 Good morning, everyone. Thank you for joining us. I'd like to, again, thank you for attending this special 150th Giant Leaps Ideas Festival event. We've had many and we're really coming close to the end of next Friday's finale. I hope all of you were able to join that as well. Today it's my pleasure to welcome Dan Skavonsky, who is the president of Lilly Research Laboratories and chief scientific officer at Eli Lilly and Company to Purdue University. Purdue has and continues to have many touch points with Eli Lilly, and we're especially pleased with our new five-year scientific research partnership that many of our faculty and students are engaged in. Eli Lilly, as all of you know, is one of the most respective pharmaceutical companies throughout the world, and it is one of Indiana's real treasures. I'm relatively new back to the state, and I have just been impressed with all of the touch points with Lilly, the Lilly Endowment, and the Lilly Foundation. They have made a tremendous difference on all of us in the state of Indiana. In addition to his role as the president of Lilly Research Laboratories and chief scientific officer, Dan serves as senior vice president of science and technology. He also has responsibility for global business development. Dan joined Lilly in 2010 when the company acquired Avid radiopharmaceuticals, where he had been CEO since he founded the company in 2004. At Lilly, Dan has held various roles, including vice president of tailored therapeutics, vice president of diabetes research, and most recently, senior vice president of clinical and product development. He just shared that his current job is one of the best in the world. Dan completed his residency training at the hospital of the University of Pennsylvania. He received both his masters and his PhD at the University of Pennsylvania. He earned his bachelor's degree in molecular biophysics and biochemistry from Yale University in 1994. Please join me in welcoming Dan to our 150th Giant Sleep Celebration, and I look forward to enjoying his presentation. What if we stopped fighting disease together with all of you? Please welcome Dan. Thank you, Teresa, for that kind introduction. And thanks all of you for being here on this gorgeous Friday morning. I'm sure there's other things that you could be doing than sitting in an auditorium, but I will try and make this an interesting morning for you. I'd also like to thank President Mitch Daniels for the invitation to speak here today. You may know that President Daniels is a Lilly alum, and he's also not the only connection that Purdue and Lilly share. Purdue and Lilly have a very long association, probably longer than most of you would guess. When Purdue established its pharmacy school in 1884, it was at the suggestion of John Newell Herty, who was an Indianapolis-based pharmacist and he was a protege of the founder of my company, Colonel Eli Lilly. Purdue's president at the time went along with the idea to start a school of pharmacy on the condition that John Herty himself would serve as its first dean, which he did. The school originally had a student body of seven and a faculty of just four. But it grew quickly, and when it moved to a new building in 1930, the furnishings in that building, the furniture in that building, was provided by the grandson of our founder and the CEO at that time, J.K. Lilly. The very first chemist ever hired by Lilly was Ernest Aberhart, and he was of course a graduate of Purdue's School of Pharmacy, pictured here with the CEO, J.K. Lilly. One of the other early deans of the school is the great grandfather of our current CEO, who by the way is also a Purdue grad. In fact, today 1,251 Purdue graduates work for Lilly. That's more than any other college in the university, other college in the country. Second place, by the way, is a school south of here in a town called Bloomington. Maybe some of you today will join Lilly Purdue Connections in the future. But I'm here today to talk about innovation. There's a lot of innovation to talk about here at Purdue. Purdue's Discovery Park, which was created with help from the Lilly Endowment, is one example. An interesting project coming to life at Purdue's Discovery Park is research into nutrition and medical needs for a hypothetical future colony of life on Mars. Of course, Lilly doesn't plan to move to Mars anytime soon. But still, I'm glad that this kind of research is happening here. And I hope that someday it will be put to use. When it does, it'll be another in Purdue's long history of achievements in the field of aeronautics and astronautics. Only six decades separated the right flyer rising from the North Carolina sky and the Apollo lunar module descending to the surface of the moon. That's an incredible amount of progress and accomplishment in such a short period of time. And Purdue helped speed it along. You provided the support. When Amelia Earhart was preparing for what would be her final flight, Purdue's board on which J.K. Lilly sat helped fund it and financed the repair of our plane. Here's a letter from J.K. Lilly to the president of Purdue, promising a donation of $2,500 for Miss Earhart's flight. You, Purdue, also provide the knowledge. Purdue graduate Cliff Turpin was part of the right team and helped redesign their motors and control system. Another Purdue grad, William J. O'Neill, helped build the Galileo spacecraft that reached Jupiter. And, of course, famously, you provided the manpower. There's a reason Purdue is known as the cradle of astronauts 25 educated here. That famously includes, of course, the first to reach the moon, Neil Armstrong, as well as the last to set foot on its surface, Gene Cernan. I don't doubt that some current and future boiler makers will eventually push that number well beyond 25. This makes an exciting time for me to visit Purdue. Not only is it your 150th anniversary, but it's, of course, the 50th anniversary of the moon landing. The moon landing remains astonishing to me five decades on. It's one of America's signature achievements, and we should celebrate it. Of course, it didn't come easily. It happened because of incredible amounts of work and sacrifice. You know this well. Two buildings on this campus are testament to that. They bear the names of Gus Grisham and Roger Chaffee, both of whom were Purdue grads, both of whom perished aboard Apollo 1, the prelaunch fire. Grisham and his crew gave their lives so others could make this one giant leap for mankind. As he said shortly before his death, if we die, we want people to accept it. We are in a risky business. And we hope if anything happens to us, it will not delay the space program. The conquest of space is worth the risk of human life. Indeed, it was. Yet reflecting on all of the sacrifices that were made in pursuit of our goal and looking back at the crowning achievement of 50 years ago, I can't help but feel a bit sad. The progress that took humans to the moon was fast incoming. But achievements in the five decades since then have been slower. Exploitation of space is simply no longer the same priority for the American people and our government that it was in the 1960s. National priorities have changed. Interest and enthusiasm of our citizens has waned. And progress has become slower. Humans first set foot on the moon 50 years ago. They stepped off it three years later. We've not been back since. Imagine the thoughts of an astronaut, an engineer, any scientist who was involved in the Apollo program in the summer of 1969 as they reflected back on the incredible progress in 60 years and projected ahead to what might be possible by the summer of 2019. Vibrantly inhabited self-sufficient space stations for sure. Exploration of Mars, no problem. Colony on Mars, quite likely. Plans were being drawn up back then. New conquests were imagined. Unfortunately, horizons that we hoped to reach half a century ago have gone unexplored. A first mission to Mars is still a dream. As a child, I was fascinated by rocketry and space exploration. Like many others, I designed and built model rockets, trying to improve their range, figure it out. I went to space camp. I experienced a childish version of astronaut training. Along with a few of my equally-minded friends, we drafted blueprints for spaceships that could carry humanity beyond the solar system. Naturally, I knew the names and histories of all of our great astronauts, and I planned to become an astronaut myself. My children, however, don't share the same sense of excitement for rocket science and space exploration. I'm not sure many children today do. Of course, there's someone long-facinated by space travel and one who sees incredible value in it. I find the decrease in our national enthusiasm somewhat saddening. But there's something else about the trajectory of space program that concerns me. In many ways, the exploration of the heavens and the eradication of disease are alike. For thousands of years, people have dreamt of flight. And for thousands of years, people have dreamt of curing disease. And yet it is only in the last century that we have made meaningful progress in either areas. But while our advances in space exploration have slowed, progress in disease fighting has actually accelerated. And while I don't think too many children today look up to our greatest chemists or scientists or dream of being a drug discoverer like me, I do think that we're living in the moonshot era for medicine. What we have accomplished in medicine in the past century is astonishing. What we are poised to do in the coming decades will be nothing short of miraculous. I'm reminded of this every morning when I walk into work at Eli Lilly and Company. This statue sits in our lobby. And here is the image that inspired it. This photo taken in 1922 is a young patient, J.L., stricken with diabetes and literally dying in his mother's arms. For thousands of years, diabetes was a mystery, confounding doctors who hope to treat it, killing those who it afflicted like this young man. Doctors suggested cures that were a little more than shots in the dark, rides on horseback, severe diets of potatoes or oats. By the early 20th century, those suffering from diabetes were prescribed 400 calories a day on a dangerous starvation diet. Still, it didn't stop the disease. The diabetes diagnosis remained a little more than a death sentence. Then in 1923, collaborating with Banting and Best at the University of Toronto, Lilly introduced Iletton, the first commercially available insulin in the United States. It revolutionized the way those suffering from diabetes lived and it replaced certain fatality with a chance for long and active lives. The work of drug hunters and their collaboration with Lilly gave J.L. and countless others a reprieve. It solved a century's old riddle. Today, thanks to insulin, diabetes is a treatable condition, not certain death. Polio also likely affected humans for thousands of years. There were occasional outbreaks in the United States in the 19th century, but it became a full-blown epidemic in the early 1900s. Appearing in summer months, moving from town to town, it brought a form of near hysteria with it. Thousands were diagnosed and thousands became paralyzed and died. Children were particularly vulnerable. Families were quarantined. The names of infected patients were published in the newspapers. There were no treatments. Ideas suggested by doctors such as baths in almond flour were futile. At the tail end of massive trials, Jonas Salk and his research team created a vaccine using dead strains of the virus. By 1953, 57,000 cases of polio were reported. 3,000 of those patients died. The next year, the Salk vaccine was approved and 15 years later, the total number of paralytic cases in the United States was just 53. Today, it is, of course, zero. Lily was the largest manufacturer of the Salk vaccine. We designed a separate building for its production and Salk himself described the company's efforts as something beautiful to behold. If production of insulin was our kitty-hawk, eradication of polio was surely our first moon landing. And an important milestone in the advancement of vaccines. Childhood vaccinations have together created a radical and once unimaginable improvement in human health. The resulting decreases in childhood mortality have fundamentally changed human society around the world. With increasing odds that a child survives to adulthood, birth rates always go down. As families get smaller, women are freed to contribute in other ways to society. And with increased investment concentrated on a smaller number of young children who are now likely to survive to adulthood, education thrives and ultimately prosperity increases. And the wheel of science accelerates again, allowing even greater advances for society. Let me share another example from our moonshot era. For thousands of years, humans had experimented with the use of fungi for medical purposes. But only about 90 years ago, Dr. Alexander Fleming discovered that penicillium mold secretes an active substance that can kill bacteria. Progress was slow for the first decade. Then the research was accelerated in the early 1940s when scientists treated sick mice for the first time with a purified form of penicillin. This coincided with World War II. Soldiers who suffered from wounds and injuries were getting septic and dying. A mass effort began among the allies to scale up the production of this new infection fighter in order to save lives and win the war. It crossed continents and countries. While the Allied Command planned the invasion of Normandy, back in the US, companies like Lilly played their part in the World War effort. In Indianapolis, the work began with an air conditioner and a flat bottle. Soon production grew more sophisticated. An old warehouse was crowded with two quart milk bottles laying side by side, penicillin growing inside. By 1944, the company had its first tank full. The following year, the new wonder drug was available for mass use. Soldiers suffering from sepsis in field hospitals were treated quickly and effectively. Cases of gangrene were eliminated. This secret weapon, a wonder drug, saved thousands of soldiers' lives and then helped them defeat Hitler and save Europe. And Lilly was probably one of the largest producers for the US government. This creation of modern antibiotics was surely another successful moonshot for modern medicine. Fundamentally, changing again the course of human history. Lilly contributed not just by making penicillin but inventing important antibiotics, drugs like vancomycin, erythromycin, as well as the entire class of cephalosporins, including powerful drugs like Keflex and C-chlor. As a result of this work, society changed once again. Communical diseases, which were once a leading cause of death in the United States, became a footnote on mortality tables. As a result of progress in treating or preventing infectious disease, life expectancy skyrocketed. Moving from just 45 years at birth at the turn of the century to nearly 80 years today. Changes in life expectancy have driven a growth in the elderly share of our population from just 4% to 17%. And the number of elderly in our country have increased over 15-fold. These demographic changes have in turn impacted how we spend corporate and government money on healthcare, driving costs to treat newly important chronic diseases like cardiovascular disease, Alzheimer's disease, and type 2 diabetes, which along with cancer are today's leading causes of death. Today, the moonshots continue. Let me share a few modern examples just from Lilly's lab. Psoriasis is a disease that affects millions of Americans characterized by scaly skin lesions and other symptoms including severe forms of arthritis. There were no major breakthroughs in treatment of psoriasis until about 20 years ago with the dawn of biologic therapy and anti-TNFs. And you could see on this graph 30 to 40% of patients on anti-TNFs could achieve this high level of response, 90% clearance of the symptoms of their disease. People held this as a miracle for treatment of psoriasis. But look what we've done even in the short time since then. Scientists at Lilly and elsewhere continue to track down the genetic basis of the disease identifying a gene and protein IL-17 as a potential player. Biopsies from the skin of patients suffering from psoriasis showed a particular type of helper T-cell that secreted IL-17 was enriched in patients with psoriasis and our scientists at Lilly created an antibody to block IL-17 and tested it in patients. And the results are what you can see here. We and others now have drugs that block IL-17 approved and available for patients and up to 80% of patients can now achieve near total response and clearance of psoriasis. But once seemed impossible, today is routine for most patients with this disease. Migraine is another significant medical illness. About 36 million Americans suffer from migraine. Most of them women, mostly working age, many of them with families. Many patients with migraine suffer 10 or more attacks in a given month. They often suffer in silence with incredible costs to productivity, society, family life. Scientists at Lilly and elsewhere discovered that when a patient was having a migraine attack, the levels of a particular peptide that can serve as a neurotransmitter called CGRP were elevated in the blood. In difficult experiments, they also learned that if you injected purified CGRP into patients who were prone to migraine attacks, it would stimulate an immediate headache. So our scientists designed an antibody to attempt to block the effect of CGRP in the body and test it in migraine patients. In the clinical trials that were later published in journals like JAMA, New England Journal of Medicine, we studied patients who had severe forms of migraine, on average, 10 attacks a month in this trial. By the end of the trial, the incidence of migraine in these patients on average had dropped in half. Imagine that. And a significant fraction of patients had no migraine attacks at all in a given month. Now drugs like ours and others that block CGRP are available and widely used to prevent migraine attacks in patients. Shown here are the results of a drug that we're testing for cancer. This drug, Selpracatinib, we're testing in lung cancer. It's not designed to treat every patient with lung cancer. This drug targets just about 2% of people with lung cancer. Those patients who have a mutation of fusion in a particular gene called RET, we know that that genetic abnormality fuels the tumor growth. And scientists set out to try and design a specific small molecule inhibitor against RET. Testing it out in patients who had their tumor sequenced and just in those patients who had this genetic abnormality, the results are shown here. Each line on this graph represents an individual patient. If the line is going up, their tumor is growing as it was when they entered the trial. If the line is going down, they're responding to this drug and their tumor is shrinking. This particular graph shows patients with metastatic lung cancer. So the disease is spread to other organs in the body. Many patients in this trial had spread of disease even to their brain. And these patients had failed most other available therapies. They were at the end of the line for treatment of lung cancer. In a setting like this, we would be excited to see 20 or 30% of patients responding. What we actually saw was 70% of patients responding and the trial continues on. This is an example of what we consider to be precision medicine, identifying just the right patients who are likely to respond to a therapy, designing the drug to target their particular abnormality and then testing it in those patients. We also work in type two diabetes. Of course, type two diabetes and obesity are a major cause of mortality in society today as a driver of heart disease and stroke. This drug called terzepotide is a dual agonist of two incretin pathways, GIP and GLP-1. We designed this peptide and tested it in patients with type two diabetes. And here you can see results from the first phase two trial of this drug, testing it for six months in patients. And the results were really astounding. So on the left is hemoglobin A1C. It's a marker of long-term glucose control. We had dramatic results here. And at the highest dose of this drug, nearly a third of the patients at the end of the trial, when we looked at their long-term glucose control, it was indistinguishable from a patient who did not have diabetes. They were normal in their glucose control. Something that's never been achieved before in type two diabetes and has never been thought to be possible in patients with this disease. On the right side, you can see another powerful effect of this drug, weight loss. And in this phase two trial and six months at the highest dose of the drug we tested, patients lost on average 11 kilos, 25 pounds of weight loss. Imagine losing 25 pounds for a person with obesity. Many of these patients returned to normal body weight, normal weight, normal glucose control. The ability to reverse type two diabetes is something that we strive for and now we believe could be possible in the future. From insulin to penicillin, from the Salk vaccine to our recent discoveries for migraine, psoriasis, cancer and type two diabetes. These achievements are our equivalent of Kitty Hawk, the Mercury program, the Apollo mission, moonshot after moonshot after moonshot. We are firmly in an era of multiple moonshots. We've come so far so fast and perhaps because of the speed, we take some things for granted. Certainly there are diseases that once killed with regularity that struck fear across the world whose names children born today will never even know. They've been banished to the historical record and many more will join them in coming years. Diseases like Alzheimer's, heart disease, cancer even. May someday be little remembered or feared. But here I have to put an asterisk. Earlier this month, Gallup released a poll ranking the popularity of US industries. Pharmaceutical companies ranked dead last. Behind banking industry, behind the oil industry, even behind the US government. How could it be? 60% of our country thinks poorly of the industry that brought all of these medical miracles to life. They don't see us as akin to astronauts. Far from it. I think they see us as Darth Vader as a Star Wars fan. I take some objection to that. But scan the headlines. You'll see drug makers described as evil, greedy or even criminal. Watch congressional hearings. You'll see us described as that and you'll hear the assertion that drugs don't come from pharmaceutical companies, that they come from academic and government funded research. They believe that large pharmaceutical companies just swoop in at the end of the process and profit off the discoveries of others. I didn't come here today to absolve the pharmaceutical industry. I'm not gonna tell you that companies in it have not made mistakes, that some of our unpopularity may be self-inflicted. Nor will I tell you that drug making begins and ends with pharmaceutical companies. But this I don't hesitate to say. Without large drug makers, the medical equivalent of a mission to Mars will never launch. Moonshots are impossible. The next wave of disease eradication will never crest. You don't have to strain your eyes to see what the future could hold though for medicine. We will engineer cells in the laboratory to create programmable disease fighters that can be re-implanted into the body to cure cancer or autoimmune disease. This is happening already today. In our labs at Eli Lilly, we're engineering stem cells in the lab to become pancreatic beta cells. We're encapsulating them so we can transplant them back into patients and permanently cure type one diabetes. We hope to make our own product, insulin, obsolete someday. It's working in animal models. We'll be testing it in patients soon. For diseases like Alzheimer's disease, we've created new tools that allow us to track the disease in living patients and test potential treatments more quickly. In an individual subject, we can watch the ravages of the disease spread from neuron to neuron by sequential imaging and we can treat them with drugs designed to stop the spread of the disease. Every day, we draw near to meaningful therapies for this difficult diseases. And we are engineering RNA to create a whole new category of drugs. We're using messenger RNA to coax patients' own cells in their body into creating their own cancer vaccines. We're using SI RNA to turn off genes in nerves that are implicated in pain and genes in the brain that cause neuro-generative disease. Our missions to Mars are within reach. The impact of medical advances in the next 50 years will be just as great as it has been in the last 50 years. The chances of all this unfolding though will greatly decrease without large pharmaceutical companies. They will be zero in fact. We can't fight disease without companies like Lilly. And if we stop fighting disease, so many lives will be lost. The cost will be devastating. My mission as Chief Scientific Officer of Lilly is to make sure that half a century from now, we don't look back on this. On this, our moonshot era of medicine and lament how fleeting it was. My charge is to make sure patients and their loved ones are not still waiting on answers for the diseases that we have it in our power to stop or will soon. At Lilly, we continue to advance the science. We never stop innovating. But our ability to do this does depend on factors beyond our control. If we're viewed as villains, if society sees ever less value in our efforts, the framework in which we innovate is in jeopardy. I say this not simply as a representative of Eli Lilly and Company, but as someone who's seen and played a part in the ecosystem in which drugs are created and diseases are fought. As a doctor, I've participated in patient care. As an academic scientist, I've worked on basic research. I've participated in drug creating process, both by founding and leading a biotech company and now leading research and development at one of the largest pharmaceutical companies in America. Through these experiences, I've learned that there's multiple indispensable players in the advancement of medicines. All of these players together form an ecosystem. In the last one I mentioned, the big pharma companies are also crucial for breakthroughs. Those who argue otherwise who doubt the worth of drug discovery and drug development should consider what the healthcare landscape would look like without it. No insulin, no polio vaccine, no antibiotics, no treatments for psoriasis, migraine, cancer. It's not an encouraging image. Modern-day medicines are not magic. They don't come from a flash of inspiration and then ready for patients. Rather, they're the result of a long and difficult and expensive R&D process. On average, drugs take 10 years from target to launch and the success rate for projects is far less than 1%. Thousands of researchers are involved in the process for each project and it costs nearly $3 billion to bring a single successful drug forward. Yes, academic research often begins this process but the task of discovering, developing, producing, distributing drugs falls to the pharmaceutical companies and it's an enormous undertaking. Think about this, the invention of rockets had to be followed by NASA's massive efforts to send man to the moon and bring them back safely. In the same way, academic discoveries must be followed by the massive efforts of pharmaceutical companies to create safe and effective medicines. The accomplishments of the last century, sending humans into space and the moon, stopping diabetes and polio were not fated to happen. They weren't inevitable. The course of human history does not naturally tend towards the betterment of the human condition or the eradication of disease. It only happens because of incredible amounts of work and sacrifice. It only happens because of imagination and collaboration. We see this both in the history of space exploration and the history of fighting disease. These are two of the most challenging pursuits known to humans. Yet much like America's space program with its tragedies and struggles, pushing the boundaries of medicine remains a highly rewarding pursuit, one that helps and inspires millions. Here at Purdue, both of these pursuits are alive and well. Here on this campus where Armstrong, Grissom, and Cernan all walked, the study of rocket science continues and students still look towards the stars. The new space age driven by the private sector may be upon us. Purdue is preparing to play its part. And of course, here in West Lafayette, the quest to understand and end disease goes on just as it does at Lilly. It has to. We're facing formidable challenges as a society. Life expectancy in America has declined in recent years. We have epidemics in pain and addiction, mental health and gun violence. We have incredibly important work to do now and in the future. Those of you who are passionate about fighting disease and alleviating human suffering, be aware, be engaged when it comes to policies affecting innovation. Continue to support and encourage science education and research funding. Do all you can to demonstrate the value in what we do. Regardless of the opinion polls and in the face of challenges, I remain optimistic that our moonshot era in medicine will indeed give way to even greater accomplishments. Companies like Lilly and institutions like Purdue have unlocked mysteries and found answers in the past. Let's continue on to reach and explore new frontiers in the future. Thank you very much. Excellent. I believe we have a panel discussion next. I want to thank Dan for the really inspiring presentation. It really captures the contribution from both Lilly and Purdue to society. And in the next 30 minutes, I like that we have faculty panel discussion with Dan. And I would like to maybe first introduce the panel. We have John Tesmer who is a Water Professor in Cancer Structure Biology. And John specialized in understanding the molecular basis of G protein coupled receptor signaling. And he also interested in developing a structure-based design to target the GPCR kinase for cardiovascular disease. Next to John is Aron Ghosh, the Rothwell Distinguished Professor in Chemistry and Medicinal Chemistry. Aron actually is the inventor and discoverer of the Ronova, which is an FDA approved drugs for treating HIV and AIDS. And it was approved in 2006 when the widely used medicine to combat these diseases. Aron's lab also continuously improved this therapy for HIV but also expand to other therapeutic area in Alzheimer, for example. Next is Jackie Linnis. She's a mother, gross professor in biomedical engineering. Her expertise is really a microfluid. She specialized in invention of porn and cure diagnostic and molecular sensors for substance abuses. And then we have Chris Roche, the professor of medicinal chemistry molecular pharmacology. And John Dana Krinsky, director of Purdue Institute of Integrative Neuroscience. Chris was trained as a neuroscientist and biochemist and specialized in protein aggregation and relevant to neurodegenerative diseases in particular Parkinson's Alzheimer diseases. My name is Zongying Zhang. I'm a professor of medicinal chemistry molecular pharmacology and director of Purdue Institute for Drug Discovery. So I want to just start. You made a very strong case about the need, the importance of public support, appreciation of innovation, and in supporting our fight against diseases. And so clearly there's a, all of us in the room need to really to have responsibility to advocate and support society and funding agency to continue our research. But I want to turn into a technical aspect of drug discovery. That is, despite all the advances you highlighted that we've made to improve human health over the last 100 years, there's still too far many human diseases and they're still not curable and not even be manageable today. And so there's often said that drug discovery is not rocket science. It is not. But if we could send a human being to the moon 50 years ago, why current disease so difficult? So I just want to open up this to the panel and what is about drug discovery that's so difficult? You want me to start? Well, of course there's two aspects to it. One is just a complexity of human biology and understanding how to impact that biology in a way that affects a specific disease. Sometimes we get sort of lucky where there's one specific target that we know impacts the disease. The example I showed in, all of the examples really in infectious disease, you know what causes the disease, you kill the organism, solve the disease. Those are great successes. Sometimes even in complex diseases like psoriasis, you can find a linchpin in the disease in the case of Isle 17. Impacting that practically cures the disease. But more often it's a combination of factors that cause disease and that becomes really hard. And we don't always have the right scientific methodologies really to test the idea that you need to impact at multiple places in the biology of a cell or an organism to change the disease core. So I think that's one of the big challenges. The other is when we look at all the different targets in a cell, there are some that have been up until now generally off limits. Just things that we can't hit with small molecules that are inside the cell. We can't hit them with antibodies. And so we sort of shut our shoulders. I think that's changed with gene therapy and RNA therapies and other more advanced new ways of making drugs. We're getting to the point where any target we want, we can access it. And I think that's a huge advance. Other panels members agree to chime in. First of all, I would like to thank you for a really very motivating lecture. As you mentioned that our students, our younger generations, they're not pursuing science or medicine or drug discovery. Can you comment on why? Why do you think there's less interest towards drug discovery or pursuing rocket science? What is your perception here? I am not an expert in childhood education or in why people choose different things. But like many people, I've watched my own kids go through their science education and teachers matter so much. It's so important to have an inspiring teacher or mentor that gets kids excited about science and technology. So I think that's one aspect we need to invest more in science education. The other, for sure, must be the things that we see on the news. If we vilify the people who work to make new drugs, who will wanna go in that profession? Okay, my second question is, if you look at the history of drug discovery, all emanated from natural products, you know the history of Eli Lilly's discovery and the help of the penicillin to hand-comicin. So natural product plays such an important role. At the same time, if you look at today's Lilly's effort, all the natural product isolation, all of these things has been dismantled. And you are actually, even company like Eli Lilly, making large molecules, large library of molecules, hoping one of them become a drug. So this kind of perception also really not helpful for what is happening today. Today we understand a lot of disease in molecular level. Protein structures are known. We know where exactly catalysis is happening. Structure-based design of molecules is very important. If you look at the history since late 2000, so we have probably 60 to 80 drugs literally developed based upon structure-based, protein structure-based. On the other hand, now you can see company like Eli Lilly dismantling medicinal chemistry, which is basically making molecules overseas. And this teamwork with medicinal chemists, biologists, pharmacologists work together, that is not happening. So my perception is probably the students are not enjoying the scientific discovery. What can we do to bring them back? Yeah, that might be partially true. Of course, I hope we're not dismantling medicinal chemistry, but I do agree with your comment that it would be better to have multidisciplinary integrated groups. I think if we see chemists as just people who make molecules and biologists as people who study cells, it won't work. We need chemists who understand biology and biologists who understand chemistry and we need them working together closely, probably with physicians who take care of patients as well. And that isn't always the way that pharmaceutical companies have been structured in the past, so I do think that's important. With respect to natural products, of course, there was an era of phenotypic screens where you would just test different things on cells or organisms and see what happened and look for one that looked like it was improving disease. And then we moved towards, as you described it, molecularly targeted therapeutics, which has been great. But actually now I do see an opportunity to do more phenotypic screens because we can actually now, for the first time, have the tools to deconvolute the target. So when you see a natural product that impacts biology of a cell or an organism, you can figure out how. Whereas in the past, it was kind of a mystery and often drugs would launch a decade before we would even know what their molecular basis of effect was. So there's some hope there as well. And I'm not gonna take too much time. So my last comment here, your talk is extremely motivational and also philosophical. So now, I know what Eli Lilly is doing, at least from reading their emphasis, is putting huge effort in biologics. And biologics, one of the problems is, of course, biologics are tremendous, curing a lot of disease, unthinkable. At the same time, the major problems of all biologics is your tinkering with immune system. And basic problem, there is infection, right? So just imagine that penicillin was not discovered and vancomycin was not there, Eli Lilly. What would have been the situation? So can you comment on that? Biologics have many advantages, I think over small molecules. Primarily though, it's the specificity that they interact with their targets. So as you well know, small molecules often hit multiple different targets and it's hard to get them to be exquisitely specific for just one target. With biologics, it's much easier and more highly predictive. And so if we have a target that is outside of the cell, that's on the cell surface or secreted, that we wanna inhibit, and sometimes if we wanna activate it, biologics are the fastest, most efficient way by creating an antibody against that target to make a drug that we can test in patients. Now because they're injectables, that's the primary drawback, not really immune modulation, but because they're injectables that patients have to inject into their body, we often then try to follow up with a small molecule that can be made into a pill, which patients often prefer. I do want to, yeah, Chris? Sure, I'd like to go back to Zhongyan's initial question as well about why diseases have proven to be very difficult to cure from the perspective of neurodegenerative diseases. There's a lot of interest in those diseases here on campus, they're becoming more and more prevalent in society and of course you mentioned an interest at Eli Lilly and so to answer that question, I would say that there are three obvious obstacles. First of all, that there are multiple forms of diseases that we actually consider a single disease, so there's probably not just one form of Parkinson's disease, so it gets to the point of precision medicine or the need for it. Secondly, the fact that these diseases are largely underway or 50% complete potentially by the time they're diagnosed with current neurological criteria for diagnosis. And then the third is the fact that they're very slowly evolving and so that slow evolution poses clear issues with respect to clinical trials and so I'm wondering what Lilly's perspective would be with respect to some of those obstacles. Agree wholeheartedly on all of those challenges and probably they together account in totality like for the failure of progress in developing therapies for these diseases which we've participated in. We've learned from those failures and so we've tried to address them. So one is molecular phenotyping of patients with imaging so that we try and get a more homogenous group of patients. We can also do that earlier in the disease stage so try and get them before they're symptomatic before the disease has passed the point of no return. And then finally, I think we and others are probably turning more and more towards rare subtypes of neurodegenerative disease where there's a known genetic abnormality. It's likely to be a very homogenous population with a rapid disease course. If we can intervene in those diseases then I think we can learn something that we can take back to the vast majority of sporadic Alzheimer's or Parkinson's patients. But it's been certainly a humbling experience working in neurodegenerative disease for the last 20 years. Absolutely. So Jackie. As somebody who works in diagnostics that was the type of thing I very much appreciate that you can't treat what you can't detect and to be able to do better detection but how do you envision sort of the improving technologies as we're in this more connected, more digital world are those gonna be able to benefit the type of treatment and detection that you see coming out of Lily? I don't know yet. I do know that like molecular phenotyping of disease is incredibly important. And so like it has paid off in oncology already and that's the example I showed. You can sequence tumors, identify the genetic mutations, target drugs outside of oncology. There hasn't been much progress, unfortunately. We generally still treat diseases as symptomatic clusters. The question that you have specifically is could we use digital devices, wearables, massive amounts of data from Google or whomever that's spying on us to like figure out what specific disease you have. I don't know. It's often talked about that like if you had enough data and artificial intelligence it'll pull out some cluster of actionable disease but as of yet I can't think of a single example of success there. So we're investing there but I don't know. It must be true and it must work eventually but I probably could have said that 10 years ago maybe 10 years from now. John? Right, I just want to get back to your initial question. Why do we have disease? And one of the reasons that we will always have disease is our remarkable ability as living organisms to adapt. And when we send drugs into our systems the proteins that we're targeting the genes will mutate in cancer in particular. So there's always going to be this resistance mechanism building up against any treatment and we see it with antibacterials for example on a living organism scale. In cancer patients you see it in people being treated for AIDS and related symptoms you get this resistance mechanism. So there's always going to need to be this drive to innovate and find the next tool that you use to help these patients. And I don't see how that's going to happen of a big pharma having a massive effort to find these new compounds and new therapies. And it's almost a little disheartening that if you find a nice treatment for a small lung cell, carcinoma for example, you just know that those patients on that treatment long enough are probably going to regress and there's mutations. What's the philosophy in the industry then? You have a great cancer drug that you know probably your patients are going to revert. We know that almost certainly will. So for example, the example that I showed, the Red Inhibitor, as soon as we started that program or it was actually a biotech company that required those scientists, they said, okay, we anticipate that there's going to be mechanisms of resistance. We have some hypothesis based on cell experiments, what that will be and we're already starting to make the second generation drug. At the same time as I make the first one, the second generation drug that anticipates the mechanism of resistance, by the time the first one was in clinical trials and we had the first patient who developed resistance to the drug, we took their tumor, we sequenced it, we determined the mechanism of resistance and continue to adapt our research program. Now the challenge there, and we'll have a drug, a follow on drug that targets the mechanism of resistance, the challenge there is that the populations that you can treat get smaller and smaller, it's just like antibiotics. If you have a great new antibiotic that treats highly antibiotic resistant organisms, the first thing everyone's going to do is put it on the shelf and say, never use this unless a patient has this organism because we don't want to develop resistance to that. That's not a great economic model for drug companies when it takes billions of dollars to develop a new drug. The same thing sort of happens in oncology, as you say, okay, here's the likely mechanism of resistance, there's usually many, patients have other things, it's a smaller and smaller population as you go down the road. And so how can we develop those drugs much more efficiently because if it's $3 billion a pop, we just won't be able to do it. So I think that's something we have to figure out. FDA has to help us with and we're working on it. That's a great point. So I'm gonna start another question, but I do want to have an opportunity for the audience to ask questions. So I just wanted to, so you mentioned the, academic industry collaboration. So traditionally, the university are making their new discovery, training the next generation of scientists and the commercialization really depends on the pharmaceutical companies. As of many recent years, there are many, many academic drug discovery center being established. I just wondered from the panel what's our view about, you know, what's the value proposition this center is bringing to the ecosystem? In drug discovery. I'll let the panelists chime in first. You guys probably have firsthand experience. Well, I'll just start with, I don't have a great deal of experience working with industry in terms of collaborating on projects. In our work on looking at GPCR kinase inhibitors, I was approached by folks in industry who wanted to know how I solve structures so that they can start their own rational design programs there. And I didn't start my own attempts to find inhibitors until the companies that I was working with gave up. They weren't necessarily trying maybe the best screens for the targets that we were working on and I understood these targets very well on a molecular level. And so we decided to use that knowledge to figure out how to do it better. There's many reasons why drug companies give up on projects. They get bought out. They get new corporate leadership who decide that they have different emphasis areas. Or they just don't find anything that works. And so it's impossible for me to know not being an insider of what the reasons are. But we've had a felt remarkable success by really getting to know the molecules that we are targeting. As opposed to a very hands-off approach, well, if we have a million compounds and rescreen them, we're gonna find something and develop them from there. Both approaches work, but I think where the academic really excels is just knowing from a very targeted way how you might go about designing better therapeutics for some of these targets. I think some of the advantages of these centers is that diversity that can come together between individuals knowing very different molecules with folks who have very different ideas about how to use them and being able to bring together folks with funding and research support around that, it's really beneficial to see not just an interesting science question, but then how can that translate to really actually changing people's lives? I personally believe that industry, academia, relationship is very, very vital for drug discovery today. You know the history of Eli Lilly. Ted Teller, Princeton University, he was making butterfly pigments, and then he was also collaborating, he was a consultant at Eli Lilly and helping developing our heterocyclic molecule. They team up, and ultimately Princeton, in collaboration, Ted Teller's group at Princeton, in collaboration with Eli Lilly, they actually developed this drug called Olimtasolid, and that is actually blockbuster drug, and so you can imagine that these kind of things are not possible because sometimes in academic laboratory our emphasis on new target, new opportunity, also we go typically some areas where nobody ever walked, part of the reason is if you work in the area where Eli Lilly is working, government is not gonna give us funding, so funding is always difficult. I can tell you for myself, I was working and collaborating with Olimtasolid Institute of Health because I did not have any other biological expertise, and when we created a molecule and we have naive ideas how to really, how to combat drug resistance, and I, scientists just asked me, so what have you created? And they actually took the lead, and they took this molecule all the way, and then put this in the federal registry, and all the biotech company came, and they basically developed this drug. So I think that it is really remarkable that today so many academicians are working in cutting edge areas, and our basic problem here is we are actually teaching training students, we are not here to really discover drug, but what we teach and train students today, and that is actually not only helping academic research, but also helping companies like Eli Lilly. So this partnership is actually very, very, very important partnership. Agree, agree, and I think though, unfortunately, there are just too many hurdles for collaboration between academia and industry. It's so complicated to get these collaborations started, like scientists on both sides have a meeting in the mind and they wanna work together and they're excited, and then there's just all these layers of bureaucracy and red tape on both sides that like make it so frustrating. Yeah, and that I agree. But Purdue has been an exception, I just wanna say that it's probably because of the great history between our two institutions and leaders who are like-minded that we were able to enter into this sort of unique relationship with Purdue with this five-year agreement that sort of covers lots of different areas that has dramatically facilitated interactions between our scientists. We've tried to replicate that in other places and we haven't been able to. So I think it is something unique and should be a model. So I have a really small request to you. Yeah, all right. These are my colleagues here, so I can talk to them all the time. So you're very close to our president, Mitch Daniel. So tell him- He's not gonna listen to me, right? Yeah, cut down the bureaucracy. I will tell you my personal experience. Eli Lilly's scientist, they contacted me about six, seven years ago. They wanted to have a sample of a natural product. We created a Largazole and they found that, you know, they do not have access to these. And it took me literally over eight months to send this compound to Eli Lilly, just because, you know, so many bureaucracy, they just don't want me to send, you know, all the MTA. So this is what we face, you know, just imagine what we also face with the grants, you know. So please tell- I'll give my best. Yeah. No problem. I'd like to really have some time for the audience. Oh, I'm sorry. Go ahead. Thank you for being here, doctor. I appreciate your passion that is clear. I may be just, we may be drowning in a system and I'm describing the water, but when you talk about pharmaceuticals being vilified, you have the saculars, you have EpiPens going up exponentially. You've got, you know, just problem after problem after problem. You're a trillion dollar industry with roughly a 20% profit margin. There's huge money involved. There has to be money involved in it, but the system is set up at cross-purposes. I don't know how you fix it, but I want you closer to the patient side when drugs are released because I don't know that the financial side is ever gonna understand or see that through their blind spot of revenue, whereas I want you there moving medicine forward. So go burn the whole system down, rebuild it and at a correct purpose and make it all very workable and fair, equitable globally. Thanks. Of course, I would like that too. Not on behalf of Lilly, like on behalf of patients, right? Because there's no question that patients are suffering. There are some bad actors in the industry, as I said, and you pointed out, it's not representative of most of us, but patients like, and we haven't spoken of drug pricing here, but that's clearly what's at the root of all this, patients are suffering. At the pharmacy counter, they're paying crazy amounts of money that's not coming to us for their medicines and it's going up every year, which is crazy. And yet on the national level, when the Federal Reserve meets to talk about inflation and disinflation, they point out drug pricing as a disinflationary, a deflationary trend, because drug pricing is going down every year, but the patients are paying more every year. If you look at the overall healthcare system, drug pricing, 50 years ago, drugs were 10% of our healthcare economy. Today they're 10% of our healthcare economy, but everybody thinks that it's like drugs that have caused the growth in our healthcare economy. So there's definitely a problem, and the problem is what patients have to pay for their medicines at the pharmacy. I don't think industry can solve this alone. There's a lot of interest in Washington in solving it, but then there's also a lot of gridlock in Washington, so who knows how this will turn out, but I do hope there'll be something quite different than we have today in the future. Is there a question over there? Thank you guys for your engaging discussions. It's been great to hear. I agree that I think the farm industry and the food industry, which I'm part of, is unnecessarily vilified, and I think probably a lot of that goes back to education. So I have a question for the group of, clearly the government's failed, academia's failed in many ways to educate the public in these areas. When does we reach a tipping point where industry steps in and starts spending money to correct this problem? Should I start? Yeah. We try, I mean, there's this go boldly campaign. It's kind of like Got Milk, right? I guess the farm cow industry started, where like all the pharma companies contribute to our parent organization, Pharma, to just put out science stories on TV of scientists who are working on really cool stuff to help treat serious diseases. But it's like such a small piece compared to all of the other forces that are speaking against the industry. I don't know what more we could do. I mean, for me, it's sort of just going back to the patients and the science and like the remarkable progress that we've made. How can you take that for granted? And the remarkable progress has yet to be made. Just have to keep telling the story, I think. I don't know if others have better ideas. I think what you did today is really very representative. I think showing the history. I think you're right. There are going to be people, people who don't have a concept of polio and giving a really clear indication of what the world might look like if these triumphs hadn't happened. I think more and more of that in different contexts would be very valuable. Mary? Hello, I'm a graduate student and so we are constantly comparing if we want to go into industry and academia and something we worry about is the next big bubble. And so what if we spend 10, 20 years in academia on one protein, one disease and with all this new precision medicine, how as a student do we prepare ourselves to find the next bubble field and get the skill sets to be able to train? Yeah, you want to be in the bubble. Is that what you're saying? Because sometimes they pop. I don't know. Maybe the other panelists have ideas of where what's exciting now. Well, how do you tell? I don't know if you need to worry about that so much. I would follow your passion, you know, and as a graduate student I've always told my trainees your job here is to pick up a lot of skills and as many diverse skills and to think intelligently about the problems in front of you. The many of my trainees have gone on in the industry and are working in pharma or in a billion places like that. They're not doing anything remotely similar to what they did when they worked for me. Yet they're highly successful scientists. I like to think because I help them think scientifically about their problems. And so I don't think you have to worry that you're pigeonholing yourself by learning one technique that's gonna attack, you know, biological therapy or immunotherapy, for example, that you can't transition into something else. I just haven't personally seen that. Yeah, that'd be a big issue. That's perfect advice. I mean, when we hire people from our academia, like rarely it's because of their particular domain expertise that we want someone to continue working on what they worked on in academia. It's just as you said, we're looking for people who've been trained to think scientifically, who are curious and motivated and willing to work hard and are quick learners. And so I for one don't like do anything that I was trained at. I was trained to look under a microscope at slides. That doesn't help me do my job. But what helps me is being trained to be a good scientist, to care about patience, to work hard, to focus on quality. Those things are important. So you mentioned there's a long connection Purdue and Lilly. We have over 1200 graduate actually working on Lilly. So we're really looking forward to working on more closely with Lilly and to train the next generation of drug developers. But with that, I would like to really close the panel session because Dan has other things on the agenda. I really want to thank Dan for participating. There's a 150th year anniversary. I give a very inspiring talk. I want to thank all the panelists for a very engaging discussion. Thank you everyone for being here. Thank you. Thank you. Thank you. It's an honor to be here.