When somebody gets a fever in a poor country, there is no quick or easy way to tell whether it’s a symptom of flu, malaria, a bacterial invader, or some other bug.
And if you don’t what it is, then it’s hard to treat.
So it’s only natural that shrinking modern diagnostic tools into a lightweight box that’s fast, accurate, cheap, and rugged enough for the African bush is one of the big ideas the Bill & Melinda Gates Foundation has supported in the past five years. The instrument is now starting to take shape under the direction of a team at the University of Washington, through what’s called the DxBox, which looks a little like the popular video game console with a similar name. And this particular box is entering a delicate phase in which big decisions are being made about whether it is really ready for a prime time commercial push, in which it could help healthcare workers better diagnose millions of people.
The original Gates grant, worth $15.4 million over five years, went to a diverse collaboration between a pair of bioengineering labs at the University of Washington, global health experts at Seattle-based PATH, and a couple of commercial partners in Redmond, WA-based Micronics and what used to be called Bothell, WA-based Nanogen (now part of ELITech Group). Four years have now passed by since the first check arrived. As the lead scientist on the project, UW bioengineering chair Paul Yager, put it in a recent UW symposium, “it’s put up or shut up time.”
What he really meant is that enough work has been done that it’s time to size up the real-world commercial potential of the product, or maybe spend some more time back at the drawing board. “You have to take what’s in a lab here in Seattle and scrunch it down to that,” Yager said, pointing to a prototype sitting on a shelf in his office, when I followed up recently. “It’s probably about two years away.”
So after all of the long hours from 40 UW graduate students and postdocs, another 60 professionals outside the UW, and a lot of trial and error to meet all the demanding requirements of a portable diagnostic, what can this DxBox really do?
It is made to take a pinprick of blood, which a health worker squeezes onto a cartridge that slides into an 8-pound prototype device. All the health worker needs to do is hit “run,” and the pumps and valves inside the little box perform two kinds of automatic diagnostic tests. One is an immunoassay test that uses conventional antibodies, not all that different from a pregnancy test, that are made to bind with certain microbial invaders or antibodies that people produce in response to a certain infection. The other test is a more precise nucleic acid assay, which is supposed to identify microbes at the DNA level. Both tests are made to spit out an answer on an LCD screen in whatever the worker’s native language is, within 30 minutes, to identify the patient’s illness, Yager says. And the machine can run a full day on a laptop battery in places without electricity, Yager says.
The DxBox was designed to screen for six common illnesses that are associated with high fevers—flu, malaria, typhoid, rickettsial infections, measles, and dengue. Even from the start, the machine wasn’t made to be comprehensive, since it doesn’t screen for two of the biggest killers in the developing world—HIV and tuberculosis. (Although the machine could be engineered to test for those as well with more funding, Yager says). It also doesn’t provide quantitative data on the precise amount of, say, a viral infection in the blood, which might help a doctor decide what dose or drug regimen to prescribe.
“We didn’t invent new ways to do DNA amplification, we’re just packaging them such that they can be practiced in the developing world,” Yager says.
But the DxBox can provide a simple answer, which is an improvement over trying to get biological samples shipped over long, often hot distances to a central lab that’s probably overextended, Yager says. Getting the diagnosis right is important, because when in doubt, doctors will often prescribe antimalarials or antibiotics even when they shouldn’t, which contributes to drug resistance over time, and can subject patients to unnecessary drug side effects.
“What does the end user want? The yes/no answer of what [illness] the patient has is what they want,” Yager says.
How accurate the device will be in real-world situations is still unknown. The UW team got grant money to build the machine, but not to run a field trial in Africa, in which direct comparisons could be made between the DxBox and state-of-the-art laboratory tools. Instead, the DxBox team has had some samples shipped from Kenya, Nepal, Nicaragua to do some comparisons on the lab bench. Yager didn’t say how accurate it really is, other than to say it works well for four of the diseases it is supposed to screen for, but not so well for flu and typhoid.
The biggest questions I still wanted to get answered are more about business. How much will the machine cost? How much will it cost to make at large scale? How much should it reasonably sell for? Who will buy it? And who could step up as a commercial partner with global distribution reach? Will the Gates Foundation actually buy some of the machines to create some initial market demand, and leave it up to the commercial partners to make their profits by selling the machine in the U.S., Europe, and Japan?
Yager didn’t want to answer a lot of these questions, because some of them were being worked out behind closed doors as we spoke. He did say that he thinks there is a U.S. commercial market for the DxBox that could provide some returns for business partners, because its only real competitor would be Sunnyvale, CA-based Cepheid’s GeneXpert, which Yager said “does less, and is slower.”
The Gates Foundation makes it clear that when it bankrolls a project, the end result needs to be made available to those who need it most. But if a commercial partner is going to be involved, it needs to find a way to do that while generating a financial return, Yager says. “How does the Gates Foundation deal with success?” Yager says. “It’s a big deal, and an important question. To get this out there, it will not be free.”
Complicating matters further is the messy little question of how soon the DxBox might become obsolete. The leading edge of research now is in paper-based diagnostics, in which prolific Harvard University chemist George Whitesides is a leader (and which the Yager team recently just won a $1 million federal grant to pursue). Essentially, by embedding microfluidic technology into cheap paper, and dropping a pinprick of blood on the paper, this could create what Whitesides has called “the one-cent diagnostic.” These pieces of paper can be paired with cell phones, which are common in the developing world, that would have applications that could photograph and interpret the information on the paper so that a health care worker can get an accurate diagnosis on the spot.
But while that work looks further into the future, Yager doesn’t want financiers, or partners, to forget about the DxBox and what it can do right around the corner.
“The paper-based diagnostic is the encore, it’s five years out,” Yager says. “This [DxBox] is two years out, and it will be able to do stuff the paper test won’t do.”
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