When Edus Houston Warren III was 12 years old, he read about Norman Borlaug, a plant breeder turned father of the green revolution who won the Nobel Peace Prize in 1970 for his work. To Hootie, the name his sister gave him that he still goes by today, Borlaug was a hero, and while he grew up in the suburbs of New Jersey rather than a farm in Minnesota, he went to college wanting to be an agronomist. Ultimately, he went into medicine, but when he picked up The Boston Globe in 1990 while a student at Harvard Medical School, he read about another Nobel Prize winner, Dr. Don Thomas, who would inspire him to join the team at Fred Hutch.
Dr. Warren, who designed and led the Fred Hutch’s first clinical trial on T-cell therapy for leukemia patients, has focused on global oncology for the past five years. He spoke with Devex about his mission to transform cancer care in the developing world. To this day, Hootie carries a little plastic picture of Borlaug in his briefcase, because while botany was not his path, global impact remains his goal.
The conversation has been edited for length and clarity.
I know your path was inspired in part by Don Thomas, who was the director of the clinical research division at Fred Hutch, and won the Nobel Prize for his discovery that bone marrow transplants could save the lives of blood cancer patients. But reading about Norman Borlaug inspired you to have a global impact, and it seems like one of the challenges of global oncology is that cancer breakthroughs developed in the United States do not make it to the developing world. So how have you built on the work of Don Thomas while also maintaining your global focus?
I’ve been here for 24 years, and I’ve practiced what I would characterize as quaternary care medicine, very highly specialized medicine, that is primarily allogeneic bone marrow transplantation for the treatment of leukemia blood cancers. And I was really drawn to that because of the therapeutic principle that provides the foundation that is the rationale for doing transplant, which is the fact that the patients who get an allogeneic transplant and don’t relapse owe it to their donor’s immune system — what we call the graft-versus-leukemia effect. And when I read about that in The Boston Globe, I just thought it was fascinating and decided I wanted to study that, so I made that decision on that day.
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I’ve spent a lot of my career here broadly speaking within the field of cancer immunology trying to understand how the immune system might eliminate cancer cells, what happens when it fails, and what underlies the elimination of tumors when it’s successful, which isn’t as often as we’d like. But over the years, I’ve never lost sight of a global focus, and the very visceral desire to contribute on a broad scale to the health of large populations.
I’ve been lucky to be a witness to a scientific revolution that really has transformed oncology into a vastly different field than it was when I was in medical school. And over the last five to eight years, I’ve become increasingly interested in extending the benefits of the breathtaking advances that we generate on a daily basis here and in other elite cancer centers across the country and extending them to the large majority of the global population who don’t really have access to those advances yet.
It’s important we extract the operative principles that might enable the development of an immunotherapy that could be adapted to a low-resource setting. As low- and middle-income countries develop, it’s expected more and more of population in those countries will have access to what we would consider high-tech medicine. But that will take a while, and in the meantime, I think there’s an enormous and compelling rationale and imperative for trying to take the scientific principles and therapeutic principles that underlie the efficacy of high-tech medicines and see if we can adapt them.
It’s really a challenge to our creativity and our imagination: How can we exploit the therapeutic principle that lies at heart of, say, allogeneic bone marrow transplantation or CAR-T Cell Therapy and adapt that to a low resource setting? That gets me very excited and I think that’s really the challenge for global oncology.
Like other organizations working on global oncology, the Fred Hutch faces a cancer funding gap. While more than 70 percent of cancer deaths happen in low- and middle-income countries, most global health funding for cancer is minimal in these countries compared to funding for other diseases. How do you plan to deal with this?
There is growing recognition that noncommunicable diseases, not the least of which is cancer, are responsible for an increasing fraction of global illness. And that’s true on every continent. NCDs are increasing steadily in prevalence in all countries across all income levels and steadily increasing as an attributable cause of disability adjusted life years, or DALYs, as well as deaths. But the funding is lagging behind the recognition of the growing importance of NCDs as a factor in global health.
The newly-launched African Access Initiative hopes to bring affordable cancer treatment and advanced cancer research and technology to sub-Saharan Africa. Four countries selected for the first phase of this initiative will benefit from partnerships with oncology companies to expand in-country capacity to treat cancer and reduce cancer deaths.
I think there are signs, encouraging signs, that funding priorities are shifting. But to this day, still a large fraction of say the funds that are targeted for biomedical population health in low- and middle-income countries are devoted and directed toward communicable diseases, most notably HIV, malaria, tuberculosis. Those are still enormous problems. And it is encouraging that thanks in large part to the resources that have been devoted to these problems, there’s been enormous progress. But with that progress on communicable diseases has come the realization that noncommunicable disease accounts for a growing proportion of DALYs and deaths. And readjusting, refocusing, redirecting our biomedical health resources and biomedical research resources to reflect that changing proportion is something we need to do.
What we do here at the Fred Hutch has potential global impact, but to realize that and to enable that impact, we have to adapt it appropriately. Some of the complex and technically sophisticated therapies that we deliver here are not going to be feasible in sub-Saharan Africa for quite some time. But we want to use our creativity and imagination, which we have no shortage of, to think about how we can take the principles that make these miraculous and jaw-dropping and breathtaking interventions just as effective, perhaps in a slightly different way, in a setting where the resources are far more limited.
We really can’t wait for development to eliminate the differences in health resources. I think there’s an enormous imperative for developing resource-stratified or resource level-adapted treatments that can extend the benefits of this unbelievable oncology revolution that I’ve witnessed over the past quarter century to the 90 percent plus of the world’s population who don’t have access to that yet. We can take advantage of technologies that can be implemented in the field in a way that doesn't rely on highly centralized health systems, that are resource replete and deliver sophisticated medical care in settings that we’ve never been able to touch before.
I think it will require just basically getting people to explicitly ask themselves: “Okay, here’s something that we can do here. The mechanisms by which this works are X, Y, and Z. How can we take that principle, the operative mechanisms, and develop resource appropriate implementations that will be useful and cost effective in a low-resource setting?” I hope to push my colleagues to think about how what they produce might be applicable to a low resource setting and I want to emphasize that.
Can you talk about how partnerships, in addition to funding, will be essential to the success of the Global Oncology Program?
Partnerships is a very high priority and something that, when I assumed this job, I was asked to pursue quite explicitly. There’s enormous potential for partnerships with pharmaceutical manufacturers to work collaboratively to increase the availability of current generation of state-of-the-art anticancer drugs and agents in areas where the medicines available now are just the legacy medicines we’ve had for 50 years. Immunotherapy drugs are probably the best example.
One of the most interesting developments in this oncologic revolution that I’ve witnessed over the past 20 years has been drugs that somehow exploit the immune system in their mechanisms of efficacy. There are two drugs we spend most of our drug cancer dollars on here every year: Rituximab and Trastuzumab, which is otherwise known as Herceptin. These drugs have transformed the treatment of B cell lymphoma and breast cancer, and the impact of that is impossible to quantify. But those drugs are not widely available in low-income countries. They’re very hard to come by in Uganda, for example, and across sub-Saharan Africa.
One email I just sent was to Roche, the parent company for Genentech, to talk about their sponsoring a trial of a subcutaneous formulation of Rituximab that we could use for lymphoma patients at the Uganda Cancer Institute. Partnerships of that nature are something we would very much like to cultivate and nurture. And I think they have enormous potential to improve cancer care in all low- and middle-income countries.
In sub-Saharan Africa, we’re in negotiations with Merck - at least we’ve had conversations with them - to explore use of one of their monoclonal antibodies that have a different mechanism of action. The drug is called Pembrolizumab, and it works basically by taking the brakes off the immune system. Those types of drugs, immune checkpoint inhibitors, have been licensed for I think eight different cancers now, and counting. They’re effective in all kinds of cancers that have largely been difficult to treat with chemotherapy before, such as non-small cell lung cancer and bladder cancer and melanoma. But in general, they’re very expensive drugs. So partnering with pharmaceuticals to make it possible to make these drugs available for use in low- and middle-income countries is something we’re very much interested in.
We don’t have agreements yet but we’d love to pursue agreements because we think these drugs would have terrific value in settings such as Uganda and sub-Saharan Africa and elsewhere.
I know you’re often traveling back and forth between Kampala, Uganda and Seattle, Washington. The China Initiative is also a priority. Can you talk about how you plan to balance your time between the Global Oncology program’s work in Uganda, China, and elsewhere?
“We don’t claim to be everywhere. But what we want to do is research with global impact. And that’s the important thing. We want our research to be cutting edge and innovative and have global impact.”— Dr. Edus Houston Warren, head of global oncology at the Fred Hutchinson Cancer Research Center
Most of our global oncology efforts are now based in Uganda. We built a beautiful 25,000 square foot building in collaboration with the Uganda Cancer Institute and so our global oncology activities are dominated by this collaboration we established 10 years ago. But we’re exploring research opportunities elsewhere for a number of different reasons.
Fred Hutch has collaborated with Chinese medical researchers for decades and the reasons for that are numerous, one of which is China’s vast population. It also has an interesting blend of advanced urban and poor rural areas. They have growing investment in and political will for biomedical and public health research. The Fred Hutch launched a collaboration in 2010 with the Chinese Center for Disease Control and Prevention. The focus of that was on infection associated cancers, environmental health, cancer biomarkers.
And we hope that segment of our activities will grow. One out of every 6 people walking on the planet is in China. There’s 1.4 billion chinese and 7.5 billion people on the planet. And so I think there is enormous scientific possibility and potential in oncology research that we can do in collaboration with Chinese scientists and investigators.
We don’t have a global footprint. We don’t claim to be everywhere. But what we want to do is research with global impact. And that’s the important thing. We want our research to be cutting edge and innovative and have global impact.
That’s how I’m moving forward in pursuing our studies and that’s the way I want to lead our global oncology program. We want to address the problems and principles that may be applicable to one malignancy in one location but will be more broadly applicable to other malignancies that are common in different settings. We really want to emphasize global impact. That's my credo.
Update, June 26, 2017: This article has been updated to clarify that Fred Hutch does not yet have agreements with Merck and Roche.