MacArthur Winner Adapts High-Tech Medicine to Third World

http://jamanetwork.com/journals/jama/fullarticle/2601108

At a time when budgets for science and global health seem under threat, Rebecca Richards-Kortum, PhD, is doubling down on efforts to bring modern medicine to the developing world at a fraction of the cost. The Rice University bioengineer, winner of a 2016 MacArthur Fellowship, a $625,000 award often called a “genius grant,” specializes in helping countries with limited resources fight widespread afflictions like infant mortality, cancer, and malaria, using cheap, ingenious equivalents of advanced technologies.

Little in her background suggested that she would one day be a leader in addressing global health care inequities. As a University of Nebraska sophomore from a small, quasi-rural community, she was astonished when the chairman of the physics department invited her to join his research laboratory. “I didn’t know that research was even a thing,” she recalls. “I thought college professors just taught class.”

From those humble beginnings, by way of the Massachusetts Institute of Technology, has come an innovative overachiever. Richards-Kortum not only harnesses nanotechnology, molecular imaging, and optical contrast agents in collaborating closely on a stream of translational projects with MD Anderson Cancer Center, Baylor College of Medicine, the University of Texas Health Science Center, and others, but also in 2007 founded Rice 360° Institute for Global Health, an undergraduate program whose mission is “to prepare students to lead tomorrow’s global health workforce.” Key to the curriculum is Beyond Traditional Borders, a class she coteaches with longtime faculty colleague Maria Oden, PhD, in which students design and implement new technologies to solve actual global health challenges—often on-site in Africa.

Pivotal was a 2006 trip that Richards-Kortum and Oden, director of Rice’s Oshman Engineering Design Kitchen, took to Malawi for the opening of the Baylor College of Medicine-Abbott Fund Children’s Clinical Center of Excellence-Malawi, a pediatric AIDS clinic in Lilongwe whose staff also supports the neighboring Kamuzu Central Hospital and takes pediatric referrals from across the country. The trip opened their eyes to the tremendous need there for affordable medical services. Their work now extends to Brazil, Rwanda, El Salvador, and other underresourced nations.

Richards-Kortum recently spoke with JAMA about past and future projects and the need to bring the benefits of the bench to bedsides worldwide. The following is an edited version of the interview.

JAMA: You recently won a MacArthur Fellowship. Do you feel like a genius?

Dr. Richards-Kortum: No, definitely not. I feel like it's an amazing opportunity, both from the perspective of having unrestricted resources to doing things that might take much longer otherwise. The validation makes it a lot easier to bring other partners to the table to amplify what we want to do.

JAMA: What are those things?

Dr. Richards-Kortum: We've been trying to develop technologies to improve newborn health in Malawi. I’m going to use all of the resources toward expanding that work.

JAMA: You and your colleague Maria Oden took a trip there in 2006. How did it affect you?

Dr. Richards-Kortum: It truly was transformative. I came home with a whole different set of professional goals and a very different view of what global health inequity looks like. It was one thing to read about it, or teach about it, and then a very different thing to see it.

JAMA: What struck you in particular?

Dr. Richards-Kortum: The role technology could play. In the neonatal ward of one hospital I saw a lack of technology but also a room full of donated equipment that didn't function in that environment because when the line voltage spiked, the digital electronics would get destroyed, or the filters to keep dust out were inadequate to the environmental conditions. Or a specific brand of [accessory] was needed to work with a particular piece of equipment, and the hospital couldn't source that brand. So, it's not just that you need equipment, but that you need a really different kind of equipment. That inspired what has turned into a very large effort. How do you approach design to get something affordable, rugged, and easy to maintain in environments that exist in low- and middle-income countries?

JAMA: What was the first design your students worked on?

Dr. Richards-Kortum: One of the first problems came from the Medical Brigade Organization, which worked in the rural areas of the country. They wanted a way to do a basic physical exam, and basic laboratory tests. So we made a diagnostic laboratory in a backpack. It had all the tools you need to do a basic physical exam, as well as simple laboratory tests. It was powered by a laptop battery, with a solar panel, so if you didn't have access to wall power, you could recharge the battery using the solar panel.

JAMA: You said neonatal survival has been your primary focus the past 5 years. What have you done in that regard?

Dr. Richards-Kortum: A big challenge is that premature babies need breathing support from a continuous positive air pressure machine, but the hospitals just didn't have the resources. Typical CPAP machines cost about $6000 and require a piped source of oxygen and air. They don't have either. So we presented a team of students with the challenge of building a low-cost bubble CPAP machine, and they had the brilliant idea of using aquarium pumps as the flow driver in the system because it is a very inexpensive pump designed to run forever and is available at Petco. They were able to demonstrate that their $350 prototype delivered the same flow and pressure as the system used therapeutically at Texas Children's Hospital. A later evaluation showed that survival of premature babies suffering from respiratory distress syndrome improved from 24% to just over 64%.

JAMA: What else have your students come up with?

Dr. Richards-Kortum: A syringe pump that’s very inexpensive and mostly runs on mechanical power. A big challenge with syringe pumps is if the power is going on and off, your infusion stops. So the students’ insight was to take the kind of spring you have in your garage door opener and use it to power the pressing of the plunger of the syringe. Then a little battery-powered motor controls the rate at which that energy is released to greatly reduce the amount of electrical energy that's required. That device is now in clinical evaluation [at Queen Elizabeth Central Hospital in Blantyre, Malawi], both for delivering magnesium sulfate to women with preeclampsia, as well as providing fluid to newborns.

JAMA: Didn’t you also figure out a way to use body heat as a substitute for electricity to get reactions in HIV diagnostic tests?

Dr. Richards-Kortum: There are a lot of isothermal amplification methods, and the one we looked at was recombinase polymerase amplification (RPA). The ideal temperature for RPA amplification is in the same window as body temperature. So we did a simple study to see if you can use body heat to power the reaction and you can.

JAMA: Your abstract says the heat comes from the axillae. Armpits, yes?

Dr. Richards-Kortum: Yep.

JAMA: Who are your inspirations?

Dr. Richards-Kortum: There's an amazing pediatrician in Malawi named Liz Molyneux. She taught me 2 important lessons. One is that in places like Malawi what's important is to enable clinicians to do simple things well, to not get too focused on complexity. The other is that it's important to work within the system, because if you don't, the likelihood that any change that you introduce will stick is so much lower.

JAMA: How much time do you spend in the field?

Dr. Richards-Kortum: I go to Malawi 3 or 4 times a year. We have projects in Brazil, so I’m usually there 4 times, and in El Salvador probably the same.

JAMA: You have 6 children. How do you balance all that?

Dr. Richards-Kortum: My husband is amazing. But you know, you figure it out a day at a time. I do tell people I have very loose standards at home and it’s only halfway a joke. I have served frozen waffles off the floor for dinner.

JAMA: Can you describe your efforts to fight malaria?

Dr. Richards-Kortum: We have been working to develop very low-cost, portable, battery-powered microscopes that can be used to image and quantify the presence of the parasite in circulating blood without the need to take a physical specimen. This “needle-free” approach eliminates the pain and biohazards associated with taking a blood sample—and it doesn’t require consumable reagents. We have validated this in animal models and are preparing for the first clinical evaluation.

JAMA: You also have an optical spectroscopy and imaging lab at Rice. What does it do?

Dr. Richards-Kortum: We focus on using optical imaging or spectroscopic measurement to improve point-of-care diagnostics. A lot of the work is improving early detection of precancerous lesions. If you’re looking for them, typically a physician in the US would look at the epithelium at risk. If they see signs consistent with precancerous lesions, they'll take a biopsy, which gets sent to the histology laboratory, and it'll get sectioned and stained, and a pathologist or cytotechnologist will look at it under a microscope. So there's this whole infrastructure of equipment and human resources, and you end up with a delay of a week or so before the answer gets back to the patient.

If you're working in a low-resource setting, all those issues are a problem. In Malawi, the infrastructure doesn't exist. There's no modern histology laboratory, and in the entire country, there's fewer than 5 pathologists. So we're seeking ways that you can, via fiber optic florescence microscopy, get that same information without taking a biopsy, that you can image those changes in vivo. We're trying to develop automated image analysis algorithms, so that you can use image processing to say, “Yes, this is a precancerous lesion,” and then immediately provide treatment for it, so that you can collapse screening, diagnosis, and treatment in a single visit. Otherwise the patient might not come back to get the results. Also, potentially you can put this in the hands of providers with less expertise: nurses, or even community health workers to do initial screening and diagnosis.

JAMA: What kind of cancers are we speaking of?

Dr. Richards-Kortum: We've been looking at cervical, oral, and esophageal. In cervical and oral, you have pretty easy access to visualize the cervix or the oral mucosa. In the esophagus, though, right now you need to first do a traditional endoscopy. But there are exciting approaches using capsule-based endoscopy where you can swallow a pill-sized imager, and get that same kind of information.

JAMA: How would you treat these cancers? If you're in the United States, you have chemotherapy and radiation. Not there, unfortunately.

Dr. Richards-Kortum: That's why it's important to identify these lesions when they're still at the pre-cancerous stage, because at that point, excisional therapies are completely curative. So, if you just excise the epithelium that contains the precancerous cells, you can prevent their progression. You can do that with cryotherapy, with an electrosurgical excision, or with laser ablation. There's lots of approaches. I think this is a really nice example of where the same kinds of technologies that could be useful in places like Malawi could be very useful everywhere in the United States.

JAMA: Yes, there are certainly communities here in the States that are almost as resource-deprived as Malawi.

Dr. Richards-Kortum: Absolutely. So it's exciting because in the US, health care access is a big challenge, largely driven by economics. If we can identify opportunities for low-cost technology that can intervene at early stages of chronic diseases, I think that's absolutely where we should be putting our energy.