Interview with Stanley Crooke
Stanley (Stan) Crooke has spoken with Anindya Bagchi, Giovanni Paternostro and Guy Salvesen. Stan is the founder and former CEO of Ionis Pharmaceuticals. He has been also an academic scientist, a leader in large pharma companies and a physician. He is now a philanthropist, having founded the n-Lorem Foundation, to use the antisense technology developed at Ionis for patients with very rare genetic diseases, where the commercial model did not suffice.
Dear Stan,
Our first question is about your inspiring personal journey. You started as a scientist, you worked for pharma in leadership positions, you were an academic scientist, you were a practicing doctor. And then, of course, you had an important role as a biotech founder. And now you are a philanthropist. What is the common element of all the roles you have played?
Stan:
Well, my early life was different from most scientists. Where I grew up I had never known anyone who graduated from high school, other than teachers, and I made them the enemy, which is just a part of the stupidity of being young. And so, the truest answer to a common theme is that I was desperate to be anywhere doing anything other than what I saw around me.
And so, desperation, and the sense of just finding a different kind of life than the life I had experienced. I thought smart people were engineers, and I was interested in airplanes, so I started as an aeronautical engineering student. Ultimately, because my girlfriend at the time, my first wife, was very sick, and I didn't have any money, I moved back to Indianapolis to go to school there, and the only trade school was a pharmacy school, so I went to pharmacy. I was also working in drugstores. And I was a terrible student, I never went to class. Then the Dean asked me if I wanted to go to graduate school. I'd never thought about it, but I said: yeah, I'll go. I went on to do a Master in Pharmacology, while I was running a drugstore, and I just got interested in cancer. Actually, I was also briefly enrolled in law school at the same time. Ultimately, I applied to medical schools. I got rejected by almost all, but got accepted by Baylor, and the person who really did change my life was a long-term Chairman of Pharmacology there, Harris Busch, who was a pioneering scientist. My first job was sequencing RNA, using the Sanger method, which was impossible. And so, the beginning was just luck. And then I discovered the joy of science in Harris's lab.
The idea of being paid to ask questions is just an incredible thing for somebody who has no experience outside of inner-city poverty. I was working in that lab, and I fell in love with the idea of science. Then, the first time I was on the wards, on the clinic, just the idea that I would have somebody's life in my hands, and they would be trusting me to take care of them, had a big effect on me.
Those things made an indelible impression, changed me in many ways. I guess the theme, if you want me to find the theme, it's wanting to do science at the edge of science, in the service of patients.
I was already about to be promoted to Associate Professor when I finished my residency. While I was a medical student, a young man was sent to us. I was on the Hematology/Oncology service. He was sent to us because he had an abdominal mass, and, of course, a young man with an abdominal mass has testicular cancer until proven otherwise. He had indeed a disseminated testicular cancer. I think he was maybe a year younger than I was. And telling him he was going to die in six months, was... made a difference. We had this drug; I was just a member of a team. I wasn't doing anything with it, but we had an experimental drug called bleomycin. I got fascinated with bleomycin. It's an amazing drug. So many strange sugars, it is a glycopeptide. It causes DNA damage through iron mediator redox. This was before restriction enzymes were identified. And it had an amazingly different toxicity, compared to any kind of cancer drug. So, I stopped my research and started working on bleomycin. I wanted to work on the analog, so I called the company that had the bleomycin license, Bristol Myers, asking if they had a job. In those days, for people like me, I was an MD PhD with maybe 15, 20 publications by the time I finished my residency, this was uncommon. And Harris, who became as close a figure to a father as I ever had, was not happy. Luckily, his office was on the third floor, and he could not open the windows, otherwise he'd have thrown me out, for sure.
I went to Bristol Myers. They didn't have a cancer program, so I built that. I think we put nine anticancer drugs on the market in the first 5 years, including bleomycin and cisplatin. And when Larry Einhorn added vinblastine to that, we cured testicular cancer. I thought that would be the highlight of my career.
At the time the company didn't have any molecular biology. I don't know how you could practice science without molecular biology. I got my boss to give me $40,000, and I started a lab at Baylor. Harris loaned me a bunch of equipment, gave me some space, and I built a lab there. I think we published 100 papers in five years. I trained five or six PhDs, a couple of master’s students, and I just did the work I wanted to do. And it's always been about drugs and patients and science. I decided early on that if I could make one good drug, that was vastly more leverage than I could ever do as a single practicing physician or a teacher, and now, I think, up to about 30 drugs are on the market as a result of things I did. So, it turned out. It was a random walk among opportunities, as I think of it, and I was just lucky enough to encounter things that caught my attention, and lucky enough to be accepted in a place where I didn't deserve to be accepted. I still don't know why Baylor took me. I got rejected by almost every medical school in the world. I wish I could tell you: I had the dream. No, my only dream was to be out of the neighborhood I was in and to have more money than I had. And luckily, I found my way to what has been, really, a great privilege, to have had the career I have.
If you're interested in patients, which I am, I still miss seeing patients, and you're interested in science, it's pretty good to be interested in the drugs that you can make to make people better. Once I discovered that, it was the center of my life. I'm sorry not to give a better answer.
Giovanni:
No, that's perfect.
Anindya:
That's perfect.
Guy:
Can I ask what might be an awkward question, but it looks like you're sort of man that can field awkward questions, do you have a scientific hero?
Stan:
If I had to pick somebody who, I think, did magically beautiful work, that would be Tom Cech. Really great innovations typically come from orthogonal thinking.
I was trained in RNA biochemistry, and I love RNA. It's just a joyous place to be. And I had my RNA degrade all the time, because I was pretty lousy in the lab. And I always put it off to RNases on my fingers, or I coughed into the stuff. I know that I ignored what Dr. Cech didn't. I ignored it. Everybody else ignored it, except him. He refused to step away from the problem and discovered ribozyme. And if you look at that work, it's just the kind of science that I enjoy the most, which is one step at a time, asking ever more detail, ever more thoughtful questions. He starts out, Why the hell's my RNA degrading? And then moves on to show that it's structured RNA, it's capable of cleaving RNA, and then works out the mechanism, and then, of course, the field explodes. That is an example of the kind of persistent, focused, step by step evolution in the quality of the questions. Which is the science I admire most.
Of course, I also recognize Harris Busch. He introduced me to RNA; he taught me to do science and what it was like to be a physician. He taught me to be much more demanding of myself and others than I was. Because he's a funny, tough guy, and I learned from his strength; I also learned from watching his weaknesses. I think too few people learn effectively from their experiences. You learn from people around you and your mentors, by watching their strengths, and also their weaknesses and where they failed. Harris had almost a thousand publications when he retired. I thought for a while that he deserved a Nobel Prize. I now don't think so. I think the reason is that he didn't have the patience to ask the big questions. We were sequencing these small molecular weight nuclear RNAs, and everyone in the lab really wanted to think about what they do. Harris wanted to do all the sequences, it was perfectly logical. Once you have the sequence, you know the molecule, you can be doing things with it. But mostly, I think we didn't work on what small molecular weight nuclear RNAs do, because Harris was too impatient to get the next JBC paper. The science that I admire the most is persistent lifetime science that accepts the risk of failure, and the risk of looking stupid. And, if we had combined all the power in that lab, all the sequence information we had, we would have quickly understood that these RNAs are involved in something called splicing. We didn't even know what splicing was back in 1970s. If I had to pick a hero, it would be Tom Cech, because of the quality of his ideation, the persistence of his effort, and how the sophistication of the questions he asked became much greater as he learned more and reduced it to the chemistry of ribozymes. This was an amazing piece of work.
Giovanni:
Can you tell us about the Foundation you have created?
Stan:
It all started in 2019 or 2018. I was visited by two sets of parents, two different families, and each had a boy who had a toxic gain of function mutation, we now know, in a gene that encodes the alpha subunit of Nav1.2, which is the main sodium channel in the CNS. The gene is SCN2A. And naturally, if you have that kind of mutation, you have a terrible syndrome, which includes intractable seizures. And they visited to see if Ionis could make an antisense oligo (ASO) for that. And I had to tell them that it was simply too small an indication for us to pursue. I felt terrible about that. As I thought about it, I realized that the technology we'd invented was good enough that if we could turn the organization loose on it, we could have an ASO for them. I could give it to them for free. And that struck me as insane. I mean, I come from a generation where a drug is 3 billion bucks. I checked my math and... it still it worked.
As I got into their problem, I got into the extremely rare genetic disease, what I call nano-rare. And the more I looked, the more I realized that there are a ton of these nano-rare mutations. I define nano-rare as a pathogenic mutation with a known prevalence of less than 30 patients worldwide. So, very tiny. Certainly not commercial. But in the aggregate, probably tens of millions of patients. I met some of these patients, and they were the most desperate, alone, hopeless human beings I'd ever met.
The more I thought about it, the more I realized: I know this technology, I have it, I led its creation. It's the only technology that I think can even try to help these patients. How can I not try it? And ultimately, I decided to found n-Lorem to try to help these patients. It's the rest of my career, it turned out to be a much greater privilege than I ever dreamt. There are patients in need, and I have a tool that can be used to help them. Why not? What am I going to do? It was time for me. I wanted to pass Ionis on. We were very strong, well-funded. Everything was in place. The organization was solid. If I was going to leave, I needed to leave then. And I felt I should. And what are the options? I don't play golf. I don't have a yacht. I hike. That's all I do. I hike and watch sports and read and play chess. That's it. Or I can sit on boards and pontificate and make some more millions of dollars. None of that compared to trying to help these patients. So, it was a pretty easy decision to do, and it's been absolutely wonderful.
Anindya:
A joyous, joyous experience. I'm just getting goosebumps right now, just hearing you.
Stan:
These people are just isolated. If you have one of these mutations, the average time from symptoms onset to diagnosis is five years. But the average doesn't tell you the entire truth. The spread is a few months to 36 years. They go through all the misery you can imagine. The first feedback they get is: it's just development, no big deal. Then it goes through various misdiagnoses. The first boy of the two boys who had the SCN2A mutation had 24 or 25 misdiagnoses, and one correct diagnosis. And all kinds of ineffective therapies get tried on them, and of course that makes the disease worse. Just patients in need, and I thought that this was maybe the most exciting scientific opportunity that I'd ever seen. These are all patients with heroic changes in phenotype, driven by a definable, understandable, single variable. Each a single gene mutation. I thought we could learn incredible amounts about health and disease from these patients.
Then I wrote to the senior leaders of the drug division of the FDA. Janet Woodcock was there at the time, and others. And I was astonished to get responses from all three people I wrote to within 30 minutes. I had never gotten a response from the FDA in 30 minutes. And they were all positive. And so, I felt that it was likely that there would be regulatory support for trying to do this. Then the FDA said they were going to put some guidance out for ASOs for these diseases. I didn't work with the FDA, I don't want to suggest that, but during the public comments phase I made extensive proposals to the FDA, and almost all of them were adopted in the final guidance. That guidance is an enormous step for the FDA. I'm still astonished it happened. The guidance allows us to go to man with only iPSC pharmacology data with the patient's cells and a three-month rodent toxicology study. And then we go straight to patients. We can study what's wrong with patients in their own cells. That's an amazing thing. Talk about the miracles of science. That's a miracle. And we can use that information. We don't have to mess around with animal models, which mislead more often than they lead. And then go to man and ask, does it work? Right now, we have a greater than 90% success rate. And I'm prepared to draw the conclusion that if we correct the cellular phenotype, we correct the clinical phenotype. So far, that's what our data teach. That's an amazing step. This will evolve over time, I believe, to an opportunity to really use patient cells as a surrogate for a lot of the wasted time that we have in drug development. And learn from these patients.
What we're learning is already amazing. I was taught, if you have a developmental delay, it's baked in. It's forever. Wrong. It's completely wrong. We now know there's vastly more plasticity in the CNS. We have patients who lost skills, demonstrable skills, measurable skills. They never had them, or lost them decades ago, and now they are recovering them. And we have patients who never walked, walking. They couldn't control the movements well enough because they had ataxia. Just learning that developmental delays can be addressed even later in life is a giant step for medical science. I could go on and on about all the things we're learning. It's an opportunity to help patients. It is science at its best, and I'm hoping that it will help change the way we think about health and disease.
I've been arguing for more than a decade that we need to discard traditional definitions of disease. They're just archaic descriptions of what patients look like when they get sick enough to come to the doctor. They get in the way. Think about it. Type 2 diabetes is at least 20 diseases. There are many genetic factors, and then, of course, there are environmental overlays. Yet we, if we make a drug, have to prove that it works at least a little for all diabetic patients. That means we miss the opportunity to make the best drug for a particular type of diabetes. So, I think it's time to get rid of all that. We've been taught to focus on treating disease. That's a bad idea.
Have you ever looked up the definition of health? The primary definition is the absence of disease. Think about that. The single most important thing in your life defined in negative terms. The second most common definition is the ability to cope with day-to-day needs. If that's health, I don't want it. So, I'm hoping, and I'm not the only one doing this, but I'm hoping that n-Lorem will help drive a focus on health. Defining what a healthy phenotype is. How do we maintain a healthy phenotype. And using these single variable patients to help teach us how a single variable interacts with all the networks in the body, to create what we see as a terrible disease.
We have the patient cells now that we can use. We have antisense as a tool to directly affect a genetic disease, and we can use that information. And we have a ton of network analysis capability now that we didn't have. You take all the omics that we can do, and you combine all that with these patients, and we should be able to learn much more about health and disease, I think.
I hope this will change the way we think about it. It's time. We shouldn't be thinking about disease. We should be thinking about health. I'm not the first to say that, I'm certainly not the only one, but I'm the only one with these patients and the data which is going to help us.
Giovanni:
Do you make iPSC in your Foundation, or do you have collaborators?
Stan:
Yeah, that it's pretty straightforward now. And cheaper than before. It's straightforward now that somebody showed us how to do it. When we have troubles finding an ASO for people, the reason it's often that the iPSC derived cell of interest is fragile. And we just can't grow them. There are some mutations, we're learning, for which the cells just do not survive. A lot of these neurological diseases appear to be diseases of differentiation rather than of cell death.
If you think about it, if it's cell death, how would you reacquire the skills you lost? We went back and looked, and most of the problems that we're seeing occur in some stages of differentiation to neurons, in the central nervous system at least. In other organs, we don't have enough experience yet to be able to say much. It is a unique scientific opportunity. It's also a unique opportunity to be a physician. In fact, it's like practicing medicine again for me, one patient at a time, one family at a time. Of course, we're blinded, but most of our patients unblind us, so we know the families, we know the people.
Most people in the industry care about patients. That is why they join the industry. But it gets lost. You have to please shareholders. They're paying the bills. Here, at n-Lorem, everything we do is focused on the well-being of a patient, and that's wonderfully clarifying.
We're not focused on trying to understand a gene. We don't do that. We are one patient at a time. It's doctor's office. Somebody comes in, and then we go to work. Now we have so many CNS patients that we probably have a pretty good sense of the major genes involved where pathogenic mutations can result in severe neural development diseases. But it takes a while, especially for people who've been thinking about drugs, it takes a while to get used to the idea that we're not developing a drug for a population.
It's one patient, and that means you have to pay attention to the phenotype of that patient. In the central nervous system, we're getting more repeat genes than new genes. We're treating 45 or 46 patients now, and we've handled probably 450 applications, and we've accepted more than 200, I think it may be closing in on 250. So, we're a six-year-old biotech company with 45 clinical programs and 45 different drugs in the clinic. And about 250 drug discovery development programs, and the applications keep coming in. So, we've shown that you can do it. You can do it safely, if you know the technology and use industrialized systems. You can't be an amateur. There are a lot of amateurs out there who read a review and think they know something about the technology.
We can do it safely and we can do it at scale. All that is behind us, and really our only challenge is raising enough money. My hope is by the end of the year, we'll be at $700,000 a life, start to finish. We start a drug discovery program for that patient. It's a brand-new drug. And we treat for life for less than $700,000. That patient, untreated, we estimate, there's no good numbers, but we expect would cost healthcare system $3 to $4 million in his life. We are already saving money. And to think that you can take a human life, and find a medicine, just take that life, and make it better; these are still very advanced disease people, but they now can function, for $700,000 for that patient's life. That is pretty amazing. We're pleased where we are. It's still daunting to raise all the money and do what we're doing and do it right and make sure that every patient gets the best ASO, and it is treated safely. But so far, we've had spectacular success.
Guy:
Stan, that sounds great. Can you tell us what you see the role of public funding is in your projects?
Stan:
Obviously public funding brought us where we are. Without genomics, without transcriptomics, without proteomics, without iPSCs, we wouldn't be here. We all stand on the shoulders of the great scientists and physicians that preceded us. We are on this scaffold of knowledge that has been created over the last several hundred years, and really hit its zenith in the funding of American science. Public financing is the basis of all this and will continue to be the core basis of the dances that are far reaching enough, and to enable things like those I'm doing. I believe in peer review, and I believe that the reason American science has been so good is that it wasn't directed. It was investigator-initiated.
But we're doing something that no one has ever done before, and it doesn't fit. And so we haven't had any real success in the NIH grants that we have filed, yet. We have raised money from donors. It's like a biotech company, but unlike most biotech companies, which are nonprofitable, we're actually designed to be nonprofitable. I ran Ionis for 30 years as a nonprofitable biotech company. I know how to do that. And hopefully we will be profitable before 30 years. You collateralize your sources of funding. We're treading on the fact that people know I know antisense, and we have partners with commercial companies. It has to be very specific. Everything has to be just right to show that it helps meet our mission. And, then, there's lots of donors. My wife and I have donated maybe $12 or $13 million of our money, which we've given to n-Lorem.
Giovanni:
Is the health insurance of the patient paying for anything?
Stan:
No, for these drugs, there's no path to approval. We treat for life under an IND. In America there's no way to get insurance companies to cover an unapproved therapy. The care of patients is paid for by insurance companies. We've designed a modified crossover design, and we ask only for information that's consistent with optimal care. We try to keep the cost down. It's still reasonably costly for institutions, and that has been a real problem for us. But the FDA is moving much faster than I would have dreamt it would, toward finding a commercial path that's economically sensible. The thing that has to be solved to make this commercially possible is not the science, it's the economics. And that boils down to having a development path that is economically justifiable with regard to the return on that investment. And I think that's going to happen. They're moving really rapidly, and, of course, the data we have, the information saying that it can be done and done safely, I think, is critical. We are hoping that there will be a commercial path, that companies will get interested in it, because it's far less costly than trying to make a drug for a large indication.
I think some revenue model could work where you have a significant phase 4 commitment required. We'll see what issues. If that issues, I think that n-Lorem will continue to stay nonprofitable and do what's needed, which is make their drugs. But I've done every kind of deal that you can do in biotech, and so I'll find plenty of commercial partners, if it goes on and develop more broadly. And then that will be a source of continuing revenue for us, which will mean that we can continue to deliver the innovation that's needed, and I don't have to worry about trying to build a salesforce, which I don't want to do. I never actually did.
We're in an enormously different place from where we were six years ago, and much different from what I thought. And I think the FDA is thoughtfully moving toward a commercial path for nano-rare drugs.
If that can be done successfully, then we have this whole cadre of patients, that we didn't know existed until genomics, that really had been left behind. And if we can participate in making that happen, then we've taken these millions and millions of patients without hope, and created a path that should mean that many fewer patients get left behind. And that's what we want. I also want to use our experience to drive whole-genome sequencing into newborn evaluation protocols. There's no reason, no reason at all, that patients have to go five years and longer to get diagnosed. If we had whole-genome sequencing at birth, we would know the patients at risk, and if the risk was substantial enough, we could treat pre-symptomatically. Look at Spinraza, our drug for SMA. Biogen did the pre-symptomatic study with Type 1 SMA. We now have patients who are 10, 11 years old that are perfectly normal, other than they have to go in every few months and get an intrathecal injection of Spinraza. It's very clear. The earlier you treat, the better the outcome is. And what's better than treating before you get sick and avoiding getting sick? I want to drive whole-genome sequencing as part of newborn screening protocols. People are worried about labels, and I get all that, and we have to protect against that. But, my God, to allow that fear to get in the way of figuring out who might be sick and who isn't, seems pretty stupid to me. I'd rather have a healthy child then a very sick child.
I think we'll see that come to fruition here in the next few years. It's already happening in other countries, as the UK. The UAE is sequencing all newborns, including all the guest workers. Think how competitively advantaged they will be with that information. A healthier population is a cheaper population and a more productive population. You don't have to be humanitarian, just an economist. What would you do if you wanted to run a country and make it successful? Well, I'd like to have my healthy population work as hard as I can get them to work and live as long as I can. And I'd like to have as few sick people eating my dollars in care as I can. Singapore and UAE are going to be highly competitively advantaged. Aside from the science that they're going to be able to do, that other countries will not have even the knowledge to do. So, we need to get that going into the US, and hopefully we'll have a commercial path for these drugs.
Giovanni:
If you obtain a genome, you have to think how to interpret it, and if you consider an antisense therapy, you have to predict its effect. You can do experimental tests, but wouldn't it be much easier to have a prediction done by AI? When someone asked you about AI, you said that AI can be an important tool, but also that we have to make sure that humans are in control of it, and that we can preserve innovation. What is your view about these developments in science?
Stan:
I'll just say it again. AI is a tool. It's a powerful tool. I know that it can learn. But in the end, innovation is an individual event. And I believe that most people are more limited by their fears than by their abilities. And what is the second most significant fear that modern man has? I'll say death is number one. But what's the second most frightening thing to modern man? Looking stupid. People will do anything to avoid looking stupid. And if you're going to think orthogonally, if you're going to be innovative, if you're going to do things that have never been done before, you're going to look stupid sometimes. You're going to fail. I spent 25 years with people dismissing what I was doing at Ionis. That was hard on all of us. That was tough. It was really hard. I mean, to send a paper in, with antisense in the title, and get it rejected, just because it was antisense. As a scientist, that hurts.
It all depends on how you use a tool. And I think if you invest AI with mythical power, that becomes an additional inhibitory element to the really novel thinkers, who think orthogonally, and will have an idea that may be wrong, could be stupid, but if they don't say it, you never know it. If you do that, you will destroy innovation. If you put AI where it belongs, is an adjunct to the human brain. To the innovator. Running an innovation-dependent organization is very different from running an execution-dependent one. An innovation-dependent organization is successful primarily by the fraction of innovators it has in the organization, and how encouraged they are to be innovative. If AI liberates people to be more risk taking and more orthogonal in their thinking, in your organization, you will have done a great thing. If you invest AI with the power of some mythical creature, and it inhibits that kind of thinking, you will have done great harm to the opportunity for innovation in your organization. That's what I think.
Anindya:
That's a great insight. That's a truly great insight.
Stan:
All you have to do is manage innovation for a lifetime, and you know these things. I mean, the guys in your lab that do the great things, they're few and far between. And they're usually pretty difficult to deal with. That's the thing about innovators, you have to give them enough room, they can be pains. You have to be willing to live with misery if you want innovators. By large, really innovative people are difficult. They see the world as it is, and the world as they think it should be, and they don't like it. At Ionis I joked, but it was dead serious, that I went out and recruited for weird.
I wanted people in the organization to know that the only thing that mattered was ideas. And being right. If you're wrong, you can waste billions of dollars, and if you are right, whatever you spent didn't matter. That's our business, right? In the innovation business, if it turns out you're right, it doesn't matter how many mistakes you made, how much money you spent, doesn't matter. And if you're wrong, you wasted every bit of your time and money.
Anindya:
This resonated so well because I always ask myself, why certain places in the world produce most of the innovations. This is the right answer.
Stan:
The other thing I worked hard on was to make people feel elite. We needed that because we were dismissed for so long. And we had a 4% turnover, compared to a typical 26% biotech turnover. Despite all the misery, nobody left. Because we felt we were doing good things, and we felt elite. You know, we're smarter than the rest of those... And so, it's a feel, it's an environment where really innovative people can thrive, and that has to be an environment where being quirky, being odd, being a pain is allowable, within very defined limits. Again, AI can help it, or it can destroy it.
Anindya:
I will just add one thing. For many years, Barbara McClintock was ignored. And when she got the Nobel Prize, and this was told to me by a mentor of mine, she just had one thing to say: you guys didn't understand. All these years of ignoring didn't hurt her pride. She just knew that they didn't understand. You need an ecosystem where Barbara McClintock can thrive.
Stan:
Drug discovery and development are the hardest thing. I've encountered three things that are hard in my life. And they're all dismissed by people who never did them.
One is to be a good parent. The best you can come out is even, so the kids don't hate you, they're not too screwed up.
The second is to discover a drug.
And the third is to create a new platform for drug discovery.
One of the challenges in drug discovery and development is that you have to combine, in some way, an innovation-dependent environment, with the ability to execute. That's what really makes building a great drug discovery development organization so hard, to find a way to mix those. Not lose the ability to execute, but not sacrifice the ability to innovate to the process of executing. I think most big pharma fail, because they get so big, among other things. Another thing is, making drugs take such a long time. And the innovators wear out. You can see them, and they started out innovative, and you look at them in their 50s, and they wouldn't have an innovative idea, they wouldn't know an innovative idea if it hits them in the head.
We're talking about leadership and that's why I've stayed an active scientist throughout my career. I would never give up science for administration. But if you want to lead science, you need to be perseverant.
Giovanni:
One point that came out from the discussion on this website is that if we want humans to be in charge, and not AI, we should advance human collective intelligence, especially among scientists. But of course, as you point out, we need collective intelligence that allows for innovation, and in which each innovator is recognized.
Stan:
If you think about the other question earlier, about why some places are consistently innovative, it's also because there is more than just a collective intellect, there is a collective energy. It's the individual intellect freed to be risk-taking in an environment that foments novel ideas, and a collective spirit that is intensely demanding, yet supportive of individuals. That's when you see great things. That's the MRC. That's Stanford, when Lederberg and Kornberg were there. How do you create that? I don't really know for sure, but I think it boils down to starting with the commitment to create an environment where innovation is fostered and collective. And accretive. It's also having the time to build all that into an elite place. There are times and places that have done that well, and there are times and places that haven't. You can see the difference. Harvard, people go to Harvard despite all the misery, because they want to be elite. That kind of environment builds on itself, and everyone in the environment gets better. That's another test of whether you've done it right, are people better because of the environment?
Giovanni:
Our last question is also related to your personal history. Other scientists might arrive at the stage at which you are and wonder if they should continue the next part of their scientific lives as philanthropists. Not everyone can do it in the same way as you did, but is there any insight you can provide from your own experience?
Stan:
Well, at some level I'm not sure I see a difference, if you're motivated in your career by a desire to ask more sophisticated questions tomorrow. And you're motivated by a desire to do something of value for your species. I'm privileged to be a physician, I think about patients.
You stay alive and alert, and as you approach different phases in your career, you have different questions. You are financially in a different place. You're different as you age. Then if there's an opportunity that takes all the knowledge that you have, and the energy that you have, and the interest you have, in asking sophisticated questions, and helping, then it will be just a natural thing to move forward. I think everything begins with you. I mean, what kind of person are you? Are you a scientist at heart? Are you driven by the need to understand things in a more sophisticated way tomorrow than you did today? And do you care about others? I think if you have that, then you'll find very good ways to spend your time. If you don't, you'll play golf or do something else.
Giovanni:
Many thanks Stan. This is the type of question you also answer by example. We can look at what you did and think about it.
Anindya:
This was such a great experience Stan.
Guy:
I think Stan has done a fantastic job of answering the questions and stimulating our discussion.
Stan:
Many thanks to you all. Let's stay in touch.