Myles H. Akabas

MD-PhD programs prepare physicians for research-focused careers. The challenge for admissions committees is to select from among their applicants those who will achieve this goal, becoming leaders in academic medicine and biomedical research. Although holistic practices are encouraged, the temptation remains to use metrics such as grade point average, Medical College Admission Test scores, and postbaccalaureate gap length, combined with race and ethnicity, age at college graduation, and sex to select whom to interview and admit. Here, we asked whether any of these metrics predict performance in training or career paths after graduation. Data were drawn from the National MD-PhD Program Outcomes Study with information on 4,659 alumni and 593 MD-PhD graduates of the Albert Einstein College of Medicine and the University of Pennsylvania. The Penn-Einstein dataset included admissions committee summative scores, attrition, and the number and impact of PhD publications. Output metrics included time to degree, eventual employment in workplaces consistent with MD-PhD training goals, and self-reported research effort. Data were analyzed using machine learning and multivariate linear regression. The results show that none of the applicant metrics, individually or collectively, predicted in-program performance, future research effort, or eventual workplace choices even when comparisons were limited to those in the top and bottom quintiles.

To reduce debt burden and encourage the pursuit of research-focused careers, most MD-PhD programs provide medical school tuition remission and an annual stipend. However, prolonged training compared with MD physicians postpones the time until MD-PhD physicians earn a full salary. We compared lifetime earning potential for MD-PhD physicians in academia with their MD colleagues in the same clinical specialty. We examined the relationship between earning potential based on specialty and the likelihood that MD-PhD physicians reported being engaged predominantly in research. Lifetime earning potential was estimated using 2020–2021 debt and compensation data for 77,701 academic physicians across 47 specialties. Self-reported research effort for 3,025 MD-PhD program alumni in academia was taken from the National MD-PhD Program Outcomes Study. We found that (a) MD-PhD physicians had a lower lifetime earning potential than MD physicians in the same specialty; (b) there was an inverse relationship between earning potential and research effort in different specialties, with MD-PhD physicians in high-earning specialties tending to spend less time on research; and (c) despite this, MD-PhD physicians in academia were more likely to choose clinical fields that allow more time for research.

The earliest MD-PhD programs were small and enrolled mostly men. Here, we show that since 2014 there has been a steady increase in the number of women in MD-PhD programs, the number of women reaching parity with men in 2023. This change was due to an increase in female applicants, a decrease in male applicants, and an increase in the acceptance rate for women, which had previously been lower than that for men. Data from the National MD-PhD Program Outcomes Study show that training duration has been similar for men and women, as have most choices of medical specialties and workplaces. However, women were less likely to have full-time faculty appointments, fewer had NIH grants, and those in the most recent graduation cohort at the time of the survey reported spending less time on research than men. Previously cited reasons for these differences include disproportionate childcare responsibilities, a paucity of role models, insufficient recognition, and gender bias. Institutions can and should address these obstacles, but training programs can help by preparing their graduates to succeed despite the systemic obstacles. The alternative is a persistent gender gap in the physician-scientist workforce, lost opportunities to benefit from diverse perspectives, and a diminished impact of valuable training resources.

Previous studies on attrition from MD-PhD programs have shown that students who self-identify as Black are more likely to withdraw before graduating than Hispanic students and students not from groups underrepresented in medicine (non-UIM). Here, we analyzed data collected for the National MD-PhD Program Outcomes Study, a national effort to track the careers of over 10,000 individuals who have graduated from MD-PhD programs over the past 60 years. On average, Black trainees took slightly longer to graduate, were less likely to choose careers in academia, and were more likely to enter nonacademic clinical practice; although, none of these differences were large. Black graduates were also more likely to choose careers in surgery or internal medicine, or entirely forego residency, and less likely to choose pediatrics, pathology, or neurology. Among those in academia, average research effort rates self-reported by Black, Hispanic, and non-UIM alumni were indistinguishable, as were rates of obtaining research grants and mentored training awards. However, the proportion of Black and Hispanic alumni who reported having NIH research grants was lower than that of non-UIM alumni, and the NIH career development to research project grant (K-to-R) conversion rate was lower for Black alumni. We propose that the reasons for these differences reflect experiences before, during, and after training and, therefore, conclude with action items that address each of these stages.

The 2014 NIH Physician-Scientist Workforce Working Group predicted a future shortage of physician-scientists. Subsequent studies have highlighted disparities in MD-PhD admissions based on race, income, and education. Our analysis of data from the Association of American Medical Colleges covering 2014–2021 (15,156 applicants and 6,840 acceptees) revealed that acceptance into US MD-PhD programs correlates with research experience, family income, and research publications. The number of research experiences associated with parental education and family income. Applicants were more likely to be accepted with a family income greater than $50,000 or with one or more publications or presentations. Applicants were less likely to be accepted if they had parents without a graduate degree, were Black/African American, were first-generation college students, or were reapplicants, irrespective of the number of research experiences, publications, or presentations. These findings underscore an admissions bias that favors candidates from affluent and highly educated families, while disadvantaging underrepresented minorities.

Malaria remains a major public health threat for billions of people worldwide. Infection with obligate intracellular, unicellular parasites from the genus Plasmodium causes malaria. Plasmodium falciparum causes the deadliest form of human malaria. Plasmodium parasites are purine auxotrophic. They rely on purine import from the host red blood cell cytoplasm via equilibrative nucleoside transporters to supply substrates to the purine salvage pathway. We previously developed a high throughput screening assay to identify inhibitors of the P. falciparum Equilibrative Nucleoside Transporter Type 1 (PfENT1). Screening a small molecule library identified PfENT1 inhibitors that blocked proliferation of P. falciparum parasites in in vitro culture. The goal of the current work was to validate a high-resolution model of PfENT1 predicted by the AlphaFold protein structure prediction program. We superimposed the predicted PfENT1 structure on the human homologue structure, hENT1, and developed a structure-based sequence alignment. We mutated the residues in PfENT1 aligned with and flanking the residues in hENT1 that interact with the purine analog, nitrobenzylthioinosine (NBMPR). Mutation of the PfENT1 residues Q135, D287, and R291 that are predicted to form hydrogen bonds to purine nucleosides eliminated purine and pyrimidine transport function in various yeast-based growth and radiolabeled substrate uptake assays. Mutation of two flanking residues, W53 and S290, also resulted in inactive protein. Mutation of L50 that forms hydrophobic interactions with the purine nucleobase reduced transport function. Based on our results the AlphaFold predicted structure for PfENT1 may be useful in guiding medicinal chemistry efforts to improve the potency of our PfENT1 inhibitors.

Postgraduate physician-scientist training programs (PSTPs) enhance the experiences of physician-scientist trainees following medical school graduation. PSTPs usually span residency and fellowship training, but this varies widely by institution. Applicant competitiveness for these programs would be enhanced, and unnecessary trainee anxiety relieved, by a clear understanding of what factors define a successful PSTP matriculant. Such information would also be invaluable to PSTP directors and would allow benchmarking of their admissions processes with peer programs. We conducted a survey of PSTP directors across the US to understand the importance they placed on components of PSTP applications. Of 41 survey respondents, most were from internal medicine and pediatrics residency programs. Of all components in the application, two elements were considered very important by a majority of PSTP directors: (a) having one or more first-author publications and (b) the thesis advisor’s letter. Less weight was consistently placed on factors often considered more relevant for non-physician-scientist postgraduate applicants — such as US Medical Licensing Examination scores, awards, and leadership activities. The data presented here highlight important metrics for PSTP applicants and directors and suggest that indicators of scientific productivity and commitment to research outweigh traditional quantitative measures of medical school performance.

The average age when physician-scientists begin their career has been rising. Here, we focused on one contributor to this change: the increasingly common decision by candidates to postpone applying to MD-PhD programs until after college. This creates a time gap between college and medical school. Data were obtained from 3544 trainees in 73 programs, 72 program directors, and AAMC databases. From 2013 to 2020, the prevalence of gaps rose from 53% to 75%, with the time usually spent doing research. Gap prevalence for MD students also increased but not to the same extent and for different reasons. Differences by gender, underrepresented status, and program size were minimal. Most candidates who took a gap did so because they believed it would improve their chances of admission, but gaps were as common among those not accepted to MD-PhD programs as among those who were. Many program directors preferred candidates with gaps, believing without evidence that gaps reflects greater commitment. Although candidates with gaps were more likely to have a publication at the time of admission, gaps were not associated with a shorter time to degree nor have they been shown to improve outcomes. Together, these observations raise concerns that, by promoting gaps after college, current admissions practices have had unintended consequences without commensurate advantages.