Jim Heath, PhD

Could you give a quick 30-second overview of your career? 

I started in science as an undergraduate when I learned you could get paid to work in a lab. My professor asked me what my major was, and he was a chemistry professor, so I told him my major was chemistry. That was the moment I became a chemistry major. 

I then went to graduate school at Rice University for my PhD in chemistry. I had a famous thesis – I discovered a molecule called fullerene, a classic carbon molecule, which won my advisor the Nobel Prize a decade later. 

Following that, I went to Berkeley for a postdoc in astronomy before accepting a research staff position at an IBM basic research lab. The position was very academic in nature and I began exploring the world of nanomaterials. I got that job at IBM in the early 1990s. I ended up getting a lot of results published, but I thought this probably wasn’t the place to make my future.

I started as an Assistant Professor at UCLA. At UCLA, I kept developing nanotech and we also did a lot of solid-state physics. We had a very big project to build a molecular computing machine that still holds the world record for memory density. We built a 160,000-bit memory circuit that was smaller than a white blood cell, and it worked. All that was to develop a manufacturing approach that worked at molecular dimensions with the perfections you associate with microchips.

Once we had that manufacturing approach, I thought, “Could we use that to start looking at biology?” I don’t know if you all know the history of biology – biology was very phenomenological for many years. I’m a physical scientist, and am not very interested in descriptive stuff. I left UCLA and moved to Caltech. UCLA is a good place, but Caltech is singular. There, I began developing tools for biology quantitatively and at the single-cell level. A lot of those tools became vital. We commercialized them. They became important as metrics for cancer immunotherapies. 

I became intrigued by the idea of developing tools that could help us understand how we could harness the immune system to cure cancer. I became more involved in the biology side of that. If you guys had asked me 10 years ago, I would’ve said that cancer like melanoma was a death sentence. Now, your chance at five years of survival is like 75%. Luckily, other cancers have followed suit, and that’s because we have learned how to harness the immune system.

In biology, people study things in mice. Mice live for two years, but humans live for 100 years. The systems in humans are widely different from mice. As we develop these tools that allow us to resolve heterogeneity of biology at the single-cell level, to do millions of measures over time even from a drop of blood or so, it becomes possible to ask the fundamental biology questions by studying humans directly, bringing systems biology to humans. I came [to Seattle] and took over ISB about five years ago because ISB had developed this affiliation with the Providence healthcare system, which allowed us to begin thinking about how we can do science at scale. This is what’s really required because everybody is different from everybody else. Unless you can capture a statistical representation of the population, you’re just looking at the tail of the elephant. For the past five years, we’ve been creating these types of programs. That's my career in about as short as I can give it to you.

Why did you make the change from chemistry to biomedicine and pharmacy in your research? 

I wouldn’t say that I’ve done that. If you look at all the things I’ve done since I started, there were fullerenes, material science and chemistry, solid state physics, bioengineering, biology, and computation. I don’t think it’s changing fields. We have these universities set up in a Germanic structure (which is as boring as it sounds) where chemists sit in one building and physicists sit in another.

If there's a problem that interests you, like building a molecular computer, you aren’t going to solve it by just using chemistry, material science, or electrical engineering.

But take one problem and tell me it's just a chemistry problem or just a physics problem. For instance, our environment. You have to understand chemistry, how to engineer systems, battery energy, energy harvesting, and social consequences of forest fires. It's a problem that doesn't fit into one discipline. Same thing as healthcare. There’s biology involved, there’s molecules involved, and there's new technology involved. If there's a problem that interests you, like building a molecular computer, you aren’t going to solve it by just using chemistry, material science, or electrical engineering. The same thing goes for issues we are working on now. I don’t just think of myself as just a chemist or just a biologist. That's the great thing about academics: As long as people will fund you, you can do whatever you want to do. 

How do you think the technology to cure cancer will evolve in 20 years? 

I think we will increasingly learn how to better harness the immune system. Even though I’m not a medical doctor, I’m currently leading a clinical trial on cancers that are driven by viruses, such as HPV-driven cancers. These include all head and neck cancers, cervical cancers, and about a half dozen other cancers. We are actually reengineering every patient's immune system to attack the cancer. I think that will be curative – not just a treatment, but a cure. When you engineer the patient's immune system, you also engineer immunological memory into the patient. The cancer’s not coming back. That doesn't mean you are going to do it right the first time, that’s why it's science. I think the first time will be pretty good, the second time will be great, and by the third time, we will actually know how to do it. 

However, that's just one cancer. Every cancer is its own challenge. There are accessibility issues and organ issues. For example, pancreatic cancers are really hard. One reason is because nobody knows they have it until it's almost too late. Breast cancer is usually caught early because you can check for it easily. Very few people die of breast cancer anymore. Brain cancer is a crazy complicated cancer. But in all of these, the cancer looks different from the self. It has genetic mutations which are not the same things as the genome you inherited from your father and mother. That means the immune system recognizes the cancer as a foreign entity. The cancer will defend itself against the immune system, and if you can overcome those defenses, the immune system will remove the cancer. That's how melanoma got to where it is now.

However, the brain is really hard. Glioblastoma is probably the most extreme version of that because the brain really protects itself against everything. The cancer and the brain will actually invoke those same protection mechanisms. But I think most other cancers will be cured, or they'll be chronic diseases, meaning you’ll have them and live with them. 

One technology that we have been developing here, which I think is really critical, allows us to treat every single person that comes into the clinic.

We have a pretty diverse group here [at ISB] but if you look at immunotherapies and how they're used in the clinic right now, it's not intentional, but the design of some immunotherapies like cell-based immunotherapies basically succeeds and benefits white people. Not our therapy, but the standard cell therapy would. That’s because the way that your body sees and presents fragments of the HPV virus, which is what your immune system recognizes to kill the cancer cells, is not the same. All of us are different but the most common presentation is one that is shared amongst Caucasians. As a result, a lot of cell therapies that have come out treat a very limited subset of the population. One technology that we have been developing here, which I think is really critical, allows us to treat every single person that comes into the clinic, and the trial we are launching is specifically to show that we can do that. 

I think there's been an increasing awareness in the healthcare field. You actually have to have a treatment that works across everybody. Not only is it the right thing to do, it's the most economically viable thing in the long run. The other limitation is that we work with Providence which has 51 hospitals. Providence only runs trials in Portland, Seattle and Los Angeles. There are 41 Providence medical sites that don’t run clinical trials. There’s not a single clinical trial in Alaska, at least away from the Native sites, and even those aren’t advanced clinical trials. If you have a therapy that is designed to treat everyone, how do you actually treat everyone? That’s a problem we are working on pretty aggressively.

Everybody agrees right now that our healthcare system is basically broken. If you ask a big medical provider like Providence or Kaiser, they double down on this “beds and heads” model. Build a hospital, fill it up. That's how they make money. The technologies we have now allow us to turn any community clinic in the nation into a trial site. That’s the goal. When we talk about systems approaches, we think about a treatment that is powerful and that uses the whole system [of the human body]. Try to change that system, so that anybody who qualifies for that therapy can actually receive that treatment.

How do you connect music and science? In what ways have you been able to continue music, and has it advanced your scientific career at all? 

I’ve played music for a long time. I actually played in a professional-legged bar band when I was a postdoc. Turns out, you don’t have to be as good as a “professional” to actually play as a professional. Initially, I actually went to school as an English and music major, and that was when I had that conversation with that chemistry professor. I think you have to have fun doing science or science isn't worth it, but I also think you have to have fun doing other things. I don’t know if science naturally blends itself into a work-life balance, but you need to have something else, and music has provided that for me for a long time. 

You mentioned that, 10 years ago, melanoma would have been a death sentence. You also had a Town Hall with Meghan O’Rourke, who wrote “The Invisible Kingdom.” What are some ways that your outlook on chronic illness has evolved?

Chronic illnesses are largely caused by autoimmune conditions. You could argue that if you turned cancer into a chronic disease, it's now an immune condition because your immune system keeps it in check. Psoriasis, arthritis, MS – they're all immune issues/chronic diseases. 

If you pick up a textbook and read what is supposed to happen when you get an infection and how you're supposed to resolve that infection, that all comes from studying mice. Let’s say we have this nice pathway for infection and infection resolution that comes from our picture of immunology, and you ask, “How well does that apply to humans?” And let's say we can score humans. Humans score 10 (perfect, it works great) to 0 (very different). Normally, in science, you take some score, and here’s the percentage of people that have a 0-10. This immune score will look like a Gaussian distribution. Not so in this case. In this case, either you have it, or you don’t. If I tried to give you a score on how good your T-cell memory formation is, it looks like that (referencing either 0 or 10). If you're at 0, where you have a lousy T-cell memory, you have a good chance of whatever attacked your immune system flaring up again because your body forgot about it. If you look at many of these auto-immune diseases, that's what they do. They flare up again and again. If you look at the genetics of these people, sure enough, they have a risk factor for auto-immune disease. I think we are only beginning to understand what we need to do to get a handle on chronic disease. It’s complicated. But the last thing you want to do is create a mouse chronic disease model. You need to study it in humans. We have this project we are working on now to try to capture that. 

The problem with humans is that you can’t sample the organs with the immune system, like the spleen and thymus, but you can look in the blood. But, if you have an organ donor like a motorcycle victim with an organ donor card and can collect their spleen, you can keep that spleen alive for 30 days. During that time, you can vaccinate, perturb, and try to give it a chronic disease. So we have this project right now on spleens, where we have a broad distribution of spleens across ages and ethnicities, so you have that heterogeneity. We are vaccinating those spleens and looking at how you develop immunity against a threat. It’s going to be way different; I can’t tell you what we are finding. We are just doing those experiments. 

I think we are only beginning to understand what we need to do to get a handle on chronic disease.

That’s the kind of thing you need to do to really get a handle on something complicated like a chronic disease. Some people find that some chronic diseases protect you against other diseases. Why is that? No idea.