René Vidal, at the podium, introduces the event “ChatGPT turns one: How is generative AI reshaping science?” Bhuvnesh Jain, left at the table, moderated the discussion with Sudeep Bhatia, Konrad Kording, Andrew Zahrt, and Nick Pangakis.
As a neuroscientist surveying the landscape of generative AI—artificial intelligence capable of generating text, images, or other media—Konrad Kording cites two potential directions forward: One is the “weird future” of political use and manipulation, and the other is the “power tool direction,” where people use ChatGPT to get information as they would use a drill to build furniture.
“I’m not sure which of those two directions we’re going but I think a lot of the AI people are working to move us into the power tool direction,” says Kording, a Penn Integrates Knowledge (PIK) University professor with appointments in the Perelman School of Medicine and School of Engineering and Applied Science. Reflecting on how generative AI is shifting the paradigm of science as a discipline, Kording said he thinks “it will push science as a whole into a much more collaborative direction,” though he has concerns about ChatGPT’s blind spots.
Kording joined three University of Pennsylvania researchers from the chemistry, political science, and psychology departments sharing their perspectives in the recent panel “ChatGPT turns one: How is generative AI reshaping science?” PIK Professor René Vidal opened the event, which was hosted by the School of Arts & Sciences’ Data Driven Discovery Initiative (DDDI), and Bhuvnesh Jain, physics and astronomy professor and co-faculty director of DDDI, moderated the discussion.
“Generative AI is moving so rapidly that even if it’s a snapshot, it will be very interesting for all of us to get that snapshot from these wonderful experts,” Jain said. OpenAI launched ChatGPT, a large language model (LLM)-based chatbot, on Nov. 30, 2022, and it rapidly ascended to ubiquity in news reports, faculty discussions, and research papers. Colin Twomey, interim executive director of DDDI, told Penn Today that it’s an open question as to how it will change the landscape of scientific research, and the` idea of the event was to solicit colleagues’ opinions on interesting directions in their fields.
Konrad Paul Kording is Nathan Francis Mossell University Professor in Bioengineering and Computer and Information Science in Penn Engineering and in Neuroscience in the Perelman School of Medicine.
Daeyeon Lee (left), Oren Friedman (center) and Sergei Vinogradov (right)
Each year, the Nemirovsky Engineering and Medicine Opportunity (NEMO) Prize, funded by Penn Health-Tech, awards $80,000 to a collaborative team of researchers from the University of Pennsylvania’s Perelman School of Medicine and the School of Engineering and Applied Science for early-stage, interdisciplinary ideas.
This year, the NEMO Prize has been awarded to Penn Engineering’s Daeyeon Lee, Russel Pearce and Elizabeth Crimian Heuer Professor in Chemical and Biomolecular Engineering, Oren Friedman, Associate Professor of Clinical Otorhinolaryngology in the Perelman School of Medicine, and Sergei Vinogradov, Professor in the Department of Biochemistry and Biophysics in the Perelman School of Medicine and the Department of Chemistry in the School of Arts & Sciences. Together, they are developing a new therapy that improves the survival and success of soft-tissue grafts used in reconstructive surgery.
More than one million people receive soft-tissue reconstructive surgery for reasons such as tissue trauma, cancer or birth defects. Autologous tissue transplants are those where cells and tissue such as fat, skin or cartilage are moved from one part of a patient’s body to another. As the tissue comes from the patient, there is little risk of transplant rejection. However, nearly one in four autologous transplants fail due to tissue hypoxia, or lack of oxygen. When transplants fail the only corrective option is more surgery. Many techniques have been proposed and even carried out to help oxygenate soft tissue before it is transplanted to avoid failures, but current solutions are time consuming and expensive. Some even have negative side effects. A new therapy to help oxygenate tissue quickly, safely and cost-effectively would not only increase successful outcomes of reconstructive surgery, but could be widely applied to other medical challenges.
The therapy proposed by this year’s NEMO Prize recipients is a conglomerate or polymer of microparticles that can encapsulate oxygen and disperse it in sustainable and controlled doses to specific locations over periods of time up to 72 hours. This gradual release of oxygen into the tissue from the time it is transplanted to the time it functionally reconnects to the body’s vascular system is essential to keeping the tissue alive.
“The microparticle design consists of an oxygenated core encapsulated in a polymer shell that enables the sustained release of oxygen from the particle,” says Lee. “The polymer composition and thickness can be controlled to optimize the release rate, making it adaptable to the needs of the hypoxic tissue.”
These life-saving particles are designed to be integrated into the tissue before transplantation. However, because they exist on the microscale, they can also be applied as a topical cream or injected into tissue after transplantation.
“Because the microparticles are applied directly into tissues topically or by interstitial injection (rather than being administered intravenously), they surpass the need for vascular channels to reach the hypoxic tissue,” says Friedman. “Their micron-scale size combined with their interstitial administration, minimizes the probability of diffusion away from the injury site or uptake into the circulatory system. The polymers we plan to use are FDA approved for sustained-release drug delivery, biocompatible and biodegrade within weeks in the body, presenting minimal risk of side effects.”
The research team is currently testing their technology in fat cells. Fat is an ideal first application because it is minimally invasive as an injectable filler, making it versatile in remodeling scars and healing injury sites. It is also the soft tissue type most prone to hypoxia during transplant surgeries, increasing the urgency for oxygenation therapy in this particular tissue type.
NAM, founded in 1970, is an independent organization of professionals that advises the entire scientific community on critical health care issues. Each year, NAM chooses up to 10 new ELHM Scholars who are early-to-mid-career professionals from a wide range of health-related fields, including biomedical engineering, internal medicine, psychiatry, radiology and journalism to serve a three-year term.
“We are delighted that Dr. de la Fuente is receiving recognition from the National Academy of Medicine for his breakthrough contributions and exceptional leadership in the life sciences,” says Vijay Kumar, Nemirovsky Family Dean of Penn Engineering. “His pioneering work using computers to accelerate antibiotic discovery is extraordinary. We proudly celebrate his selection as part of this outstanding group of scholars.”
In an era peppered by breathless discussions about artificial intelligence—pro and con—it makes sense to feel uncertain, or at least want to slow down and get a better grasp of where this is all headed. Trusting machines to do things typically reserved for humans is a little fantastical, historically reserved for science fiction rather than science.
Not so much for César de la Fuente, PhD, the Presidential Assistant Professor in Psychiatry, Microbiology, Chemical and Biomolecular Engineering, and Bioengineering in Penn’s Perelman School of Medicine and School of Engineering and Applied Science. Driven by his transdisciplinary background, de la Fuente leads the Machine Biology Group at Penn: aimed at harnessing machines to drive biological and medical advances.
“Biology is complexity, right? You need chemistry, you need mathematics, physics and computer science, and principles and concepts from all these different areas, to try to begin to understand the complexity of biology,” he said. “That’s how I became a scientist.”
Kathleen J. Stebe and Michel Koo urge “the academic community to adopt a coordinated approach uniting dental medicine and engineering to support research, training and entrepreneurship to address unmet needs and spur oral health care innovations.” (Image: Min Jun Oh and Seokyoung Yoon)
Penn’s Center for Innovation & Precision Dentistry (CiPD) is the first cross-disciplinary initiative in the nation to unite oral-craniofacial health sciences and engineering.
In just two years since CiPD was founded, the outcomes of this newly conceived research partnership have proven its value: microrobots that clean teeth for people with limited mobility, a completely new understanding of bacterial physics in tooth decay, enzymes from plant chloroplasts that degrade plaque, promising futures for lipid nanoparticles in oral cancer treatment and new techniques and materials to restore nerves in facial reconstructive surgery.
In addition, CiPD is training the next generation of dentists, scientists and engineers through an NIH/NIDCR-sponsored postdoctoral training program as well as fellowships from industry.
The center’s Founding Co-Directors, Kathleen J. Stebe, Richer & Elizabeth Goodwin Professor in Chemical and Biomolecular Engineering, and Michel Koo, Professor of Orthodontics in Penn Dental Medicine, published an editorial in the Journal of Dental Research, planting a flag for CiPD’s mission and encouraging others to mirror its method.
The two urge “the academic community to adopt a coordinated approach uniting dental medicine and engineering to support research, training and entrepreneurship to address unmet needs and spur oral health care innovations.”
On September 14, Wexford Science & Technology, LLC and the University of Pennsylvania announced that the University has signed a lease for new laboratory space that will usher in a wave of novel vaccine, therapeutics, and engineered diagnostics research to West Philadelphia. Research teams from Penn are poised to move into 115,000 square feet of space at One uCity Square, the 13-story, 400,000 square foot purpose-built lab and office building within the vibrant uCity Square Knowledge Community being developed by Wexford. This is the largest lease in the building, encompassing four floors, and bringing the building to over 90% leased. The building currently includes industry tenants Century Therapeutics (NASDAQ: IPSC), Integral Molecular, Exponent (NASDAQ: EXPO), and Charles River Laboratories (NYSE: CRL).
The new University space will house Penn Medicine’s Institute for RNA Innovation and Penn Engineering’s Center for Precision Engineering for Health, underscoring the University’s commitment to a multi-disciplinary and collaborative approach to research that will attract and retain the best talent and engage partners from across the region. Penn’s decision to locate at One uCity Square reinforces uCity Square’s evolution as a central cluster of academic, clinical, commercial, entrepreneurial, and amenity spaces for the area’s innovation ecosystem, and further cements Philadelphia’s position as a top life sciences market.
Jonathan Epstein, MD, Executive Vice Dean and Chief Scientific Officer of Penn Medicine, shared his anticipation for the opportunities that lie ahead: “Penn Medicine is proud to build on its existing clinical presence in uCity Square and establish an innovative and collaborative research presence at the heart of uCity Square’s multidisciplinary innovation ecosystem. This strategic move underscores our commitment to accelerating advancements in biomedical research, industry collaboration, and equipping our talented teams with the resources they need to shape the future of healthcare.”
Locating the Penn Institute for RNA Innovation in the heart of the uCity Square community brings together researchers across disciplines who are already pursuing new vaccines and treatments, and better ways to deliver them. Their shared work will help to power the next phase of vaccine discovery and development.
Likewise, anchoring the work of Penn Engineering’s Center in the One uCity Square space will allow the School’s multi-disciplinary researchers and their collaborators to advance new clinical and diagnostic methods that will focus on intelligent therapeutics, genome design, diagnostics for discovery of human biology, and engineering the human immune shield.
“Penn Engineering has made a substantial commitment to precision engineering for health, an area that is not only important and relevant to engineering, but also critical to the future of humanity,” said Vijay Kumar, Nemirovsky Family Dean of Penn Engineering. “The space in One uCity Square will add another 30,000 square feet of space for our engineers to develop technologies that will fight future pandemics, cure incurable diseases, and extend healthy life spans around the world.”
Spearheading the Penn Institute for RNA Innovation will be Drew Weissman, MD, PhD, the Roberts Family Professor for Vaccine Research, who along with Katalin Karikó, PhD, adjunct professor of Neurosurgery, discovered foundational mRNA technology that enabled the creation of vital vaccine technology, including the FDA-approved mRNA-based COVID-19 vaccines developed by Pfizer-BioNTech and Moderna.
In this new space at One uCity Square, Weissman and his research team and collaborators will further pursue their groundbreaking research efforts with a goal to develop new therapeutics and vaccines and initiate clinical trials for other devastating diseases.
In addition, two established researchers will join the Institute at One uCity Square: Harvey Friedman, MD, a professor of Infectious Diseases, who leads a team researching various vaccines. He will be joined by Vladimir Muzykantov, MD, PhD, Founders Professor in Nanoparticle Research, who focuses on several projects related to targeting the delivery of drugs, including mRNA, to create more effective, targeted pathways to deliver drugs to the vascular system, treating a wide range of diseases that impact the brain, lung, heart, and blood.
Dan Hammer, Alfred G. and Meta A. Ennis Professor in the Departments of Bioengineering and Chemical and Biomolecular Engineering in Penn Engineering and Director of the Center for Precision Engineering for Health, will oversee the Center’s innovations in diagnostics and delivery, cellular and tissue engineering, and the development of new devices that integrate novel materials with human tissues. The Center will bring together scholars from all departments within Penn Engineering and will help to foster increased collaboration with campus colleagues at Penn’s Perelman School of Medicine and with industry partners.
Joining the Center researchers in One uCity Square are Noor Momin, Sherry Gao, and Michael Mitchell. Noor Momin, who will join Penn Engineering in early 2024 as an assistant professor in Bioengineering, will leverage her lab’s expertise in cardiovascular immunology, protein engineering and pharmacokinetic modeling to develop next-generation treatments and diagnostics for cardiovascular diseases.
Fat is a normal and necessary part of the body. Fat cells store and release energy, as well as play significant roles in hormonal regulation and immunity.
Engineers and scientists at the University of Pennsylvania are the first to discover fat-filled lipid droplets’ (pictured above in green) surprising capability to indent and puncture the nucleus, the organelle which contains and regulates a cell’s DNA.
In recent decades, a concerning rise in metabolic illnesses – such as cardiovascular disease, high blood pressure and diabetes – has focused scientific attention on the biology and chemistry of fat, resulting in a wealth of information about how fat cells work.
But fat cells and their metabolic activities are only part of the story.
Fat-filled lipid droplets, tiny spheres of fat many times smaller than fat cells, are a growing subject of scientific interest. Found inside many different cell types, these lipid particles have long been little understood. Studies have begun to illuminate these droplets’ participation in metabolic functions and cellular protection, but we still know next to nothing about the physical nature of fat.
Now, researchers at the University of Pennsylvania School of Engineering and Applied Science have looked beyond biochemistry to publish groundbreaking work on the physics of these droplets, revealing them to be a potential threat to a cell’s nucleus. In the August issue of the Journal of Cell Biology, they are the first to discover fat-filled lipid droplets’ surprising capability to indent and puncture the nucleus, the organelle which contains and regulates a cell’s DNA.
The stakes of their findings are high: a ruptured nucleus can lead to elevated DNA damage that is characteristic of many diseases, including cancer.
“Intuitively, people think of fat as soft,” says Discher. “And on a cellular level it is. But at this small size of droplet— measuring just a few microns rather than the hundreds of microns of a mature fat cell—it stops being soft. Its shape has a much higher curvature, bending other objects very sharply. This changes its physics in the cell. It can deform. It can damage. It can rupture.”
Fabrication steps of the biodegradable BC substrate and the electrochemical devices. (1) Incubation of the bacterium Gluconacetobacter hansenii. (2) BC substrate collected and treated, resulting in a clear sheet. (3) The biodegradable BC sheet is screen-printed, (4) resulting in a device with 3 electrodes, (4) which are cut out using a scissor, (5) resulting in a portable, biodegradable, and inexpensive electrochemical sensor.
The availability of rapid, accessible testing was integral to overcoming the worst surges of the COVID-19 pandemic, and will be necessary to keep up with emerging variants. However, these tests come with unfortunate costs.
Polymerase chain reaction (PCR) tests, the “gold standard” for diagnostic testing, are hampered by waste. They require significant time (results can take up to a day or more) as well as specialized equipment and labor, all of which increase costs. The sophistication of PCR tests makes them harder to tweak, and therefore slower to respond to new variants. They also carry environmental impacts. For example, most biosensor tests developed to date use printed circuit boards, or PCBs, the same materials used in computers. PCBs are difficult to recycle and slow to biodegrade, using large amounts of metal, plastic and non-eco-friendly materials.
In addition, most PCR tests end up in landfills, resulting in material waste and secondary contamination. An analysis by the World Health Organization (WHO) estimated that, as of February 2022, “over 140 million test kits, with a potential to generate 2,600 tonnes of non-infectious waste (mainly plastic) and 731,000 litres of chemical waste (equivalent to one-third of an Olympic-size swimming pool) have been shipped.”
In order to balance the need for fast, affordable and accurate testing while addressing these environmental concerns, César de la Fuente, Presidential Assistant Professor in Bioengineering and Chemical and Biomolecular Engineering in the School of Engineering and Applied Science, with additional primary appointments in Psychiatry and Microbiology within the Perelman School of Medicine, has turned his attention to the urgent need for “green” testing materials.
The de la Fuente lab has been working on creative ways to create faster and cheaper testing for COVID-19 since the outbreak of the pandemic. Utilizing his lab’s focus on machine biology and the treatment of infectious disease, they created RAPID, an aptly named test that generates results in minutes with a high degree of accuracy. An even more cost-effective version, called LEAD, was created using electrodes made from graphite. A third test, called COLOR, was a low-cost optodiagnostic test printed on cotton swabs.
The team’s latest innovation incorporates the speed and cost-effectiveness of previous tests with eco-friendly materials. In a paper published in Cell Reports Physical Science, the group introduces a new test made from Bacterial Cellulose (BC), an organic compound synthesized from several strains of bacteria, as a substitute for PCBs.
Marrying artificial intelligence with advanced experimental methods, the Machine Biology Group has mined the ancient past for future medical breakthroughs, bringing extinct molecules back to life. (Image credit: Ella Marushchenko)
“We need to think big in antibiotics research,” says Cesar de la Fuente. “Over one million people die every year from drug-resistant infections, and this is predicted to reach 10 million by 2050. There hasn’t been a truly new class of antibiotics in decades, and there are so few of us tackling this issue that we need to be thinking about more than just new drugs. We need new frameworks.”
Marrying artificial intelligence with advanced experimental methods, the group has mined the ancient past for future medical breakthroughs. In a recent study published in CellHost and Microbe, the team has launched the field of “molecular de-extinction.”
Our genomes – our genetic material – and the genomes of our ancient ancestors, express proteins with natural antimicrobial properties. “Molecular de-extinction” hypothesizes that these molecules could be prime candidates for safe new drugs. Naturally produced and selected through evolution, these molecules offer promising advantages over molecular discovery using AI alone.
In this paper, the team explored the proteomic expressions of two extinct organisms –Neanderthals and Denisovans, archaic precursors to the human species – and found dozens of small protein sequences with antibiotic qualities. Their lab then worked to synthesize these molecules, bringing these long-since-vanished chemistries back to life.
“The computer gives us a sequence of amino acids,” says de la Fuente. “These are the building blocks of a peptide, a small protein. Then we can make these molecules using a method called ‘solid-phase chemical synthesis.’ We translate the recipe of amino acids into an actual molecule and then build it.”
The team next applied these molecules to pathogens in a dish and in mice to test the veracity and efficacy of their computational predictions.
“The ones that worked, worked quite well,” continues de la Fuente. “In two cases, the peptides were comparable – if not better – than the standard of care. The ones that didn’t work helped us learn what needed to be improved in our AI tools. We think this research opens the door to new ways of thinking about antibiotics and drug discovery, and this first step will allow scientists to explore it with increasing creativity and precision.”
Artificial intelligence is a new addition to the infectious disease researcher’s toolbox. Yet in merely half a decade, AI has accelerated progress on some of the most urgent issues in medical science and public health. Researchers in this field blend knowledge of life sciences with skill in computation, chemistry and design, satisfying decades-long appeals for interdisciplinary tactics to treat these disorders and stop their spread.
Diseases are “infectious” when they are caused by organisms, including parasites, viruses, bacteria and fungi. People and animals can contract infectious diseases from their environments or food, or through interactions with one another. Some, but not all, are contagious.
Infectious diseases are an intractable global challenge, posing problems that continue to grow in severity even as science has offered a steady pace of solutions. The world continues to become more interconnected, bringing people into new kinds and levels of relation, and the climate crisis is throwing environmental and ecological networks out of balance. Diseases that were once treatable by drugs have become resistant, and new drug discovery is more costly than ever. Uneven resource distribution means that certain parts of the world are perennial hotspots for diseases that others never fear.
In the paper, de la Fuente and co-authors assess the progress, limitations and promise of research in AI and infectious diseases in three major areas of inquiry: anti-infective drug discovery, infection biology, and diagnostics for infectious diseases.
