publication date: May. 13, 2016

Conversation with The Cancer Letter

Agus: $200 Million Interdisciplinary Institute to Focus on Data Modeling 

 

A few years ago, at dinner with technology entrepreneur Larry Ellison, David Agus, director of the University of Southern California Center for Applied Molecular Medicine, mentioned his dream of opening an interdisciplinary cancer research center.

“I said, it really would be an amazing thing if we could start to get people in one place and have residences, so the greatest physicists, mathematicians, engineers can actually come in and live there and be engrossed in cancer,” said Agus, professor at the Keck School of Medicine of USC and the USC Viterbi School of Engineering.

“Well, how much would it be to kind of put together such a building and program?” Ellison, Oracle Corporation’s chairman of the board and chief technology officer, said to Agus at the time.

“You know, about $200 million,” Agus said.

“Done,” Ellison responded.

The gift was announced May 11.

The Lawrence J. Ellison Institute for Transformative Medicine of USC will combine interdisciplinary research with holistic prevention and treatment of cancer. Agus will lead the institute.

Agus spoke with Matthew Ong, a reporter with The Cancer Letter.

 

Matthew Ong: How did the Ellison Institute come about? Whose idea was it and how did it happen?

David Agus: Who I blame for this, in the beginning, is a remarkable woman who used to be the deputy director of the National Cancer Institute, named Anna Barker. She came up with this program called Physical Sciences in Oncology, and the idea very simply was to kind of mix different disciplines—physical sciences with what we all do in the oncology world and put them together. It changed my research focus, it changed everything in how I think about the disease. It really has been transformative.

So my lab now is physicists, mathematicians, and engineers; it was going very well. And I would tell Larry Ellison about this—we would meet as friends, and we would have dinner and I would talk about this. He saw my excitement. Then I said, “It really would be an amazing thing if we could start to get thinkers in one place and have residences so the greatest physicists, mathematicians, engineers can actually come in and live there and be engrossed in cancer.”

About four or five years ago, I got invited to the Aspen Ideas Festival with Murray Gell-Mann, the physicist who discovered the quark and string theory; he won the Nobel Prize in 1969, when I was four.

He interviewed me on cancer and how he questioned me opened my eyes to thinking about new things. He made me realize that physicists, engineers, and mathematicians view the world differently than we do. And almost by definition, we in the cancer world haven’t succeeded, because we’re still losing the war on cancer, so we need new ways of approaching it.

If we get to make the place where they can come and actually see, smell and be a part of the disease, we can really approach things differently.

And Larry said, “Well, how much would it be to kind of put together such a building and program?” I said, “You know, about $200 million.” He said, “Done.” And I said, “What?”

I almost fell off my chair. And he said, “To me, money doesn’t mean anything, but progress does, and I really want to make a difference, because I’ve had some of my closest friends and relatives die of this disease.”

His mother died at a young age, and he wanted to make an impact. This was perfect—it really aligned. I didn’t ask him for anything, but he just jumped forward and said, “I get it, I want to be a part of it.”

MO: Will the Ellison Institute be the first of its kind in oncology?

DA: I really think it’s the first of its kind of a place that melds the sciences together in an experiential way to attack cancer.

Certainly, there are labs across the country that do that in physical sciences, but this is a dedicated institute with the residences—the hope is that it becomes not one institution—but with these residences, whether you’re at Harvard or Oxford or the University of Copenhagen, you can come here and experience it. The war on cancer is not institution-by-institution; we’re all fighting the same enemy.

We really want to put together a place where we can all work as a team and bring in people and whoever the experts are, wherever they are, to work as part of that team.

The center is planned to open in approximately two to three years. The center is operational today on a research basis, just without a formal residence.

MO: Will the institute be part of USC Norris Comprehensive Cancer Center, or is it independent? Is it under any particular umbrella, school or department at USC?

DA: The good thing is we’re not under one department. It’s a separate institute that reports to the provost, which I think is powerful, because in today’s world, only one department gets credit for a grant or this and that.

We want to rise above that. Clinical care is part of the Norris Cancer Center, but we are a standalone institute that’s part of USC, affiliated with Norris.

The NIH funds the conservative work remarkably, and I love that. But when you get gifts like this, you have to push the limits, try to do things differently.

MO: How will the $200 million investment be used?

DA: The building, which is about 110,000 square feet, will have a cancer clinic, and it will have a wellness clinic, because of the continuum there we need to study.

It will have an engineering lab for people to rotate in with an idea, and if the idea works, they stay, and if it doesn’t, they go back to where they were at the university.

They’ll have a think-tank, where people can talk and converse about these ideas. They’ll have the residences. Also, the place will have a technology center, where there will be DNA sequencing, metabolomics, proteomics—they’ll all be there.

The building’s going to be designed so that students can walk around and tour and see these remarkable technologies and be engrossed and hopefully become aspirational for them to go into the field. It will be designed so they can go on these tours without disturbing the occupants in the labs or the clinics. Patients will have a choice as to whether they want to be in a place where people actually watch you getting your treatments to demystify it for people as a part of the education process, or it can be private. The patient will have that choice.

Our job, while we treat cancer, is to change how we treat cancer. So it really is meant more to study and learn than to be a high-volume clinic. Most of the money is going for the building, the technology to go inside the building, and there is a significant portion that is left to help run the program, and that, together with our NIH grants and other support from other foundations, is going to allow us to hopefully continue to run this and really make a difference.

MO: I note that there will be emphasis on transformative and holistic medicine, and especially data. What are the specific research goals for the new center?

DA: Our goal is very simple: to make a difference. But one of the things we realized early on, is that data is paramount. There will be a program where we’re starting to gather data from around the world and be a repository for data—in a privacy-protected way—for researchers to analyze large datasets, potentially harmonize together and make them larger, and to really push the limits of Big Data as it applies to the field of cancer and progress.

To us, data is critical. At the same time, we’re going to have the standard programs in biology, engineering and ‘omics, but our goal is to work more of a hub-and-spoke model, to work with the best in each discipline across the country to help work together to get an answer.

My mantra is that of Andy Grove, at the time the CEO of Intel, and Andy famously said, “There’s no technology that will win, technology itself will win,” and I believe that.

You’re not going to have the winner be genomics vs. proteomics or metabolomics or microbiomics—it’s all of them together. And so the challenge is integrating them, and building models that bring in multiple technologies. So again, I view this as a team approach.

We’re a small group; around the country and around the world, we have some of the greatest researchers in different disciplines. The hope is we can integrate them and work together.

MO: Did you say that the center would be working on a database? What will that look like?

DA: We’re not creating a database, but we’re going to be a repository of data. The volume we see is rather small, but we can start to pull datasets from across the world, bring them together in one place, and harmonize them and develop models.

We have a program that we develop models: just like you can see models for hurricanes off Florida, they can go route A, B or C. And after the hurricane, they’ll say which model was right and why were the others wrong, and each model gets better.

We want to start to develop that in cancer. There are about several good models now, and when we start to put them in one place where people can plug in good data and say which model predicted what happened—whether it be the animal, the patient with cancer—and we can start to improve the models with this iterant feedback loops.

The Breast Cancer Research Foundation funded us for a few years to start to put together this repository of models, and we’ve been working with about seven groups across the world on some of these datasets. We’re in conversation with others to bring them.

Obviously, now we have the resources, we’re hoping to do that in a much more scaled, bigger way.

MO: The public focus right now is on oncology bioinformatics, thanks to Vice President Joe Biden’s moonshot, and many groups are working towards that data-sharing goal. Why do you think the time has come for oncology to start looking in this direction, and what specialty will this center bring to the table?

DA: With the convergence of electronic medical records with the convergence of more standardized data elements and data collection, data has more utility.

We’re in a field now where we’re starting to see some wins. There’s a beautiful paper last year saying that if you’re on a beta-blocker with ovarian cancer, you live longer than if you’re not. Over and over, we’ve seen big data having impact. What you need for a field to take off is wins. We’re starting to have them.

Where we can add help, and where our strength is, is in two areas: we have a fantastic group led by Carl Kesselman [division director of the Information Sciences Institute at USC Viterbi School of Engineering], who has built large databases to hold disparate data—whether it be genomic data, proteomic data, clinical trial data—start to pull them into one database. Carl and our group have really put in a paramount effort.

Second, we have a large group of modelers. There’s no question, there are much better groups in the world to collect data. There are much better people who are statisticians to analyze it. What we’re good at is modeling it, and so our focus is going to be creating models—go-forward models based on the data, where we can prove or disprove hypotheses. Our team has been doing that: taking various data sources and putting them together in one model set. I think that’s going to be our focus.

MO: Will you be speaking with Biden or working with his office? Do you see a potential role for the Ellison Institute in the moonshot’s focus on data?

DA: I already have. When he announced it in Davos, I was there, and we spent time together. I’ll spend time with him next month. Greg Simon, who is running the program now, is a close friend.

I, like many cancer docs, was skeptical in the beginning about the moonshot program.

And then we were in Davos in January, and Biden said, “You know, my goal is not to cure cancer. It’d be great, but I don’t think I will have any role in that. But if something was to take 10 years and I can make it happen in five years, I’ve had a major success. I want to remove hurdles and roadblocks.”

That was such a mature way of looking at it. That really impressed me. We all in the field have hurdles that we know of, whether it be regulatory, IRB, collaborations with institutions or pharmaceutical companies, etc. If he can remove some of those hurdles and make it easier for us to do what we’re good at, the moonshot is going to be a tremendous success.

I love now that he is taking on data—it’s one of the first things—and I think it’s fantastic. Obviously, our program is built on the premise of sharing data, that we’re going to work with other institutions who have data and use their data and hopefully improve by harmonizing with other datasets and developing the models. Biden is removing a lot of the hurdles that we would’ve faced, and I applaud him and his team for that.

I wrote a piece in The New York Times two months ago about data. What I pushed for is that we have to change the attitude on data in this country. There’s an attitude that “My data is private, you stay away from it, if it gets out there, I can have irreparable harm.”

We have to go and push for people who use the data, who allow the data to be used for research, to be recognized as heroes. And they are part of the solution, not the problem.

I think the Biden effort will go a long way in that regard. I will play whatever role they require of me, I will support them and I’m so excited that we have powerful people in Washington who get it, who are behind this.

MO: Are there any academic partners? Will this be an USC-centric effort, or will the Ellison Institute be recruiting or partnering with researchers and oncologists across the U.S.?

DA: We are partnering with oncology centers across the world. We now have multiple existing collaborations that will hopefully continue to grow and get new ones.

Our goal is not to reinvent anything. If somebody is doing something well, we want to work with them. We have too much duplication in the field of cancer in this country. If everybody is good at something and we all work together, we’re going to get big advances.

It’s a lot easier and more efficient to get progress if I collaborate with people, than if I bring them in. If I can bring somebody in as a collaborator and give them an appointment, literally overnight—the whole notion of having to go through a year of university reviewing them—we restructured this on purpose to allow those almost instant collaborations.

MO: It sounds like you’re integrating a number of existing programs across departments into the center; is that accurate?

DA: Yes. I’m a believer in people, not departments. It’s getting people in different disciplines and bringing them into one place. To me, it’s human capital that will win against cancer, not institutions or dollars or programs. It’s individuals with very smart ideas.

MO: Are there industry partnerships in the works?

DA: We work with a number of technology providers to work with their technology and to integrate it into the fields of cancer research and cancer care. We push a number of technology companies to innovate newer technologies that we need. I don’t want to push an individual technology or company, but we’re certainly good at leveraging. We have multiple technology partners now—what I want to be is to push them and say, “You’re going to win here, but we’re going to help you make your technology better or find a new indication and then you win.”

MO: What is the business model for sustaining the center’s activities beyond the initial $200 million investment?

DA: NIH grants, foundation grants, philanthropy, all of those will help. Every project that we do, the criteria are that it has to be able to be translated to patients very quickly.

Those in general are relatively easy projects to get funding for. We’re lucky in that regard. The funding climate now is definitely pushed more to the translational side. The basic scientists have more difficulty in the current funding climate—I understand their pain and suffering right now—but the translational cancer field is a little bit easier.

MO: What’s an example of promising, translatable research going on now at USC that the center will be able to leverage?

DA: There’s a paper that came out earlier last year where they look at the eyelids of patients. The eyelid is the one spot on the body where you don’t put sunscreen. When they looked at the eyelid, they found many of the DNA mutations associated with cancer from the UV radiation, yet the patients didn’t have cancer.

What we’ve learned is that DNA mutations are necessary for cancer, but not sufficient. You need a receptive environment. One of the challenges is developing data elements to describe environments. So one of our biggest programs and I think one of the contributions that hopefully we can make in the near term are to create data elements that describe the environment.

How do you say that which environment is receptive vs. not for this cancer or that cancer on a personalized basis? Our modelers, our statisticians, our mathematicians, our physicists have worked together to try to develop data elements to describe that system which is us. It’s pretty cool.

MO: Will the center be working with others beyond the academic cancer center realm, including federal entities like NCI and NIH?

DA: We have significant collaborations with the NCI, we have big programs with the National Health Service in the UK.

These are staggering assets with remarkable people to work with. They’ve been anywhere from just giving us advice to actual formal collaborations. They’re a big part of what we do.

MO: Where do you see the Ellison Institute in say, five or 10 years? When you look back, what will be the difference you hope the institute will have made?

DA: My dream is that every patient with cancer, when they’re diagnosed, we can take their information, their data elements, and put them into a model. And that model will tell us what will be the natural history of the cancer.

It will tell us what they will or won’t respond to, instead of right now where we’re kind of doing it based on simple characteristics—this is an estrogen-positive breast cancer, therefore we do x or y. We have to evolve to be more fine-grained in how we approach clinical decisions.

I think our big contribution will to be to develop these models so we can plug data in and start to know answers. We’re privileged in that, literally, labs across the world are generating the data that will make these models work. So it’s not the if-we-will-develop-it-here approach, but everybody works on it and we’re going to pull it together and create these models.

This is not a case where a researcher gets a big gift and he’s set for life, he doesn’t have to apply for grants. The pressure has been put on us by one of the strongest, most powerful, smartest people in the world, saying, “Make a difference soon.”

So I sleep less now that we have this gift than before, because this is a burden on our shoulders—and the burden is to make a difference.

I, like every cancer doctor that reads The Cancer Letter—there’s very little media that focuses on this in a critical way, you do, and I love that. I see the pain and suffering on a daily basis because of this horrible disease.

That’s what motivates all of us to work, and that’s why we get the small amount of sleep we do, that’s why we worry and think about this issue every day. We have to do better.

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