GEN Biotechnology

Volume 1, Number 6, 2022

ª Mary Ann Liebert, Inc.
DOI: 10.1089/genbio.2022.29063.rla

ASKED & ANSWERED

A Conversation with Biotech Pioneer Robert Langer

Robert Langer,1,2,* John Sterling,3 and Anjali A. Sarkar4

Dubbed the Edison of Medicine by Harvard Business Review, biotech pioneer Robert Langer shares his thoughts on his remark-
able career, influences, cofounding more than 40 companies including Moderna, and the future of drug delivery, mRNA vac-
cines, nanotechnology, and tissue engineering.

F
or the past 38 years, biotech pioneer Robert Langer, David H.
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Koch Institute professor of chemical engineering at MIT, and

cofounder of Moderna, has always been available and open
to questions from Genetic Engineering & Biotechnology News (GEN).
During his guest appearance on ‘‘The State of Biotech’’ virtual
summit organized by GEN last September, Langer took a stroll
down memory lane with John Sterling, GEN Editor-in-Chief and
Anjali A. Sarkar, Senior Science & Technology Editor at GEN (Fig. 1).
Langer revealed factors that led him to take up a career in sci-
ence (instead of selling ice cream) and recalled the individuals
who inspired and supported him along his journey. Replying
with characteristic candor, integrity, and humility, Langer,
whose impressive list of accomplishments include founding
more than 40 biotech companies and receiving the Queen Eliz-
abeth Prize, discusses the success of ‘‘Operation Warp Speed,’’
which helped fast-track Moderna’s COVID-19 vaccine in 2020,
current challenges in drug delivery, the future of nanotechnol-
ogy and mRNA therapeutics, as well as tips on attracting
funds for high-risk-high-return projects.
(This interview has been edited for length and clarity.)

How and when did you become interested in science?

Langer: When I was a little boy, we had Gilbert chemistry sets,

biology sets, microscope sets, and erector sets. I remember
my dad and mom got them for me as presents. With the micro-
scope set, you got to watch shrimp eggs hatch. I have always
loved magic. With the chemistry set, you could mix different
chemicals and get color changes. With the erector set, you
could build robots and rocket launchers. I suppose that was the
earliest, although I would not say that led me to a career in sci- Robert Langer, David H. Koch Institute
ence. I would go back and forth in grammar and high school Professor of Chemical Engineering at MIT.
about what I liked and did not like, but that experience certainly
got me fascinated with some of the things that science could do.
a visionary scientist. He had this idea that if you could stop blood
Who are the main researchers who influenced your career vessels, then maybe you could stop cancer. He was criticized for his
and life? ideas, his science, just like I have been criticized for mine. Yet he
always believed everything was possible and kept trying. Ulti-
The person that influenced my career and my life the most was mately, his work affected many people. He pioneered angiogene-
Judah Folkman. He was my postdoctoral advisor. He was terrific— sis inhibitors, which would lead to Avastin and many other drugs.

1
David H. Koch Institute for Integrative Cancer Research and 2Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; 3Editor in
Chief, Genetic Engineering & Biotechnology News; and 4Senior Science & Technology Editor, Genetic Engineering & Biotechnology News.

*Address correspondence to: Robert Langer, Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139 USA, E-mail: rlanger@mit.edu

479
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FIG. 1. State of Biotech. Bob Langer was interviewed by GEN editors John Sterling and Anjali Sarkar during the magazine’s virtual
event in September 2022. (Credit: GEN)
After working with Folkman for 3 years, I thought I had done
important things, but nobody else believed it. I published an ar-
ticle in Science1 on the first angiogenesis inhibitors and one in
Nature2 on the first ways you could ever design microparticles
or nanoparticles that could deliver macromolecules, which
includes RNA and DNA, that were widely criticized.
People said those were impossible. My first nine research
grants were turned down! I could not get a job as a faculty mem-
ber in chemical engineering. I ended up getting a job in the nu-
trition department, where a lot of the people did not want me to
stay. The senior faculty felt my drug delivery ideas were unim-
portant. But I had two very good friends who were about my
age—Mike Marletta and Alex Klibanov. We would have lunches
every Saturday, and we supported each other. Both Mike, who is
now at UC Berkeley, and Alex, who is emeritus at MIT, continue
to be two of my closest friends. They gave me great advice that
was very important to me.
Your team’s work has led to the development of tissues and
even entire organ systems in the culture dish. It is intriguing
to contemplate the limits of tissue engineering’s role in re-
generative medicine in conjunction with advances in tech-
nologies such as cryopreservation and gene therapies, in
extending human life. Do you think these advances can in-
crease longevity?
I do feel that they will increase longevity. Maybe they already are
doing it in some ways. If somebody today gets burned, they can
have artificial skin. That certainly will make their life a lot better.
Some of the things going on in tissue engineering clinical trials,
such as making new blood vessels, which Laura Niklason has
ASKED & ANSWERED
been doing at Humacyte; making new spinal cords, as InVivo
Therapeutics is doing; making new pancreas, which Vertex, Sigi-
lon, and Pancryos are doing; [treating] hearing loss, which Fre-
quency Therapeutics is doing—there are so many examples.
Then there is the whole area of drug testing because you can
make organs and tissues on a chip. That will also accelerate find-
ing new drugs that are safe and efficacious. There are others such
as EpiBone, which Nina Tandon, who is one of my students, is
doing. You could go on and on. There will be all kinds of ways
that will make people’s lives better and hopefully longer.
Are the current challenges in drug delivery primarily in tar-
geting, timing, bioavailability, or biodegradation, or a com-
bination of all of these?
A combination of all of them. Every single challenge you men-
tioned is important, and more. Targeting is important. Going
through barriers is important. Stability is important. There is
no limit to the number of things that we can do better to
make people have healthier happier lives.
What is new in time-controlled drug release technology?
A lot of things! It depends whether you look at things that are
already in advanced clinical trials or out on the market or new
things coming up. A clear example of where drug delivery has
made a difference is in nanoparticles. If you did not have nanopar-
ticles, you would not have the mRNA therapeutics or vaccines.
There are many others that are also important. For example,
Giovanni Traverso, professor at MIT, and I, working with the Bill &
Melinda Gates Foundation, came up with pills you could
 ASKED & ANSWERED
swallow that could last a week or even a month. Lyndra Thera-
peutics is developing them. It is exciting! They are now in ad-
vanced phase II trials for schizophrenia. They are doing a
once-a-month birth control capsule. They are doing a malaria
drug. A whole bunch of things. Something similar to that
could really revolutionize the way drugs are given because
you could give a drug for the entire course of treatment.
It is so important because not only do people keep forgetting
to take them (myself included) but often when you get peaks
even with once-a-day [drugs]. The peaks are much less when
you give it once a week or once a month. So, the side effects
are also much less. Traverso and I also came up with a way to
deliver large molecules such as insulin or RNA orally. Novo Nor-
disk just funded us, and they are in clinical trials. We published
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this in Science3 and Nature.4 They call it a robot pill!
Other examples are microneedle patches that we and others
are working on, targeting systems, which I think will extend be-
yond just the liver and that Alnylam and others are working on,
people are working on exosomes—a lot of very exciting things
are emerging in the clinic.
You have developed an invisible ink that can store people’s
medical histories and vaccination records under their skin.
What got you interested in this innovation and how is this
being implemented?
This came from funding from the Gates Foundation, which has
been very interested in a range of things that can help people—
new methods of nutrition, methods of single-injection vaccina-
tions, new birth control systems, because people do not come
back [for repeated treatments]. I should point out that this system
you mentioned is purely voluntary. The idea is like a tattoo they
give you at a football game or a concert. Of course, there you
can see the tattoo. This one you do not see until you shine a cer-
tain type of light. It will tell you everything that might be impor-
tant in case of a medical emergency. It may tell you when to
get your next shot, like what vaccine you have taken, when you
took it, what lot number, and so on.
What will be some of the key contributions of nanotechnol-
ogy to life sciences and medicine in the next decade?
If you look at the pipelines of companies such as Moderna
(Fig. 2), BioNtech, and others, you will see all kinds of vaccines
that will be put in nanoparticles. You generally have to use
nanoparticles to deliver something the size of mRNA or siRNA.
If you do not put them in a nanoparticle, they will get destroyed.
The nanoparticle protects them and allows the therapy. That will
also now be true for other RNA drugs. It could be true for other
large molecule drugs that they will be putting in microparticles
or nanoparticles. You will see more clinical trials, where drugs
are given that way. I could also see that having an effect on var-
ious gene editing or gene therapy approaches as well.
You have reportedly established or cofounded some 40 com-
panies. Is that number accurate, and are they all still around
either independently or as part of acquiring companies?
481
FIG. 2. Moderna headquarters in Cambridge,
Massachusetts. (Credit: Fletcher/Wiki, CC-BY)
Well, it is more than 40, right?! I do not know. Now it may be 43.
A lot depends how you count. Sometimes people license our
patents and I am not even involved in the companies. Other
times, I have come up with some stuff along with others. But
40 is a pretty good number. I would say more than 90% of
them are around in one way or another either as existing com-
panies or they have been acquired by larger or medium-sized
companies.
Perhaps the best-known company you have cofounded is
Moderna, whose mRNA vaccine for COVID-19 has full FDA
approval. How did you come to be a founding director of
that company and one of its largest shareholders?
It is really four of us: Derrick Rossi, Kenneth Chien, Noubar
Afeyan, and myself. Derrick was at Harvard along with Ken. Der-
rick came to see me one day, because Tim Springer, Ihad sug-
gested he visit me. He was interested in starting a company. He
showed me different possible models. I was very impressed
with the science and then we talked to Noubar [Flagship Pioneer-
ing], who was excited about it. I should point out that other inves-
tors had seen this before and did not think very much of it, but
both Noubar and I thought that this could be a game changer.
Then we talked to Ken Chien, who is a well-known cardiologist,
and he would also get involved. So, the four of us started it.
The biggest financier was Flagship, in the beginning.
People wanted me to be a director. I end up being a director
of quite a few companies. I am not sure I necessarily always want
to be director, but if I can help, I want to do that. So I did! It has
been an honor and pleasure to be associated with Moderna.
Some people have said we have invested [financially]. I do not
think any of us invested more than 50 cents. It was more our sweat
equity that got us the shares. Flagship did put in funding. They
have been terrific and Noubar has been an outstanding director,
but we were fortunate that we found a great CEO, Stéphane Ban-
cel, and a great president Stephen Hoge, and an outstanding team.
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Co-founders of Moderna. (Top) Derrick Rossi (Harvard Medical
School), (middle) Kenneth Chien (Karolinska Institute, Sweden), and
(bottom) Noubar Afeyan (Flagship Pioneering).
ASKED & ANSWERED
I have known Noubar for many years. I was on his thesis com-
mittee when he was at MIT. Maybe that also dates me! He
started a company, Perceptive Biosystems. It was a rapid and
precise chromatography [company] based on work that had
been done at Purdue, and that he extended and did a great
job on. I was on the scientific advisory board of that too. Then
he started Flagship Pioneering and they have been involved
in starting many highly successful companies.
How much of a role did the Trump Administration’s Opera-
tion Warp Speed initiative play in getting the COVID vaccine
fast-tracked for FDA approval?
I do not know about fast-tracked for FDA approval or to whom
ultimately to give credit. I had heard that Operation Warp Speed
came from one of the people at FDA originally. But obviously it
takes a lot of work to get it through any political administration.
So, whoever did so, that was a really good thing. Operation
Warp Speed accelerated many things.
Although the press and public seem to think that Moderna is
here today because of federal funding, that is incorrect. If it was
not for investors putting in billions of dollars in 2010 to get Mod-
erna to the point where we had 13 products (including eight vac-
cines), in clinical trials, the COVID vaccine would never have
happened. The second key thing was Operation Warp Speed.
That definitely helped with the FDA. It was not just money. Mon-
cef Slaoui [former head of Operation Warp Speed] and others did
a great job in moving things through and really betting on a num-
ber of companies, although Moderna, BioNtech, and Pfizer ended
up being the most successful.
What are some of the other diseases against which mRNA
vaccines can provide protection?
Flu is an obvious one. Epstein Bar Virus, Zika, and other viruses.
They are talking about vaccines for multiple sclerosis. There is
really no limit. But mRNA is not just for vaccines, it is also for
therapeutics—heart disease and cancer. We are working with
Vertex on cystic fibrosis. There are many rare diseases that
mRNA can be used for. One of the exciting things that does
go back to vaccines, but it is a very different concept, is thera-
peutic vaccines. Of course, the most exciting one is for cancer.
You might be able to train the immune system to make mRNA
that can eliminate a person’s cancer cells. It is a pretty unlim-
ited technology.
Moderna shares reportedly pushed you into the billionaire
category. How much have you reflected on that, given
your growing up as the son of a liquor store owner in
Albany, New York?
I never dreamed any of that would happen. That certainly was
not my goal when I started these. I have not sold any shares
from Moderna either. I believe in the company, and I am not
about to want to encourage anti-vaxxers.
Even before Moderna, I remember winning the Queen Eliza-
beth Prize, which is similar to the engineering Nobel Prize. They
 ASKED & ANSWERED
said I have improved or saved more than 2 billion lives. That
means a lot to me. When I went into research, it was partly be-
cause I loved science and experimenting, but part of it was also
to have an impact on the world. That Moderna has been suc-
cessful and helped so many people, means a great deal to
me. That the research we have done at MIT and that the compa-
nies that I have helped start have affected so many people,
means a great deal to me. I suppose money is emblematic of
some of that, but it is the impact that we have had that
means the most.
My dad was a super hard worker, and I only wish he was
around today to see how we are doing—not because of the
wealth, but because of the personal things such as my kids
and my wife and all the things that I have been able to do
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through being an MIT professor.
Your career continues to be multifaceted. How do you focus
and integrate your efforts to follow such a diverse range of
projects?
They do have a common theme: creating or designing materials
for use in medicine and other areas. Nanoparticles, microparti-
cles, and tissue engineering—all of them build on figuring out
the right materials and understanding the material science,
then applying it in different ways. That has even been true in
things that would seem anomalous to medicine, like when we
started Living Proof with Jennifer Aniston [star of Friends] that
made hairsprays that would prevent frizz! That was also very
successful, but that, again, was material science. It was brand
new materials, old materials repurposed in novel ways, or
safer materials. To me, it is really a single theme.
[Another integrating force is] working with students to help
them come up with projects that will solve problems in delivery
and tissue engineering, understand better how materials work,
perhaps develop new methods or new chemical synthesis. For
example, right now we are designing new biomaterials that we
can make, degrade, maybe even in a matter of minutes if they
create problems or if we think they could build up in the environ-
ment. Also, materials that have shape memory that you can shine
lights on and they will tie surgical knots or perform some medical
function.
Did your love for magic shape your love for chemistry or
your career?
Yes, it has and it does. I have actually done magic shows and I
loved chemistry when I was a little boy. I would put one set of
chemicals, maybe blue, and another maybe yellow and mix
them together in a beaker and all of a sudden, maybe it
would turn pink. That always fascinated and excited me. On a
very different note, when I was a postdoc with Judah Folkman,
I was trying to stop blood vessels from growing. Joseph Vacanti,
a surgeon at Mass General, was another one of my close friends
and colleagues. He and I developed a lot of tissue engineering
principles. I remember one day I was giving a magic show for
his children, and he said, Bob’s a magician—he makes blood
vessels disappear!
483
Your first controlled release polymer enabled the discovery of
angiogenesis inhibitors, but it took nearly 28 years to get FDA
approval. What is the source of this level of perseverance?
A couple of things. One, I have been very stubborn, and two, I
have really believed that the things that we were doing would
make a difference. If we do not succeed right away, I am willing
to keep pushing until we do succeed, one way or the other.
What is your secret for fundraising for your projects?
One, I realize that if you are dealing with a funding agency, you
are playing in their ballpark. You need to understand their rules.
If you write a grant to the NIH, my experience has been, they
want you to have a lot of initial data. That is very important
when money is tight, and it often is with the federal govern-
ment. Study sections will tell you why your grant will not
work. So, you want to have a lot of evidence showing that it
will work.
You also want to think of innovative ways to get funding. We
have written to cancer foundations and diabetes foundations.
There, you want to come up with something that will meet
their goals. They may be less concerned about preliminary
data and more concerned that you may be able to treat their dis-
ease. If you are dealing with industry, one of the things I found is
that if I had patents that would be very important, because that
would really give them some value.
The other thing I have tried to do is look for funds in unusual
places. When I was a graduate student at MIT, I helped start this
school for poor high school students called The Group school.
And one of the things I did, other than teach math and science
and try to develop those programs, was raise money for the
school. I found that there were all kinds of places to raise
funds. I think I found 17 different places in MIT alone, where I
was able to get some funding for this school and we got
money from the federal government by arguing that we were
preventing drug abuse. Then when I did stuff at MIT, I would
look at companies, foreign governments, and different founda-
tions—places that most people would probably never write to. I
would just try to find funding wherever I could.
Do you think responsibilities in life keep scientists from
being radically innovative like you?
Well, I do not know that I am a radically innovative scientist. I re-
ally love science. I think there are different ways. I have certainly
seen people struggle, get rejections, and have various responsi-
bilities, but somehow, people persevere. Obviously, if you have
had the good fortune to have good funding and a good educa-
tion, I think it certainly makes it easier for you. But some people I
have seen are just very determined. They are going to do well.
No matter what happens, they keep trying.
Your laboratory includes members from very different back-
grounds working in an interdisciplinary manner. How do
you maintain this fluidity and diversity among the students
you mentor?
 484
I have been very fortunate. I have had great students and a won-
derful staff. It is a team effort. MIT has also been a wonderful place
to be because of your colleagues and the students. Being in a
school like that has made my life easier. Cambridge has been a
wonderful environment because of the outstanding medical
schools and hospitals and the whole infrastructure that exists.
What is your approach to spinning out companies? When
does the technology, in your view, have what it needs, to
take it commercial?
The first criterion is that we have come up with some break-
through that leads to what I call a platform technology. Nanopar-
ticles could be a platform technology because you could put drug
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A, B, or C in them. Tissue engineering and mRNA are platform
technologies. The second criterion is that we would have at
least one outstanding article, ideally in a top journal. The third
thing would be that we have filed and have very good intellectual
property, ideally even blocking intellectual property.
Fourth would be that the technology might make a number
of products. Fifth is that we have got proof of principle, ideally in
higher-level animals. And finally, usually most of the time I have
done it because my students or colleagues have wanted to do it.
They have come to see me excited about doing it. If you have
students or colleagues who are working full time at the com-
pany and they truly believe in the science because they helped
create it, they walk through walls to make their technology work
and that has been so important.
What do the next couple of years hold for you?
I hope I will not slow down right now. Our laboratory is bigger
than it has ever been, even though I am 74! We are doing a
lot with the Gates Foundation on creating new technologies
for the developing world. We are spinning out new companies
because the students want to do that. They want to see their dis-
coveries make a difference.
As long as my health is good, I will keep going. I will keep
doing whatever I can to try to train more people and get
more ideas out to the world to help others.
You have helped numerous postdocs start their own compa-
nies. What are the challenges in moving an idea from acade-
mia into industry?
ASKED & ANSWERED
I was naive when I first started out. I thought, if I just published
articles, people would use the work that we did to create prod-
ucts. Although on the positive side people did refer and cite our
articles—our articles have been cited more than 375,000 times,
and that is certainly good—that does not mean you get prod-
ucts out that are going to help people. I remember, after
about 10 years of not getting any traction on the drug delivery
work, a couple of large companies wanted to license some of
our patents. I was really excited about that. Unfortunately,
even though that led to grants and consulting fees, it did not
lead to them creating products. That made me very sad.
Then my friend Alex Klibanov suggested we start our own
company. So, we started Enzytech, which later merged with
Alkermes. They created quite a few products based on micro-
spheres that could help people with opioid problems, schizo-
phrenia, type 2 diabetes, and so forth. I could see these little
companies with our students could make a huge impact. So, I
kept doing it. Some of the small biotech companies we
started—Moderna, Enzytech/Alkermes, and Momenta—got
pretty big and that will continue. I am hardly the only one
who is doing it. They [companies] have had a giant impact on
the world, and I just want to see more things come out to im-
prove people’s lives, their health, and relieve suffering.
What are some ideas that are currently at the verge of im-
possibility in biotechnology but may not remain impossible
in the next decade?
If we are talking about a 10-year window, delivering drugs to the
brain with appreciable bioavailability could become possible.
Getting good organs and tissues on a chip that are validated
by the human condition so that you could reduce animals and
human testing could be another.
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