5 Leadership Learnings In Preventative Cancer Vaccine Development
By Stephen Albert Johnston, Calviri
Since the invention of the smallpox vaccine in 1796, we’ve known that vaccine development is no simple endeavor. While it’s become much easier over the past 228 years, it can still sometimes feel like an insurmountable challenge. While mRNA vaccines for COVID-19 came onto the market quickly, saving countless lives in the process, these vaccines and other RNA-based vaccines have been widely criticized for their potentially serious side effects and short development periods. We’ve been living with the belief that drugs should take 10 to 20 years to develop for so long that we’ve become closed off to the potential for something better. And I know this story all too well. Calviri has been developing an RNA vaccine to prevent cancer for more than 20 years and repeatedly faced the nearly universal belief that it’s impossible. But we’ve learned a number of interesting and important lessons along the way.
1. Always Be Working At The “Edge”
Most new vaccines are being developed at the “edge,” and when you’re trying to accomplish something at the edge, there’s no shortage of people lined up to tell you the many reasons why you will fail. They may be right, but they may not. Any time you hear, “We always have done it this way,” the situation is ripe for a new approach. And that’s the importance of innovating. The COVID-19 vaccine is an mRNA-based vaccine that was called a miracle because of the sheer speed with which it was developed and came onto the market, but it’s a shame to call it that. Really, it was scientists operating at the edge, combining years of research and drug evolution to innovate a renaissance in vaccine science on a dime. And that’s going to be true no matter what type of new vaccine technology is being developed, whether it be for a superbug, or in Calviri’s case, a preventative pancancer vaccine.
2. Expect Opposition, Because It Will Come
If you’re doing something very important, you’re going to have opposition. Just like the line of naysayers who think you’ll fail, your opposers may actively seek to make this happen. Early in Calviri’s efforts to develop a preventative pancancer vaccine, we had the distinction of Nature writing an editorial saying we should stop our effort because “everyone knows you can’t make a preventative cancer vaccine.” My comments weren’t included in the article; they never even asked. And not one colleague asked me about it, either. They were probably too embarrassed for me. Opposition also can take the form of others ignoring your work completely. As frustrating as the opposition can be, it is also good. It forces you to repeatedly reassess your work and ensure that you’re on firm ground. And if you are, ignore the opposition and stick with the work.
3. Find (And Value) A Few Worthy Supporters… You’re Going To Need Them
Developing a new and innovative vaccine can be — and probably will be — a long and sometimes lonely road. But the truth is that you can’t go it alone. Finding and cultivating objective, intelligent, and connected supporters is an invaluable effort in the vaccine development journey. Depending on the broad — or very limited — acceptance of your goals, ideas, and research, it may take considerable time and effort to find these supporters, but I assure you that it is worth it. There will be challenging times along the journey, and the moral or potentially financial support from these patrons and friends can bridge the crisis and ensure that your project lives on another day. Finding these types of supporters — the ones who can help to fund your work or connect you with people who can — requires work on your part. It means going to conferences and sharing your work, putting on a suit and tie, talking to reporters about your work, asking your network for connections, and sometimes making cold calls.
It also cannot be said enough that collaborations with other researchers, where possible, can make all the difference. In the case of COVID-19, collaborations of scientists formed all around the world and contributed to quick maneuvers and that “miracle” vaccine. Importantly, those collaborations created new networks and bridges that may be used time and again in the development of future novel drugs. The internet has made it easier than ever to connect with other scientists and start meaningful collaborations.
4. When Approaching Problems, Take The “Bio” Out Of Biologics
We all hear scientists say that the systems they are studying are complicated, probably no more so than in cancer research. For decades, we’ve convinced ourselves that all cancers are personal, and so the treatments, too, must be personal and complicated. This complexity then demands genome sequencing for many tumors, more basic research, and the development of yet even more complex therapies. But to quote Ronald Reagan, a lot of things that seem complicated have simple solutions if you just stop and think about them. To put it another way, if you take the “bio” out of “biologic,” you’re left with logic. And logic is simple to apply.
Take Zika virus, for example. There is an mRNA vaccine in development right now for this disease. We already know and understand that the disease can have far-reaching consequences in all populations. But during the height of the spread of Zika, we — science as a whole — overcomplicated the situation, causing delays and, later, efficacy issues in clinical trials. By the time these issues were resolved, the spread of Zika had waned, taking with it the pressure to develop a vaccine that could have protected over 27,000 people this year so far.
5. Design Your Vaccine Trials Well
While sometimes, the failure of a drug trial is unavoidable, the reality is that most of the time drugs fail due to poor planning or a misunderstanding of the processes surrounding trials and drug development. Though most vaccine trials are based on well-established designs, these designs are not perfect. And, importantly, they are only a guide. It pays to imagine all of the possible outcomes of a trial, then create primary and secondary endpoints that incorporate unique possibilities, as many as possible. But even the basic planning is not enough to make a trial go well. It is also worth the time, effort, and expense to collect samples from trial participants, or vaccinees, before, during, and after the trial. Importantly, the number one missed opportunity I’ve run into is when simple-to-obtain samples aren’t collected before vaccination, leaving a significant gap in the data.
Conclusion
When you’re developing lifesaving and world-changing vaccines at the edge — where many scientists will not go — you’re going to face more than your fair share of challenges and opposition. But the more opposition you face, the more you will know you’re on the right track. With a well-designed study, a few good supporters in your corner, and the willingness to see opposition as a positive thing, there’s nothing that can stop you. As Calviri approaches a major milestone and breakthrough on the path to our “impossible” preventative pancancer vaccine, it’s more than obvious to our team that every challenge or lesson was more like a dare to make it happen.
About The Author:
Stephen Albert Johnston is the founder of Calviri and its central technologies. He is also director of the Arizona State University (ASU) Biodesign Institute’s Center for Innovations in Medicine and professor in the School of Life Sciences. Previously, he has been a founder of Eliance, Inc. (Macrogenics), Synbody Biotechnology, and HealthTell, Inc. Johnston has published almost 200 peer-reviewed papers and holds 45 patents. Prior to his appointment at ASU, he was professor and director of the Center for Biomedical Inventions at UT-Southwestern Medical Center and professor of biology and biomedical engineering at Duke University. He is a member of the National Academy of Inventors. He received his B.S. and Ph.D. degrees from the University of Wisconsin.