Lab Meeting: Robert Langer
“Don’t do something incremental, do something you think will really have a big impact.”
In a room full of politicians, Nobel laureates, supreme court justices, actors and artists, Dr. Robert Langer stood out from the crowd.
I first encountered Bob at the 2017 Academy of Achievement summit, which brings together established scientific, political, and artistic leaders with "exceptional” young people for a weekend of lectures, dinners, and discussions. An exceptionally average medical student myself, I was happy to have wrangled an invitation, and for the chance to meet some of my scientific heroes.
Though I am not an engineer by training, I knew the legend of Langer—his storied 1976 Nature paper as a post-doc with Judah Folkman demonstrating sustained release of large biomolecules from small particles, his rise through the ranks of MIT faculty, dual election to the National Academy of Engineering and National Academy of Sciences in 1992, and current appointment as one of twelve Institute Professors at MIT. Along the way he has coauthored over 1400 papers and won the Lemelson prize in 1998 for being “one of history’s most prolific inventors in medicine.” He has co-founded dozens of biotech companies, including Moderna. In his current capacity as the David H. Koch Professor at MIT, he runs the largest biomedical engineering lab in the world, employing around 100 researchers.
On the podium, delivering his lecture at the Academy of Achievement, it was not only his accomplishments that made Bob Langer stand out. He has an amazing ability to simplify complex ideas, and clearly convey the importance of his work and how it directly impacts human life. Everyone in the audience came away feeling energized and hopeful for the future after hearing Langer speak. In the interview below, Dr. Langer wishes he had played more chess: “when I was really little, I was pretty good…I’d be terrible today,” he says with a smile. I’d argue that Dr. Langer is a chess player by nature, thinking several steps ahead and forecasting how an engineering advance today can enable a medical breakthrough tomorrow.
Sitting in the audience, squeezed into my suit and tie—with the fewest achievements at this “Academy of Achievement”—I hoped to run into Bob again and hear more from him about his life, career and thoughts on science. Almost 5 years to the date, we sat down virtually to do just that.
Below are selected answers from an interview with Robert Langer in July 2022:
1. Name an overlooked scientist, whom you feel strongly that every grad student (or med student) should know well enough, to be able to describe their major findings. What were the killer experiments?
There are three that come to mind. One is an engineer named Philo Farnsworth. He actually invented television when he was in high school. It is often overlooked. There is a great book named The Last Lone Inventor [by Evan Schwartz]. TV is obviously an important invention, which goes without saying. He is certainly overlooked.
The second one I put down is Chuck Hull. He invented 3D printing and built the first 3D printing machine. It is amazing to me that he hasn’t won any huge awards, as far as I know.
The last one I put down is Ram Sasisekharan. People won Nobel prizes for sequencing major classes of biomolecules. The people who sequenced proteins and DNA won Nobel prizes. Ram was actually the first to sequence polysaccharides, which is the third class. This seems to have gone overlooked. Nonetheless I started a company with him called Momenta which got bought by Johnson and Johnson for 6.5 billion dollars, which is not too bad. The sequencing of polysaccharides was a paper they published in Science in 1999. That always seemed to me like a really important area.
I think a lot of things do get published and do get credit. But these three if you ask most scientists, engineers or people, they wouldn’t know. The first two discoveries are of course very widely used, and the third not only opened the door to sequencing all complex polysaccharides but saved many lives by solving a major worldwide heparin contamination crisis in 2008.
2. What are you reading in your free time?
Right now, I am a slow reader because I am working on so many things. But I am reading the Everything Store [by Brad Stone] about Amazon. Never is another one, by Ken Follet, I like reading that stuff, you know fiction. The third one is Code Breaker [by Walter Isaacson] on Jennifer Doudna, and the fourth one is Queen’s Gambit [by Walter Tevis].
When I was really little like 6 or 7, I played chess and I was pretty good, but after that I didn’t play very much and I’d be terrible today. But I did like it when I was little and wish I had played more. I thought they did a fantastic job with the Netflix TV show [Queen’s Gambit], and it followed the book very closely.
3. What was your first taste of science? Briefly, what about this initial experience drew you in? Who was your first great scientific mentor?
When I was young there were these sets called “Gilbert sets.” They made erector sets, chemistry sets and microscope sets so you could watch shrimp eggs hatch. And that was definitely my first taste of science.
4. What has been your scientific high point? — What do you consider to be the most exhilarating discovery or set of discoveries you have been involved in throughout your career?
I put two things down for this and they tie together a bit. One is when I was a post-doc back in the mid 70s and I was trying to develop systems that could deliver large molecules from tiny particles. People told me that this was impossible because of two things. One, is that you were using organic solvents to do this encapsulation, and two that if you put large molecules inside these tiny particles, they would be too big to get out. I failed hundreds of times. I tried this over and over again, with all different designs and materials and I kept failing. But I developed these little microscope slides. I would have a gel on the slide and make a hole where I could put particles, and then add things to the gels that indicated whether molecules were coming out of the particle. When released, the gel would change colors. Finally, after hundreds of times I did see a change, we could release large molecules for a hundred days, which was certainly very exciting to me. In the Nature paper we wrote in 1976 it not only showed people were wrong about what they thought, but also turns out to be the first time that nucleic acids were delivered from tiny particles.
This leads me to the second thing. If I go 45 years later, one of the companies I helped start was Moderna. One of the things we used at Moderna were tiny particles that could deliver RNA. When we started Moderna it was criticized by supposed experts and scientists and analysts saying it wouldn’t work. In May of 2020 the Boston Globe had a big front-page article saying ‘this is not how you do science’ with my picture on the front. But the moment I want to tell you about is 6 months after that when we had a board meeting for Moderna, and we broke the code [clinical trial blinding]. What was amazing was that out of the 15,000 (treated patients) not a single one went to the hospital. When they broke the news, everyone is in the board room was thrilled, it was an incredible moment.
I tie these two things together. The first is what I did and the other Moderna really deserves the credit, but it was still very amazing and exciting.
5. What set of research questions or projects has you most excited about coming into lab today?
Let me mention two. We are doing a lot of work funded by the Gates Foundation building on our earlier work to improve nutrition in the developing world. One is a system that you can inject into a patient and is a ‘self-boosting’ vaccine. You give one shot which is a cocktail of nanoparticles that we can program to break, so to speak, at different times: time zero, two months, one year. We’ve gotten up to eleven boosts. This has the potential to greatly improve compliance in the developing world, where repeated injections is an issue, or in our world too it can lead to higher antibody titers. We have also been developing ways of giving nutrition better. We have developed ways of taking Iron and Vitamin A which are not heat stable, and we can protect these nutrients to make them bioavailable to patients.
The second big area is tissue engineering, which is an area we helped start. We are working on trying to create organs and tissue on a chip. We are working with Li-Huei Tsai at MIT to make a brain on a chip, and Gio Traverso at MIT to make a GI tract on a chip. We are also making other tissues and organs in the body. All these things I hope can make a major impact on medical therapy and also someday minimize animal and human testing.
6. Who are a couple up-and-coming scientists (lab < 10yr old) in your area, or more broadly, whom you think we should watch? Why is their work so exciting to you?
I have three that are my former students. One is Shriya Srinivasan who is a post-doc with me and Gio Traverso, and has done amazing work. She is just about to start her lab soon. She is combining engineering approaches to help people walk, has made split ventilators and is making these inventions accessible to people in India. Another is Alex Abramson who was a graduate student with me, and then went to Stanford as a post-doc, and is now joining Georgia Tech. He came up with a pill you could swallow modeled after a leopard tortoise. The beauty of this is you have a little needle in it and you can swallow it and it will inject insulin, always into the wall of the GI tract due to its center of mass. We published papers in Science and Nature on this, and now Novo Nordisk is doing human testing. Another great scientist is Ritu Raman. She was a postdoc with me, and she came up with different ways of combining mechanical engineering in medicine. She is now an Assistant professor at MIT.
7. What is one piece of advice for a young scientist aspiring to have a career in academia, and make some important discoveries?
The biggest one is to dream big dreams. So many times, when you try to do something really important in science or invent something a lot of people will tell you that it is impossible, that it will never work. But I think that is very rarely true, if you keep trying and sticking to things there is very little that is truly impossible.
Another thing is to not do something incremental, do something you think will really have a big impact. A fourth thing is if someone is doing something in academia, try to raise a substantial amount of money. That always helps.
8. Who was your biggest mentor, and what made them so great?
Judah Folkman absolutely was for me, and there were many things that made him so great. A lot of people criticized the work he did on angiogenesis, but he never gave up. He was a great role model for me to see.
9. How do you balance running a busy lab with being an entrepreneur and starting companies? What advice would you give to young scientists interested in entrepreneurship?
If you are in academics, I would always put the academics first. Try to get tenure before doing too much. But I also think entrepreneurship is wonderful because it can magnify the impact of your work. I found that if I didn’t start companies with my students, those technologies wouldn’t be used today. When I started in the 1970s I was naïve enough to think that if I wrote papers people would use them, but that didn’t happen outside of academic citations. If they [inventions] were really going to lead to therapies for patients, you have to have the companies.