Q&A With Dr. John Madigan, Author of Awakening at Birth

Distinguished Professor Emeritus of the University of California, Davis Dr. John E. Madigan has released a new book, "Awakening at Birth: What the Newborn Foal Revealed About Birth, Consciousness, and Neurodevelopment." With a foreword by renowned animal behaviorist Temple Grandin, PhD, "Awakening at Birth" tells a medical mystery story that extends well beyond veterinary medicine: a veterinarian investigating newborn foals discovers biological signals that may change how we understand the transition to consciousness at birth, with potential implications for infant care and neurodevelopment. The book tells the story of how Madigan developed and tested at UC Davis what has become known as the "Madigan Squeeze," a simple, noninvasive tactile procedure that mimics birth canal pressure and can rapidly reverse brain sedation and awaken some newborn foals that exhibit "dummy foal" behaviors. Dummy foals are foals that after birth don't immediately nurse and bond with their mother and instead act confused and aimless. These foals require intensive care until they exhibit normal behaviors, and are at risk of dying from the condition. The Madigan Squeeze procedure is now used globally. Videos documenting the squeeze technique have generated approximately 15 million views on YouTube alone. A global pioneer in equine neonatal health and founder of the first equine neonatal intensive care unit at UC Davis, Madigan also collaborated early on with human physicians to help understand the health and care of newborn foals. His book explores the implications of birth, the brain, and the transition from fetal life to wakefulness across species. UC Davis publicity caught up with Madigan and asked questions that the book awakened. UC Davis: In an age of complex medical advancements that rely on advanced biological and technical solutions, the development of a simple treatment like the Madigan Squeeze seemed almost like a one-in-a-million breakthrough. What can we learn from the identification of this treatment? John Madigan: One of the most remarkable lessons from this discovery is that a major medical treatment breakthrough does not always require complex technology. Sometimes it begins with careful observation, asking the right questions, and recognizing what has been overlooked. Perhaps the most important lesson is what the extraordinary response revealed about the underlying biology. We believe we identified a previously unrecognized problem in some newborn animals: a failure to make the normal transition from the unconscious or sleep-like state of fetal life to wakefulness and consciousness after birth. Our research suggests that the physical pressures and sensory experiences of the birth process may help signal this neurological awakening. When those processes are disrupted or altered, some newborns may fail to make that transition normally. The Madigan Squeeze appears, in some affected animals, to reproduce part of the sensory signaling needed to facilitate that awakening. The implications extend far beyond veterinary medicine. They raise important questions about what happens during human birth, how the newborn brain transitions to consciousness, and whether events surrounding birth may influence early adaptation and subsequent neurodevelopment. We are continuing to explore these questions. The newborn foal gives us a unique window into the awakening brain because its neurological transition at birth becomes visible through behavior within hours—not months or years. Normal foals stand within an hour, nurse within two to three hours, and bond and move with the mare. With the foal, we can see when the transition fails. And when an intervention succeeds, we can see the change almost immediately. In human infants, the developmental consequences of early experiences may not become apparent until much later. For me, the greatest lesson is that something very significant can begin with careful observation of animals or humans; it can inspire science to study fundamental biological processes that remain poorly understood. Sometimes a remarkably simple intervention can open the door to an entirely new understanding of one of life's most important processes. That is not to say that technology is not important. We have used the advanced scientific tools here to investigate, measure and understand the specific neurosteroids driving birth processes. I was particularly honored by something Temple Grandin wrote in the foreword to my book: "Dr. Madigan is an innovator with keen abilities on observing how animals behave. The veterinary profession needs more good observers because they may have the best clinical skills." Coming from Temple, who has devoted her career to understanding animal behavior, that meant a great deal to me. We have extraordinary scientific technologies available today, but we should never underestimate the importance of simply watching animals carefully, using observation to recognize when something isn't right, and asking why. Sometimes the most important scientific discoveries begin not with a sophisticated instrument, but with someone noticing something that others have overlooked. UCD: You used UC Davis' connection to human medicine early on when you founded the Equine Neonatal Intensive Care Unit (now called the Lucy G. Whittier Neonatal Intensive Care Unit) at UC Davis' veterinary hospital and collaborated with a neonatologist at UC Davis Health in the process. Now you're using your discoveries related to the Madigan Squeeze to raise questions that could benefit neonatal human medicine. Do you think veterinary and human health would benefit from more collaborative research? JM: Absolutely. We have an extraordinary opportunity at the UC Davis Weill School of Veterinary Medicine to collaborate with our School of Medicine and with researchers at other institutions, including UCSF and Stanford. Some of the most important medical discoveries can come from looking across species and recognizing the biological processes we share. When we first observed the remarkable awakening of maladjusted foals after the Madigan Squeeze, questions immediately arose. If pressure from the birth canal helps signal the newborn brain to awaken, what happens when that process is bypassed during a cesarean section? Could similar neurological and hormonal transitions occur in human infants? At that time, I learned that the Bill & Melinda Gates Foundation was seeking "bold ideas" with potential applications in human medicine. I submitted a proposal based on our discoveries in foals, and our UC Davis team received a grant through the Foundation's Grand Challenges Explorations program. Researchers at Stanford University reached out to collaborate, and together we conducted a study of newborns that was subsequently published in the Journal of Perinatology. We found that infants delivered by cesarean section showed a less pronounced decline in certain neuroactive steroids during the first two days of life than those delivered vaginally. These included hormones associated with the regulation of brain activity, which we had also investigated in maladjusted foals. Of course, this does not mean that babies born by cesarean section are maladjusted. But it does show that the hormonal transition after birth can vary depending on how the infant is delivered. That was an important finding, and the question arose from our observations in veterinary medicine. It also led us to consider the potential importance of sensory experiences after birth. One example is kangaroo mother care, which includes prolonged skin-to-skin contact between a mother and her newborn. We believe that sustained gentle pressure and tactile stimulation may provide some of the same sensory signals we are investigating with the Madigan Squeeze. The World Health Organization recommends kangaroo mother care for preterm and low-birth-weight infants because of its demonstrated benefits, including improved survival. Remarkably, long-term research following children into young adulthood has also shown lasting benefits in neurodevelopment, behavior, and social functioning. These findings raise fascinating questions. Could sensory signals associated with birth and early maternal contact influence the neurological transition from fetal life to consciousness? Could understanding these mechanisms improve neonatal care and even long-term neurodevelopment? We don't yet have all the answers, but these are important questions worth investigating. That is what makes collaborative research so valuable. Our work began with a problem affecting newborn foals, led to a practical treatment now used internationally, and opened a new window into understanding the biological events surrounding human birth. We're certainly not the only researchers at UC Davis making these connections. Many faculty members at the Weill School of Veterinary Medicine have made discoveries that advance human health. This is the tremendous promise of One Health: animal and human biology are deeply connected, and advances in one can lead to breakthroughs in the other. I've also been fortunate to work under three outstanding deans at the school, including Bennie Osburn, Michael Lairmore, and our current dean, Mark Stetter. All three have proactively recognized the importance of One Health and encouraged connections between veterinary and human medicine. Their leadership has fostered an environment where discoveries in animals can lead to new insights and opportunities to improve human health. I believe one of veterinary medicine's greatest opportunities is not simply applying discoveries from human medicine to animals but making discoveries in animals that help us better understand and improve human health. UCD: Your partnership with equine professionals, both other veterinarians but also owners and other non-medical people involved in the horse industry, seems essential to your breakthroughs. What can you say about researchers' relationships with the animals they treat and study? JM: That's a very important question for me personally, because I believe the relationships we develop with the owners of the animals we care for can be just as important to discovery as the research itself. In fact, the first successful Madigan Squeeze on a maladjusted foal probably wouldn't have happened without the trust that developed over many years between me and one of our longtime clients, Ellen Jackson, the owner of Victory Rose Thoroughbreds. Ellen called me about a newborn foal that was eight hours old and still wasn't nursing. For several reasons, she couldn't bring the foal to our neonatal intensive care unit at UC Davis. She asked me, "Is there anything new we can try, John?" One detail caught my attention. She told me the foal had a very rapid birth. At the time, we hypothesized that pressure during passage through the birth canal might signal the foal's brain, helping it transition from the sleep-like state of fetal life to wakefulness after birth. I asked Ellen, "Would you be willing to try something new that's never been tried on a maladjusted foal?" She said, "Absolutely. If it might help and if it's safe." I explained that we had already tested the procedure on eight normal foals and had evidence that it could be performed safely. I drove to her farm. There was no hospital, no team of residents, no drugs, and no sophisticated equipment. Just me, Ellen, a newborn foal, and an idea grounded in our research. We applied a soft rope restraint around the foal's chest to simulate the pressure experienced during birth. After about 20 minutes, we released the restraint. The foal stood up, walked over to its mother, and nursed. Only minutes earlier, this animal had wandered for eight hours, disconnected from its mother and unable to nurse normally. And here's an important point: there was no established experimental animal model for neonatal maladjustment. We couldn't simply reproduce the condition whenever we wanted to test an idea. Imagine calling a horse owner and saying, "I've got an idea. Your foal isn't nursing and seems disconnected from the world. I'd like to put a rope around its chest, apply pressure until it lies down and appears to go to sleep, and then see if it wakes up behaving like a normal foal." That's a bold idea! You had better have someone who knows you and trusts your judgment. That trust didn't happen overnight. It developed through years of caring for Ellen's horses, making farm calls in the middle of the night, treating critically ill foals, bringing them into our intensive care unit, and communicating openly about their care. For me, this illustrates something fundamental about veterinary medicine. Our patients can't tell us what's wrong. We depend on the people who know them best—the owners, breeders, farm managers, and caretakers who observe these animals every day. Their observations can help a veterinarian diagnose a problem or explore new ideas. It is interesting that the first description of this condition in newborn foals was in 1930, and the veterinarian's observation led him to write that the foals' behavior was as if they were still in the womb. Observation was the only thing they had back then. I've always loved working with horses. I also love the connection with the clients who own and care for these wonderful animals. The Madigan Squeeze possibility came from clues in scientific investigation. But a relationship built on years of trust made its first successful application possible. Often, a discovery in veterinary medicine begins with a partnership between the researcher, the animal, and the people who care for it. UCD: You obviously put a lot of work in documenting the story of the Madigan Squeeze and articulating the lessons of it in this book. What else can people expect from you in the future? JM: Although "Awakening at Birth" tells how we discovered the Madigan Squeeze and what we learned along the way, I don't see it as the end of the story. In many ways, I think we're just beginning to understand the broader biological implications of what we discovered. Our team at UC Davis, the Equine Comparative Neurology Group led by Dr. Monica Aleman, has been discussing the next steps to better understand the mechanisms behind the transition to consciousness at birth. One particularly promising direction involves newborn pigs. Our comparative neurology research team has just completed a study, now being prepared for publication, examining neuroactive steroids in neonatal piglets. Looking ahead, one exciting possibility is developing a simple bedside biomarker that could help us determine whether a newborn has successfully completed the neurological transition from fetal life to wakefulness and consciousness. It could ultimately help us better understand and improve newborn survival and adaptation, and potentially long-term neurodevelopment. For me, one of the most exciting aspects of scientific discovery is that answering one question often leads to several more important ones. The Madigan Squeeze began as an attempt to help a newborn foal, but it has raised a broader scientific question: What awakens the brain at birth, and how can understanding that process improve newborns' lives across species? What began as an observation of a newborn foal might one day lead to a simple bedside test that helps clinicians better understand the neurological transition at birth across species. Madigan's book, "Awakening at Birth: What the Newborn Foal Revealed About Birth, Consciousness, and Neurodevelopment" can be purchased on Amazon. This Q&A was conducted by Tom Hinds for UC Davis.