be summarized by the following five points:

(1) Preventing fatal overdose incidents. A retrospective analysis of North America’s first SCF in Vancouver, Canada, revealed a significant 35% decrease in overdose rates within a 500-meter radius of the center, compared to a 9.3% decrease in the rest of the city. Similarly, following the opening of a SCF in Sydney, Australia, ambulance calls decreased 80% in the surrounding area5. Contrary to concerns about increased overdose rates due to ‘acceptance’ of drug usage, there is no evidence that OPCs lead to higher drug usage rates. Therefore, these centers provide a public health benefit not only to facility users, but society.

(2) Decreasing the transmission of bloodborne pathogens. Approximately half of worldwide HIV-Hepatitis C (HCV) co-infections occur in people who inject drugs. Injection drug use accounts for one-third of HCV deaths and 10% of new global HIV infections8. Despite limited implementation of SCFs in the United States, HIV testing rates among injection drug users were notably higher at 57% compared to the general population’s rate of 14.8% between 2017 and 2018. Treatment for HIV positive individuals costs were approximately $30,000-$50,000 annually, and HCV-related costs are approximately $53,000. Implementing SCFs and syringe exchange programs are associated with a 50% reduction in new cases of HIV and HCV infections. Distinguished from SCFs, syringe exchange centers, such as Denver, CO’s Harm Reduction Action Center, primarily focus on furnishing sterile supplies, such as syringes and alcohol swabs, without providing direct supervision or oversight during.

(3) Facilitating access to addiction treatment, social support, and healthcare. People who use drugs face significant challenges in accessing adequate medical care due to stigma, the high cost of medical and rehabilitation treatment, and inaccessibility of services (e.g., lack of transportation, especially for drug users living in rural areas). These are massive barriers to care for an already vulnerable population. Additionally, the illegal status of drugs like heroin further discourages seeking assistance due to the fear of criminal charges. OPCs serve as a crucial access point for persons who inject drugs, providing syringe exchange, overdose prevention, on-site medical professionals, and addiction treatment services. Notably, in early February 2023 the first overthe-counter naloxone nasal spray received approval. Naloxone is a potent opioid receptor antagonist capable of immediately reversing overdoses.

(4) Mitigating the issue of syringe litter and reducing public drug use. Public concern over syringe litter associated with individuals who inject drugs stems from both environmental and public health risks, including the potential spread of Hepatitis C and HIV. However, implementation of SCFs in various cities and countries have consistently demonstrated a decrease in the rate of public usage of injection drug use. These facilities not only reduce syringe litter but also promote safer injection practices, with participants reporting decreased rates of syringe sharing, improved injection safety, and more frequent cleaning of injection sites. These outcomes collectively contribute to enhanced safety for both the community and persons who inject drugs.

(5) Delivering cost savings to the community through proactive support instead of reactive measures like street overdose interventions and associated hospital expenses. Numerous reviews have discussed the cost of SCFs, consistently concluding that they generate cost savings of $5-7 for every dollar invested. A study from King County, Wash., found that each hospitalization resulting from a non-fatal overdose costs $17,083. Methods have been developed to assign a monetary value to prevented deaths, typically by calculating

The Pharmacologist • September 2023

the difference between the mean age of people who inject drugs and the standard age of retirement, then multiplying it by the annual per capita income. In the case of King County, the economic value attributed to preventing each fatal overdose is estimated at $566,539. Therefore, implementing these centers represents a massive cost-saving measure for communities across the United States. California’s SB57, vetoed by Gov. Newsom (Nov 2022), would have authorized OPCs. Pennsylvania’s SB 165 seeks to ban OPCs, and Gov. Scott of Vermont signed H.728 (June 2022), imposing a similar ban. In

The Pharmacologist • September 2023

2021, Pennsylvania and California saw daily overdose deaths averaging 14 and 20, respectively; OPCs have proven effective in reducing such fatalities. However, Colorado’s HB 23-1202, Overdose Prevention Center Authorization, passed the House and awaits Senate approval. It is vital to support nationwide adoption of OPCs whenever such legislation appears on the ballot, as they play a crucial role in preventing fatal overdose incidents, mitigating syringe litter and public drug use, enhancing access to addiction treatment and healthcare, and delivering cost savings to the community.

Journals News Call for Papers on Therapeutic Treatments for Genitourinary and Gastrointestinal Disorders for JPET A special section titled “Therapeutic Approaches to Treat Disorders of the Genitourinary and Gastrointestinal Tracts” is being planned for publication in the August 2024 issue of JPET. This special section will feature research elucidating pathophysiological mechanisms of genitourinary (GU) and gastrointestinal (GI) disorders, aimed at identifying clinical biomarkers, developing diagnostic tests, and evaluating the latest therapeutic approaches to minimize symptoms and disease progression in affected patients. Original clinical, basic science, and translational research pertaining to pharmacological, immunologic, hormonal, stem cell, and other therapeutic approaches to treat disorders of the GI and GU tracts will be considered for publication. Full-length original research manuscripts describing repurposed or innovative drug interventions, as well as evaluation of existing treatments, drug delivery systems, and improved therapeutics for GU and GI disorders, are especially welcome. Journal editors highly encourage research papers describing innovative models/ mechanisms to test the latest therapeutic interventions,

sex and age differences, and preclinical/clinical evaluation of lead compounds. Short research reports on novel mechanisms, signaling pathways, and therapeutic targets for understanding the pathophysiology of GI and GU diseases are also considered. Original articles addressing any aspect of the aforementioned topics will be considered. “Expert opinion” reports and mini reviews on the latest advances in GU and GI pharmacology are also encouraged. Please send a pre-submission inquiry including title, author information, abstract, and significance statement to JPET prior to full submission. Guest editors Dr. Anna Malykhina and/or Dr. Luke Grundy will review these inquiries, respond to the authors’ comments, and assess whether final approval will be granted for a full submission. There are no submission fees or page charges for publishing in this special issue, and the accepted manuscript version is published immediately online. All submissions must refer to the journal’s Instructions to Authors, and the submission deadline is December 19, 2023.

DMD Announces New Special Section: “Perspective on Drug Metabolism and Disposition” The ASPET journal Drug Metabolism and Disposition (DMD) commemorates its 50th Anniversary with a special section titled “Perspective on Drug Metabolism and Disposition.” In Part I of the special

section, DMD associate editors share their insights on specific topics within their areas of expertise, shedding light on significant subjects in the field. Noteworthy articles include:

The Pharmacologist • September 2023

■ “Human Absorption, Distribution, Metabolism, and Excretion Studies: Origins, Innovations, and Importance,” in which Dr. R. Scott Obach and colleagues at Pfizer, Inc., offer a historical review exploring the origins of ADME studies, showcasing the advancements made since George de Hevesy’s pioneering work, and emphasizing DMD’s role as a vital platform for disseminating findings. ■ Dr. David S. Riddick’s review article, “Fifty Years of Aryl Hydrocarbon Receptor Research as Reflected in the Pages of Drug Metabolism and Disposition,” examines the effects of pollutant chemicals on hormone functions and the disruption of hepatic P450 enzymes. It offers a decade-by-decade summary of historical discoveries in the aryl hydrocarbon receptor field. ■ “Epigenetic Mechanisms Contribute to Intraindividual Variations of Drug Metabolism Mediated by Cytochrome P450 Enzymes” by Dr. Xiao-bo Zhong and a colleague from the Univ. of Connecticut explores the role of epigenetic modifications, such as DNA methylation and histone

modifications, in intraindividual variations of drug metabolism. ■ Dr. Aiming Yu and colleague’s contribution, “Recombinant Technologies Facilitate Drug Metabolism, Pharmacokinetics, and General Biomedical Research,” highlights the use of bioengineered RNA agents for investigating ADME gene regulation and other areas of biomedical research. ■ Dr. Nina Isoherranen and colleagues’ review, “Impact of Intracellular Lipid Binding Proteins (iLBPs) on Endogenous and Xenobiotic Ligand Metabolism and Disposition,” provides an indepth examination of various aspects of iLBPs, focusing on their potential contributions to xenobiotic distribution and metabolism. More articles are forthcoming in Part II of the special section, providing additional perspectives on drug metabolism and disposition. All content in “Perspective on Drug Metabolism and Disposition,” published in DMD’s June 2023 issue (51/6), is freely accessible through December 31, 2023.

Highlighted Trainee Authors Congratulations to the latest Highlighted Trainee Authors selected for Drug Metabolism and Disposition, The Journal of Pharmacology and Experimental Therapeutics, and Molecular Pharmacology:

Drug Metabolism and Disposition ■ Jing Jin (Univ. of Connecticut) – June ■ Miaki Makiguchi (Lab. of Drug Metab. and Pharmacol. at Showa Pharm. Univ.) – July ■ Dr. Laken Kruger (National Center for Advancing Translational Sciences) – August Jing Jin

Miaki Makiguchi

Dr. Laken Kruger

Yasmin Alkhlaif

Zengtao Wang

Dr. Ronan Lordan

JPET ■ Yasmin Alkhlaif (Virginia Commonwealth Univ.) – June ■ Zengtao Wang (Univ. of Minnesota) – July ■ Dr. Ronan Lordan (Univ. of Pennsylvania) – August

The Pharmacologist • September 2023

Molecular Pharmacology ■ Wataru Koizumi (Fujifilm Wako Pure Chemical Corporation) – June ■ Dr. Alexander Vizurraga (Deep Apple Therapeutics) – July ■ Chaseley McKenzie (Florey Institute of Neuroscience and Mental Health) – August

Wataru Koizumi

Dr. Alexander Vizurraga

Chaseley McKenzie

A brief description of their areas of research, current projects, the anticipated impact of their work, and what they enjoy when not in the lab is online at https://bit.ly/2yX1YeH. We congratulate all of them for being selected.

Peer Review Week September 25-29, 2023, marks the 9th Annual Peer Review Week. The theme for this year’s global event, which celebrates the important role of peer review in maintaining research quality, is “Peer Review and the Future of Publishing.” Some of our editors have weighed in on the question:

“What is your take on Peer Review and where it’s going?” Dr. Beverley GreenwoodVan Meerveld, Editor of The Journal of Pharmacology and Experimental Therapeutics: “The peer-review process, while not perfect, is an important and essential mechanism to ensure the scientific quality, experimental rigor, and level of trust in all submissions to ASPET journals. Reviewers, who are anonymous and unpaid, are being asked to judge the validity, significance, and originality of submitted manuscripts, we well as to look for flaws and finally to recommend improvements. Key to successful reviewing is to find well-trained reviewers with not only expertise in

their research field but also a wellrounded level of experience in the entire review process. At JPET, we recognize that we must play a role in preparing the next generation of reviewers, and we believe that there is a need for comprehensive reviewer training, especially for junior scientists. Therefore, in 2023, JPET developed a new Editorial Fellowship Program. This is a one-year program for individuals with a relevant background to build important skills as a peer reviewer and editor. The program provides an in-depth opportunity to work interactively with a JPET editor, learning important elements of the editorial process including triaging, peer review, and editorial decisions. Fellows also participate in JPET editorial board meetings and meet quarterly together to discuss aspects of the editorial process. JPET editors also encouraged ASPET to recognize the contributions made by reviewers, and in 2023, ASPET developed an award for the top performing reviewers. The future of the peer review process also involves improving the author experience. The use of the pre-submission inquiry process is proving to be enormously popular and is allowing authors to determine the suitability or “fit” of their research for one of our four ASPET journals. I believe that the future of the review process should include providing

The Pharmacologist • September 2023

reviewers with automated reports. These reports include information from image forensics, plagiarism software, as well as tools for assessing experimental rigor including information on blinding, randomization, sample size calculations, and ethical approval statements. Reviewers should be able to review these reports before initiating review of a submitted manuscript. These reports will serve as a valuable supporting role in the review process and hopefully allow reviewers to judge papers and submit reviews in a timely manner.”

Dr. Mike Jarvis, Editor of Pharmacology Research & Perspectives: “Peer review is foundationally important to ensuring the scientific quality of published research. While not a perfect system, editorial boards are highly dependent on the efforts and wisdom of peer reviewers to help authors improve their manuscripts. Specific, objective, actionable, and constructive feedback to authors not only helps authors identify and correct ambiguities in their papers, but also often leads to new insights. Addressing peer review feedback is an excellent opportunity for trainees to pressure test their scientific reasoning and communications. The peer review process itself will continue to evolve and remains a critical component of scientific research.”

Dr. Lynette Daws, Editor of Pharmacological Reviews: “Peer review is the backbone ensuring integrity of published works. It ensures that data are of the highest quality, that all necessary controls

The Pharmacologist • September 2023

are included, that experiments can be reproduced, and that research has been conducted ethically. Peer review is essential for evaluating the originality of scientific reports and reviews. For peer review to work in an unbiased fashion, anonymity of reviewers is crucial. While there has been a push from some journals to do away with protecting the identity of reviewers, this could be the undoing of the peer review process.”

Dr. Xinxin Ding, Editor of Drug Metabolism and Disposition: “As a society journal, we enjoy the loyalty of our members. More than 50% of our reviews are conducted by editorial board members, who are carefully selected and wellregarded experts in the field. I think we will continue to have this advantage as we navigate any changes in the publishing landscape and be confident that our authors enjoy high-quality peer review.”

Dr. John Tesmer, Editor of Molecular Pharmacology: “Peer review is a tool by which the authors of grants and papers can get expert feedback on their proposals and manuscripts, respectively. Overall, it leads to improved submissions and publications, and it would be a loss not to have it as an integral part of our scientific community. But it only works well when the reviewers are savvy in the art of review. Going forward we might see more emphasis on training junior investigators in this arena. And maybe they should be paid for their effort.”

Membership News ASPET welcomes new members. The Society offers a variety of member benefits, including publications, ASPET meetings, ASPETConnect online community, ASPET Career Center, public affairs and advocacy, ASPET awards, ASPET divisions and more.

New Members Regular Members Abdulhakim Abubakar, Ahmadu Bello Univ, Nigeria Millicent Acquah, Kwame Nkrumah Univ, Ghana Ukpe Ajima, Univ of Jos, Nigeria Eman Alefishat, Khalifa Univ, Gulf Med Univ, United Arab Emirates Zhiqiang An, The Univ of Texas Health Science Center at Houston Hadar Arien Zakay, The Hebrew Univ, Israel Joshua Asante, Kwame Nkrumah Univ, Ghana Vahe Bedian, Viridian Therapeutics, MA Andrej Belancic, Clinical Hospital Centre Rijeka, Croatia Blase Billack, St Joh’s Univ, NY Hemanth K. Boyina, Anurag Univ, India Sharada T. Buddha, Saint Xavier Univ, IL Jordi Camarasa, Univ of Barcelona, Spain Raveen Chauhan, Shoolini Univ, India Werner Cordier, Univ of Pretoria, South Africa Olamide O. Crown, Jackson State Univ, MS Ntokozo S. Dambuza, Nelson Mandela Univ, South Africa Collet Dandara, Univ of Cape Town, South Africa Feng Deng, Univ of Helsinki, Finland Bhargavi Desai, Maliba Pharmacy Coll, India Lorena Dima, Transilvania Univ of Brasov, Romania Sharron Dolan, Glasgow Caledonian Univ, United Kingdom Omotayo O. Ebong, Rivers State Univ, Nigeria Priyadarshand Galappatthy, Univ of Colombo, Sri Lanka Juan P. Garcia, Univ Claeh, Uruguay Behnam Ghorbanzadeh, I, Dezful Univ of Med Sci, Iran Vikram Gota, ACTREC, Tata Memorial Center, India Sabrice Guerrier

Girdhari Lal Gupta, SVKM’s NMIMS, India Steven R. Hall, Lancaster Univ, United Kingdom Audrey Hamachila, Univ of Zambia, Zambia Dolores Hambardzumyan, Mount Sinai School of Medicine, NY Diana Hulboy, Focus Biomolecules, PA Hassan M. Ibrahim, Ahmadu Bello Univ, Nigeria Ismaila O. Ishola, Univ of Lagos, Nigeria John Janetzko, Stanford Univ, CA Baiba Jansone, Univ of Latvia, Latvia Marina Junqueira Santiago, MacQuarie Univ, Australia Ashish Kakkar, Postgraduate Institute of Medical Education and Research, India Amin Kamel, Regulus Therapeutics, Inc., CA Onur Kanisicak, Univ of Cincinnati, OH Georgios Kararigas, Univ of Iceland Nilima A. Kshirsagar, Med Res Govt of India Preeti V. Kulkarni, Gahlot Inst of Pharmacy, India Herve Le Louet, CIOMS/Takeda, Switzerland Makhotso R. Lekhooa, North West Univ, South Africa Aashish Manglik, Univ of California, San Francisco Vanessa Marensi, Univ of Chester, United Kingdom Lauren T. May, Monash Univ, Australia Zhangyin Ming, Tongji Med Coll, Huazhong Univ of Sci & Tech, China Xiulei Mo, Emory Univ, GA Darko Modun, Univ of Split, Croatia Tsitsi G. Monera-Penduka, Vitaccess, United Kingdom Benjamin R. Myers, Univ of Utah Sch of Med Muhammad Naveed, Univ of Szeged, Hungary Manjunath Nookala Krishnamurthy, ACTREC-Tata Memorial Centre, India Sanelisiwe Nzuza, Nelson Mandela Univ, South Africa Martha N. Ofokansi, Univ of Nigeria Michael Ofori, Hilla Limann Technical Univ, Ghana

The Pharmacologist • September 2023

Modupe O. Ogunrombi, Sefako Makgatho Health Sciences Univ, South Africa George Owusu, Univ of Energy and Natural Resources, Ghana Sunday Oyedemi, Nottingham Trent Univ, United Kingdom Marie-Neolle Paludetto, Univ of Helsinki, Finland Prashanth Patnaik, Spartan Hlth Sci Univ, Saint Lucia Smita Pattanaik, Post Graduate Institute of Medical Education and Research, India Minoli Perera, Northwestern Univ, IL Amanda L. Persons, Rush Univ, IL Anupama Pradosh, ACTREC, Tata Memorial Hospital, India Ajay Prakash, Post Graduate Institute of Medical Education (PGIMER), India Avi Priel, The Hebrew Univ, Israel Riana Rahmawati, Univ Islam Indonesia Muhammad Ali Rajput, Gulf Medical Univ, United Arab Emirates Rossana Roncato, Univ of Udine, Italy Shakta Mani Satyam, Rak Medical and Health Sci Univ, United Arab Emirates Robert Sears, The Nathan Kline Institute and NYUSOM, NY David M. Shackleford, Monash Univ, Australia Megan Shuey, Vanderbilt Univ, TN Shree Lakshm Devi Singaravelu, Windsor Univ Sch of Med, Saint Kitts And Nevis Harmanjit Singh, Government Med Coll and Hosp, India Shivendra V. Singh, Univ of Pittsburgh Cancer Inst, PA Surender Singh, All India Inst of Med Sci, India Shweta Sinha, Post Grad Inst. of Med Educ and Res (PGIMER), India Donna M. Slater, Univ of Calgary, Canada Brandi L. Soldo S Clare Stanford, Univ College London, United Kingdom Susil Stephen, Central Coast Local Health District, Australia S Chakradhara Rao Uppugunduri, Univ of Geneva, Switzerland Shoban B. Varthya, AIIMS Jodhpur, India Areti-Maria Vasilogianni, The Univ of Manchester, United Kingdom Olafs Volrats, Univ of Latvia, Latvia Merja Voutilainen, Univ of Helsinki, Finland

The Pharmacologist • September 2023

Jenny Wen, Kumquat Biosciences, CA Tri Widyawati, Univ Sumatera Utara, Indonesia Miao Yan, The Second Xiangya Hosp of Central South Univ, China Cafer Yildirim, Ankara Univ, Turkey

Affiliate Members Lujain Aloum, Khalifa Univ, United Arab Emirates Fatima A. Ismaeili, Primary Healthcare Corp, Qatar Reagan Ivey Eloise Kuijer, Univ of Bath, UK Henry Mugerwa, Joint Clinical Res Centre, Uganda Maria Francesca Nani, Federico II Univ, Italy Aisha N. Rayashi, Primary Health Care Corp, Qatar Anil K. Sahu, AIIMS, New Delhi, India Sarah Seeley, Ohio Northern Univ, OH Vimal Singh, Gulf Med Univ, United Arab Emirates Obaalologhi Wilfred, Ritman Univ, Nigeria

Postdoctoral Members Abdmajid S. Hwej, Univ of Glasgow, United Kingdom Mukesh Kumar, The Univ of Hong Kong Bikash Medhi, Post Grad Inst of Med Educ & Res, India Aishatu Shehu, Ahmadu Bello Univ, Nigeria Baiba Svalbe, Latvian Inst of Organic Synthesis, Latvia Haily Traxler, Univ of Kentucky

Graduate Student Members Oluwatobi D. Akinsanya, Rosalind Franklin Univ, IL Sarah K. Al Saad, Univ of Pittsburgh, PA Mia Allen, Wake Forest Univ School of Medicine, NC Lauren Anderson, Univ of California, Davis Fatima Auwal, King’s College London, United Kingdom Ishumeet Kaur Bajwa, Post Grad Inst of Med Educ and Res (PGIMER), India Moleboheng E. Binyane, Walter Sisulu Univ, South Africa Kelvin Cheung, Univ of Nottingham, United Kingdom Dillon Clemmer, Univ of Kentucky Weverton C. Coelho Silva, Univ of Sao Paulo, Brazil Matt Collins, Duke Univ, NC Dehan Comez, Univ of Nottingham, United Kingdom Kelly Conger, Univ of Illinois Chicago Kenneth B. David, Kaduna State Univ, Nigeria Peace Doe, Kwame Nkrumah Univ of Sci and Tech, Ghana Haritha George, Univ of Illinois Chicago Ayush Goel, Univ College of Medical Sci, India Md Mahmudul Hasan, Univ Paris-Saclay, France Fiona Healy, Univ of Liverpool, United Kingdom

Kylie Hornaday, Univ of Calgary, Canada Md. Monir Hossain, King’s College London, United Kingdom Mariya Jacob, Univ of Glasgow, United Kingdom Anna Kelis, King’s College London, United Kingdom Ashok Kumar, Post Grad Inst of Med Educ & Res (PGIMER), India Camille Ledoux, Univ of Texas Medical Branch Kaisa Litonius, Univ of HelsinkI, Finland Chenge Liu, Cornell Univ Med Col, NY Ronan Lordan, Univ of Pennsylvania , PA Chitaranjan Mahapatra, Indian Inst of Technology, India Kelli McDonald, Auburn Univ, AL Shamiso Mlambo, Univ of Pretoria, South Africa Aiman S. Mohammed, Univ of Szeged, Hungary Tyler A. Natof, Southern Illinois Univ School of Medicine Comfort S. Nyarko Snr, Kwame Hkrumah Univ of Sci and Tech, Ghana Kwabena Oteng-Boahen, Central Univ Ghana Hafiza Parkar, Univ of Pretoria, South Africa Lauren C. Parr, Vanderbilt Univ, TN Rashmi A. Patil, Poona College of Pharmacy, Bharati Vidyapeeth, India Varsha Rathore, National Tsing Hua Univ, Coll of Med, Taiwan, Province Of China Nimmy Robin, Univ of Glasgow, United Kingdom Aryan Shekarabi, Univ of Minnesota Sathyanarayani Srishanmuganathan, King’s College of London, United Kingdom Elizabeth Tom, Univ of Glasgow, United Kingdom Paige Van Ditta, Univ of Alabama Andrea Woodcox, Univ of Kentucky Vaishali Yadav, Jamia Hamdard Univ, India Alina Zorn, Univ of Glasgow, United Kingdom

Post-baccalaureate Students Christopher M. Babcock, Univ of Michigan Kamden T. Kuklinski, Washington Univ Sch of Med, IL

Undergraduate Students Erica J. Acox, Delaware State University Astha Adroja, Rutgers, The State Univ of New Jersey Caylee A. Brown, Univ of Maryland, Baltimore County Autumn E. Buck, Mount Aloysius College, PA Madison A. Bunce, Univ of Texas at Dallas Tom Cai, Ernest Mario School of Pharmacy, NJ Chloe Chung, Case Western Reserve Univ, NJ Emily N. Clark, Univ at Buffalo, NY

Aracelys Colon, North Carolina Central Univ Brendan T. Connor, Rowan Univ, NJ Adrita Dasgupta, Rutgers University New Brunswick, NJ Sophia D. Fanzini, Univ of Maryland Jasmine D. Ferguson, North Carolina A&T State Univ Anaya J. Forte, North Carolina Central Univ Rain M. Freidt, Univ of North Dakota Alison E. Fullington, Univ of Washington Caleb J. Glenn, Howard University, DC Aakanksh Goskonda, Univ of North Carolina Chapel Hill Jaedyn D. Haverstock, Miami Univ Lib Raul Hernandez Robles, Morgan Community College, CO Caroline Hertweck, Univ of North Carolina Nhan Huynh, Wabash College, IN Chioma T. Ibeanu, Univ of North Carolina at Chapel Hill Andrew Jelinsky, Rutgers University, NJ Lafilissa Joao, North Carolina Central Univ Ben R. Kean, PPD Inc., OH Komal Kumar, Indiana Univ Benjamin Leid, Central Washington Univ Minghao Li, Wake Forest Univ, NC Oliver J. Liu, Virginia Commonwealth Univ Colton C. Lough, Washington State Univ Marc Louis, John Jay College of Criminal Justice, NY Bradley T. Ludington, Vanderbilt Univ, TX Inocent T. Maturure, The College of St. Scholastica, MN Stephanie P. Mera, High Point Univ, NJ Shuchi V. Merai, Rutgers Univ, NJ Charlese Miller, Georgia State Univ Andrei Mistreanu, Univ of North Carolina Amanda L. Murphey, Hiram College, OH Richard C. Nicosia, SUNY Buffalo, NY Nicole Ntim, Univ of Cincinnati, OH Kelly Nugent, Univ of Michigan Eve Painter, The College of Wooster, OH Chelsea Park, Univ of Virginia Taylor M. Peach, Univ of Cincinnati, KY Evan J. Peters, Univ of Notre Dame, OH Chi D. Phan, Univ of California, Davis Nathan Reudink, Gonzaga Univ, WA Armando J. Rios, Rutgers University Samuel L. Roberts, Univ at Buffalo, NY Mateo J. Rodriguez, Northeastern Univ, MA Hailey D. Rosenfield, Univ of Vermont Maria Ruszkiewicz, Rutgers Univ, NJ

The Pharmacologist • September 2023

Ceylin K. Sahin, Lake Forest College, IL Nancy Sergieva, Glasgow Caledonian Univ Caitlin Shaw, College of Saint Benedict, MN Alexandra A. Smith, College of Saint Benedict, MN Heather Song, Ohio State Univ Catherine M. Stephens, Syracuse Univ, NY

BreAnne D. Stewart, Spokane Falls Community College, WA Jaden Troiano, Univ at Buffalo, NY Sarah L. Whittington, Univ of North Carolina Luke A. Wykoff, Univ of North Carolina at Chapel Hill Salma K. Youssef, North Carolina Central Univ

In Memoriam Salvatore Joseph Enna, PhD. FASPET (1944-2023) was ASPET Past President (20002001) and also selected as an ASPET Fellow in the inaugural Class 2019. Dr. Enna served for six years as editor of The Journal of Pharmacology and Experimental Therapeutics and also served as co-editor of Current Protocols in Pharmacology, Editor-in-Chief of Biochemical Pharmacology, Executive Editor-in-Chief of Pharmacology and Therapeutics and Series Editor of Advances in Pharmacology. Along with his significant impact on pharmacology, Dr. Enna left just as big an impression on many of his colleagues. Several share reflections of how he impacted their lives and the greater pharmacology community. “Sam was one of the kindest people I have ever known, not to mention an outstanding, world class scientist.” Dr. Robert Ruffalo “Sam’s academic and pharmaceutical career as well as his editorial contributions and ASPET leadership roles had an enormous impact on the field of pharmacology. Sam’s earnest enthusiasm for pharmacology was contagious. His midwestern demeanor and chuckle always made you feel that you not only were his colleague but also his friend. He will be missed by all that knew him.” Dr. John Lazo, Past ASPET President “Sam’s passing was, without question, a global loss to the discipline of pharmacology and to the countless number of individuals who had the opportunity over the years to receive and reap the benefits and the joy of knowing and appreciating him. Similar to a diamond, Sam had many facets beyond his radiating

The Pharmacologist • September 2023

personality that were treasured and appreciated. In addition to his achievements, both scientific and administrative, Sam had a commanding presence, a warm and endearing sense of humor and, always, a welcoming and engaging manner. These attributes were also, on occasion, accompanied by a cajoling and unyielding request to take on one of his many initiatives. In my experience, he always succeeded. Sam will remain in the hearts and minds of all with whom he came into contact as someone with an unparalleled passion and unrelenting dedication to serve and elevate national and international pharmacology societies as well as their members. He was indeed pharmacology’s ambassador to the world.” Dr. Jim Barrett, Past ASPET President Benjamin G. Zimmerman, PhD, (1934-2023) of St. Paul, Minn. passed away on April 9, 2023, at the age of 88. Ben had been a long-time member of ASPET. Dr. Zimmerman grew up in New Jersey, attended Columbia University in New York as an undergraduate and received his PhD degree from the Department of Pharmacology at the University of Michigan. He did a postdoctoral fellowship in Pharmacology at the University of Iowa and subsequently joined Lederle laboratories in Pearl River, N.Y. After a short stint at Lederle, Dr. Zimmerman was recruited to the University of MinnesotaMinneapolis, Department of Pharmacology, where he resided and conducted research and taught for the next 40 years. The focus of Dr. Zimmerman’s research was on mechanisms of blood flow regulation, including neurogenic vasodilation, the renin angiotensin (RAS) system and the etiology of hypertension. Local generation of angiotensin by the kidney and the

interaction of the RAS with the sympathetic nervous system were particular interests of his. He also conducted breakthrough research on prostaglandins and kinins and how these vasoactive hormones counterbalance the RAS. Dr. Zimmerman was internationally recognized as a top pharmacologist for his contributions to research in hypertension. His research laid the foundation for the development of new blood pressure lowering drugs. He was honored as a Fellow of the Council on Hypertension of the American Heart Association. Dr. Zimmerman cared for the students and postdoctoral fellows trained in his laboratory at the University of Minnesota. He guided them closely and

never gave up on them. Many went on to successful academic, medical and industrial careers. He worked in the laboratory himself throughout his career and stayed close to his trainees work. Dr. Zimmerman was predeceased by his parents, Paul Zimmerman and Cecile Zimmerman; his wife Brenda Zimmerman; and his son-in-law Howard Linsk. He is survived by his daughters, Karen Linsk and Laura Singer (Jonathan), and his grandson Aaron Singer. Memorials preferred to the University of Minnesota Ben G. Zimmerman Fund, https://makingagift.umn. edu, the American Heart Association, or the Ben G. Zimmerman Pharmacology Travel Award (https://med. umn.edu/pharmacology/awards).

The Pharmacologist • September 2023

Chapter News MAPS to Hold Annual Meeting at UPenn The 2023 Mid-Atlantic Pharmacology Society Annual Meeting will be held Friday, October 20, 2023, at the University of Pennsylvania, Smilow Center for Translational Research in Philadelphia, Pa. The theme of this year’s meeting will be “The Pharmacology of Mental Health.” Each meeting consists of talks organized around a topic of current interest in pharmacology and a competitive poster session. A renowned scientist (several of these have been Nobel laureates) is invited to present the Keynote lecture on the major theme of the meeting. After the Keynote presentation, threeto-five scientists from the region will give 30-minute presentations on their area of expertise as it relates to the theme of the meeting. Two trainees also are invited to present their research in 10-minute talks as part of the symposium. Time for the audience to ask questions is always provided and discussion is encouraged. The annual Biotechnology Roundtable follows the talks, engaging the audience in lively Q&A with a panel of three-to-four scientific representatives from regional biotechnology companies. The meeting schedule includes time for poster viewing and networking over lunch and at the awards reception.

The Pharmacologist • September 2023

In some years, MAPS annual meetings have also included workshops about careers in pharmacology for students and postdoctoral researchers. The Society seeks to maintain a dynamic existence and draws upon its Board of Councilors, as well as members, to suggest new and timely topics for each meeting. Interested in attending? Register at https://tinyurl.com/mwr9f6up.

Consider submitting your work to an ASPET Journal! ASPET members gain access to all content in the journals, along with reduced or waived fees if they publish. Here’s what our journal editors have to say: “ASPET’s Drug Metabolism and Disposition (DMD) journal wants to become “an instrument of greatest usefulness to the community of workers in the field.” This noble wish has been an important guiding principle for the journal as it stood the test of time and became the leading journal in the drug metabolism and disposition field. Over the past 50 years, DMD has published nearly 9,000 papers. It is the journal of choice for publishing first rate fundamental as well as translational drug metabolism and disposition research, where new trends, regulations, and concepts are introduced, differing opinions are debated, and important works from PhD dissertations and new drug approval pipelines are archived.” XINXIN DING, PHD Editor-in-Chief, Drug Metabolism and Disposition

“At the Journal of Pharmacology and Experimental Therapeutics (JPET), we are committed to growing our readership and making sure published papers have the impact they deserve. Please submit to JPET Special Sections to help to shape our future. You can choose from three new special sections on 1) Quantitative Systems Pharmacology, 2) Clinical Pharmacology and 3) Protein and Peptide Therapeutics.” BEVERLEY GREENWOOD-VAN MEERVELD, PHD, AGAF, FACG, FASPET Editor-in-Chief, Journal of Pharmacology and Experimental Therapeutics

“Pharmacological Reviews provides comprehensive and authoritative articles from thought leaders in the field, making it a one-of-a-kind resource for all interested in the pharmacology of a broad range of areas, crossing the bounds of a wide cross-section of physiological systems. Pharmacological Reviews ranks first for citation half-life and boasts a 2021 impact factor of 20.5. Its comprehensive reviews bring readers up to date with the most current state of knowledge in both classical and new pharmacological spaces.” LYN DAWS, PHD Editor-in-Chief, Pharmacological Reviews

ASPET publishes four highly respected and widely read journals that provide rapid publication and easy access on mobile devices, tablets and desktop computers. The Society co-publishes a wholly open access journal with the British Pharmacological Society and Wiley. Since the launch of JPET in 1909, ASPET has provided scientists in pharmacology and related fields with leading primary research and review articles. ASPET members have access to all journal content as a member benefit.

Dear Subscribers to The Pharmacologist, We appreciate you as loyal readers of ASPET’s flagship magazine. Thank you for your commitment to The Pharmacologist over the years. Your article submissions, story ideas and follow-up have kept us moving forward for decades. With that in mind, we want you to know that we are preparing to launch a new look and feel, and frequency for the magazine. This September 2023 issue of The Pharmacologist will be the last printed issue in this format. Starting in 2024, The Pharmacologist will be distributed in an electronic format only. It will also move to a monthly distribution full of news and information that impacts ASPET members and the broader pharmacology community. The magazine will contain a monthly Cover Story, Features, Member Highlights and Advocacy Impact along with regular columns, ASPET membership news and Highlighted Trainee Authors from ASPET Journals. You will also continue to receive a Message from the President (a recap and outlook from ASPET’s president), A Note from Dave’s Desk (news and information from Executive Officer Dave Jackson), a Leadership Profile (insight on ASPET’s leadership) and other news and information that you can use. We continue to welcome your story ideas and input, and we look forward to receiving them. If you have content for consideration or you are interested in becoming a contributing writer, please let us know your interest via ThePharmacologist@aspet.org. We look forward to serving you through this new partnership in the years to come. Sincerely, ASPET Leadership

The Pharmacologist • September 2023

PRSRT STD US POSTAGE PAID MANASSAS VA PERMIT #250

American Society for Pharmacology and Experimental Therapeutics (ASPET) 1801 Rockville Pike, Suite 210 Rockville, Maryland 20852-1633

The Pharmacologists September 2023

Articles inside

Call for Papers on Therapeutic Treatments for Genitourinary and Gastrointestinal Disorders for JPET

Securing the Early Career Research Pipeline

From Patents to Patients: Rethinking Drug Patent Rights for a More Accessible Future

Biological Lab Hazard Risks in Politically Unstable Countries

Diversity in STEM

Science Policy News

Pharmacology for Cats and Dogs

ASPET 2024 Annual Meeting News

Leadership Profile

The President