Carl, What is next on your list for discovery for Clinical Diagnostics?
Right now I'm focusing on, "high-resolution melting analysis". DNA melting is a very simple process that turns out to be very powerful. If done at high-resolution, most downstream processing after PCR is unnecessary. For example, SNP genotyping can be performed without labeled probes (Clin Chem 49:853;2003, Clin Chem 50:1156;2004, and Clin Chem 50:1328;2004)and mutation scanning can be done without separations (Clin Chem 50:1748;2004). These techniques should change the way genetic analysis is performed in both the clinical and research environments. If your asking what's next to be discovered, we'll both have to wait and see...
I am really impressed with your achievements. I would like to know if you have training sessions for younger scientists to pass down your knowledge and experience; especially for international clinical chemists.
You are kind. We have a molecular diagnostics fellowship at the University of Utah/ARUP. There is also a, "real-time PCR" minifellowship for five half days (with the other half usually spect skiiing) that is usually offered each year. Both of these are run through ARUP. My research laboratory at the University also hosts visiting scholars and has post-doctoral positions from time-to-time.
Dr. Wittwer, I don't have a question. I just wanted to let you know that it was refreshing to learn that someone else enjoyed the book Flatland. Bill Korzun, Ph.D., DABCC, MT(ASCP) Virginia Commonwealth University
Dear Bill: Flatland is a classic. I believe there is a sequal, "Sphereland", but don't remember if it's the same author. Watch your corners! Carl
Dr. Wittwer- How did it occur to you to use glass capillaries and hot air to speed up the PCR process? Do you envision something that could help others to achieve a more high-throughput means of genotyping in a closed tube-based system?
The suggestion to use capillaries and hot air came from David Hillyard over lunch (Univ. Utah/ARUP). The speed came later by experiment, showing that PCR was slow only because of conventional tubes and instrumentation (Anal Biochem 186:328;1990). Concerning high-throughput genotyping in a closed-tube system, we have recently morphed the LightTyper (a 96/384 format instrument that requires labeled probes) into a "LightScanner". This instrument uses a simple dye (LCGreen) and unlabeled probes for genotyping (Clin Chem. 50:1328;2004). The LightScanner (which also doubles as a closed-tube mutation scanner) will be released by the company, Idado Technology, this summer.
Dr. Wittwer, There have been great advances in molecular diagnositcs and the use of these techniques in the clinical laboratory. Although it is in it's earliest stages of development, it seems as though proteomics is following suit. Great attention is being given, appropriately, to these new fields yet it often seems to be at the expense of the more "traditional" approaches in laboratory medicine: the quantification of a particular analyte in the diagnosis and management of disease. What is your insight into the impact that these new technologies will have on the utilization of laboratory data by physicians?
In retrospect, adoption of DNA/RNA diagnostics into the clinical laboratory has been slow and expensive. Only now is it paying off for most laboratories. I suspect proteomics will follow suit. There will be lots of false starts and clinical utility will come slowly. As you imply, hopefully this will not be at the expense of our patients, who rely on today's conventional diagnosis and management. The driving forces for DNA/RNA and proteomic diagnostics are myriad, including academic, commercial, and governmental forces. It is the matrix in which we live.