The Bioinformatics CRO Podcast

Episode 6 with Tony Altar

We speak with C. Anthony Altar, PhD, president and COO of Splice Therapeutics, about his successful career in neuropharmacology and his role in pioneering the sport of skateboarding in the 1960’s. (Recorded on November 19, 2020)

On The Bioinformatics CRO Podcast, we sit down with scientists to discuss interesting topics across biomedical research and to explore what made them who they are today.

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Transcript of Episode 6: Tony Altar

Grant: Welcome to The Bioinformatics CRO Podcast. I’m Grant Belgard, and joining me today is Tony Altar. Tony, would you like to introduce yourself?

Tony: Hi Grant. Yeah, it’s great to be here on the podcast. My name is Tony Altar. I have a PhD degree in neuroscience. I’ve spent the major part of my career working on neuropharmacology, neuroscience and helping to develop drugs for people with psychiatric conditions. More recently, I’ve been involved in the neurological side of brain disorders. And as a result, I’ve moved my career more from the pharmacological approach to gene therapy and genetic approaches, because I think neurological disorders are more caused by genetic problems and problems at the early expression of genes, as opposed to drug mechanisms for psychiatric disorders. So I’ve really moved my career quite a bit, just in the last 10 years.

Grant: Great. Let’s talk about your career. Maybe start from the beginning because I think it’s a pretty interesting path, but maybe if we can go way back to child Tony, what kinds of things were you into? How did you end up in science? What possibilities did you entertain?

Tony: I love that question, Grant, because I think for all of us, understanding the origins of our own careers, our own interests are really informative and important. I think those are some of the enduring parts of our personality that help us through the tough times, as well as the good times in our career. So for me, that’s true as well. My interest in science started with my own father who was a fairly successful theoretical physicist, and extended to- I guess I would call him my second father- a man named Art Yuwiler, who ran a neurobiochemistry laboratory. Which, at the age of 17 when I started working there, I don’t think I could even pronounce neurobiochemistry, nor did I really understand much of what these guys in the lab were saying, but it was a fascinating experience. Between my upbringing from my mother and father’s side and love of science and then the ability to actually conduct science at such an early age, that helps set a path for me.

Grant: Where did you grow up?

Tony: I grew up in West Los Angeles. enjoyed the area near UCLA, near the ocean. It was a great place to be. We moved there in the late fifties and lived there. I did my schooling at UCLA, UC Santa Barbara, UC Irvine. So a good dose of California through my entire education.

Grant: What pulled you away from California in the end?

Tony: Well, having luckily married my wife Kristen, I needed to start paying the bills. I also did want to work in the pharmacology industry, especially helping discover and develop drugs for the CNS. So I moved to the East coast to come work at a company called Ciba-Geigy. Now it’s known as Novartis, so that was a great opportunity after my postdoc at UC Irvine to really put into play the creative process that I always dreamed about doing. In fact, it was back in Dr. Yuwiler’s laboratory where I had a small desk, and right next to my desk, there was a little placard from Upjohn Pharmaceuticals and it said, “The best way to create new therapies for brain disorders is to understand the basis of those brain disorders.” And that always stayed with me. Understanding the cause of disease, if you know that you can actually have a real opportunity to come up with a new approach and come up with therapies. And I believe that today more than ever.

Grant: What got you into the brain?

Tony: I got interested in the brain- actually another figure in my life, a good friend of mine Doc Renneker, who is now a very famous surfing guy, Mark Renneker and I used to skateboard every weekend at UCLA. That’s where we got pretty good at skateboarding in the very earliest days of the sport. Mark’s father was a psychiatrist, and we used to chat about the brain and his patients to some extent. I was always fascinated about the whole possibility that you could help people with psychiatric problems by talking with them and by giving them drugs. There was also around that time in the middle of the late sixties, as you can imagine with the psychedelic revolution that came along.

Tony: We got really interested in this whole idea that a single molecule completely changes someone’s personality. It could completely change their insights into the world. To me, that hasn’t gone away as an interest. It’s coming full circle now. So that was really interesting to me because I realized that a single molecule like an LSD or psilocybin can have such profound effects when given as a pill, then our own neurochemistry when subtly changed could explain things like depression, like schizophrenia. So that was kind of an epiphany that I added up at a pretty early age, and working in the neuro biochemistry lab reinforced that thinking as well. So I think that was part of it, the cultural milieu of Los Angeles at that time and the whole country, really. Being able to address it from a scientific perspective and then use it, those were all great recipes for my career.

Grant: So you went into biotech, and one thing I’ve always found interesting about your career, Tony, is you spent almost your entire career postdoc in industry, but you’ve published like a successful academic. How have you done that? How have you managed to keep that up? 

Tony: It’s an interesting question because the general idea is if someone’s in academia, they have to publish or perish, and if they’re in a drug company, they don’t want to tell anybody anything about what they’re doing. I was somehow able to do both. I’m really not sure the answer to that, because I did a lot of publishing at the university of California. I think I published three or four papers before I even got my PhD, but the bulk of my publications was at places like Genentech, Regeneron, out of Ciba-Geigy. Actually, every company I’ve ever worked at. I don’t know, maybe they were a little more permissive for us, but at most of those companies, there was also a high priority placed on excellent science. Publications showing the world what was being done, that was a great recruiting tool.

Tony: I think the companies I worked in always put a high premium on that kind of academic excellence as well as developing compounds. So maybe part of it, to answer your question, was being able to be at places that fostered that kind of environment. The resources at those companies to this very day were always very good. Yeah. We had lots of opportunities to do the work and didn’t have to worry about writing grants. We could spend our time writing papers and stuff. That’s another reason I was always attracted to the pharmaceutical industry, because you really did have that emphasis on research and production rather than scrounging for money and trying to placate reviewers and play the academic game. I was pretty turned off about by the time I was done with my postdoc.

Grant: So how can one as a founder and/or manager create an environment that’s conducive to that?

Tony: That’s a very important question, and I’m faced with that now as I start my own new company with a co-founder. A company that’s focused on gene therapy that we’re really very excited about. This is an important question. You want to attract the best and the brightest, which was the mantra at Genentech and other companies I’ve been at. It was really important to hire the best people, but you have to retain them, too. We have to like our boss. That’s the number one factor for why people leave. They don’t get along with their boss. They need to have a scientific career that’s successful and really productive. That’s another reason that you retain people, because they love the environment they’re in and make great results and are rewarded with publications. You have to see an end product in a company.

Tony: Most people that work in companies are there for some of those reasons I mentioned. They have resources, the pay is good, the environment can be outstanding with other colleagues, but we’re also there because we want to make a difference for human health. We want to really create something like a pill that makes a schizophrenic patient better, or a gene therapy product that helps with a neurological decision, or a pharmacogenomic product that gets patients on the right medications for their ADHD. I’ve been allowed to succeed in all of those spheres. So the best way to retain people has a lot to do with how you recruit them because the people coming into a company see the people who were there. A big part of the decision is to the boss but also the colleagues. Who am I going to work with in this new environment?

Tony: If they’re excited, they’re doing high quality work, and they’re hitting all of those criteria I just mentioned, those interviews are going to go great. I remember an interview I had at Regeneron when I decided to go there and work with Len Schleifer, George Yancopoulos, and the team. The best part of that whole interview process was we went out to dinner one night and there were ten people who came to dinner. We had this fantastic discussion around a big table about all the science that was going on, things I’d been doing at Genentech at the time. I think after that dinner, I pretty much decided I’m coming here. So you recruit with the people who are there, you retain by allowing the new people who’ve just come in to also succeed, and you have a high ethical standard.

Tony: You run a company where there’s no smoke and mirrors, where there’s real results, where the science is first rate, and you can publish in the best journals. As long as you can manage scientists to achieve that way, you’re a good scientific manager. And the rest will just fall.

My expression for managing scientists is you manage by letting them do good science, and then the other problems, which will always arise- competition, maybe some jealousies that come along, frictions that develop, uncertainties. These always will come up in any lab environment, but as long as the results are these high level achievements, everybody will benefit. One thing to really pay attention to here is that- and in retrospect, I’ve become very aware of this- when you look back at the companies you’ve been working at, or universities too, it’s the team you worked with and the treatments you got as a team that you talk about.

Tony: I really don’t talk much about my own individual accomplishments. I talk about what we did at Otsuka and discovering and developing Abilify as a huge team. Eventually, it was a hundred people along with another company, Bristol Myers Squibb, and more than a hundred to do the clinical work. We as a team developed this best in class drug for schizophrenia, depression, and bipolar disorder. No one person does that, but it’s the team that you’re working with. It really makes the difference. I do believe in that. The best management and the best way to retain people is you encourage that team feeling. You have the team succeed.

Grant: I don’t know if you’re allowed to talk about that, but can you talk about the development of Abilify and what the thinking was around that? How it went down?

Tony: Sure. Oh, I’m allowed to talk because it’s mostly been published. And in fact, Otsuka is another example of an outstanding company. They’re a Japanese pharmaceutical company. It really started back in the 1980s when I was working along with some other people on trying to come up with a partial dopamine D2 agonist. D2, meaning a dopamine D2-type of receptor. The theory was actually promoted by Dr. Arvid Carlsson. Arvid won the Nobel prize in 2000 because he discovered dopamine. Not a shabby thing. Leading to theories about schizophrenia and Parkinson’s disease, and Arvid proposed very early that perhaps instead of blocking a dopamine receptor to treat schizophrenia, which was already known, you could actually put in a partial agonist, which didn’t block the receptor, but it quieted the receptors activity to an intermediate level.

Tony: Whereas a receptor blocker will stop all activity. That’ll treat schizophrenia, but it also creates lots of side effects. So Dr. Carlsson proposed that a partial dopamine D2 receptor agonist would lower excessive tone, but bring lower tone up to a sort of a middle level. I worked on that in the early 1980s, and at Ciba-Geigy, we brought some drugs to the clinic. Unfortunately, those drugs have some liver metabolism problems and the company was really quite conservative and didn’t pursue it any further than that. So when I got the opportunity to interview at Otsuka to head up their global neuroscience department, I looked at this early clinical data and some of the ideas about the mechanism, I realized this was very similar to the work I’d already done.

Tony: But now we were 15 years later. I was able to take that job and manage the team in Japan and in the US. We further profiled the compound. One of the important things about Abilify is, turns out, it’s not only a partial dopamine receptor agonist. We discovered that it’s a partial serotonin agonist as well. We realized it could not only treat schizophrenia, but depression and bipolar disorder because of what Arvid Carlsson, who now was one of our consultants, called a serotonin-dopamine system stabilizer. I thought that was a brilliant concept. That went on to be a marketing tool to describe how Abilify works. There are ten times more people with depression than schizophrenia and two to three times more people with bipolar than schizophrenia. The result was, Abilify was the largest grossing drug worldwide in 2014, and I think to this day has treated millions and millions of patients. I’ve been blessed that I was able to work with Dr. Carlsson on this project and with this fantastic team, both at Otsuka and Bristol Myers Squibb to get this really important drug made. All this is publicly known. There’ve been many imitators since.

Grant: Yeah, that’s a huge accomplishment.

Tony: Well, there’s an important term here for that accomplishment and it’s persistence. Persistence is probably the most important single attribute that we as scientists have to embody, because we’re not going to succeed the first time. If we persist, however, it will eventually succeed. Sometimes we have to come full circle. So I had to go from my work at Ciba-Geigy to coming back to a new company to finally get that project finished. That’s a really important thing, is to persist.

Grant: So what, what most excites you in the field of neuropsychiatry? What do you think will have the biggest impact for patients in the next 20 years?

Tony: I think for psychiatry, it’s maybe a little harder to say than for neurology, where I was hoping you were going with the question. In psychiatry, the reason I’m a little more hesitant is because a lot of our psychiatric knowledge has come from how drugs work and which drugs work. By luck, we happened to come across an antidepressant and that we elaborate on those kinds of drugs without really understanding why people are depressed in the first place. The targets in psychiatry are not as clear. There have been some significant breakthroughs with a class of drugs called muscarinic agonists, which for schizophrenia have been proven now to be very effective.

Tony: That may only be the second receptor target that has never been validated for treating schizophrenia. Luckily in the early 2005, my team at a company called Psychiatric Genomics discovered that very approach. It’s been finally capitalized by a company called Karuna. They made a drug that is actually a muscarinic agonist that’s coupled with another drug, and that has proven to be very effective against schizophrenia.

Tony: That may be only the second target after dopamine receptors to treat schizophrenia. I’ve luckily been involved in both the partial dopamine agonist innovation and now maybe this muscarinic agonist, if indeed further trials continue to show that it’s so effective. I think those are the most critical approaches, perhaps one of the most important breakthroughs in psychiatry today, because I don’t think it’s only going to be useful in schizophrenia. I think it may also be useful for Alzheimer’s disease because a very similar story about muscarinic receptor sub activation has been made for Alzheimer’s disease as well. So it could well be that this very same drug, which was made originally at Eli Lilly, could be useful in treating Alzheimer’s disease. Of course, that would be a huge breakthrough.

Grant: What if you were to answer the same question for neurology? Would it be the same answer with the muscarinic receptor?

Tony: Well, maybe for Alzheimer’s it actually could. I mean, Alzheimer’s patients do have a deficiency of muscarinic receptors, signaling, and metabolism of brain neurons as a result. So that could be, but I don’t think that’s going to be the final answer because I think that kind of approach treats some of the symptoms of the disease but not the cause. Therein lies the real difference between neurology and psychiatry. So for neurology, I think a lot of these causes are at the epigenetic level. We know that’s true for many disorders. We know that for Alzheimer’s, we know it about ALS, we know it for Parkinson’s disease, we know it from Huntington’s disease, and the list goes on and on. For all of these diseases, there’s always a subgroup or often a subgroup of patients for whom the genetic mutation that they inherited is the cause of the disorder.

Tony: You don’t see that in psychiatry. That there’s very few of any chains that have been linked to psychiatric conditions, let alone with the penetrance that you see for the neurological mutations. We have a huge opportunity now in neurology to know that at least for a subset of patients- sometimes it’s all of them like Huntington’s disease- where there’s a genetic mutation that is the cause. We know the targets, which is quite different to what you have in psychiatry where we hardly have a clue about what the target is. So that’s where I see it as a huge advantage. Because it’s a genetic problem, the nucleus and the gene expression of nuclear DNA is often the cause of why those patients go on to develop these neurological conditions.

Tony: I think for neurological conditions, gene therapy is a much more viable option, and we’ve already seen that proven in just the last few years with the approval of Spinraza for spinal muscular atrophy and Luxturna for a form of blindness, both of which are due to inherited mutations in genes important for those systems that are diseased.

Grant: Cool. Shifting gears a bit, can you tell us about your skateboarding?

Tony: Ah, skateboarding. Sure.

Grant: When did you get into it?

Tony: Well, I was very lucky. I got into it very early on, and I mentioned I got all of my training in Los Angeles. I went through the Los Angeles Unified School District System at places like Paul Revere Junior High School and Palisades High. I was involved from the very earliest days. Some of my buddies like John Fries, there was a first national skateboard champion. And the year after John, I was able to compete in the same tournament. I did pretty well. Part of that is because we lived in West LA where, I think as far as we can tell, the sport originated. If it didn’t certainly originate there, we kind of did a lot of the improvements. So for me, skateboarding is- today it’s a way for me to keep my brain in shape. I don’t do it just for the fun of it. It’s a great aerobic sport. I know it requires a lot of balance, coordination, persistence. It’s tiring to do it right.

Tony: It’s a full workout. I partly do it for that. There’s a lot of similarities with science and what we did in the early days. We innovated, we had to make our own skateboards where we would cut roller skates in half and then put them on either end of the board. We needed to figure out new materials to make the boards from. At the same time, it was fun. Got chased away by dogs and angry adults. I was eventually able to compete at the highest level. There’s a lot of similarities with scientific achievement. It was only later that my buddies and I, looking back, realized that we were on the forefront of a brand new sport. Totally in awe with what people are doing nowadays on a skateboard.

Tony: But we were part of that early, very early phase. I think it was exciting at the time. I see science in a similar way. I still like to do science because it helps keep my brain in shape too, to think a lot. I have to innovate, I have to plan new stuff, work in an area that no one else has been working on, and carve out new territory. There’s kind of a similar process going on there.

Grant: Tell us about the polyurethane wheels.

Tony: Because my best friend at the time, Mark Renneker, and I did a lot of skateboarding and because Hobie, which is a manufacturer of skateboards and sponsored a lot of skateboard tournaments in Santa Monica, I was able to get into the tournament scene. Luckily in 1966, I was on a skateboard team. At that time, we were skateboarding on a rubbery cork wheel. It was okay, but if you have a little pebble, the skateboard would just stop dead, and you’d go flying. So, it made you very cautious. One day our skateboard team, we were sitting around a table and our captain of the team. He came in with his paper bag, and he poured out this bunch of wheels on the table. They were all these white polyurethane wheels which we’d never seen before.

Tony: In fact, most of us had been skateboarding on metal wheels just a few years before. And we looked at these wheels. We realized immediately what this might mean, and we put them on our boards and sure enough, the boards were much easier to navigate. You could go over little rocks and not get stopped. You had a lot more contact with the surface. And luckily I think I was able to continue to compete at various tournaments, including the national tournament on those new wheels. That really helped. It was a nice example of where an innovative tool really helped you jump ahead.

Tony: Funny to think about these polyurethane wheels. It turns out they weren’t the absolute first polyurethane wheels never made for a skateboard. I mean, that bag came from one batch that had just been made. No other skateboard wheels had ever been made. When I talked to the experts who really follow skateboard lore, if I asked them when they thought the first polyurethane wheels came out, they’d say mid 1970s. We were almost ten years earlier with these wheels. I still have them, of course. Nice collector piece.

Grant: Find all the people who’ve written on the history of skateboarding and set them straight. 

Tony: Yeah, there’s this one guy. We had a big rally at the Smithsonian museum about five years ago. Tony Hawk showed up, Rodney Mullen, and all the great guys came. We already knew some of them when one gentleman who was The Professor, they call him because he professes to have all this knowledge about skateboarding, and he’s a good skateboarder himself, but he was wearing a white lab coat. He was a skateboard expert, and he was the guy that bought the first polyurethane wheels, out in the mid-1970s. Actually, the Smithsonian wanted the board that I have with those wheels on it, but I wouldn’t give it to them.

Grant: Nice. So how did you come to live a stone’s throw from NIH?

Tony: Oh, when Otsuka hired me to head up global neuroscience, the Otsuka lab was here in Rockville, Maryland, so we moved out at that time. 

Grant: What changes have you seen in the biotech scene on the 270 corridor?

Tony: I think the biotech scene along the 270 corridor is really starting to come on to its own. It’s always been a great promise, and there’s always been biotech companies. As I mentioned, I headed up one of them called Psychiatric Genomics in Gaithersburg. It never really became a Mecca like Boston, and it still isn’t quite to that level, but in the last five years, I think things have really been picking up. I know having found new laboratory space ourselves in just the last few months, lab space is still a premium and very large laboratory facilities are now being created and moved into very quickly. Companies like Novavax, Regenexx Bio, MedImmune, and AstraZeneca that took over the MedImmune site.

Tony: There’s a lot of activity that’s building now from some very successful companies. I think it’s starting to really pick up. Having NIH here, having the FDA here, having a lot of other pharma and other organizations that are associated with our industry certainly doesn’t hurt. There’s a lot of really talented people in this area. I’m just surprised it’s taken as long as it has. It’s a great area to live in, and housing’s affordable here. A lot of talent, a lot of universities. I think it’s just going to continue to build out.

Grant: if you were a young biomedical scientist just leaving academia, what geographic area would you head towards? Obviously there are many biotech ecosystems around the world. Which do you think might have the most promise if you’re looking out over the next generation or two?

Tony: Geography is important, but I define geography more than by the laboratory geography. I’d rather be in a great lab that’s in a good institution almost anywhere in the country, compared to being in, let’s say a San Francisco area, in not so good a lab or not, let’s say a more competitive and tight situation. I think the local environment is more important if the lab is fostering excellent research, and people are productive, much like I described for companies themselves. I think that’s the most important thing for a person to choose. The other thing though, besides geography is the opportunity that you find in that first job after a postdoc.

Tony: So, are there innovative techniques and new methods that are coming out of that group that you’re working with? Are they giving you projects that allow you to see your field of science in a way that no one else has been able to look at before? I’m a big proponent on new methods. I think new methods are almost always the key. Look at the CRISPR Nobel Prize that was just awarded. It’s a new method that was realized first for basic biology, but then exploited for its potential therapeutic use. That creates a field day for you. If you come into a lab with new techniques, new ways of seeing science, new ways of exploiting science, everything you do is going to be innovative and important. I would encourage people to think about doing stuff that’s on the cutting edge, as opposed to coming into a lab to put the dot the I’s and cross the T’s on the principal investigator’s work. You don’t really want to be there because that’s going to be stuff where many other people have already been.

Tony: When you go into the marketplace, let’s say your next job, you want to be able to be in a position to say, “I’ve carved out this whole new area. I see that you’re expanding in that area. I’d love to work with your team.” I’ve seen that in the gene therapy field. For example, about five years ago, there was a whole big breakthrough in gene therapy delivery, ways of getting gene therapy products into the brain or into specific tissues. That was a huge area, and it’s continuing to build, it’s continuing to show promise. I noticed that all the young investigators that were working in that field were getting jobs and moving to new places, new companies. All these guys are getting great offers to move, and that’s because the field was seeing the growth of this area. I wanted people with those skills to help those other concerns move to where they needed to be. That’s why the innovative stuff where you can see a real application in the commercial world, I think is the best single geography to consider, not so much where that lab happens to be.

Grant: What do you think will be the big changes coming to biotech as an industry in the coming years?

Tony: I think one of the big changes is in the field of bioinformatics. I’ve actually been a bit skeptical about big data and bioinformatics for a while. Partly I think that’s because bioinformaticians sometimes don’t have a good handle on the biology that they’re trying to uncover through their methods. At the same time, I can give biologists a little bit of grief too, because I think we as biologists need to do a better job knowing about statistics and bioinformatic databases and what they can and can’t provide. Getting quality data has been a real limitation. Just RNA-seq data, for example, can take a whole variety of forms. There are many different ways to measure RNAs, and how you measure it has a huge impact on the interpretations you make. I see a lot of people just blindly measuring the RNA, and they don’t really know what they’re actually measuring. Is it nuclear? Is it cytoplasmic?

Tony: Is it both? Is it cell-type specific? The questions go on and on, and these are important questions. But to answer your question about where I think things are going on in biotechnology, I think bioinformatics will come to play a bigger and bigger role as quality data is provided, as tools are created to analyze that, as people understand better on both sides of the equation what we’re looking at and how we’re interpreting it. I think there’ll be quite a revolution in how we can target disease therapies through what we learned from the bioinformatic analysis.

Grant: That’s good news for us.

Tony: Well, partly working with you, Grant. You’ve helped us actually understand some important properties along the way. I think it’s just going to get better as these methods continue to unravel what’s going on and in gene expression and gene processing for these diseases that are clearly genetic in nature. I think that’s the second level of great excitement for the biotechnology field is using these targets and these mechanisms that we’re learning about to come up with therapies. We were a bit lucky. Well, maybe I shouldn’t say lucky. We worked very hard to find this muscarinic receptor target for schizophrenia.

Tony: That was basically a four year odyssey, but it worked. The reason I say we were lucky is the cells that we used in our in-vitro assay happened to have muscarinic receptors. We knew that was always going to be a limitation. Do the cells even have the receptor mechanisms that you’re going to be evaluating? Often, people don’t even ask that question. We did a whole profiling, so we knew what those cell lines express, so we knew what candidates could come up because they were there, and the other receptor candidates we’d never learned about cause they weren’t expressed. But those are the kinds of questions that we have to ask.

Tony: I think the good thing for bioinformatics experts to keep in mind is to learn the biology about what you’re being asked to analyze. You have to be aware of the experimental design and really know about the material that you’re analyzing, whether it’s RNA-seq data or cell-based data. What are the constraints? What don’t you never learn about because the cells don’t express those players, or you’re looking at the wrong cell type, so you can never learn about the mechanism of disease because the disease is due to another cell. You have to learn about the biology, and it’s not just one sided. The biologists also have to learn about what they’re asking the bioinformatics person to analyze, what the limitations or possibilities are from that data.

Grant: So, you’ve worked remotely a pretty good chunk of your recent career, at least. Can you comment on what you’ve learned from that? And do you have any advice in this time of COVID where everyone’s working remotely, most everyone’s managing remotely. How do you pull it off?

Tony: Well, I’m actually about not to pull it off. I’m about to be back in the lab. I’m really looking forward to that. Learning molecular biology skills and applying what I’ve been learning over the last few years of genetics. I’m not a big fan of remote work. Certainly, it can be done. I’m a bigger fan of remote meetings. I don’t think people need to get on a plane and travel across the country for a one-hour meeting. I’ve even heard of a person once. He flew all the way from here to Asia for dinner. When dinner was over, he was put on a plane and he came back. I mean, this is crazy, and it’s not very helpful to our environment as well.

Tony: I think we have a real responsibility to preserve and improve our environment. I think remote meetings are fantastic. I’m seeing that as a real advantage, but the workplace is different. I think people really should be, when possible, in a similar physical proximity to one another. Especially in a laboratory environment where you have to be there to do the actual work. Hopefully when our COVID-19 vaccines come along and people start wearing masks and behaving properly, we can abruptly put an end to this pandemic. People will look at the best of all these worlds. We’ll have remote meetings. We’ll be back in the workplace. Our commutes may be five days a week, maybe there’ll be three and four. We mix it up a bit and just work to our own better advantage for all of these things.

Grant: Do you care to prognosticate about what will happen with COVID? When will things start to get back to normal?

Tony: I can’t. I’m not an expert, but one thing is really clear. If we all behave ourselves in a concerted way and show discipline about wearing masks, about keeping our social distance, about not having these large gatherings, and the vaccine becomes available, which it looks like it will. We do all of those things. As of January 20th, I would give it then another four months before we see a real improvement. And by the end of the year, we’ll be back almost to normal, but that’s the most optimistic scenario. The harsh reality is there are a lot of people who still will refuse to wear masks and won’t want to get vaccinated, and that won’t stop the process, but it will slow it down quite a bit.

Grant: What surprised you the most about this pandemic and the response?

Tony: I guess what surprised me the most about this pandemic is how so many people will refuse to wear masks. We ask our soldiers who go to war, to wear 50 pounds of gear and to go into battle wearing that kind of gear every day and literally risking their life to fight an enemy. Here we have COVID-19 as an enemy, and I’m shocked when I see people who aren’t willing to wear a one ounce mask and actually defeat an enemy that’s killed more people than these wars. I really don’t know what’s up about that, except that maybe it has become a political statement for people who just don’t like to be told what to do. We live in a society where we have to drive the speed limit. We have to follow certain laws, and this to me seems like a great example of just another minor adjustment that people should be making.

Tony: And most do. In many areas, the compliance is 90% and above, but it isn’t everywhere. If we all pull together and make these small adjustments, our economy can recover much more quickly in the long run. That surprises me that I even have to say things like this or parenting what other people say. That’s the big surprise, which seemed like this should just happen as a matter of common sense.

Grant: It’s a bit depressing.

Tony: Yeah, it is, but I think we’ll get through this, and the vaccines, I think will make a huge difference. 

Grant: As a final question, maybe a bit of a humdinger. What do you think most scientists today have wrong?

Tony: Well, let me rephrase the question a little bit. What do I think scientists nowadays, especially the younger group of scientists coming into industry really need to pay particular attention to? We all need to pay attention to the limitations of the data that we simply download from the internet. You know, I remember the first scientist who said, “Well, I’m going to Google that term and look up the answer.” I thought, what are you crazy? Aren’t you going to go to the library stacks and pull out the journal articles or read the articles and figure it all out. Both methods are clearly limited, but nowadays people do go to Google and they type in pretty much anything they want to learn about science. You certainly can learn a lot. There’s no question. It’s a fantastic tool, but the problem and what people get wrong is that’s kind of where it stops. They go, “Well, I read, I saw on the web that you can use this app. That’s what we’re going to do.” 

Tony: What they don’t do then, they don’t say, “Well, gee, is that assay really the right one for me? Or can I compare it with two others that I learned about? What I have to do empirically in the lab to answer for myself that what I’m reading and learning from the internet it’s true.” That’s what I see as a real problem. I hear this from other people who train students and see the new crops coming and going. There doesn’t seem to be as much willingness to run the empirical foundational studies that are needed to convince you that you’re on the right path. And so scientists often can move into the wrong direction, and they’re doomed to fail from the get go. You have to do the experiments in the lab to convince yourself that you’re on the right path.

Tony: Is your analytical tool sensitive enough? Does it give you the kind of information that you need? Is it analyzing the right materials to even answer the question? All of these kinds of things. I’m a big believer of positive controls and negative controls. You want to run your assay with outcomes you fully expect. We did an RNA-seq study recently where the database that was provided by Grant’s company. The first experiment I did when Grant provided the data to me was I said, “Okay, if this data is correctly provided from Grant’s team, I should be able to recreate the figure from which the data was deposited.” And sure enough, we exactly recreated the data that was in the publication for one gene.

Tony: And that gave me confidence that the other genes are going to give probably accurate results. So that’s the kind of stuff you need to do. You need to convince yourself in the lab empirically that you’re on the right track, and not just assume that because you found a method somewhere that that’s going to work. We all know most methods that you just snag from somewhere don’t work. You’ve got to tweak them, and then sadly enough, many of the results that we get in papers can’t be replicated. So the way to get it right is to have the right methods, and show that you can produce reproducible results that convinced herself that the methods are right. I mentioned persistence is important. Replication is my other favorite word in science. We have to be able to replicate what we’ve done and what other people have done with similar methods before we have any confidence that we’re on the right track.

Grant: Couldn’t agree more. Well, thank you so much for joining us today, Tony. It was great. 

Tony: Great pleasure to be with you, Grant, and I look forward to seeing great things out of your own organization and from all of us who really are committed to putting all of this that we’ve been talking about together, so that we can help people get over inherited diseases, acquired diseases, and even those that are spontaneous. There’s a lot to be learned. There’s really no end to what medical science is going to be able to achieve, and t’s just exciting to be part of this. 

Grant: What will science do next?