The Future of Medicines 10 04 19

The Future of Medicines 10 04 19

October 30, 2019 0 By Jose Scott


(audience chattering) (footsteps) (tapping on mic) – 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 are
able to join that as well. Today it’s my pleasure to
welcome Dan Skovronsky, 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 respected
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 the founding– 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 residenccy 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 Giants Leap celebration. And I look forward to
enjoying his presentation “What If We Stopped Fighting Disease?” Together with all of
you, please welcome Dan. (audience applauding) Thank you. – Thank you. Thank you, Theresa, 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 inside an auditorium, but I will try and make this
an interesting morning for you. I’d also like to than
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 Hurty, 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 Hurty himself would serve as it’s 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 Eberhardt,
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 (audience laughing) in a town called Bloomington. Maybe someday 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 any time 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 astronomics. Only six decades separated
the Wright 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’d be her final
flight, Purdue’s board, on which J.K. Lilly sat, helped fund it and financed the repair of her 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 provided the knowledge. Purdue graduate Cliff Turpin
was part of the Wright team and helped redesign their
motors and control system. Another Purdue grad, William J. O’Neil, 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 Boilermakers 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 a testament to that. They bear the names of Gus
Grissom and Roger Chaffee, both of whom were Purdue grads, both of whom perished aboard Apollo 1 in a prelaunch fire. Grissom 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, in 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 in coming, but achievements in the
five decades since then have been slower. Exploration 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 moon–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. Our 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, tried 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, as someone long
fascinated 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 am 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, JL, stricken with diabetes and literally dying in his mother’s arms. For thousands of years,
diabetes was a mystery, confounding doctors who hoped to treat it, killing those who it
afflicted, like this young man. Doctors suggested cures
that were 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. A diabetes diagnosis remained little more than a death sentence. Then in 1923, collaborating
with Banting and Best at the University of Toronto,
Lilly introduced isletin, 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 JL and
countless others a reprieve. It solved a centuries old riddle. Today, thanks to insulin,
diabetes is a treatable condition, not certain death. Polio also likely effected
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. Three thousand 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. Lilly 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
certainly 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 free 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, Doctor 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 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 proudly 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 Ceclor. As a result of this work,
society changed once again. Communicable 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 II 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 effects a million– effects 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 can 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 hailed 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 protein
IL17 as a potential player. Biopsies from the skin of
patients suffering from psoriasis showed a particular type of helper T cell that secreted IL17 was enriched in with patients with psoriasis, and our scientists at
Lilly created an antibody to block IL17 and tested it in patients, and the results are what you can see here. We and others now have drugs that block IL17 approved
and available for patients, and up to 80% of patients can now achieve near total response and
clearance of psoriasis. What once seemed impossible, today is routine for most
patients with this disease. Migraine is another
significant medical illness. About 36,000,000 Americans
suffer from migraine, most of them women, mostly working age, many of them with families. Many patients with migraines
suffer 10 or more attacks in a given month. They often suffer in silence
with incredible costs to productivity, society, and 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 and 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 Selpercatinib
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 or 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 has 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 II diabetes. Of course, Type II diabetes
and obesity are a major cause of mortality in society today as a driver of heart disease and stroke. This drug called Tirzepatide
is a dual agonist of two incretin pathways, GIP and GLP-1. We designed this peptide
and tested it in patients with Type II diabetes, and
here you can see results for the first phase II 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 II 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 II trial, in 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
II 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 II 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 some day 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. (audience laughing) 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 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 reimplanted 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 I 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 nearer
to meaningful therapies for these 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 siRNA to
turn off genes in nerves that are implicated in pain and genes in the brain that
cause neurodegenerative 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. There 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 have
participate 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. And 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 him 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 effecting 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. (audience applauding) Excellent. I believe we have a panel discussion next. – Thank you very much. Good job. – My pleasure. – 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’d like– we have faculty panel discussion with Dan. And I would like to, maybe
first introduce the panel. We have John Tesmer,
who is Walther professor in cancer structural biology, and John specialize in
understanding the molecular basis of G protein coupled-receptor signaling, and he also interests in
developing structure based design to target the GPCR kinases
in cardiovascular disease. Next to John is Arun Ghosh, the Rothwell distinguished professor in chemistry and medicinal chemistry. Arun actually is the inventor
and discoverer of Darunivar, which is an FDA approved drugs
for treating HIV and AIDS and was approved in 2006, one of the widely used medicine
to combat these diseases. Arun’s lab also continues
to improve this therapy for HIV and also expand to
other therapeutic areas, in Alzheimer’s, for example. Next is Jackie Linnes, she’s Martha Ross professor
in biomedical engineering. Her expertise is really in microfluid. She specialize in invention
of point of care diagnostic and molecular sensors
for substance abuses. And then we have Chris Rochet is a professor of medicinal chemistry
and molecular pharmacology. And John Donna Krenicki, director of Purdue Institute
of Integrative Neurosciences. Chris was trained as a
neuroscientist and biochemist and specialize in protein aggregation and in relevant to
neurodegenerative diseases in particular Parkinson
Alzheimer diseases. My name is Zhong-Yin Zhang. I’m a professor in medicinal chemistry and molecular pharmacology and director of Purdue
Institute for Drug Discovery. So, I want to just to 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, you know, all of us in the room need to really to have responsibility
to advocate and support and society and funding agency
to continue our research. But I wanted to turn into a technical aspect of drug discovery. There is despite all of the
advances you highlighted, that we’ve made to improve human health over the last hundred years, there’s still too far many human diseases that are still not curable and not even too 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 curing disease so difficult? So, I just want to open
up this to the panel. And what is about drug
discovery that’s so difficult? – Do you want me to start? Well, you know, of course,
it’s–there’s two aspects to it. One is just the complexity
of human biology and understanding how
to impact that biology in a way that effects 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 can 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 case was IL17. 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
multiple places in the biology of the cell or an organism
to change disease course. So, I think that’s one
of the big challenges. The other is when we look at all of the different targets in a cell, there are some that have been up till now generally off limits, just things that we can’t hit. We have small molecules
that are inside the cell, and we can’t hit them with antibodies, and so we sort of shrug our shoulders. I think that’s changed with
gene therapy and RNA therapies and other more advanced
new ways of making drugs. We can–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
are free to chime in. – Yeah, first of all, I would
like to thank you for the really very motivating lecture. As you mentioned that our students and 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, you know, pursuing rocket science? What is your, you know, perception? – Yeah, I am not an expert
in childhood education or in why people choose different things, but I, you know, 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 want to go in that profession? – And my second question is, if you look at the history
of drug discovery, you know, all amounted from natural
products, you know, the history of Eli Lilly, discovery and help with the
penicillin to vancomycin. 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 actually even
company like Eli Lilly making large molecule,
large library of molecules, hoping one of them become a drug. So, this kind of perception
also really not helpful for, you know, what is happening today. Today, we no understand lot of, you know, disease in molecular level. Protein structures are known. We know where exactly, you
know, catalysis happening. You know, structure versus design of the molecules is very important. If you look at the history
since late 19th to 2000, so we have probably 60 to
80 drugs literally developed just upon structure base,
protein structure based. On the other hand, now you
can see company like Eli Lilly dismantling many small
chemistry, which is basically, you know, all of making
molecules overseas, and you know, this teamwork was medicinal
chemist, biologist, pharmacologist, work together. That is not happening. So my perception is probably that students are not enjoying
the scientific discovery. What can you do to bring that 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
integrative groups. I think if we see chemists
as just sort of 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
the pharmaceutical companies have been structured in the past. So, I do think that’s important. With respect to natural
products of course, you know, 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 ’cause 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
the cell or organism, you can figure out how, whereas in the past it
was kind of a mystery, and often drugs would launch, you know, a decade before we would even know what their molecular basis of effect was. So, there’s some hope there as well. – I’m not going to take much time. So, my last comment here. You know, your talk is extremely motivational
and also philosophical. So, now Eli Lilly, you know–I
know what Eli Lilly’s doing, at least from, you know, reading. Their emphasis is putting
huge effort in biologics, and biologics from all the problems. Of course, biologics are
tremendous, you know, curing a lot of disease unthinkable. At the same time, the major
problems are all biologics is you are 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 situations? 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 its 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 want to inhibit, and sometimes we want to 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 in to a pill,
which patients often prefer. – [Zhong-Yin] I do want to– Yeah, Chris. – Sure, I’d like to go back to Zhong-Yin’s initial question as well about why diseases are 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 under way 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, at least some of those obstacles. – I agree wholeheartedly
on all of those challenges. And probably, they together
account in totality like for the failure of
progress and development of therapy 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 rarer 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 on neurodegenerative disease
for the last 20 years. – [Man] Excellent. – [Zhong-Yin] So, Jackie. – As somebody who works in diagnostics, that was the type of thing
that 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 treatments and detection that you see coming out of Lilly? – 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 systematic clusters. The question that you
asked specifically is could we use digital devices, wearables, massive amounts of data from Google or whomever is spying on us, to like figure out what
specific disease you have. I don’t know. It’s often talked about, though. Like if you had enough data
and artificial intelligence that’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’m, you know, I don’t know. It must be true, and it
must work eventually. But I probably could have
said that 10 years ago and maybe 10 years from now. – [Zhong-Yin] John. – Right, I just want to get
back to you’re initial question: Why do we have disease? And, you know, one of the reasons that we will always have disease is our remarkable ability as
living organisms to adapt, you know, and when we send
drugs into our systems, the proteins that we were
targeting, the genes will mutate, you know, and cancer in particular. So, there’s always gonna be
this resistance mechanism building up against any
treatment, you know. 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 gonna
need to be this drive to innovate and find the next tool that you can use to help these patients. And I don’t see how that’s
gonna happen without big pharma, you know, you know,
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 small lung cell
carcinoma, for example, you just know that those patients on that treatment long
enough are probably going to regress and the mutations. And what’s the philosophy
in the industry then, you know, to–you know, you
have a great cancer drug, but you know probably, you know your patients
are gonna revert, so… – We know they almost certainly will. So for example, the example that I showed, the RET inhibitor. As soon as we started that program– or it was actually a biotech
company that we acquired, those scientists they said, “Okay, we anticipate “that there is gonna be
mechanisms of resistance. “We have some hypothesis
base on cell experiments “what that will be, and
we’re already starting “to make the second generation drug,” at the same time as they’re
making 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 continued 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. Like if you have a great new antibiotic that treats highly antibiotic
resistant organisms, the first thing everyone’s gonna 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
Mahala 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 die of 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. – [Zhong-Yin] 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, you know, there’s academic industry collaboration. So, traditionally, the university are making the new discovery, training the next
generation of scientists, and the commercialization
really it depends on the pharmaceutical companies. As we’ve many recent years, there are many, many academic drug discovery centers being established. I just wondered from the
panel, what’s our view about, you know, what the value proposition these centers bring 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, and I 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 mine 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, you know, they get bought out, you know, 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, what the reasons are. But we’ve had, I’ve 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 we screen them, we’re going to find something
and develop them from there. Both approaches work, but I think where the academics really
excel is just knowing from a very targeted way, you know, 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, you know, individuals knowing very different molecules in 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 is 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 high, though, for drug
discovery today, you know, the history of Eli Lilly. Ted Taylor, Princeton University, he was making butterfly pigments, and then he was also collaborating. He was a consultant at Eli
Lilly and helping, you know, developing a heterocyclic molecule. They team up, and ultimately,
Princeton in collaboration– Ted Taylor’s group at Princeton
in collaboration Eli Lilly, they actually developed
this drug called Alimta, and that is actually blockbuster drug. And so you can imagine that, you know, these kind of things are not possible because sometimes in academic
laboratory our interest is in new target, new opportunity. So, we go typically some areas where nobody ever walked out
of the business, you know. If you are in the area
where Eli Lilly’s working, government is not gonna give us funding. So funding is always difficult. I can tell you from myself, you know, I was working while we’re
doing as on seeded help, because I did not have
any biological expertise, and when we created a molecule
and we have a naive ideas how to really, how to come, you know, combat drug resistance, and
I scientist just asked me, he says, “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, another biologic company
came and they, you know, basically developed this drug. So, you know, I think that
it is remarkable that, you know, 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 of the mind, and they want to 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. – Yep, that I agree. – But Purdue has been an exception. Like, I just want to say that, you know, and 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. These are my colleagues here, so I can talk to them all the time. So you are very close to
our president Mr. Daniel, so tell him– (audience laughing) cut down…
– He’s not gonna listen to me. – Yeah, cut down the bureaucracy. I’ll pay my personal experience. Eli Lilly’s scientist, you know, they contacted me almost, you
know, six, seven years ago. They wanted to have a sample of a natural product we
created called 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. I’ll end here. So, this is what we face, you know. Just imagine what we also face
with the grants, you know. So, please tell him. – I’ll do my best. (audience and panelists laughing) No problems.
– I’d like to really have some time for the audience. Okay, go ahead. – [Man] Thank you for being here, doctor. I appreciate your passion that is clear. I may be just–we may be
drowning in the system, and I’m describing the water, but when you talk about
pharmaceuticals being vilified, you have the Sacklers, 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 let it correct purpose and make it all very workable and fair,
equitable, globally. – Yeah, 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 that’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. And patients are suffering
at the pharmacy counter. They’re paying crazy amounts of money, that’s not coming to us, for their medicines, and yet–and
it’s going up every year, like–which is crazy. And yet, on the national level, you know, when the Federal Reserve meets to talk about inflation and disinflation, they point out drug pricing
as a disinflationary, a deflationary trend, ’cause drug pricing’s
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’ll turn out, but I do hope there’ll be
something quite different than we have today in the future. – There’s a question over there. – [Man] Thank you guys. Very engaging discussion. It’s been great to hear. I agree that I think the pharm industry and the food industry,
which I’m a 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 it reach a tipping point where industry steps in
and starts spending money to correct this problem? – Should I start? (audience laughs) So, we try. I mean there’s this Go Boldly campaign. It’s kind of like Got
Milk, right, that the– I guess the farm cow industry started where like all the pharma
companies contribute to the 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
that is yet to be made. We just have to keep
telling the story, I think. And if others have better ideas… – I think what you did today
is really very representative. I think showing the history, you know. I think you’re right, there
are going to be people who don’t have a concept of toil and getting 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. – You ready? – [Woman] Yes. 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, you
know, 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– (squelching noise muffles voice) do we prepare ourselves– How do we as a student prepare ourselves to find the next bubble
field and get the skill sets to be able to train? – Yeah. So you want to be in the bubble,
is that what you’re saying? ‘Cause sometimes they pop. (audience and panelists laughing) I don’t know. Maybe the other panelists
have ideas of where– what’s exciting now. – Well, how do you tell it? 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, you’re 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. Many of my trainees have
gone on and to the industry and are working in pharma or
in ADVI and 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’d like to think because I helped 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, a biological therapy or
immunotherapy, for example, that you can’t transition
into something else. I just haven’t personally seen
that yet to be a big issue. – That’s perfect advice. I mean, when we hire people from 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 good scientist, to care about patients, to
work hard, to focus on quality. Those things are important. – So you mentioned there
is a long connection Purdue and Lilly, and we have over 1,200 students graduate actually working at Lilly, so we really looking forward to working close
– We want more. with Lilly and to train
the next generation of drug developers. But with that I would to
really close the panel session because Dan also has other
things on the agenda. I really want to thank
Dan for participating in this 150 year anniversary. You gave a very inspiring talk. I want to thank all of the panelists for a very engaging discussion. Thank you, everyone for being here today. – No problem. (audience and panelists applauding) – Thank you, it’s an honor to be here. – That was a good talk. – Yeah, good comments.