Once upon a time at TEDMED: The story behind a groundbreaking cancer research collaboration

When we heard that two former TEDMED speakers, Drs. David Agus and Anthony Atala, had been awarded an NIH grant to develop the first-ever integrated bioengineered/computational model of metastatic colon cancer, TEDMED investigated the backstory of their unique collaboration.

It turns out the two met at TEDMED, which makes us proud; our mission is to be a petrie dish in which minds from many realms can mingle and imagine entirely new phenomena. The Agus/Atala collaboration is one example of many — a book arose from a chance meeting in the mens’ room at one TEDMED – and has the potential to make a huge impact on human health.

We asked David Agus to explain how it all came about.

Can you describe how you and Dr. Atala got the idea for this project?

I heard his talk, and he heard mine, and we met at a speaker reception – TEDMED is also very much about what happens between the talks.  When you speak at TEDMED, you’re presenting so the general audience can understand.  But when the two of us got together, we were talking about not just where the technology is today, but where could it go in the future.

shutterstock_75799198We’re both from different domains — I’m an oncologist; Anthony is a surgeon. My group has developed methods of computational cancer modeling; he has a system upon which you can put in a cancer cell and model its growth. Some of the biggest advances in science happen when you cross domains. The NIH had put out a call for submissions to help answer provocative questions in cancer.  So we said, ‘Can we put our two technologies together and make this happen?’

TEDMED has always been viewed as an organization for presenting big ideas about science and medicine.  But it’s also an organization for progress. You get people in the room, you give them a substrate — normally a glass of wine — and let them go, and things happen.

What drew you together to work on this?

Listen, we’re both nerds, we’re both into science, but we’re also both clinicians who take care of patients, and that combination is unusual.  We’re also both driven by seeing people dying from disease. It took a couple of years for this project to come to fruition, but both of us are very fortunate to have remarkable teams to help us do that. Many organizations don’t have the resources to do the pilot experiments and to take the risk.

What does it take to get researchers from various fields to come together on something like this?  Are other critical areas making strides?

For good or for bad, cancer doctors are willing to take a lot more risk than those in other areas.  The cancer field is on the forefront of change; the patients want to take more risk, and regulatory agencies have given us the leeway to do so. We don’t have a choice. There have been over a million published papers on cancer; billions of dollars spent on research. Yet, our understanding of disease metastases has made very little progress. We’re obligated to do things differently. For a more chronic disease like Alzheimer’s, risk taking has a different scenario.

Will current students of science and medicine have an easier time of crossing bridges for collaborative discovery once they begin their careers? 

The notion of cross domain thinking, and getting a physician and mathematician and stem cell scientist together is novel and new. Science rewards only the first author and last author on publications, and we’re talking about a team here of six scientists. Who’s going to get credit?  We have to push change.

What have been some of your favorite TEDMED talks?

One experience that truly changed me was hearing Jay Walker talk about the history of the flu. I was shocked; I thought it would be the goofiest presentation in the world. Yet it changed the ways I’ve thought about things and impacted many things that I think and what I write about.

I’ve started going back to primary sources and the historical side of medicine, whether with Hippocrates and epidemiology, or the plague in London. Doctors take care of patients and create observations that may be even more valuable today.  Back then, we had hours to observe, and we’ve lost that power. Anecdotes and stories are all we have to go on in medicine, and these are stories we need to pay serious attention to.

Have you started other collaborations at TEDMED? 

For me, it’s about the relationships I’ve developed, a broad network of individuals whom I now talk to on a regular basis who have ideas that inspire me. For example, Danny Hillis and I met separately at TEDMED, and it’s led to a lot of collaborative work.

When I go to a cancer meeting, it’s only cancer doctors there. The beauty of TEDMED is that we really get people from many different domains coming together. It may not be a direct influence – you do this part of a problem, and I’ll do that — but hearing how others from different disciplines solved problems changes how you approach your own.

TEDMED speakers Agus and Atala collaborate to study how cancer tumors grow

Using three-­‐dimensional organ creation, three-time TEDMED speaker David Agus of the Keck Medicine of University of Southern California (USC) will lead a team that aims to discover clues to metastatic cancer growth by developing a first-ever integrated bioengineered/computational model of metastatic colon cancer.

Agus is the principal investigator of a $2.3 million, four-­year “Provocative Questions” grant awarded recently by the National Cancer Institute (NCI), a division of the National Institutes of Health (NIH). The project title is “An Integrative Computational and Bioengineered Tissue Model of Metastasis.”  Agus is a pioneer in computational cancer modelling, particularly in the area of proteomics.

Co-authoring the study is TEDMED 2010 speaker Anthony Atala, MD, professor and director of the Wake Forest Institute for Regenerative Medicine (WFIRM) and chair of the department of urology at Wake Forest University. His team engineered the first lab-grown organ to be implanted into a human — a bladder — and is developing experimental fabrication technology that can “print” human tissue on demand.

The first phase of the project will be to calibrate a model with data from bioengineered liver tissue. Phase two will subject the growing tumors to physical changes likely to affect them in the human body, including alterations to oxygenation and drug treatment. In the third phase, the team will compare simulations of tumor growth in actual patients with outcome data from these patients.

USC co-­authors include Heinz-­Josef Lenz, M.D., professor of medicine and preventive medicine and associate director for clinical research and co-­‐leader of the Gastrointestinal Cancers program at the Keck School, as well as Paul Macklin, Ph.D., assistant professor of research, and Dan Ruderman, Ph.D., assistant professor of research medicine, at the Center for Applied Molecular Medicine. Also co-authoring from WFIRM is Shay Soker, Ph.D., professor.

Below, David Agus speaks at TEDMED 2010 on “A new strategy in the war against cancer.”

The NCI Provocative Questions project was launched in 2012 and is based on 20 important questions from the research community, intended to stimulate researchers to seek out especially effective and imaginative ways to study cancer. According to the NCI, the questions are categorized into five themes: Cancer prevention and risk; mechanisms of tumor development or recurrence; tumor detection, diagnosis and prognosis; cancer therapy and outcomes; clinical effectiveness.

Anthony Atala talks at TEDMED 2010 about growing organs in the lab.