July 2008
Paul Yager and his project partners are on the verge of something big.
They are on schedule to introduce new technology that will revolutionize diagnostic testing around the world a little more than two years from now when their five-year project comes to its conclusion. Remarkable results are expected, first dramatically improving diagnoses for malaria and other diseases in the developing world, then prompting significant changes in first-world heath care.
Yager, the acting chair and a professor of the University of Washington’s Department of Bioengineering, still remembers first hearing about point-of-care diagnostics at UW.
“I was actually first introduced to the idea by someone from the laboratory medicine department here,” he recalled. “They had one of the first point-of-care instruments that anybody had manufactured.
Yager addresses the topic in his new UWTV video, “Point-of-Care Diagnostics for the Developing World.”
Since 1992, Yager and others at UW have been working to use microfabrication in point-of-care diagnostics development.
With major advances in technology and the ability to move electrons around, the next question was, Yager explained, what about moving liquids around efficiently?
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“I come from a chemistry and biochemistry background, and most people still think of chemistry as being on the scale of things like a coffee cup. That’s the size in which you do your experiments when you learn chemistry: You pour two things in a beaker. And that’s just essentially unnecessarily wasteful. You can get the same result in a much smaller beaker.
“I had spent a bunch of time doing optical experiments, on very small amounts of liquids, and realized, why couldn’t we do everything at that size scale?”
It was a career-changing idea for Yager.
“Point-of-care diagnostics was the technological, or the application, pull, where you realize you could then move things away from big, centralized laboratories into the doctors’ offices, and eventually the home.
“My first interest was in the part I understood: how it could affect medicine in my world. And then, gradually, particularly when we started really spending time with the folks at PATH, it became clear that you could pull the blinders off and think not just about U.S. domestic and developed world stuff, but the developing world was a possibility as well.”
That possibility was inspiration for Yager’s current point-of-care diagnostics project. By improving this technology, health care workers will be able to correctly diagnose, treat and adjust medication levels for infectious diseases from remote locations and accurately identify outbreaks.
Yager’s goals line up with those of project partners PATH and the Bill & Melinda Gates Foundation, which both aim to target infectious diseases.
“That’s a very laudable goal, and a reasonable target to go after, but also a very challenging one and we’re delighted we can play some role in dealing with this problem.
“The Gates Foundation has been the major catalyst to allow us to think big. We’ve been doing smaller projects, but very few entities have the clout to be able to say, 'here’s the technology, here’s a pathway to commercialization.' They provided us a stage, a raised platform from which to operate. It’s gotten us a lot of attention, and that’s a very good thing for the field, almost independent of what we do, simply because it means this is a technology which is now ready for primetime.”
“And a lot of big companies are paying very close attention to this and are busily working with their own partners and developing their own products. So we’re going to see the technology advance and get to market much faster because of our project. In a sense, even if we failed, the visibility will have been created; the idea’s out there and it’s moving very rapidly now. If we’re successful, even better.”
Drawing off the shorthand term for diagnostics, the project is called the “DxBox,” a nod to Microsoft. That’s not likely to be the name of the final commercial project.
“The primary goal of the project was to diagnose a patient for a range of conditions, not just one thing at a time, but to be able to differentiate causes of disease. PATH suggested that we go after rapid onset fevers as a category of problems that exists in the developing world for which you can incorrectly diagnose someone unless you get really detailed information.”
“If you treat someone for malaria, but they have something else, you actually give them drugs that are hard on their systems, so you can actually kill them by treating them for the wrong thing.
“The initial target was six different fever-causing pathogens and they include malaria, typhoid and dengue fever, influenza, measles and Rickettsial Diseases. There’s a range of different pathogens, all of which could present as you showing up with a high fever.
“The DxBox is designed with two chemical technologies meant to monitor different types of blood chemistry issues,” Yager explained.
“We decided to go with a finger-stick blood sample as a small, easy-to-obtain sample, but it’s very small. Small is good for the patient, but it’s a technological challenge to find enough of the analyte in a very small sample of blood.
“What we wanted to do is take that very small sample and split it two ways. And on one side, we would look for proteins. We use what’s called an immunoassay, which is an assay that uses a biological molecule called an antibody, which is typically generated in animals or bacteria.”
This component of the test seeks out either protiens from the pathogens or antibodies produced by the patient against the pathogens.
“You don’t have to have the pathogen left in your bloodstream,” Yager explained. “You will have those antibodies around for a couple of weeks.”
“The other side of the sample goes into a different line, and there we amplify nucleic acids. And specifically what we’re doing is amplifying little pieces of nucleic acids, six different ones, one for each pathogen, that would tell us if a very specific piece of the DNA or RNA of a pathogen was present in the blood.”
This portion of the test looks for the virus or the bacterium in the blood sample, which appear in early stages of disease.
The duality of this testing method will detect disease from onset to weeks after the initial infection.
Now nearly at the end of the third year of the project, Yager’s focus seems set on placing the product in the hands of its intended users. Seeing commercialization come to fruition takes many players.
“This isn’t just a university project,” Yager explained. “There’s myself and Patrick Stayton at UW; there is Nanogen Corporation; there is PATH, a nonprofit organization; and Micronics, a start-up company that I helped to found out of technology out of our group; and their subsidiary, Invetech, that’s working with them to develop the box and the cards and the system. It’s Micronics' responsibility under the grant to actually come up with a pathway to see to it that it can be commercialized. That may occur with assistance from the Gates Foundation, or may be completely independent.
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“Our hope is that by the end of the fifth year we’ll already have products being sold in the developing world.”
Though this technology is currently aimed at the developing world, it will prove useful closer to home as well.
“Most of us have pretty good access to doctors when we live here in a city like Seattle,” Yager explained. “The people who don’t have as good access to medical care are elderly people who aren’t as mobile, poor people in general, people who live in rural areas, even in this country.”
Likely applications for these populations include tracking chronic conditions, early detection of disease and monitoring drug levels of persons on a medication regimen.
“Being able to adjust medication doses for lifestyle changes and changes of life of all sorts would be a really, really major advance in how we deal with medications,” Yager said. “For the domestic market, in a sense, that’s one of the highest priorities.”
Putting this high-tech self-measurement into the hands of patients creates its own concerns.
“You could imagine that the wrong personality type could take this the wrong way,” Yager said. “You could imagine that giving somebody too much information could drive them crazy. So I think you’d want to be selective in which people did this.
A successful launch in the developing world may be just what is needed to spur countries like the U.S. into adopting the same technology.
“My guess is that a lot of this technology is going to be developed by organizations like the Gates Foundation for global health purposes and then be channeled back into the domestic market. Any technology like this has the potential to be disruptive," Yager said.
“So, for example, point-of-care testing, in theory, threatens the jobs of those people in large, centralized laboratories. Those are businesses. Those businesses do not like the idea that you and I would go home and monitor drug levels. If today the controlled FDA-approved method of doing that is through samples taken at your doctor’s office and then sent to a centralized laboratory, that’s politics, that’s business.
“That’s why I think a lot of this technology’s going to develop for the developing world, places where they don’t have the infrastructure in place in the same way that cell phones are now ubiquitous in parts of Africa where there was no way they were going to get land lines in. There was no infrastructure to push out of the way. It simply was put in place. So in a sense, parts of the developing world have leap-frogged us in terms of types of infrastructure and modern infrastructure they’re able to put in because there’s nothing to push out of the way. I think that may be what we see in this kind of diagnostics in that we will find that other places other than the United States, where we are so good at having entrenched entities controlling the political situation and the flow of government funds, we’ll find it happening faster elsewhere then moving back, and simply because we’re going to be embarrassed when some other entity has better health care than we do.”
For Yager, imagining the future is part of his job.
“I think it’s really important to live a little while in the future, not in today, but keep your head somewhere 20, 100 years out and almost spend your time looking back from that vantage point and saying, ‘Which one was the right choice, guys?’
“That’s what I think we can do fairly well in bioengineering. We have a lot of options. Part of my job, both as a scientist and as acting chair of the department, is to identify some of those pathways.”
Yager’s office bookshelves provide plenty of inspiration for the future, explored in the pages of numerous science fiction novels.
“I tend to live in that 100 years in the future, so I love to spout off on all the cool things I think would happen with medicine,” Yager said, his eyes scanning the spines of his futuristic book collection.
One of the biggest obstacles facing today’s bioengineers is the foreign body reaction, Yager said.
“It basically treats everything you put in it like it was a splinter,” he said. “It tries to encapsulate it, and then kick it out.
“If I wanted to say where we’re going to be 100 years from now, I’d say we’ll solve that problem well enough that we can say, OK, yeah, let’s put a couple of chips in you, and we’ll have one that monitors your liver and another one the makes sure that even though you have the gene for Parkinson’s that you’re not going to develop it, and maybe you can put it off for a while; something else that will cause a blinking red light to go off in your eyeball when you’ve had too much to drink.
“You’ll have feedback into how your body is doing more directly. We’ll instrument ourselves up.”
Yager also subscribes to the grow-your-own replacement body parts theory as well.
“The bottom line is, things wear out. Hearts certainly wear out. Parts of the brain can wear out.”
Finding morally sound methods of growing body parts will be just as important as developing the technology to do so.
“They are just what I would call ethically unacceptable alternatives to these problems, so coming up with technologically practical ones is pretty much what we are going to be doing in bioengineering for the next 100 years.
“There are loads of ways to solve the problem and what I love about living in science fiction, which is something I’ve done since I was about 6 years old, is you can lay out the alternative ways you might think about solving the problem.
“I think an important thing to do is to write some new stories. I think every generation’s got to write its own science fiction because you’ve got to be thinking about what are the options out there? You’ve got to extend yourself out a few decades at least and say, ‘OK, if we could do that, would it be a good thing?’”
For more information about Inside Look features, contact Erin Lodi at erinlodi@u.washington.edu.
