What Makes a Breakthrough? “Eight Steps Back” Before Making it to the Finish Lit

by Meagan Raeke

(From left to right) Breakthrough Prize recipients Drew Weissman, Virginia M-Y Lee, Katalin Karikó, and Carl June at a reception on Feb. 13. (Image: Courtesy of Penn Medicine News)

In popular culture, scientific discovery is often portrayed in “Eureka!” moments of sudden realization: a lightbulb moment, coming sometimes by accident. But in real life—and in Penn Medicine’s rich history as a scientific innovator for more than 250 years—scientific breakthroughs can never truly be distilled down to a single, “ah-ha” moment. They’re the result of years of hard work, perseverance, and determination to keep going, despite repeated, often discouraging, barriers and setbacks. 

“Research is [like taking], four, or six, or eight steps back, and then a little stumble forward,” said Drew Weissman, MD, PhD, the Roberts Family Professor of Vaccine Research. “You keep doing that over and over and somehow, rarely, you can get to the top of the step.” 

For Weissman and his research partner, Katalin Karikó, PhD, an adjunct professor of Neurosurgery, that persistence—documented in thousands of news stories across the globe—led to the mRNA technology that enabled two lifesaving COVID-19 vaccines, earning the duo numerous accolades, including the highest scientific honor, the 2023 Nobel Prize in Medicine

Weissman and Karikó were also the 2022 recipients of the Breakthrough Prize in Life Sciences, the world’s largest science awards, popularly known as the “Oscars of Science.” Founded in 2012 by a group of web and tech luminaries including Google co-founder Sergey Brin and Meta CEO Mark Zuckerberg, the Breakthrough Prizes recognize “the world’s top scientists working in the fundamental sciences—the disciplines that ask the biggest questions and find the deepest explanations.” With six total winners, including four from the Perelman School of Medicine (PSOM), Penn stands alongside Harvard and MIT as the institutions whose researchers have been honored with the most Breakthrough Prizes. 

Virginia M.Y. Lee, PhD, the John H. Ware 3rd Professor in Alzheimer’s Research, was awarded the Prize in 2020 for discovering how different forms of misfolded proteins can move from cell to cell and lead to neurodegenerative disease progression. Carl June, MD, the Richard W. Vague Professor in Immunotherapy, is the most recent recipient and will be recognized at a star-studded red-carpet event in April for pioneering the development of CAR T cell therapy, which programs patients’ own immune cells to fight their cancer.

The four PSOM Breakthrough Prize recipients were honored on Tuesday, Feb. 13, 2024, when a new large-scale installation was unveiled in the lobby of the Biomedical Research Building to celebrate each laurate and their life-changing discoveries. During a light-hearted panel discussion, the honorees shared how a clear purpose, dogged determination, and a good sense of humor enabled their momentum forward. 

Read the full story in Penn Medicine News.

Carl June and Jon Epstein are members of the Penn Bioengineering Graduate Group. Read more stories featuring them in the BE Blog here and here, respectively.

Weissman presented the Department of Bioengineering’s 2022 Herman P. Schwan Distinguished Lecture: “Nucleoside-modified mRNA-LNP therapeutics.” Read more stories featuring Weissman in the BE Blog here.

2022 Penn Bioengineering Senior Design Teams Win Multiple Accolades

After a year of hybrid learning, Penn Bioengineering (BE) seniors were excited to return to the George H. Stephenson Foundation Educational Laboratory & Bio-MakerSpace for Senior Design (BE 495 & 496), a two-semester course in which students work in teams to conceive, design and pitch their capstone projects in bioengineering. This year’s projects include tools for monitoring health, software to improve communication for the healthcare and supply chain industries, and devices to improve patient care for women and underrepresented minorities.

The year culminated in the annual Senior Design Expo on April 13 in the Singh Center for Nanotechnology, in which the students presented their pitches to a panel of alumni judges, followed by demonstrations in the George H. Stephenson  Foundation Educational Laboratory & Bio-MakerSpace which were open to the entire Penn community. This year’s winners of the Bioengineering Senior Design Competition were teams Chrysalis, Modulo Prosthetics, and ReiniSpec.

Team 11 (ReiniSpec) From L to R: Ifeoluwa Popoola, Alexa Rybicki, JeongInn Park (TA), Caitlin Frazee, Michelle White, Caroline Kavanagh (on laptop).

The three winning teams went on to compete in the annual interdepartmental Senior Design Competition sponsored by the Penn Engineering Alumni Society. BE took home two of the four interdepartmental awards: Team Modulo Prosthetics won the “Technology and Innovation Prize,” recognizing the project which best represents the highest and best use of technology and innovation to leverage engineering principles; and Team ReiniSpec won the “Leadership Prize,” which recognizes the team which most professionally and persuasively presents their group project to incorporate a full analysis of their project scope, advantages, and challenges, and addresses the commercialization and future potential of their research.

All BE teams were also required to submit their projects to local and national competitions, and were met with resounding success. “The creativity and accomplishment of this Senior Design class is really unparalleled,” said David Meaney, Solomon R. Pollack Professor in Bioengineering, Senior Associate Dean of Penn Engineering, and instructor for Senior Design. “The number of accolades received by these students, as well as the interest in transforming their ideas into real products for patients, reached a new level that makes us extremely proud.”

Keep reading for a full list of this year’s projects and awards.

Team 1 – MEViD

MEViD (Multichannel Electrochemical Viral Diagnostic) is a modular, low cost device that leverages electrochemistry to rapidly diagnose viral diseases from saliva samples.

Team members: Yuzheng (George) Feng, Daphne Kontogiorgos-Heintz, Carisa Shah, Pranshu Suri, & Rachel Zoneraich

Team 2 – MOD EZ-IO

MOD EZ-IO is a low-cost, novel intraosseous drill that uses force and RPM readings to alert the user via an LED when they have breached cortical bone and entered cancellous bone, guiding proper IO placement.

Team members: Gregory Glova, Kaiser Okyan, Patrick Paglia, Rohan Vemu, & Tshepo Yane

Team 3 – Harvest by Grapevine

Harvest by Grapevine is a user-centric software solution that merges social network communication and supply chain logistics to connect hospitals and suppliers under one unified platform.

Team members: Nicole Bedanova, Kerry Blatney, Blake Grimes, Brenner Maull, & Lukas Yancopoulos

Team 4 – CliniCall

CliniCall helps streamline and centralize communication channels, offering a real-time monitoring device that enables on-site/attending physicians to communicate with on-call physicians through a livestream of patients and data.

Team members: Neepa Gupta, Santoshi Kandula, Sue Yun Lee, & Ronil Synghal

Team 5 – PneuSonus

PneuSonus is a low-cost, user-friendly wearable strap that aids in detecting pediatric pneumonia by using frequency analysis of sound waves transmitted through the lungs to identify specific properties related to fluid presence, a valid indicator specific to pneumonia.

Team members: Iman Hossain, Kelly Lopez, Sophia Mark, Simi Serfati, & Nicole Wojnowski

Team 6 – Chrysalis

Chrysalis is a smart swaddle system comprising an electric swaddle and accompanying iOS application that comforts neonatal abstinence syndrome infants via stochastic resonance and maternal heartbeat vibrational patterns to reduce opioid withdrawal symptoms without pharmacological intervention or constant nurse oversight as well as streamlines the Eat, Sleep, Console documentation process for nurses.

Team members: Julia Dunn, Rachel Gu, Julia Lasater, & Carolyn Zhang

Team 7 – EquitOx

EquitOx is a revolutionized fingertip pulse oximeter designed for EMS that addresses racial inequality in medicine through the use of one-off tongue-calibrated SpO2 measurements.

Team members: Ronak Bhagia, Estelle Burkhardt, Juliette Hooper, Caroline Smith, & Kevin Zhao

Team 8 – Modulo Prosthetics

Modulo Prosthetic is an adjustable, low-cost, thumb prosthetic with integrated haptic feedback that attaches to the metacarpophalangeal (MCP) joint of partial hand amputees and assists in activities of daily living (ADLs).

Team members: Alisha Agarwal, Michelle Kwon, Gary Lin, Ian Ong, & Zachary Spalding

Team 9 – Cor-Assist By Cygno Technologies

COR-ASSIST by Cygno Technologies is a low-cost intra-aortic balloon enhancement that directly supports heart function by increasing cardiac output to 2.8L/min, at a much lower cost and bleeding risk than the current Impella cardiac assist device.

Team members: Francesca Cimino, Allen Gan, Shawn Kang, Kristina Khaw, & William Zhang

Team 10 – Pedalytics

Pedalytics Footwear is a rechargeable sandal that continuously monitors foot health and prevents diabetic foot ulcer formation by novelly tracking three key metrics indicative of ulceration, temperature, oxygen saturation, and pressure, and sending alerts to patients via the Pedalytics app when metric abnormalities are detected.

Team members: Samantha Brosler, Constantine Constantinidis, Quincy Hendricks, Ananyaa Kumar, & María José Suárez

Team 11 – ReiniSpec

ReiniSpec is a redesigned speculum to improve the gynecological exam experience, increasing patient comfort with a silicone shell and using motorized arm adjustments to make it easily adjustable for each patient, while also incorporating a camera, lights, and machine learning to aid in better diagnosis by gynecologists.

Team members: Caitlin Frazee, Caroline Kavanagh, Ifeoluwa Popoola, Alexa Rybicki, & Michelle White

Learn more about the 2022 Senior Design projects, including full abstracts and photo gallery, on the Stephenson Bio-MakerSpace website.

Watch all the 2022 project pitches on the BE Labs Youtube channel 2022 Senior Design Playlist:

Week in BioE (December 8, 2017)

Brain Implant Advance to Cure Dementia

Alzheimer's
Neurofibrillary tangles in the hippocampus of a patient with Alzheimer’s disease.

The dramatic increase in life expectancy over the past couple of generations has one unfavorable consequence: an increase in the incidence of age-related dementias that include Alzheimer’s disease. Drugs like donepezil, which inhibits hydrolization of acetylcholine and thus increases its presence at the neural synapses, is one treatment that can slow the progression of these diseases, but there is currently no cure. 

An alternative technology that directly stimulates the brain with an implantable chip holds promise to reverse the effects of Alzheimer’s. At the annual meeting of the Society for Neuroscience, held last month in Washington, D.C., Dong Song, Ph.D., Research Associate Professor of Biomedical Engineering at USC’s Viterbi School of Engineering, gave a lecture on his lab’s device, which uses an array of implantable electrodes to improve human memory.

Dr. Song tested his device in epilepsy patients, who often receive implants designed to control their seizures in intractable cases. Twenty such patients volunteered to receive Dr. Song’s implant, and data from these patients showed that short-term memory increased by 15% and working memory by 25%. While additional testing is needed on more patients, it might not be long before implants like Dr. Song’s become the standard of care in treatment dementias.

Genetic Variation in the Human Microbiome

The human body is host to a veritable universe of microbes that play important roles in the organ systems and other bodily processes. E. coli, for example, is present in the large intestine and it participates in the breaking down of food for energy. Like all other forms of life, these microbes evolve. creating variations in genetic information and, ultimately, new bacteria species. Within any given species of bacteria, the number of differences in the genome sequences can vary broadly; with E. coli, some areas of the genome can vary radically between strains and cannot be explained by DNA copying errors.
   
To determine why the genome of E. coli subject to such variation, scientists at the University of Illinois, Urbana-Champaign (UIUC), led by Sergei Maslov, Ph.D., professor of bioengineering and physics at UIUC, investigated the issue by developing computational models using Multi Locus Sequence Typing (MLST). In their findings, published in Genetics, they concluded that the variation can be ascribed to the process of recombination, by which different sequences from different sources are combined into the same chromosome. When such events are frequent, they result in a sort of genetic stability in which variation in genetic information increases without speciation.

The study provides an important contribution to basic science in helping to better explain how different strains of bacteria develop, including virulent and drug-resistant strains. In addition, it sheds further light on the mechanisms underlying evolution.

A Step Closer to Water-efficient Agriculture

Drought and famine are closely related phenomena. Some plants are more resistant to drought than others, but few of these plants are fit for human consumption. Determining how plants resist drought could provide a key to engineering crops to become drought-resistant.
Investigating this topic, scientists at the Oak Ridge National Laboratory of the U.S. Department of Energy sought to understand better the process of crassulacean acid metabolism (CAM), by which drought-resistant plants keep their stomata, or pores, closed during sunlight hours to retain water and open them at night. The team reports in Nature Communications that they compared the genomes of three drought-resistant plants — orchid, pineapple, and Kalanchoë fedtschenkoi, a species of plant native to Madagascar.  Among the authors’ discoveries was a variation in a gene encoding phosphoenolpyruvate carboxylase, an enzyme that plays a role in CAM.

With this increased knowledge of the evolutionary development of drought resistance, we come a step closer to being able to expedite the evolution of plants that are typically not resistant to drought to developing the CAM mechanism and developing this resistance.

Computer Model Can Mimic Heart Attack

Heart disease remains the leading cause of death in developed countries. A major obstacle in reducing the deaths due to cardiac arrest is the inability to determine the precise mechanics unfolding in the heart when it stops suddenly. Abnormal heart rhythms (arrythmias) are a major cause of death, but the reasons how arrhythmias occur at the cellular level is poorly understood.

In a recent study published in PLOS Computational Biology,  Raimond L. Winslow, Ph.D. who is Raj and Neera Singh Professor in the Department of Biomedical Engineering at Johns Hopkins University, and his colleagues developed a computer model of calcium dynamics in cardiac cells. The model predicted a new mechanism for arrythmia that would occur when cardiac cells expelled calcium, creating an electrical charge outside the cell that could evoke an arrhythmia.

The authors believe that their research will facilitate the development of drugs to prevent cardiac arrhythmias and treatments for sudden cardiac arrest. In addition, the work shows that it could be easier to predict the statistical relationship between arrhythmias and cardiac arrest on the basis of far less data.

People and Places

Stevens Institute of Technology in Hoboken, N.J., has announced plans to divide its Department of Biomedical Engineering, Chemistry and Biological Sciences (BCB) into two new departments: the Department of Biomedical Engineering and the Department of Chemistry and Chemical Biology. Hongjun Wang, Ph.D., associate professor in the BCB department, will be the new chair of BME. Congratulations Hongjun!