A Swiss Army knife, a roll of duct tape, and whatever the room happened to contain. That was all he ever needed.
For seven seasons on ABC, from 1985 to 1992, Angus MacGyver, played with disarming ease by Richard Dean Anderson, walked into impossible situations armed with nothing more than scientific knowledge, lateral thinking, and an almost spiritual refusal to carry a gun. The show didn’t just entertain a generation; it encoded a philosophy into the American imagination. Intelligence, applied with creativity, could overcome any constraint. A paper clip was not a paper clip. A chocolate bar was not a chocolate bar. In MacGyver’s hands, the ordinary became extraordinary and the mundane became the mechanism of deliverance.
I grew up watching that show, as did millions of others who came of age in the 1980s, in households where typical evenings carried the particular electricity of network television. There was something profoundly satisfying about watching a man who relied not on firepower or brute strength, but on the architecture of his own mind. MacGyver was the patron saint of resourcefulness, the idea that what you have is always enough, if only you know how to see it differently.
What I did not understand then, but have come to understand through decades of law, enterprise, venture investments and the quiet accumulation of experience, is that MacGyver was prophecy and not fiction.
And perhaps nowhere is that prophecy more vividly fulfilled today than along a half-mile stretch of University Avenue in West Philadelphia, where Penn Medicine’s researchers have spent a generation doing what MacGyver always did: looking at what is at hand, seeing what no one else sees, and building something the world had never imagined possible.
Consider Drew Weissman.
For decades, the very idea that messenger RNA could be used as medicine was considered fringe science, too unstable, too inflammatory, too impractical to survive the brutality of biological reality. Weissman, a quietly tenacious physician-scientist at Penn’s Perelman School of Medicine, did not accept that verdict. Along with Katalin Karikó, a Hungarian-born biochemist who had been demoted by her own university (Penn) and nearly driven from science entirely for her belief in mRNA, Weissman spent years in what amounted to a creative siege. He had no billion-dollar pharmaceutical backing. He had a laboratory, a conviction, and a set of intellectual tools he was determined to reassemble into something new.
In 2005, Weissman and Karikó published the discovery that would change the architecture of medicine: a method for chemically modifying mRNA so that the body’s immune system would accept it rather than attack it. The work sat largely unnoticed for years. Then, in 2020, a novel coronavirus arrived, and within months, the modified mRNA technology Weissman and Karikó had developed at Penn formed the molecular foundation of the Pfizer/BioNTech and Moderna vaccines, the fastest vaccines in human history, administered to billions of people across the planet. In 2023, the Nobel Prize in Physiology or Medicine was awarded to both. Penn Medicine, which has a 261-year history of medical breakthroughs, had just produced perhaps its most consequential one.
But Weissman is not stopping. In the wake of the Nobel, he has continued pushing mRNA toward its next frontier. Penn Medicine today is actively developing mRNA vaccines against a range of infectious diseases. Weissman himself has spoken publicly of working on “every imaginable infectious disease.” Early research from Penn Medicine has already produced a promising mRNA vaccine designed to stop allergens from triggering immune reactions and life-threatening inflammation, opening a potential pathway to treatments for seasonal and food allergies that afflict hundreds of millions worldwide, including my daughter Genevieve. This is MacGyver thinking at its most elemental, not accepting the room as it is, but reimagining every piece of furniture as a tool.
And then there is the story of KJ Muldoon.
KJ was born in August 2024 with a diagnosis so rare it affects only one in 1.3 million infants. Severe carbamoyl phosphate synthetase 1 deficiency, CPS1 for short, meant his body could not rid itself of ammonia. Without intervention, approximately half of affected children die within their first week of life. The rest face liver transplantation, profound neurological damage, and a life circumscribed by the most fragile of metabolic margins. KJ was given roughly six months to live.
Into this room of scarcity and sorrow walked two scientists who embodied everything MacGyver ever stood for.
Kiran Musunuru, the Barry J. Gertz Professor for Translational Research at Penn Medicine and director of the Genetic and Epigenetic Origins of Disease Program, had spent years developing CRISPR-based approaches to cardiovascular disease, work currently in clinical trials in New Zealand and the United Kingdom that could one day function as a single-injection “vaccine” against heart disease, the leading cause of death worldwide. Rebecca Ahrens-Nicklas, director of the Gene Therapy for Inherited Metabolic Disorders Frontier Program at the Children’s Hospital of Philadelphia and an assistant professor at Penn Medicine, had dedicated her clinical life to rare metabolic diseases that pharmaceutical companies rarely touched because the patient populations were too small to justify the investment.
Together, working with CRISPR co-discoverer Jennifer Doudna’s team, they did something that had never been done before in the history of medicine. In under six months, a timeline that Harvard professor David Liu, whose lab developed the base-editing technique employed, called “astounding,” Musunuru and Ahrens-Nicklas designed and manufactured a bespoke gene therapy targeting KJ’s specific mutation, delivered via lipid nanoparticles to the liver. They reprogrammed his DNA. In February 2025, KJ Muldoon became the first human being in history to receive a customized, personalized CRISPR gene editing therapy. He received three infusions. By spring of 2025, he was thriving, tolerating increased dietary protein, requiring less medication, celebrating his first birthday.
The work was published in the New England Journal of Medicine and recognized by the Clinical Research Forum as one of the Top 10 Clinical Research Achievement Awards for 2026, one of four Penn studies to receive that distinction, out of submissions from nearly sixty research institutions across the country. Time magazine named Musunuru and Ahrens-Nicklas to its TIME100 Health list. The FDA, working with the Penn and CHOP team, released a new regulatory protocol creating a pathway for bespoke genetic therapies to reach market without requiring individual approval for each patient’s unique treatment.
More than 30 million Americans currently live with one of over 7,000 rare genetic diseases for which few or no treatments exist. KJ’s therapy has created the template for a new category of medicine, one in which the therapy is not designed for the disease in the abstract, but for the specific mutation in the specific patient.
Musunuru and Ahrens-Nicklas, like Weismann and at least 600 other MacGyvers at Penn, are opening the Swiss Army knife all the way and humanity is benefiting from their ingenuity and creativity.
But the MacGyver analogy, as rich as it is, demands its evolution. The scientists of Penn Medicine are not locked in a room alone with only their ingenuity. They are working in a room that is rapidly filling with the most extraordinary tools in the history of biological science.
Penn’s research enterprise operates with a $1.33 billion budget in 2026, making it one of the top research universities in the nation. Across the Perelman School of Medicine and its affiliated programs, artificial intelligence is no longer a curiosity or a departmental experiment, but a basic infrastructure.
Professor Christos Davatzikos, who holds appointments in both Radiology and Electrical and Systems Engineering, leads one of the first AI-guided radiation therapy projects in the field, using machine learning to analyze brain MRI scans and predict the future progression of neurological disease, identifying early signs before symptoms appear. David Fajgenbaum, a Penn Med physician who was diagnosed with Castleman disease during his third year of medical school and nearly died five times, co-founded Every Cure, a nonprofit biotech that uses AI to match existing, approved drugs to rare diseases that currently have no treatment. Every Cure has received $76 million in federal grants to accelerate its platform, which Fajgenbaum describes with characteristic precision: the AI can search across all drug-disease combinations in what would otherwise take 22,000 years of manual review, applying the same predictive logic that Netflix uses to recommend a film.
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And in early 2026, Penn AI announced its first recipients of the “Discovering the Future of AI” awards, including a landmark project called ApexMol, led by César de la Fuente, a researcher whose work spans artificial intelligence, biology, and medicine. ApexMol is developing an AI system that reasons about and designs biomolecules by integrating natural language with three-dimensional molecular structure, training on more than 12 million paired examples linking molecular structures with scientific text from the Protein Data Bank, PubChem, and AlphaFold predictions. The goal: accelerate drug discovery, support responses to emerging health threats, and democratize access to AI-powered molecular science for institutions that cannot afford the computational infrastructure of pharmaceutical giants.
Which brings us to Carl June.
June is the Richard W. Vague Professor in Immunotherapy at Penn Medicine, director of the Center for Cellular Immunotherapies, and the architect of one of the most consequential medical revolutions of the past half century. CAR T cell therapy, which June and his team developed at Penn after years of rejected grant applications and industry skepticism, involves engineering a patient’s own immune cells to seek and destroy cancer. In August 2017, it became the first personalized cellular therapy to receive FDA approval. There are now seven FDA-approved CAR T cell therapies in the United States. June received the 2024 Breakthrough Prize in Life Sciences, often described as the “Oscars” of Science, becoming the sixth Penn researcher to earn that honor. Repeat: he is the sixth scientist at Penn to secure this honor. Six Rings – Jordan’s Chicago Bulls-like territory.
But June is not resting. In 2025, a next-generation “armored” CAR T cell therapy developed by June and his colleagues at Penn, published in the New England Journal of Medicine, showed that the new approach diminished cancer in 81 percent of patients with B-cell lymphomas that had resisted every other available treatment, including commercially available CAR T therapies, with complete remission in 52 percent of cases, some of the earliest patients experiencing durable remission for two years or more. Penn researchers have also shown early evidence that CAR T therapy may have applications in autoimmune diseases such as lupus, where the B-cell mechanism that makes it effective against blood cancer may make it equally effective against the self-directed immune attack at the root of autoimmune conditions.
The labs at Penn Medicine are growing larger, the tools are multiplying and the scientists will not stop building.
Now imagine, truly imagine, what these minds will do as AI becomes not merely a research tool but a collaborator.
The global AI drug discovery market, valued at roughly $1.94 billion in 2025, is projected to reach $2.6 billion in 2026 and $16.49 billion by 2034, growing at a compound annual rate of 27 percent. More than 200 AI-designed drugs are now in clinical development worldwide. Eighty-one percent of pharmaceutical companies have deployed AI. Phase I clinical success rates for AI-discovered compounds are already running 80 to 90 percent, compared to 40 to 65 percent for traditionally discovered drugs, a difference that, at the scale of global pharmaceutical development, translates into tens of billions of dollars and, more importantly, into thousands of lives.
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For decades, the drug discovery pipeline has been one of the most inefficient endeavors in all of human enterprise. A compound takes, on average, ten to fifteen years to travel from hypothesis to approval. Ninety percent of drug candidates fail before they ever reach a patient. The cost of developing a single approved drug now exceeds $2 billion, when the full weight of failures is accounted for. Into this vast inefficiency, AI is arriving not as a silver bullet but as something more durable: a compression engine. The distance between a scientific hypothesis and a validated therapeutic candidate is collapsing from years to months.
What Musunuru and Ahrens-Nicklas accomplished for KJ Muldoon in six months would, under any previous paradigm, have taken years; if it could have been done at all. What Every Cure is doing for rare disease patients, systematically mapping the entire pharmacological universe for overlooked connections, was, before AI, humanly impossible. What ApexMol is attempting, training AI to design biomolecules from scratch, reasoning in three dimensions across millions of molecular structures, is the kind of scientific infrastructure that, once built, does not merely accelerate individual discoveries, but changes the grammar of discovery itself.
AI is a dragon that can fly across distances of computation that would take human minds decades to cross. A dragon that can breathe fire, generating molecular designs, protein binding predictions, drug repurposing hypotheses, and clinical trial strategies with a ferocity and volume that no army of specialists could match. A dragon that can do what thousands cannot.
But as of December 2025, no AI-discovered drug had yet received FDA approval. The most advanced AI-designed compounds are only now entering pivotal Phase III trials. For now, the technology is accelerating early-stage discovery without changing fundamental biology. Drug development is inherently high-risk, and AI cannot yet solve problems that have challenged pharmaceutical science for generations. The dragon, untamed, is merely a catastrophe and the question is who will learn to ride it.
Penn Medicine’s answer to that question is already being written. It is written in the modified mRNA that protected billions of people from a pandemic. It is written in the genome of KJ Muldoon, edited precisely and safely in a laboratory along University Avenue in the same city where Benjamin Franklin once flew a kite into a storm to understand electricity. It is written in the armored CAR T cells that found cancer where everything else had failed. It is written in AI systems now being trained to design the molecules of future medicine before a human researcher has even formulated the hypothesis.
Penn Medicine’s 261-year history, from the first medical school in the Americas to the frontiers of gene editing and AI-powered drug discovery, is, at its deepest level, a MacGyver story. It is the story of what happens when exceptionally creative, exceptionally driven people refuse to accept the room as it is. When they look at a degraded mRNA molecule and see a vaccine platform. When they look at a dying infant and see a therapy that has never existed. When they look at a patient’s own immune cells and see a living drug that can hunt cancer.
The tools are arriving now at a pace that would have staggered even the most ambitious of Penn’s founding physicians. With a $1.33 billion research engine, a community of MacGyver-like scientists who have won six Breakthrough Prizes, two Nobel Prizes, and seven of twenty national top clinical research honors in a single year, and an AI infrastructure that is only beginning to reveal what it can do, Penn Medicine stands at the most consequential threshold in the history of medicine.