Necessity is Still the Mother of InventionDec 20, 2013
Carl Wittwer, one of three health sciences faculty recently made a fellow in the National Academy of Inventors, describes his work involving PCR, a way to copy fragments of DNA by the millions to look for disease, biological pathogens, conductgenetic research and more. Using parts of hairdryers and vacuums for prototypes, Wittwer, professor of pathology, revolutionized PCR research by inventing technology that reduced the time for PCR from several hours to just 15 minutes. His invention led to the founding of Idaho Technology, now called BioFire Diagnostics Inc., which employs 500 people and makes PCR technology, diagnostic tests for identifying pathogens, biosurveillance systems and other technologies.
Announcer: Discover how the research of today will affect you tomorrow. The Science and Research Show is on the Scope.
Interviewer: Today we're speaking with Dr. Carl Wittwer, University of Utah Professor of Pathology, who recently was made a Fellow in the National Academy of Inventors, along with two other University of Utah faculty. You came to the University and one of the directives for you, in your position here, was to find new technology. What did you invent?
Dr. Carl Wittwer: I was a new professor, first academic job. And I had a small laboratory but I had a need that I wanted to do the PCR process. That involves changing temperature, usually between two or three different temperatures. And the equipment to do that, although common today, did not at that time exist. So being somewhat naive and energetic, we decided to build our own instruments. Initially they were somewhat comical instruments, derived from heaters off of hair dryers and fans off of vacuum cleaners. But with a lot of trial and error and a number of prototypes that did not work at all, or not very well, I came up with a very good replication of what was then starting to come out as PCR machines. With one exception. We were able to do it fast. We were able to change temperature very quickly. And if you think about some of the diagnostic applications for PCR, faster answers are always more useful. Typically, at that time, PCR was on a two to four hours with the rapid system. So we developed, we cut the time down to 10 to 15 minutes.
Interviewer: Okay, can you tell us what polymerase chain reaction is and what it does?
Dr. Carl Wittwer: Certainly. Long name but simple concept. Cells in your body replicate after they've made two copies of DNA. Now, you can do this in vitro or in a test tube by the polymerase chain reaction.
Interviewer: And what's the advantage of replicating DNA?
Dr. Carl Wittwer: The advantage would be to amplify that DNA so you can test the sequence of the DNA much easier. So there's only very minute amounts of DNA in most cells, and the process of amplification allows you to interrogate or look at it, ask questions about what it is doing. What the bases are, what it's coding for. And whether or not there's any variance in the DNA. So ,it's like a large magnifying glass.
Interviewer: And what then can you learn from all this DNA that you've amplified and made, I take it, millions of copies of?
Dr. Carl Wittwer: Millions of copies. You'll of course be familiar with the forensic applications that you see on television in terms of identity or ancestry. In the clinical laboratory the major applications are in three different areas. Infectious disease, DNA that should not be there in a sample from an individual. Oncology or cancer, which of course is made, or is caused by changes in DNA. And finally, in genetics. To test for genetic diseases, characteristics that you may have that other people don't have.
Interviewer: From this first invention of yours, a company called Idaho Technology was eventually born.
Dr. Carl Wittwer: Correct, yes.
Interviewer: And Idaho Technology then manufactures these devices?
Dr. Carl Wittwer: Yeah, the initial device, again, we're back in 1990 or so, so it's quite a while ago. We called it, not surprisingly, a Rapid Cycler. A niche product but people were interested in doing things quickly. And it kept the company alive for quite a while. One other thing that we developed was looking at DNA melting. So if you remember the double helix form of DNA, it's got two strands. And if you heat it up, eventually those two strands fall apart. And if you watch very carefully, about how they fall apart, you can tell an amazing amount about what that sequence is and what it does. And any changes that may have occurred in that DNA. Later on the company, which eventually changed its name to BioFire, has been very successful in getting FDA approved products that look for syndromes that are caused by infectious agents. And even though it might be a common syndrome, like a flu-like illness or gastrointestinal symptoms, there's only a limited number of organisms that can actually cause those things. So this particular device will identify the caused organism of a syndrome. All within an hour. If you think back to your experiences at the doctor's office and how long it might take to get results back to you, this has all been encapsulated in to a one hour test. In terms of genetic and infectious disease diagnostics.
Interviewer: It seems to me there's a very creative process going on when you're inventing. What makes you so creative in that area? Or what makes you want to be so creative in that area?
Dr. Carl Wittwer: Yeah, so the old catch phrase of need is the mother of invention, you have to want something. You have to want a goal. You want to be able to achieve something. Whether it's doing PCR fast, which is still one of our, one of my major goals. To take the speed of amplification as an example, at the time that we changed a multi-hour process down to 10 or 15 minutes, that was pretty extraordinary. And I remember someone had a cold call from the blue who criticized me on the phone severely and said, "Wittwer, how can you lie to the public in your scientific publications?"
So, when you really do something that's different, people will not believe what you've done. The next step usually is they'll say, "Okay, I admit that you've done it but it's not worth anything. What are you going to use it for?" Right? And then eventually you'll get some adherence. Some people who say, "Ah-ha, this actually really works." And eventually it might penetrate the market and you might be very successful in terms of company products. Of course, at that stage, usually the original inventors get forgotten. But what you need to remember is that's part of the process and it's actually success when that happens.
Interviewer: What does the future have in store for you and your research?
Dr. Carl Wittwer: We started by making PCR faster than it was at that time. And although it's taken us 20 years to revisit the speed of amplification, the speed of PCR, we now have systems that take that 10 to 15 minute process and can actually produce robust, efficient, quantitative PCR in less than a minute. So start thinking about point of care applications, where you're actually waiting for the answer. So, when you can potentially get results out in under a minute timescale, it changes the way you think about providing diagnostics. Particularly at the point of care. So, of course I'm very excited about this again. Again, currently the state of this is in prototypes that no one, that are not commercially feasible and that very few people would have the patience to work with. But in terms of proving the point, the limits of, be it, in this case, speed, you end up with those prototypes that hopefully other people will pick up and make more commercially practical.
Interviewer: And are you confident that at some point technology will be commercially available that allows physicians or whatever other providers, organizations, to come up with results in a minute or less?
Dr. Carl Wittwer: Yes. It'll happen. It has to happen because of your need, because of your desire to want things quickly. And there's no reason, once the technology has shown that you can do it, the population will drive the companies to make it available.
Interviewer: What else can we cover that you would like to, or we didn't?
Dr. Carl Wittwer: You know, most true inventions don't happen in large groups. They happen with individual people. And often they happen with individual people who don't have a lot of resources. So what that means in terms of the roll out of inventions, they usually don't happen in large companies. They happen either in small companies that are struggling to survive. Or they happen in academic labs, often small academic labs. Where someone latches on to an idea, commits themselves to it and makes it happen.
Interviewer: Which sounds like is what you did.
Dr. Carl Wittwer: Yeah, it's a lot of stubbornness. And belief in what you're doing. Even when other people don't believe in what you're doing. And believe me, they will not believe. I've had that experience.
Male: We're you're daily dose of science, conversation, medicine. This is The Scope. University of Utah Health Sciences Radio.