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Dr. Peter Siegel

Retooling a Research Career - From Engineering to Biology and Back: June 21, 2006

Peter Siegel has an amazing ability to straddle divergent worlds. He's learned to think and talk like an engineer, as well as a biologist. He's built instruments for satellites that map pollutants in the upper atmosphere and track ozone and water vapor - information critical to assess global warming. He's also in the process of modifying these instruments to image human tissue to reveal differences between normal and cancerous tissue.

Siegel, a senior research engineer at the California Institute of Technology's Jet Propulsion Laboratory and well into his fifties, has devoted his career to exploring terahertz waves: the far-infrared portion of the electromagnetic spectrum beyond visible light. Terahertz radiation has frequencies of 1 trillion cycles per second, which is 1,000 times greater than the microwave frequencies that turn ordinary corn kernels into crunchy popcorn.

"Materials in the terahertz range have absorption properties very different than optical and infrared," Siegel explains. "I figured if there are such strong differences in some substances that people can continuously use the terahertz range for identification, then maybe such differences in biomaterials exist...and I was intrigued about whether we could find other applications."

Making the Switch

So 4 years ago, a change in projects at work gave Siegel the opportunity to follow his hunch. For Siegel, who holds a B.A. in astronomy and physics from Colgate University, a master's degree in physics and a Ph.D. in electrical engineering from Columbia University, there was just one problem - the last biology class he took was as a high school freshman.

Enter the National Institutes of Health's K25 grants, designed to give mid-career physical or computer scientists, mathematicians, economists or engineers financial support to educate themselves in the biological arena. The ultimate purpose of the grant is to enable these professionals to pursue research that puts their quantitative skills to work answering questions related to health and disease.

Now three-and-a-half years into his 5-year K25 grant and several college biology and chemistry courses later, Siegel is experiencing the full spectrum of interdisciplinary research. "Rather than becoming a biologist, I used the K25 grant to expand my knowledge outside of my primary field sufficiently so that I could apply it to a totally new area," he says.

Answering Basic Questions

Scott Fraser, who specializes in developmental biology and imaging at California Institute of Technology, is one of Siegel's mentors. "Peter is an amazing force in the lab. He is working in a wavelength range that is extremely information rich," says Fraser. Creating a device to direct terahertz waves to a biological specimen requires Siegel to answer very basic operational questions such as how to mount the specimen on the device. "It's like starting at the beginning with an optical microscope to view a specimen with visible light," says Fraser. "What's exciting about Peter's work is that he's applying imaging in a biomedical setting in a wavelength range that hasn't been explored."

For Siegel, pursuing the K25 grant has been both a stimulating and humbling experience. "I had to go back to square one and learn a whole new dialect and way of thinking," he says. "My physiology course was a real eye opener because it made me realize how complex even the simplest function is in the body. Far more complex than anything I've ever seen in my entire career of engineering." But Fraser says that Siegel's rich reservoir of previous experience gives him a "whole range to draw from. He is literally one of a handful in the world that can attack these problems," says Fraser.

A New Way of Seeing

If successful, Siegel's research may produce a powerful imaging tool for studying biological specimens. Terahertz rays are far less energetic than x-rays (they don't ionize tissue - only warm it up slightly) so they don't pose the same health risks. Although terahertz rays cannot penetrate deeply into tissue due to high absorption from water they can image a few millimeters below the surface with less scattering than optical or infrared wavelengths. Terahertz rays have been used to image the extent of a tumor just beneath the skin and to visualize burns under bandages.

Collaborations with University of California-Los Angeles surgeon and K25 mentor Warren Grundfest and pathologists Dr. Harry Vinters and Dr. George Thomas are allowing Siegel to try out his novel terahertz instrumentation and staining techniques to see if they can reveal differences between cancerous and normal tissues, and to look at quantifying staging differences in Alzheimer's infected brain tissue through additional NIH grant mechanisms.

Other researchers are pursuing terahertz imaging of biological material, with a few already testing their technology in clinical trials. However, the terahertz radiation sources used are based on fast optical laser pulses which necessarily generate very broadband energy with less power per unit wavelength than the sources Siegel has been developing and using in his space science experiments.

Siegel's terahertz sources and detectors are derived from tried and true technology that is an extension of the methods originally developed for radio and radar. He believes these techniques offer more dynamic range to detect subtle or gross differences in tissue absorption as well as providing the complete bag of tricks that is commonly applied to today’s sophisticated radar imaging and recognition algorithms.

Challenges Big and Small

When Siegel decided to pursue his biological interests he knew the journey might be demanding but, oddly, it was in the classroom where he faced his biggest challenge. As he was sitting in his first biology seminar course, his only son, who happened to be a freshman attending Caltech, walked into the class with a group of friends and sat down. Seeing that his son wore a horrified expression when he caught site of him in the room, Siegel resisted the urge to wave. "Realizing that a teenager struggling to assert some independence from home would not appreciate having their father attending class with them, I didn't pay any attention to him, he didn't pay any attention to me, and his friends never found out we were related."

A mouse prostate section with tumor tissue (circle) as imaged with terahertz, optical, and staining techniques. The terahertz image shows significantly reduced absorption of terahertz radiation in this region compared to normal tissue, suggesting its usefulness for detecting tumors. Image courtesy of Peter Siegel