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Insights from Prof Robert Langer, the Most Cited Engineer in History

Professor Robert Langer, Institute Professor at the Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA

Interviewed by Rachel Donnison  Editorial Assistant, EMG-Health

Q: You studied chemical engineering before pursuing a career in biotechnology and healthcare. What spurred this change in direction, and are there any lessons that you’ve been able to translate from chemical engineering into this new field?

A: Chemical engineering was a great background to have come from. It really teaches you how to think about problems and how to solve them which I think is one of the spirits of engineering: problem solving. But when I was looking at the thesis that I was doing as a graduate student at MIT, and just in general at what chemical engineers were doing, I wasn’t that excited about it. I was looking for something that I thought could affect human life and human health in a way. I ended up working in a hospital and that really changed my life. I saw all kinds of big problems, but engineers had never really addressed a lot of these before, like creating new materials, drug delivery systems, and tissues. So for me it was a little bit like being a kid in a candy store. I saw all these problems and I had a very different perspective on them because I was an engineer. I could give you an example or two if it would be helpful, but really it was just eye opening to see all these problems and realise that I had a different point of view on how to potentially address them.

 

Q: Turning to your research interests at the moment, large molecule-controlled drug delivery seems to be a major focus. Could you explain what it is all about, why you’re so passionate about it, and what use you think it can have?

A: Well, let me start by going back many, many years: 1974. We’ve been working at this a long time. We published a paper in Nature in 1976 looking to address an initial problem presented to me by my advisor Judah Folkman. Judah Folkman had this idea that certain large molecules could stop blood vessels from growing. I didn’t know anything about biology, but it was a very controversial idea. I was given the task of developing a way to study this and to isolate and test these molecules. I was isolating these different large molecules that I thought may stop blood vessels from growing but all those assays took several months, and so I had to have a way to deliver them in an unaltered form and protect them from harm: this is what got me started. We kept on doing more and more work in this area and we continue it today, leading to various systems that are being used for treating different diseases. We’ve been working on different nanoparticles probably for the last 46 years.

For winning the Queen Elizabeth Prize for Engineering, one of the things that was pointed out was that I founded or started a number of companies. One of those companies that I started, or helped start, was a company called Moderna Therapeutics. Moderna Therapeutics has been in the news a lot lately because they have the first vaccine that’s in clinical trials for SARS-CoV-2. Others are starting to reach this stage too. Basically, the strategy involves delivering mRNA, which is also a large molecule, to the patient using nanoparticles. This is a huge example today that stems from the early work that we did many, many years ago.

So that’s why I’m passionate; I believe, whether it’s us or others, that these kinds of technologies will save and improve a lot of lives. This new era will be incredibly important: delivery of messenger RNA, delivery of short interfering RNA, delivery of gene editing tools. These are some of the drugs of the future, but because of what’s happening today with SARS-CoV-2, we are seeing more rapid implementation in the clinics.

 

Q: One of your interests include using tissue engineering as therapy. Could you tell us the current stage that the research of this technology is in and when we can expect to be seeing it used in the clinic?

A: Well, it’s already being used in the clinic for people that have burns or diabetic skin ulcers. You can make new skin this way and this has been approved by various regulatory authorities. It’s also being used in what are called ‘organs- and tissues-on-a-chip’, for reducing animal testing and human testing. But there’s a lot of different companies, some started by us and some by others, that have various tissue engineering approaches in clinical trials, a lot of them started by my students. For example, Humacyte, which is in North Carolina. They’re in very advanced stages for making new blood vessels. Frequency Therapeutics, which is in the Boston area, has new treatments for hearing loss. InVivo Therapeutics has a system in clinical trials for spinal cord repair. Some will end up working, some won’t, but I think that already there have been huge advances in that area that are being used.

 

Q: You’ve got over 1,300 issued and pending patents, so you are regarded as an inventor as well as an engineer. When you have a new idea for an innovation, what are the next steps that you take towards bringing that concept to life?

A: We do a lot of research work in our laboratory at MIT and that is usually aimed at writing papers, getting the initial patents, and maybe getting a proof of principle in animals. But what happens, of course, is if you’re going to really make a difference, in my opinion, you have to have manufacturing and clinical trials. Take Moderna for example: they employ 800 people and they have to spend a tremendous amount of money. I’ve been very involved in starting companies that can hopefully take these systems, and whatever we do in the lab, and try to bring it to patients. We start out with these early proof of principle studies, but then later on do a lot more in manufacturing and clinical trials, you need companies to help so my students and I have often helped start them. The students have often spent a long time working on some of these things at MIT and then they want to see them make a difference in the world. I’ve had students all over the world, including in England, and they’ve been very active in developing new technologies and that’s been wonderful.

 

Q: Given that over 200 of your former students now lead their own research labs and companies all around the world, what do you consider to be one of the most important lessons that you’ve taught your students to help them become world-class researchers?

A: I would say over 350 of my students and postdocs are professors: in England (such as Prof Molly Stevens, Imperial College London), and in America at MIT, over 350, maybe even 400, are professors and probably an equal number are CEOs or have started, or work in companies. We probably have something like 900 people come out of our lab already and maybe have another hundred still in the lab.

In a very broad way, I always think about it like this: when somebody’s young, and in high school or even college, the way they’re judged is by how good their answers are to somebody else’s questions. You take a test and you see how well you do. Somebody else asks the questions and you give the answers. But I think in life what’s really important is not only your ability to answer questions, but equally, if not more so, your ability to ask great questions. If you ask an unimportant question, why should it matter if you find the answer? What’s really important is to teach people how to think about asking really big questions, great big questions that can change the world. I guess my view of what I try to do as a professor is to help my students transition from being somebody who can give good answers to somebody who can ask good questions.

 

Q: You are the most cited engineer in history. What drives and motivates you to continue investigating and publishing new research?

A: What motivates me is really a couple things: 1) to ask questions that I feel can have a big impact on the world; 2) to put in the work to make those things happen, in other words not just writing the initial papers but making the next steps to move these things into the clinic in order to do real good for patients;  and 3) to work  with young people and help them in their careers to become great leaders. I look at some of the people that we’ve trained, whether it’s in England or other places, and I’m very, very proud of how they’ve done. It’s like they’re almost family.

 

Q: How often do you get to see the real-world impact that your research is having, given that you have improved and save the lives of probably more than 2 billion people worldwide?

A: Well, often enough. I mean, it’s all done indirectly: they may not know it was us who did it. But I’ve certainly gotten a lot of gratification from the different inventions we’ve created and the people who have used them to become happier or healthier.

 

Q: Of the 220 major awards that you’ve received – including the Queen Elizabeth Prize for Engineering, which is the most influential prize for engineering in the world – which prize has meant the most to you or has subsequently led to the most success in your research group?

A: Well, I actually think that the Queen Elizabeth Prize for Engineering was probably the one that’s meant the most to me. There’s several that I’m very proud of: The Breakthrough Prize, with the U.S. National Medal of Science and U.S. National Medal of Technology and Innovation. But I thought it was terrific that the Queen spent a couple hours with my family and I, as well as others. Having been to the White House, they don’t spend nearly that amount of time, so I thought that was terrific.

In terms of affecting my research, it’s hard to say. I think that when somebody gets an award, it shines a light on their students and on the field that they’re in. I think that the QEPrize did this, as well as other prizes. It was very, very special to get that prize: both the honour, but also the opportunity to go to Buckingham Palace and meet the Queen. I will never forget it, and I’m sure my family will never forget it either.