Magazine Article | August 1, 2016

How Pharma Can Create Environments That Go Beyond Being Just Cutting Edge

Source: Life Science Leader

By Rob Wright, Chief Editor, Life Science Leader
Follow Me On Twitter @RfwrightLSL

At the 2016 BIO International Convention in San Francisco (June 6-9), I had the opportunity to moderate an extremely impressive panel focused on how companies can create environments that go beyond being just cutting edge. Panelists included one of the world’s most influential scientific minds, Matthew Meyerson, M.D., Ph.D, Professor of Pathology at Dana- Farber Cancer Institute and Harvard Medical School; Verily Life Sciences’ (formerly Google Life Sciences) chief medical officer, Jessica Mega, M.D., MPH; one of the world’s biggest digital health influencers, John Nosta; Bayer AG’s top innovation officer and board of management member, Kemal Malik, MBBS; and partner of corporate development at Flagship Ventures, Jeremy Springhorn, Ph.D., whose firm has created more than 40 companies within the VentureLabs group and has been cofounders/early backers of another 45 companies. We know that, unfortunately, not everyone can attend BIO. Further, for those who do, there are so many simultaneous educational opportunities that you often have to choose between options. In an effort to prevent discussion insights from remaining within the room at BIO’s annual showcase event, Life Science Leader created an article to more broadly distribute the robust dialogue. What follows is an edited transcript from the Beyond The Cutting Edge: How To Enable Life Science Organizations Today For The Societal Challenges Of Tomorrow super session.

What Does Going Beyond The Cutting Edge Look Like?

“When thinking about going beyond the cutting edge, what does that mean?” I asked from the stage. Describing someone in their kitchen using a sharpening stick to hone a chef’s knife while preparing a family meal, it is pointed out that no matter which tool is used, a knife can only achieve a certain degree of sharpness. So how is it possible for someone to go beyond that knife’s cutting edge? Here, I pointed out the existence of industrial tools (e.g., lasers, high-pressure air or liquids) that go beyond the notion of using sharpened steel to cut or shape things. This analogy set the stage for the panelists on how they go about creating environments at their organizations that encourage beyond cutting edge/innovative thinking. After the panelists briefly introduced themselves, the first question was posed, leading to the following dialogue.

How Do You Define Cutting Edge?

MATTHEW MEYERSON: To me, cutting edge is going where nobody has gone, making discoveries nobody has made. When I think about cutting edge, I reflect back to a conversation I had as a college student. I was at a conference where I had the opportunity to speak with some very distinguished professors. One of them said to me, “Matthew, you have to understand. People don’t get any smarter. We just get new technologies. The way to do something cutting edge is to take a new technology and think about what you can do with it.” At the time, I was really annoyed by this statement because I felt it wasn’t true. But he was right. There are people who came before us and thought hard about the same kinds of problems. What really enable us today are incredible, new technologies. We’ve seen this in the computer and communications age in terms of how we handle information. We see it in genomics, with the ability to read the secrets of the genome and apply this knowledge in the making of biologics, protein therapeutics, and nucleic acid therapeutics. In chemistry, we see it with the ability to make much more complex and innovative chemical matter. All of these technological innovations are what drives our ability to do new research. We’ve discovered so much about cancer in the last 10 to 30 years, and today we are seeing it take root in new therapies. It’s not because we’re smarter or better, but because we can take advantage of new technologies that represent our collective intelligence.

JOHN NOSTA: Let me build off of that, because while I agree with you, there’s one thing that is different. Abraham Lincoln once said that if you have eight hours to chop down a tree, spend six of those sharpening your axe. While this is sage advice, the thing that is different today is speed. We live in an exponential society, and the ability to pivot and move in another direction is great, but also frightening. If you look at a standard drug development protocol, it’s one step at a time. I think that the cutting edge is inherently risky, because it pushes us along a path that has amazing velocity, both in magnitude and direction.

JESSICA MEGA: To follow up on that, while we have an obligation to utilize new technologies and to try to accelerate where possible, we also have to respect the biologic and life sciences pathways, which sometimes take time. So how do we be nimble and innovative and use the new technologies, while respecting the fact that biology is sometimes humbling? While we have to be cutting edge, we also have to be responsible.

KEMAL MALIK: The continuity and existence of Bayer is fundamentally important to the board of management and the supervisory board that employs us. Though Bayer has been around for 150 years, a key deliverable for the company’s board is to ensure it survives at least 150 more. This is kind of different from an environment focused primarily on shareholder value. When I think about what cutting edge means for Bayer, I first considered the Oxford English Dictionary’s definition — the most advanced stage of development of a thing or a process. Well, to get beyond that definition is a bit of a challenge, particularly if you’re a company that is used to doing things in a certain way. But if your driving force is to make sure that you continue to exist, you are forced to look for things that can not only be disruptive to your business, but challenge your ability to continue to exist as an organization. At Bayer, we continually challenge ourselves to evolve. For example, we started as a dye company in Germany, and yet today we are a global pharmaceutical and agricultural business. Who knows what we will be in the future? For me, the cutting edge involves looking at technologies that can challenge Bayer’s ability to survive.

JEREMY SPRINGHORN: The word “innovation” has evolved into a frequently used buzzword, and as things tend to go in cycles, at some point in the next couple of years it might actually become a derogatory term. There is a difference between how I thought about innovation while working at Alexion Pharmaceuticals versus how we think about working on the cutting edge at Flagship Ventures. At Alexion, innovation could be something as essential as life cycle management of a product. Incremental product innovation can be valuable to companies and patients. Being cutting edge at Flagship is a simple process that begins by asking the fundamental question, “What if?” and potentially ends with the creation of a company. Inherent in the notion of asking big “If only” questions is the need to be able to suspend disbelief about the limits of what science actually can do. This is what Google does, and there are a lot of parallels between Google and Flagship. If you believe everything you read in PubMed, your science will be constrained. There is a big difference between what people believe to be true and what is scientifically true, and the arbitrage between these is how we at Flagship create value and find cutting edge science.

NOSTA: I’ve never heard “suspension of disbelief” applied to the life sciences industry. That’s a fascinating phrase and a valuable dynamic. When we talk about cutting edge and the influences that drive that in life sciences, it is very much company, structure, finance, and drug development. But there is also external pressure: a sense of social urgency to address big problems like diabetes, hypertension, and cancer that are pressing the issue. In response, everybody in pharma seems to be opening these new bastions of innovation, and they are called accelerators. I would argue that the acceleration of innovation is both clinically urgent and financially expedient. MEGA: As a physician, one thing I think a lot about is how we take care of patients. We know the latest guidelines and practice evidence-based medicine. But both my parents were physicians, and they always joke that they spent a lot of time studying worms and very little time studying the next generation of viruses and the things we tend to study today. I think people who are in the life sciences space (i.e., scientists) have always known the truth of what we are heading toward. While there has always been innovation, we’ve got to keep pushing. Like the previous generation of physicians, what we know of today is not enough. How do you balance this suspension of disbelief and having new ideas that really push the limits, while also testing them in a rigorous and appropriate way?

MALIK: One of the challenges and reasons large companies have accelerators is that 90 percent of what large companies need to do is sustainable and incremental innovation. I mean, it’s not always “think the impossible,” because if we all thought the impossible with the $4 billion Bayer spends on R&D, there’s a risk we would go out of business. Our approach is to think the impossible for a small amount of money. Now, can you get the people doing their day-to-day job in R&D to also think the impossible? Probably not, and that is why we set up incubators and accelerators. Ours is called the Lifescience Center, where we focus on things like DNA editing, CRISPR, cell-based therapies, the microbiome, etc. Here is where Bayer employees can think the unthinkable, while the rest of us think about the sustainable, incremental innovation that makes up the bulk of our R&D budget. At a large organization, the challenge is having a balanced portfolio, a hurdle many small companies don’t face. Perhaps small companies can always think the unthinkable, but they could also be out of business in a year as well.

SPRINGHORN: I completely agree. Innovation at a large pharma is bound by the restrictions you would expect. It has to be plannable: People have to live by objectives. It has to be efficient: People have budgets. And, it has to be predictable: You have to know what the outcomes are. While those are the constraints Big Pharma lives under, to be an innovative entrepreneur, you have to break through those things. Often, true innovation is neither plannable nor predictable, and it’s certainly not efficient. Innovation at Flagship is an iterative process, almost like evolution, and similar to what Lockheed Martin did in the 1950s — Skunk Works that moved people outside the organization to allow them to think freely. NOSTA: Evolution is a good analogy. But we find that evolutionary progress is really a punctuated equilibrium. [Stephen] Jay Gould [an American paleontologist, evolutionary biologist, and historian of science] said that innovation is not a straight line. It’s these periods of wandering around, and then, all of a sudden, something happens. That punctuated equilibrium and suspension of disbelief is so interesting because of that inspiration, that magical thing that happens when you fall, you fall, you fall, and then one day you take a step forward, and then you fly.

MEYERSON: I think a big component of innovation is persistence. There’s the old joke about science that if you found it the first time, you wouldn’t call it research. Sometimes, when you know you’re focusing on an important problem, and that that problem is going to have important implications, you just have to keep going. I’ll just give an example from my lab. Back in 2001, two students of mine, Griffin Weber and Jay Shendure, developed a method to find new pathogens by DNA sequencing and comparing to the human genome. We worked on this method for 10 years and discovered nothing. But then, in that 10th year, another student, Alex Kostic, said, “Alright, I’d like to look at colon cancer.” I said, “You know, you’ll never find infectious agents in colon cancer. The colon’s filled with bacteria.” He responded, “Well, this is kind of suspension of disbelief and exactly why there could be a bacterium associated with cancer.” He found one. This is a great example of being persistent and the suspension of disbelief. But another big piece of innovation is just being open to new ideas. As you’re trying to solve a problem, you need to just keep trying, thinking, and looking for new ways, because there is going to be a path; it just might not be where you first envisioned.

NOSTA: I was talking with someone earlier today about measuring blood pressure, which can be done either via an in-dwelling catheter or by occluding/squeezing the artery. But now there are new methodologies looking at things like standing wave effects (e.g., Scanadu). We are also looking at red blood cell (RBC) deformation to determine its impact on blood pressure. Some of these new ways of looking at old things are interesting, because it’s not half-empty or half-full perception, but a whole new perspective, and that is essential [for innovation].

MEGA: There are certain diseases we define in a way we feel comfortable. But if you think about really diving much deeper with the tools that are there, we would be redefining. For example, think about anemia in general. If we treated everyone with B-12, we would be treating a very small fraction of anemia patients. [To better treat anemia] it took the understanding of subsetting. There are many other similar examples (e.g., diabetes). For example, I’m fairly convinced that there are many subsets of diabetes. But to really understand these subtypes, we need new tools that will allow people to think about ways to intervene in a much more precise manner. New innovative technologies are providing new insights, and, as a result, we are now on the cusp of being able to say, “Let’s be open to thinking about what we call a certain disease state.”

Moving on, I asked another question:

Beyond Persistence And Suspension Of Disbelief, What Else Are You Doing At Your Organizations To Spark The Creative Process?

SPRINGHORN: At Venture Labs, beyond the suspension of disbelief, we ask those fundamental questions of “If only” and “What if?” If only I had this, I would do X, Y, and Z. What if I can cure diabetes? What if I could provide a single microbiota through oral delivery and basically cure cancer? What if we could look at the microbiome of a plant seed and affect its traits in crops to help human sustainability? Asking those big “What if” questions and then suspending the disbelief that the technology is not there yet are necessary components to create a venture hypothesis. We think of the basics of these hypotheses, of asking the question of market potential, and whether or not the idea can be protected by creating intellectual property. From there you then work backwards to create technical feasibility. It might be that the technology is too early and may take a year or so to catch up. Instead of only working on the periphery of science and focusing only on the near term, being cutting edge requires asking big questions that look out to the horizon.

MALIK: At Bayer’s incubator, we started with the question, “What are the societal challenges we want to be involved with (e.g., feeding the world’s 9 billion or 10 billion people by the year 2050 and curing some of the big diseases)?” Then we went to the next level of iteration, such as a shortage of arable land in the world that is going to be reduced by 17 percent in the next 10 or 15 years, and we have more people. How can we end up with more efficient crop production? How can we have a world where we don’t use pesticides, but perhaps use other things? How can we look at some of the monogenic disorders, and what if we could cure those? That led to the next level of iteration, gene editing, which is where we developed the deal with CRISPR Therapeutics. So we started with the societal challenges, then asked the “What if” questions, accepting that there was an enormous amount of risk attached. But then everyone began to worry about failure. This is why we set up a small Skunk Works outside of Bayer. There we want to remove that fear of failure so they can think about big things, while the rest of us can focus on the day-to-day sustainability of the company. That’s the way we are trying to go beyond the cutting edge at Bayer.

MEGA: As a scientist and clinician, I often think about some early work we did (e.g., looking at genetic variance and trying to predict responses to certain drugs). We were driving in a certain direction because we had some early data. But along the journey, we were always aware that we may see something different. By being open and aware, we were actually able to steer in a direction that was spot-on. An important lesson to learn for any research team or group is that in order to put the puzzle pieces together so they make sense, you have to first lay the groundwork to make that next thing possible. If we are doing something that’s important, rooted in patients and a problem that matters, then we need to put our best resources forward. We need to be creative and realize that along the way there will be insights. So let’s create an environment that is conducive to that while trying to do the right thing. If you are in a research environment, and you are always willing to shut things off after three months or a year in, you will probably never learn anything. In addition, you need to be prepared for ideas to come from different places. I am continually impressed when someone approaches a well-known area of science in an orthogonal way, asking questions as to why you are thinking about something in a certain way. At Verily, we are approaching life sciences from a totally different point of view. But in addition to having a different perspective, we are also creating those intersections where you can think about things differently and allowing that to happen in a safe environment.

NOSTA: The freedom to fail is an interesting construct. Ask any Olympic athlete, Michael Jordan, or Thomas Edison. Failure defined their careers. Now, in life sciences and medicine, it’s a little tricky because failure is often tantamount to bad clinical outcomes. Further, this notion of the collaborative experience defines life sciences in many ways. In the old days of pharma, it was about controlling the process and the trial (i.e., rigid, structured). But today we have the opportunity to bring in many voices, those who don’t know what they don’t know, engineers, biologists, and even the collective intelligence of our patient and caregiver populations. I would argue that in many instances, the patient base is smarter than the clinician. Parents with kids who have severe diseases understand the disease and the trials and have a much better understanding of the nuances of their child’s condition better than any clinician. We live in a “collaboratory.”

MALIK: When I joined the industry with Bristol-Myers Squibb, I was working on Plavix (clopidogrel bisulfate), and virtually all the research we did was within Bristol. When I joined Bayer in 1995, we did the same thing. Today, however, we are working with much broader groups. Xarelto (rivaroxaban), our flagship product, was developed by Jessica Mega when she was at Harvard. The world is different now, and, as a result, we partner so much more.

NOSTA: Speaking of Xarelto, one of the investigators on that product was C. Michael Gibson, who actually has over 200,000 Twitter followers. Just think of the possible engagement. Whether you like it, it makes you nervous, or it makes you think he is a bad guy, that whole array of connectivity today is just downright freaky.

MALIK: It’s hard to explain how different it is now, working in a big company, from what it was 20 years ago. We just collaborate so much more, and the collaborations are different. When I was first at Bristol, you would go to an academic center, and, in a slightly embarrassed way, you’d give them a lot of money. No one really agreed on any outcomes or what they expected to see, and then everyone was disappointed afterward. Now it’s a lot more focused partnership that takes place face-to-face with what’s in it for you, and what’s in it for us. The collaboration component is one of the big things that is fundamentally different.

MEYERSON: I want to take off on this. We’ve had this collaboration between the Broad Institute of MIT and Harvard and Bayer for a while now, but I want to go back to how it started. Bayer was looking for academic partners. At the time, I had been thinking about how we had all these genomic discoveries, and I really wanted to be able to turn them into drugs that would reach patients. Then, just a real chance thing happened. I had given a lecture at the American Association for Cancer Research meeting in Delhi, India. Afterward, Chandra Ramanathan from Bayer came up to me and said, “You know, we at Bayer are interested in this field, and we’d like to talk about it. What can we do together?” It was a really different process. Bayer and the Broad Institute collectively came up with a vision of how we thought we could work together to advance cancer medicine. Similarly, our projects and ideas have evolved together. Our teams work together, both intellectually and scientifically. There may be chemists at the Broad Institute and chemists at Bayer who work together on a project, and it is a synergistic exchange of information, ideas, data, and material. What makes this collaboration so great is that we have very different styles and ways of thinking, which we maintain, yet we are able to bring them together.

MEGA: Can I follow up with that? One thing you said is to know your unique strength. What is the strength that you bring that no one else here wants to or can bring? The other is, how do you offer that while also coming up with creative models to be able to work together? I think you [Kemal Malik] were highlighting this idea that we’ll sit over here and we’ll put something in the middle [of the table] and see what happens. The new model is sitting side by side with collaborative partners. The piece that takes this [new model] to the next level is pressing leading technology companies to get involved in healthcare, because not doing so is doing a disservice to healthcare. The more we engage and say, “What could be more important than healthcare and improving people’s lives?” the better we will be able to accelerate things in our accelerators.

What Happens When Companies Fail To Deliver As Promised?

At this point, an audience member directs a question to Jessica Mega about a recent article that focuses on Google’s biotech venture (i.e., Verily Life Sciences) not delivering on three signature projects announced by its CEO Andrew Conrad. The questioner basically asked when nontraditional life sciences companies don’t deliver on goals and timelines of bold initiatives (e.g., the creation of a futuristic device similar to Star Trek’s iconic “Tricorder”), doesn’t that fail to honor and respect the human biology and drug development process?

MEGA: We may all want to comment on this. To create innovative environments where these “What if” moments can take place requires inspiration, courage, and dynamic leadership. When you marry that innovative space with people who have been engineers for over a decade with scientists who understand the scientific process and put that all in a collaborative environment, that’s the place where you start to make a difference. How do we create these dynamic, interesting environments and bring it together with the science itself?

SPRINGHORN: I often think about how failure is visible in the industry. In the pharma space, they have to announce clinical trial failures when a drug doesn’t work or fails to get approved. That is really all the failure we hear about. There is a large amount of stuff happening daily at the bench that never sees the light of day. Personally, I applaud an executive who is willing to make a claim and state what they think is going to happen. Because, except when you absolutely have to, biopharmaceutical companies really don’t show that much failure. Yet it exists and is part of the process. Failure is how we ultimately get better at what we do. I don’t see that as a downside at all. At Flagship, we have created an environment that uses failure in an evolutionary sense. We have a process based on the evolution of science — essentially asking those big “What if” questions from the very beginning. We start out by doing paper research in a phase we call “explorations.” That is where we try to find the bias that exists between what people and the literature believe to be true and what may actually be true. We go out to the ecosystem and talk to a lot of experts. They won’t tell us if our ideas are good, but they’ll tell us what is wrong with them, which is fine and part of the learning process.

Then, we do something that’s very interesting, something that you usually see done with products, and that is we prototype the company. We call this phase “protoco,” which is short for prototype company. We don’t name the company, but assign it a title that begins with VL, for Venture Labs, and then a number. The whole purpose of the protoco phase is to ask the killer questions. This is the difference between the solo entrepreneur sitting in their garage every day, loving and caressing a single idea. The reality is they won’t ask the hard question, because if it happens to be an answer they’re not looking for, they’ll be unemployed. At Flagship, we have money, great corporate partners, and smart people. But what we don’t have is time. We look to have well-tested companies coming out of the protoco process. For those companies that survive this phase, we will fund them as a NewCo. Many people have heard of Moderna Therapeutics, a Flagship Venture company that last year was voted to be the number one Disruptor company according to CNBC’s 2015 Disruptor 50 list, over many other startups including Airbnb and Uber. But that company started this process with an idea back in 2011 or perhaps even earlier, and it began with the fundamental question: Why can’t you actually deliver messenger RNA as a therapeutic? At that time is was a big “What if” question. Here is an example of the bias between what was thought to be true and what is actually true. For decades, people believed that because of RNA viruses, the human immune system had evolved to a point where it was finely tuned at eliminating RNA-based products and viruses. So we looked to the literature, and it is chock-full of what RNA will and won’t do. What RNAi has taught us is that you can actually change nucleotides in such a way to enable the immune system to not eliminate RNA-based structures. Nobody ever thought about actually trying to deliver a modulator in a way to give a positive effect. We asked those “What if” questions and prototyped the company within Flagship. Eventually, the company came out of stealth mode, but nobody knew about the iterative process that went into developing Moderna.

NOSTA: I’m still a fan of Google’s Tricorder, and I’m just going to put a stake in the ground here and say so. The interesting thing about this whole Tricorder concept is that it carries with it psychopathology that is so intrinsic to our being. Nobody knows what a five-tesla magnet is, and no one can relate to it. But when I grew up, there was this thing called the Tricorder that I watched on Star Trek. That reality is magical. I think that some of those problems are linked to the language, because I think nanoparticle-mediated disease detection, nanoparticle early detection of an MI [myocardial infarction] that Eric Topol is doing at Scripps, is a viable concept, but those will be largely empowered by a little thing that measures it.

A question was posed to Matthew Meyerson.

When You Have Students Working In The Labs And Failing, How Do You Allow Them To Fail Enough To Learn, But Not So Much That They Give Up?

MEYERSON: I’ve actually been thinking about the question of failure a lot. One of the most important things for people is to succeed. This is important on a level of being just one person or teams, as well as on a company level. One of the things I work hard on with students is to make sure they have a project where they are going to succeed. I always have an expectation that they will succeed on at least one project. Sometimes students might have a little portfolio of projects (i.e., low-, medium-, and high-risk). Some people are good enough that they can always succeed on high-risk projects. But for the average student or postdoc in training, they need that experience of success. Sometimes they can build a small success into a big success. For example, one of my postdocs recently published a paper on a genomic target we identified with RNAi. It was pretty simple and straightforward. Then he’s taken that same approach, and he’s just found something really audacious and surprising that builds on his early success. I think the ability to try something big has to be built on a foundation of success.

NOSTA: I think that is a key insight. What I tell my clients when they build their accelerators is [to be like a baseball hitter and] get on base, because senior management is going to pressure you. If you have failure after failure after failure, you can’t hide behind it. It’s not a home run. It’s not a grand slam. Get on base, because doing so gives you that sense of confidence and provides a sense of trajectory that can help you get to a spot further out.

MALIK: Large organizations earn the right to ask the “What if” questions. If you have a track record of success in terms of doing the more routine things, you’re then allowed to push the boundaries. The organization allows you to do some of the “What ifs” with 5 to 10 percent of the total R&D budget, to allow those questions to be asked. If you’re an R&D organization that’s consistently failed on the challenges, of course you have to report that every year during your R&D days or your investor conferences. If you’re constantly failing, you don’t earn the right to ask the “What ifs.”

MEGA: I think that’s why this concept of having a portfolio, whether it be an individual, an early-stage investor, or investigator is so important. As you are thinking about them having a portfolio, you need to also be thinking, what are some things in which we think there’s a reasonable level of success? Even if it’s iterative, that can still be something that is meaningful. Then, over time, you create. Whether for an individual, lab, company, or partnerships, thinking about things via a portfolio approach and having reasonableness on what success looks like is very productive.

MALIK: That’s exactly what we have at Bayer. We describe it as a “portfolio of innovation,” and 90 percent of this portfolio is of the iterative and sustainable variety. But that 10 percent — don’t fight without that, because, suddenly, something amazing might happen. At Bayer it is actually only 5 percent of our budget, which is still quite a lot of money (e.g., several hundred million dollars). But because the other 90 percent keeps the wheels turning, it also allows us to take a little bit of money and ask those “What if” questions.

NOSTA: Success is not like a single end point. There has to be a sense of capacity around success, because they have both financial and intellectual components. The other thing I really like about Google is it is always 10x 10x 10x. It’s not incrementalism. What’s that order of magnitude? What’s that big idea that’s going to put a one and a zero at the front of it? That’s another benchmark that is elusive and tricky, but in a lot of ways I cling to that.

MEGA: It’s hard, but having the freedom to think big is a real gift. There may be places where you stumble along the way, but as long as you’re open to new ideas and learning, working with amazing partners and people who really care, you can make a big difference.

Another question was posed from the floor.

How Do You Create A Situation Where You Have Innovation, But At The Same Time Move Forward Into Developing Products Or Technologies That Can Be Commercialized?

MEYERSON: I think it’s a little bit of having a range of projects. We have projects that are very early in the exploratory phase, where we’re trying to say, “Here’s a gene. We don’t know what this gene does or how it functions.” We started work many years ago – there’s a disease called multiple endocrine neoplasia type 1. It’s where patients get all kinds of tumors of the hormone-secreting system. We started trying to understand how this disease happens. How does it work, and what does the protein interact with? Over time, we found it interacts with a histone methyltransferase, which is important in leukemia. There was just a talk at Dana-Farber by an investigator who’s actually trying to make a drug based on disrupting this protein interface. Here’s something where you start with a really fundamental question, and it evolves over time. There are other examples. We did a chemical screen recently. We found a compound that looks like it could move very quickly into being a drug, and so we’re trying to work with our partners at Bayer to see whether we’ll be able to bring it forward and take the next step. Different people seem to get excited by different pieces of the process. A lot of moving a project forward has to do with not only having had some sort of success, but working in an area that excites you.

SPRINGHORN: I would say an area ripe for innovation is streamlining the process of getting work out of academic labs and into development and commercialization. The technology licensing offices that exist in institutions around the world know about only a fraction of the work that is actually occurring in those labs. This is particularly true because it is hard to have an up-to-date, comprehensive database of all academic research. If there was a way to have real-time, live data to know exactly what’s happening in an investigator’s lab for both the pharma and academic sides, that would be highly innovative and beneficial for creating new companies.

Another question was fielded from the floor, and the audience member shared how academic researchers have confided in him how much they enjoy the unique opportunity to share what they are thinking with the business side of the industry. Further, he attested to researchers on the business side of the equation expressing similar positive feelings related to communicating with academic counterparts. The question was then refined to:

Do You Think There Is A Way To Stimulate More Frequent And Open Dialogue Between Academic And Industry Scientists?

NOSTA: I’ll give you two letters: IP (i.e., intellectual property). You always struggle with IP. But I think the nature of privacy, open sourcing, from a variety of industries, is changing the IP dynamic a little bit. I go back to that notion of the “collaboratory” as a place where some venture people can engage. We live in an era that some people refer to as the democratization of health, and the stakeholders are fundamentally changing. Patients are more active. Folks in garages are making things that are cutting edge and breakthrough. So I think the open communication forum that you are seeking is going to come, albeit with a little bit of dragging, yelling, and screaming.

MALIK: I would be interested in what Jeremy Springhorn thinks.

SPRINGHORN: Most of the IP that forms the basis of Venture Labs companies is actually generated internally. A little-known fact is that the partnership within Flagship has over 180 issued U.S. patents. We create our own IP. In some ways you can think of us as more like an R&D organization than a venture capital firm. Academics, from Boston as well as from all around the world, come to Flagship with some great, innovative ideas. In many cases they come with only an idea or bit of science and without a management team or a business plan. But if it is a really disruptive and very fascinating technology, and if it’s the kind that makes you sit up and take pause, that’s the stuff that we’re really interested in. In those cases we will license the IP and create the company. As such we can operate both as scientific founders and business founders, and then sometimes we are just business founders.

NOSTA: I wonder if intellectual property is something that should be protected or something that should be exposed. This is because there are so many good ideas in academia that are sitting on posters on doors of classrooms. You can expose IP and still maintain that sense of ownership. But I think a more collaborative experience where people are talking about their ideas in a broader form might be a fundamental game changer.

SPRINGHORN: It’s funny you say that, because I hearken back to my early days at Alexion and business development. It was one of the greatest frustrations. Today rare disease is a hot topic that everybody seems to like. But back when Alexion was just starting out in rare diseases, it was frustrating to talk to technology licensing offices, because there was so much interesting research that would never end up getting to be the subject of a patent or anything Alexion could license. This is because most tech licensing offices were more interested in patenting research they thought would address big markets. Nobody had heard of some of the ultra-rare diseases in which some people were working, and, as a result, there were a lot of inventions that never became good intellectual property. Today, it’s a little different. But I’m sure there is research occurring that doesn’t ever get patent coverage due to funding constraints within the tech licensing offices.

How Do You Create Dynamic Environments That Spark Radical Thinking?

MEGA: The way we typically think about it is creating environments where you can think about problems in a different way. We create teams of people, some of whom are deeply steeped in traditional science or medicine, but perhaps bring a whole new element to this space. If you can create that environment and be comfortable with the nature that some things are going to work and some things aren’t, well, that is the first step. For companies like Verily, we think about information and organizing it in a way that says, “This is going to be a simple idea of we either know something or are going to do something to make a difference.” In order to make that difference, people can live on both sides. Some people can provide the knowledge with deep, new insights, which then need to be combined with people who are really interested in that area of creating new interventions. If you think about it from the “know and do” construct and how we’re going to make a change, those companies that will be successful will provide, combine, and organize those insights in a certain way, then partner appropriately. Those will be the ones to lead the way in developing new and exciting types of therapies.

NOSTA: There’s EQ (emotional quotient) and IQ, and I’ll take IQ any day. Smart is the common denominator. Show me that electrical engineer who’s just a whiz, and apply that to genomic analysis. Get them in a room, and I think sparks fly. In a traditional model, if you don’t have five years of bench science, CRISPR, or genomic experience, then we’re not going to let you on the team. The common denominator of brilliance applied in a synergistic environment is part of the magic.

MALIK: One of the reasons Bayer has survived 150 years is, somewhere along the way, our forefathers thought innovation was a pretty important component for our company. As you are successful, a lot of people think innovation is something that happens in R&D, and that we don’t have to worry about it. We want all senior managers to realize that innovation is not only important for our company, but as a life sciences company, it is the bedrock of what we do. To that end, we systematically took the top 400 people across all disciplines (e.g., finance, R&D, marketing, commercial manufacturing) through a three-day workshop on innovation. We wanted senior leaders to think about innovation, why it’s important for the company, how can we be more innovative, and how we create a culture that doesn’t fear failure and is more entrepreneurial and more risk-taking.

NOSTA: A lot of clients I work with have three-day innovation summits. Basically, what they’re doing is telling you to draw outside the lines, but they’re making the lines via this three-day summit. There’s a duality that has always bothered me. Innovation may come out of peak experience or maybe out of cognitive realities that are bigger than a methodological reality.

MALIK: I don’t like the three-day methodology. What I actually like is the cathartic process of getting different people from different disciplines in the same room. This then goes down to a country level. Bayer obviously operates in 100 countries around the world. But suddenly, at a country level, multifunctional people were coming together, and a finance person was looking at this and saying, “Why didn’t you try doing it like that? That’s the standard financial tool we use.” You get smart people, such as someone from manufacturing sharing an approach they take to a problem, or you have a chemical engineer looking at a challenge in R&D and saying, “Maybe you should try this approach.” It’s that cross-functional nature that is the real benefit.

NOSTA: Finding that proverbial light bulb, that “aha moment,” is no less tangible. We live in the world of P values (calculated probability), but I think that sometimes the magic really is the magic, and I like that. I think maybe there are some lessons learned there, too.

MEGA: I’d be open to be that.

NOSTA: Being open to feel.

MEGA: But I think that’s hard to do, as you say, in a three-day period.

MALIK: It has to be more constant. I mean, what I don’t like is that we will do our normal work, then we’ll be innovative for three days, and then we’ll go back and do normal work. What we are trying to create is a cultural shift where the entire organization moves together.

NOSTA: Introspection, contemplation, Eastern mysticism — I think, once you open that Pandora’s box of cognition, there’s a lot of very interesting things, yet we often say, “Well, that’s not science.”

What Are Your Parting Pearls Of Wisdom?

As we concluded the BIO super session panel discussion, I asked each of the panelists to share a parting pearl of wisdom.

MEYERSON: We’ve been talking about novelty, openness, and collaboration. But another foundation for innovation is quality, which requires technical expertise, scientific rigor, and being able to tell true from false. Bayer, Amgen, and a couple other major pharma companies have done really famous studies of academic scientific research. Approximately speaking, the result of this research has been that 10 percent of academic science is reproducible, while 90 percent isn’t. The knowledge that 10 percent is reproducible, and that we even know which 10 percent, is a remarkable testament to the scientific process. In other fields of human endeavor, maybe 1 percent is true. However, there we don’t even know what the 1 percent that is reproducible is, and you just have to kind of sift through it. The ability to become reproducible and doing that thoroughly, that’s an underpinning for innovation. We should never lose sight of that.

MALIK: The purpose of the session was to talk about beyond the cutting edge. I’m going to steal something that was said earlier, because I think it is really important, which is however big or small your organization is, be willing to ask that “What if” question and to think “If only.” Then, be consequential and say, “How are we going to address the ‘What if?’” We can address it in either a big or small way, but we can’t just ignore the “What if.” Think about what it could mean to your organization, and, more importantly, what it could mean for patients.

NOSTA: We are so lucky to be alive today. When I look around and see the nature of innovation, it is profound. Nothing really happened in the year 1900, though some would argue that’s not true. Similarly, if you look at the year 2000, nothing happened then, either. Y2K was the thing that didn’t happen. I would argue that things started to happen in the years 1915 and 1916 (e.g., the airplane, World War I, the Russian Revolution, special theory of relativity, the discovery of the mass of the electron). I believe the 21st century is beginning today, and we are at a true inflection point in human history where we will see massive changes that will result in a “hockey stick”-shaped growth curve. The next 100 years promise to bring what Ray Kurzweil says will be 20,000 years of technological advancement. A girl born today has a one-in-three chance of living to 100. We are at an inflection point in human history, and that should be celebrated in the context of research and innovation.

MEGA: I feel lucky. Three things that I’ve seen at the conference and that I hear today: one is that, if you put patients and people first and you work on problems that matter, your heart is in the right place. The second thing is create bold environments where we can try to make the biggest difference for the people we care about, including ourselves. The third thing is to test, iterate, accept when things do and don’t work, and keep your eyes open, because sometimes the thing that will surprise you the most ultimately will have the biggest impact.

SPRINGHORN: Ask big questions and, in doing that, don’t be afraid to fail, because failure is a part of the process. There are a lot of innovative things that happen in plain sight. Innovation is not a massive, complex process that has to be created. There are remarkable things that we can learn every day. The microbiome — people have known that there were bugs in the gut for a hundred years or longer. But nobody knew of that functionality how it might impact a person’s overall health. There are things in plain sight that just require a little bit of knowledge and a little bit of creative thinking, and we will see huge advances that result in exponential growth.