MIT's Angela Belcher on cancer, green synthesis, and getting inventions to market

Kara Miller:

Welcome to, "Instigators of Change," a Khosla Ventures podcast, where we take a look at innovative ideas, the people who come up with them, and those who invest in them.

Kara Miller:

I'm Kara Miller, and today, perhaps one of the most innovative women in the country.

Angela Belcher:

I think I've said for the last 10 years, there's never been a more important time to be a scientist or engineer. There's so many problems that need to be solved, and there's so many solutions where, at least part of the answer is from science, engineering, or invention.

Kara Miller:

Angela Belcher, a material scientist, a biological engineer, and a cancer researcher, talks about how she's racing to help patients fix the environment, and break departmental barriers, if she needs to. That's just ahead, on Instigators of Change.

Kara Miller:

This is not a normal interview, because Angela Belcher is not your typical interviewee. This is going to be more like a walk through Belcher's brain, which, to be fair, is pretty impressive. She's the head of the department of biological engineering at MIT, and she works with an array of equally impressive colleagues at the Koch Institute for Integrative Cancer Research, also at MIT. Rolling Stone has named her one of the 100 people changing the country, and she won the $500,000 Lemelson-MIT prize for invention. Even she's been surprised, as you're going to hear, at how her research has expanded, starting about a decade ago.

Angela Belcher:

The president of MIT at the time, Susan Hockfield, came to me and said, "Have you thought about working on cancer? I'm putting together this new institute, where it's going to be cancer biologists and engineers working together in the same building, in the same floors." I said, "I work on batteries, and I work on solar cells."

Kara Miller:

That, though, was about to change, because the more Belcher thought about it, the more she realized she wanted to be involved in unraveling the mysteries of cancer.

Angela Belcher:

My mom had uterine cancer when I was born. I was born, and then, she went under for a full hysterectomy, at 25.

Kara Miller:

Wow.

Angela Belcher:

And then, had reoccurring breast cancer after that, and died early from breast cancer. At the same time, I'm thinking, "Wow, I'd really want the best people working on that."

Kara Miller:

Belcher would eventually say yes to cancer research, but we will get back to that story later. If you start at the beginning, and you're wondering how a top scientist who's also gotten dozens of patents started doing what she's doing, you'll find the answer on the beach, if you look around, very carefully, for an abalone shell.

Angela Belcher:

I'm actually holding an abalone shell in my hand right here. They're really a beautiful and exquisite biomaterial. You've probably seen them before. They have this beautiful shell structure, they can be different colors. The red abalone has a red outer shell. If you flip it over, on the inside, it has this mother of Pearl, iridescent-like structure.

Kara Miller:

Belcher says that abalone shells are particularly awesome, because they're hiding a couple of secrets.

Angela Belcher:

Organisms in the ocean started making hard materials when there was increased calcium, and Silicon, and iron in the ocean. It was toxic to the sea organisms, and they repurposed the proteins that they already had, and they used them to actually capture some of these ions, or some of these metals and solution.

Kara Miller:

Basically, these organisms are doing cleanup. What's better than turning something that's annoying you into something that's actually useful? Which, in this case, is a nice, protective, nano-structured layer.

Angela Belcher:

They took a situation that wasn't good, and they built these beautiful materials, and these strong materials, and these hard materials that could protect their soft bodies. It's quite remarkable. I've spent my career based on that principle, that biology wasn't always meant to grow inorganic materials. It wasn't always meant to grow hard materials, or nano-structured materials. But, given the opportunity, they could expand their toolkit, and make really extraordinary structures, and extraordinary materials.

Kara Miller:

I know that a lot of people are going to know about CRISPR, and about the idea of changing around different sequences in the human body. I know you've worked with changing around DNA sequences, so that they can build something maybe unexpected. Tell me about the evolution of that work, and where things stand now.

Angela Belcher:

There's definitely similarities, in that, we take relatively simple structures, or simple organisms, like yeast or bacteria, or bacteriophages, viruses that infect bacteria, and we change their DNA, and add DNA, and subtract DNA, to get them to be able to construct a material that we're interested in. A lot of the earlier material we worked on were more in the electronics industry. We were making materials for touchscreen displays, for example, and we've made materials for catalyst. We've made materials for battery electrodes, both positive and negative electrodes.

In the recent years, although we still work in all those areas, we've been thinking more about environment remediation. Some recent work that we've done really goes back to thinking about abalone shells. In this case, we're using yeast, the same kind of yeast you use to make beer or bread, and we've been engineering them to, specifically, transport in toxic materials like mercury, or cadmium, or lead, and separate it out as a water purification system. We've been doing both protein engineering and metabolic engineering to get these simple organism, yeast, to clean up the oil sands-

Kara Miller:

Okay.

Angela Belcher:

For example. They're doing it by either trapping those metals, or mineralizing those metals.

Another thing that we've been working on recently, that really took a zigzag path to get where we are today in it, was engineering viruses, or bacteriophage, to make really high surface area carbons. Again, it came from a different direction. It came from us trying to build these biological carbon electrodes as part of a battery, and this was for a lithium sulfur battery. We used these beautiful structures, that are M13 bacteriophages, which are viruses that infect bacteria. I say they're beautiful because they are. They're long and skinny viruses, and they're made out of just single stranded DNA and proteins. They assemble themselves inside of a bacteria, it's really quite extraordinary. They're always the same link when they're made.

We use them as a template to make carbon-based resins, really high surface area, carbon-based resins, on the order of 2000 meters squared per gram. That's like one and a half hockey rinks of surface area per gram of material, a really high surface area. We were using it in battery electrodes, and it worked okay, but didn't have the intention that we originally wanted it to. But, we found that it was really good at absorbing poly sulfides, which were poisoning batteries. That was really interesting. We just took that material and said, "Wow, if it can do really good at absorbing these small sulfur molecules, what else can it absorb?"

We went out, and we thought, "Wow, it's great at absorbing materials that would be toxins in water, or dyes." We looked at it for materials for drug overdoses. We also looked at it for the ability to bind something very quickly. It was 30 times faster than other materials for binding. I said to myself, "What would you want to bind faster than any other molecule, if you needed to bind something really quickly?" No one else really came up with the same answer, which was me, but I said, "I'd want to use it for a chemical warfare agent. I'd want to be able to neutralize a chemical warfare agent really quickly."

Kara Miller:

The idea being, there's something in the air, but this thing you're putting out absorbs that bad thing in the air?

Angela Belcher:

It does, and it actually works quite well. We started working with collaborators in the army, to see that, sure enough, it did. It was very effective. Not only that, it neutralized the material, it broke it down into non-toxic components. And then, we started testing other toxic industrial chemicals, and it did the same. We're thinking, "Oh, that's pretty interesting." We actually scaled it, and made textiles out of it. I'm holding one of the textiles right here. You can make masks out of it.

During the beginning of the pandemic, we said, "Wow, I wonder if you can use these on masks? I wonder if you could make N 95 masks, or surgical masks better?" We developed a method with our collaborators in the army, to be able to spray it on masks, and showed that it actually can be used to increase the ability to remove toxic chemicals, but also, it can neutralize viruses. We showed that it can neutralize some viruses, and viruses very similar to SARS-CoV-2.

It's just interesting how we started with the shell, we make all kinds of different materials, and just follow where it takes us. Now, we're looking at PFAS. Now, we're looking at its ability to absorb these forever chemicals. It does so very well, from solution.

Kara Miller:

You talked a little bit about this idea of having these little pieces of nature work for you, whether it's bacteria, or viruses, or yeast, and having them do some of this work. Again, I wonder, where do you think that's headed? Do you feel like, in the next few years, we're going to have a lot more deploy... a lot of people think of bacteria and viruses as terrible things that they wouldn't want near them. Do you feel like the trajectory of that research is, yes, these little things are going to have a lot more impact in different parts of our lives?

Angela Belcher:

I think so, for sure. It's not just my work, the field is really exploding with a lot of young talent, where they're interested in synthetic biology, to produce things that biology wasn't normally intended to create. It could be drug molecules, it could be building supplies, it could be some of the things that you mentioned for environmental remediation, or CO2 to products. I think bio manufacturing is going to be a huge part of our economy in our lives, and in the years to come.

Kara Miller:

When you think about, let's say in 10 years, how my life or your life might be different because of bio manufacturing, because there's stuff being done at this kind of scale, and the consumer doesn't realize it's being done. How do you feel like a normal person's life might be changed? What is it that they interact with in a day that's different because of this work?

Angela Belcher:

I think, one of the really important things to think about, and I've thought about this since I first was fascinated with the abalone and the ocean, the abalone makes its materials in the environment which it lives in, and it doesn't add toxic materials back into the environment, because that would be no advantage to the organism itself. I think, it's the same thing when you look at bio manufacturing. If you look at using bacteria or yeast to synthesize a molecule, or synthesize a polymer, I think one of the main advantages is on demand materials, how you can reprogram an organism to make a slight modification in a small molecule, or a drug, or a polymer, to be easier to adapt to a particular application.

It could be a therapeutic, but I think, to me, one of the major advantages is going to be doing it in a way that has a lower impact on the environment. Doing it lower temperature, doing it without solvents that may have an impact on the environment. I think we're going to be able to make a lot of things biologically, and using synthetic biology, and biological roots, that are currently made in non-biologic ways.

Kara Miller:

Let's talk a little bit about the cancer work that you've been doing recently, which I know is a departure for you. If you go back in history 1971, Richard Nixon says we're going to have a big effort, we're going to defeat cancer. A lot of people know, certainly during the Obama Administration, Joe Biden, who was then the vice president, said, "This is going to be a cancer moonshot. We're going to do it." Before we get into the stuff that you're doing, what is your sense of why this effort has gone on for at least more than 50 years?

Angela Belcher:

I think that, and I'm more of an engineer than a cancer biologist, but I think that there's a perception that cancer is one disease, and it's not. It's many different diseases, and in different people, it presents different, and is treated differently. I think, grouping it all together as cancer is not the best way to look at it. I'm pretty excited about the moonshot. I'm pretty excited about the new effort and approaches that are being applied. For my personal, as I'm sitting here in the Koch Institute, it's half cancer biologists and half engineers working together. The thing that excites me about it is, looking at these different particular diseases from multiple directions. In my suite, I'm the only engineer, the rest are cancer biologists. We all have the same goal, which is to make an impact on cancer, and I work on many different kinds of cancers, I'm particularly passionate about ovarian cancer.

We bring different ideas, different approaches, and different solutions together. It's when we're sitting down at the table, or sitting in the conference room, or being side by side in the lab with these different approaches, I really feel like that's a way that we can really make an impact. I have two collaborators that are both engineers. Paula Hammond is a chemical engineer, and Sangeeta Bhatia is an electrical engineering, and a couple of other kinds of things as well. The three of us are focused on solutions for treatment, and early diagnosis, and interception of ovarian cancer. I have to say that I'm excited about so many things right now. I'm excited about energy, I'm excited about environmental remediation, but I'm really excited about early diagnostics and interception of ovarian cancer.

Kara Miller:

Do you feel like that intersection of biologists meeting engineers is how dealing with cancer is going to move forward, where these people who normally inhabit different silos start crossing silos?

Angela Belcher:

I think it's definitely important, and one of the most important pieces of that is also the clinicians, which we work closely with here, in our Institute, as well. That is an enormous part of the puzzle, these groups working together. I'm not going to say that is the answer.

Kara Miller:

Yeah.

Angela Belcher:

But, I'm hoping that tremendous progress, at least in ovarian cancer, where we're focused, will take place. Over the summer, I think the pandemic, to say it was hard is an understatement, but many of us went through different, I wouldn't say ups, but different feelings during this time, and certain times were better than others.

Kara Miller:

Right.

Angela Belcher:

I have to say one, one of the things that really helped me through was these meetings I had with this new foundation called Breakthrough Cancer. The idea was to get scientists, engineers, clinicians, and surgeons together from five different institutions around the country. We met once or twice a week, in different subgroups. I would hear from a surgeon a particular kind of problem that they had with an ovarian cancer, or clinician. I would say, "I have an idea. If we were going to approach it from an engineering perspective, I would build this kind of test, or this particular kind of device," and this is for looking for very tiny lesions on fallopian tubes, for example.

Kara Miller:

Okay.

Angela Belcher:

Then, the question would come up, "How do you sample those so that you can get a few cells, and sample them in a living tissue?" I'd say, "I don't know how to do that, but I know someone who I think would be really good at that," and I would pull in another engineer, who could think about that. Being a part of a community like that, where we all have the same goal, we all have the same goal to cure ovarian cancer, to extend women's lives, to help women get the best possible care. We all have the same goal, but we're all bringing our best tools. We're all bringing our best ideas together. We're brainstorming, and being respectful, and listening to each other's ideas, and where the limitations are, and discussing it, and at the end of the day, building a really strong team. That gives me a tremendous amount of hope.

Kara Miller:

Why are you working on ovarian cancer, particularly? Where do things stand in terms of what you are trying to do?

Angela Belcher:

It's an interesting question, and I can answer it from a couple of different directions. Over 10 years ago, I was really happy working on batteries and solar cells, and catalyst. The president of MIT at the time, Susan Hockfield, came to me and said, "Have you thought about working on cancer? I'm putting together this new Institute where it's going to be cancer biologists and engineers working together in the same building, in the same floors."

I said, "I work on batteries, and I work on solar cells." At the time, I politely declined. The reason I did is, I thought, "This is one of the most important problems. Am I close enough to this problem where I can make a difference?" Because, I don't want to work on anything where I can't make a difference.

That's one reason. As I thought about it more deeply, like many people, my family's life has been deeply affected by cancer. My mom had uterine cancer when I was born. I was born, and then, she went under for a full hysterectomy at 25.

Kara Miller:

Wow.

Angela Belcher:

And then, had reoccurring breast cancer after that, and then, died early from breast cancer. At the same time, I'm thinking, "Wow, I'd really want the best people working on that." At that time, I said, "Okay, this seems like a really fantastic opportunity." We had boot camps for cancer, for people like me, who didn't actually have a degree in biology.

Kara Miller:

Right.

Angela Belcher:

I've never worked on cancer, to learn about it. Again, to me, the key is the team that you put together. This is true in companies, this is true in your lab, I'm sure it's true in almost any field. It's the team that you put together. Everyone's just so accepting of teaching each other what they needed to know. We had these speed dating events-

Kara Miller:

Okay.

Angela Belcher:

Where we're meeting with-

Kara Miller:

Really, everybody has a PhD at this speed dating, right?

Angela Belcher:

Yes, or an MD, or both.

Kara Miller:

Or an MD, okay.

Angela Belcher:

I met Michael Beer, who was at MGH at the time, and he's an oncologist who works on ovarian cancer. He was convincing me that I should work on ovarian cancer. What I had brought to my speed date was this technology that we developed, based on our solar cell technology. It was an imaging technology to be able to look deep inside of the body, with fight.

Kara Miller:

Okay.

Angela Belcher:

It was a very rough prototype, that was version one we were on at the time. Now, we're on version six in the lab, of these instruments that we've built. Basically, what he told me is, he said, "Ovarian cancer is the cancer that you should focus on," and it's because it's diagnosed so late, and 70% of the cases are late stage ovarian cancer, and 70% of them also relapse after surgery and chemotherapy. He said, "You can make an impact if you were able to find the tumors."

Working with him, we developed image guided surgical tools, still in animals at the time, where we could find very small ovarian tumors. We built a system that would help the surgeon find these tiny tumors, and remove them. Because, the way ovarian cancer is, a lot of people think it's a single tumor in the abdominal space, but it could be lots of tumors.

Kara Miller:

Okay.

Angela Belcher:

They're usually removed surgically, and followed up by chemotherapy. We set about to help find not just the larger tumors you'd be able to see by eye, but to find tiny tumors that surgeons couldn't see by eye, by getting them to light up under certain conditions. Then, we went on and built several different instruments after that, for trying to see ovarian tumors earlier. Right now, after all these conversations that I had with these teams for breakthrough cancer, after all these conversations, we've decided to build an instrument that can scan fallopian tubes-

Kara Miller:

Okay.

Angela Belcher:

To find the very early pre-cancer lesions to ovarian cancer, so that they can be studied and better understood. Eventually, we want to take these different technologies we're using to develop a way for early diagnosis.

Kara Miller:

It sounds like there's still a long way to go to get to the point where we can diagnose ovarian cancer very early, before it's so deadly as it is now.

Angela Belcher:

That's true, but there's not only the technology that we're working on, there's people are working on new kinds of markers for ovarian cancer. My colleague Sangeeta Bhatia works on blood and urine tests for early diagnostics of ovarian cancer, and other kinds of cancers. It's a big, concerted effort with many great ideas. I think what's important is to give people the space, and the basic science to do invention, and develop new ideas. But, you need, at least I need, the reality check of interacting with cancer biologists and physicians, to see whether what we do makes sense from a diagnostic, or imaging, or treatment standpoint.

Kara Miller:

It sounds like the toolkit is expanding. When you think about the tools that existed decades ago to fight cancer, you really have a much wider array now, and different kinds of folks contributing tools and ideas that they've come up with.

Angela Belcher:

I think that's true. Look what's happened with immunotherapy in the last several years, how exciting new treatments are coming around, around that. There's a lot of interest in expanding that to other kinds of cancers, as well.

Kara Miller:

Obviously, a lot of academics, you're in this category, have created companies that spin out from their lab. What's your sense right now of that, I don't know, tug or balance between academics and their labs? Is there a lot of directions that researchers are being pulled in? Obviously, pendulum swing 10 years ago might be different from now, but where do you feel like we are now?

Angela Belcher:

I think that there's a lot of opportunity in green synthesis, and green science, environmentally friendly synthesism materials, that maybe there wasn't in the past, as much. I remember when I was first thinking about making bio materials, using real organisms, or using proteins from the organisms, the aspect that you could do it at lower temperature, and using cleaner solutions and solvents, wasn't a big draw, at least in funding. But, I think it is now. There's so much opportunity, in terms of people interested in funding solutions to reduce carbon, for example, or CO2 to products, or cleaner ways of manufacturing important precursor molecules that are used to make and grow all kinds of polymers and other materials.

Kara Miller:

When you take a little bit more of a 30,000 foot view, I know you have a good sense of MIT, but you probably also know people at different institutions all over the country, who you are in touch with. I wonder, do you worry, and maybe this is not a concern, but do you worry that great people are leaving academia because there are so many opportunities elsewhere? Or, do you think, no, that's not an issue?

Angela Belcher:

I'm not sure why I would worry about great people leaving academia, because we need great people everywhere. At MIT, it's very compatible to be both an academic and to start companies.

Kara Miller:

Okay.

Angela Belcher:

And, to consult in companies, and I know other institutions are like that as well. That's why I've always said, this is really the best job in the world, because you get to teach, you get to do research, you get to invent, and all the great things associated with being in academia. For me, and for many of my colleagues, actually translating those inventions, either to your own company or another company, to see where they can make an impact in the world, is just fantastic.

In terms of our students, our graduate students and our undergraduates, I always encourage people to follow what they're most passionate about. You could have a big impact in so many different areas, find the one that you're most excited about. That could be in academia, but it could be going straight into your own startup company, or working in a startup company. I'm not worried about that.

Kara Miller:

This is even bigger, but when you think about education, I read a quote of yours somewhere, you said, "We're in such a place on the planet where we really need new ideas, and new inventions." How are we doing on that front, when you think about people who are coming up through the pipeline?

Angela Belcher:

I've said for the last 10 years, there's never been a more important time to be a scientist or engineer. There's so many problems that need to be solved, and there's so many solutions where, at least part of the answer is from science, engineering, or invention. In that case, we need the brightest minds working on that. But, since the pandemic as well, I felt like there's never been more a important time to be a biological engineer, which I am. There's never been a more important time where we can have such an impact on the planet. That's not only through infectious disease and medicine, but it's also through agriculture, energy, and the environment.

I think the key is encouraging young people that this is important, and this is a great career path. In general, the young people that I work with, our undergraduates at MIT, are so enthusiastic about doing research that makes a difference. I can really tell you, that's the best part of coming to work every day. It gives you so much hope to be surrounded by young people that feel so excited, and driven to solve some of the most pressing problems on the planet. It gives me an amazing amount of hope.

Kara Miller:

Is there a biggest hindrance, you feel like, to commercializing the important research in your field? Is there something that you see people running into, in terms of a barrier?

Angela Belcher:

In my own particular area, most of the materials that I end up being interested in commercializing are materials. In those cases, it's been, and I think this is true in medicine and therapeutics, as well as the amount of funding it takes to get something to proof of concept, and then pilot, and then to scale, you hear about this valley of death, where you go from a working prototype which you can hold in your hand, and show it works, to something that is scaled in an industrial product, or process. I don't know the answer for how to change that, but I think that's one of the main things that I see right now.

Kara Miller:

Okay. The valley of death is between having one and having 100,000 right?

Angela Belcher:

Not necessarily having one, but having several. It depends on if you're integrating into another product, or to another process, as well. Showing something that can work on a smaller scale, and getting it into a worldwide product is definitely a challenge.

Kara Miller:

Angela Belcher is head of the Department of Biological Engineering at MIT. Angela, thank you so much for being here.

Angela Belcher:

Thank you so much for having me.

Kara Miller:

Thanks to you for listening. If you want to hear from another scientist working at the cutting edge, check out our recent episode titled, "Turning Pollution Into Jet Fuel and Yoga Pants," in which we talked to Dr. Jennifer Holmgren, a chemist and the CEO of LanzaTech. Of course, if you want to receive new episodes of the show every week, subscribe. "Instigators of Change" is produced by Matt Purdy. We'll talk to you next week.