_
_
_
_
_

Moderna co-founder Robert Langer: ‘I worry that we haven’t seen the last of Covid’

One of the most influential chemical engineers in history talked to EL PAÍS about his breakthrough developments in tissue engineering, nanotechnology and what the medicine of the future will look like

Robert Langer Moderna
Chemical engineer Robert Langer in a file photo.MIT
Nuño Domínguez

Robert S. Langer, 71, received his doctor of science degree in chemical engineering from the prestigious Massachusetts Institute of Technology (MIT), but it was quite a while before he found a job that he liked.

It was the 1970s and the only offers he got were from oil companies whose main problem was “increasing the yield of a petrochemical by 0.01%.” He tried to work in education but nobody would hire him. He had no luck in the field of medicine, either. And then he heard of a research lab run by a scientist named Judah Folkman, from the Boston Children’s Hospital. Folkman was a surgeon “who sometimes hired unusual people” and who had an idea that nobody was interested in at the time: if you could stop blood vessels from growing inside a tumor, you might stop the spread of cancer.

Together with his new mentor, Langer discovered how to deliver the molecules that could achieve it, but they were too large. Getting them to reach many internal organs was like trying to walk through a brick wall. To solve the blood vessel problem, first he had to solve the delivery problem. The researchers showed it was possible to take polymer capsules and use them as tiny delivery vehicles that did not destroy macromolecules meant to block the spread of blood vessels. Their results were published in Science and Nature. Four decades later the same principle, now perfected in the form of lipid nanoparticles, lies behind the success of messenger RNA (mRNA) vaccines against Covid-19.

But back then most scientists chose to ignore these findings, while companies did not think of developing drugs based on them, at least not for many years. And so Langer decided to create his own companies to ensure that his products would “help people.”

These days Langer is is one of 12 Institute Professors at MIT, the highest honor for a faculty member. He is also the most cited chemical engineer in history, and his more than 500 patents bring in billions of euros in profits. Langer has created over 40 successful biotechnology companies, including Moderna. A recipient of over 220 awards, he has just received the BBVA Foundation’s Frontiers of Knowledge Award in Biology and Biomedicine together with Katalin Karikó and Drew Weissman, for their pioneering work on mRNA vaccines.

Langer believes that large companies are risk-averse and that it is up to governments to fund universities and public research centers to do “curiosity-driven science.” After his early experience with Folkman, this son of a liquor store owner and a housewife went on to specialize in finding new forms of drug delivery. The goal was to reach organs that existing medication could not, and to reduce the amount of pills and injections required to treat patients. For instance, would it be possible to create a pill that remains inside the stomach and releases the right dose of medicine for days, weeks, months or at specific moments? Such controlled release medication would be greatly helpful for diabetics and for the millions of people on antimalarials.

It’s important to have great universities, and to give them really good funding so they can do basic curiosity-driven research, which is the starting point for so much

Langer’s lab has produced patches against glioblastoma, one of the worst known brain tumors, as well as nanoparticles that can slowly release medication against prostate conditions and endometriosis for months. It has also developed technology to engineer tissues and regenerate the skin of burn victims.

Langer has just joined Forbes magazine’s list of billionaires. A lot of it has to do with a visit he received in 2010 at his MIT office. A young researcher from Harvard Medical School named Derrick Rossi had read Karikó's research and wanted to talk about the potential of mRNA in cell reprogramming. In a recent conversation with EL PAÍS, Langer described his upcoming projects and speculated about the medicine of the future.

Question. Almost nobody believed in you at first, not even companies. Years later, Karikó and Weissman had similar experiences. Do you think that big pharmaceutical companies are averse to important but risky ideas?

Answer. It wasn’t just the big pharmaceutical companies, it was the scientists. I got my first nine grants rejected by scientists. One of them said something like ‘he’s a chemical engineer, he knows nothing about biology, much less about cancer. We shouldn’t fund him.’ I do think that large companies, and I’ve been on boards of many, are fairly risk-averse. But small companies are less risk-averse. So many big breakthroughs have started in academic places over the years, like in my case or Karikó's, and small start-ups have made a huge difference.

That’s the beauty of science, when you create new things and you don’t know what they’re going to be useful for

Q. Did you imagine the enormous potential of Moderna when you founded it?

A. I was an advisor at Genentech [considered the first biotech company] for 30 years. Their business was making proteins and they were incredibly successful at it, but it took them years to make the proteins, to develop these big manufacturing procedures, and I could see that if you could do mRNA it would be potentially much better and faster. You could put it in nanoparticles to protect it and inject it, and in the end it’s the body that’s making the protein. You could use it with anything. When we started Moderna I remember telling my wife in 2010 “this will be the most successful biotech company in history.” At that point we didn’t know about Covid, nobody anticipated it, but it just accelerated everything. Moderna has 23 clinical trials going on not just for Covid but for cancer, heart disease and rare diseases. All of them use mRNA and nanoparticles.

Q. Do you think we are near the end of the pandemic or will we need more vaccines and medication to stop it?

A. I wish I knew, I’m not an expert, but I worry that we haven’t seen the last of Covid and we probably won’t for some time. That doesn’t mean we can’t do a lot better at controlling it. Companies can make boosters specific to variants, and in our own lab at MIT we’ve been working with the Bill and Melinda Gates Foundation for years, on things that may not help overnight but for the future, like self-boosting vaccines. It’s not ready for patients yet but with one injection you would get boosts through nanoparticles that would burst at one months, two months, five months. We are also working on things that I hope will be good for the developing world, which I call microneedle patches, almost like band-aids, and maybe one day ship them across the world.

Q. You always say you want to create things to help people and change society. What are your current goals?

A. In our lab we have around 100 people working on two areas, one is drug delivery and nanotechnology and the other is tissue engineering. We are working on new nanoparticles that can deliver different types of RNA and CRISPR [gene editing] inside cells. We also work with the Gates Foundation on pills you could swallow to last the entire course of treatment and which could be useful for mental health diseases, schizophrenia, Alzheimer’s. The Gates Foundation is also interested in antimalarials, in the possibility of taking one pill representing a two-week course of treatment.

Q. Would it have other applications?

A. Yes, in nutrition. Many people in developing countries do not get enough iron and vitamin A, and we have developed nanoparticles that can stabilize those and you could cook them or put them in boiling water or bread. And little children don’t take medicines very well so we’ve come up with Gummi bear-style medication to treat tropical diseases.

Q. Another one of your projects involves delivering medication through ultrasound?

R. Yes, we’ve been able to make little probes that can deliver drugs like in the Star Trek idea, through the skin or the intestine. It can be activated once it reaches the organ through ultrasound. We also make small devices with tiny wells that are covered with a specific material and we can make a trigger so the wells can release their charge.

Q. You also create artificial tissues?

A. That was an idea we started a long time ago, of taking materials and putting them in certain shapes to serve as structures for the cells of any mammal, which now would include stem cells. It gives you the ability to create any tissue like artificial skin for burn victims. There are clinical trials that stemmed from this work involving new blood vessels, spinal cord repair, hearing loss and cell encapsulation. And it might reduce testing in animals and people.

When we started Moderna I remember telling my wife in 2010 ‘this will be the most successful biotech company in history’

Q. Sometimes your inventions have had unexpected results, such as helping with hair regrowth.

A. [MIT colleague] Dan Anderson and I created material we thought would be useful for a range of things. We had patents on them, and our major idea was to use them for certain disease treatments, but some investors asked if they might be useful for other things like hair, so we came up with ‘material libraries’ containing thousands of materials from some of the same synthesis, which you can take out and test. So one prevents a hair frizz, another gives it more volume. The company is named Living Proof and it’s just been bought by Unilever. That’s the beauty of science, when you create new things and you don’t know what they’re going to be useful for.

Q. Do you think companies should make their patents available during the pandemic?

A. Moderna said in October 2020 that they would not enforce the patents during the pandemic, so anyone could use them.

Q. How do you think the medicines of the future will look like?

A. We’re going to see more genetic medicines and gene editing. Also more cellular therapies, like the kind of tissue engineering we are doing. And there are ways of using cells to treat cancer and we will see more of this. There will also be better delivery systems, more targeted. There will be ways of taking an entire course of treatment with one pill. We already have something people call a robot pill that stays in your digestive system, and that could one day be used to deliver insulin to diabetics.

Q. How would you advise a world leader on how to improve scientific research in their country?

A. I’ve already been asked this question by some leaders. It’s important to have great universities, and to give them really good funding so they can do basic curiosity-driven research, which is the starting point for so much.

More information

Recomendaciones EL PAÍS
Recomendaciones EL PAÍS
_
_