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The Carotenoid Cash Cows Of Utah's Center For Biomedical Optics
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"WHAT'S UP DOC?" By Randy Block
Wasatch Digital IQ - April 2001
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If you listen closely, you can hear a soft "Mooooo" sound emanating from the basement of the Dixon Laser Institute on the University of Utah campus. "MooOOoo. MooOOoo-lah." Somebody let another one of those cash cows loose and it's running around like a bull in a laser shop.
Thankfully, two brave cowboys are riding the bull: Werner Gellermann, PhD, and Robert McClane of the Center for Biomedical Optics in Salt Lake City, designated a "Center of Excellence" in 1999. These entrepreneurial laser pioneers are another growing success story from Utah's Centers of Excellence Program, a state economic development tool that accelerates local technology growth through rapid development and commercialization of university technologies.
In the stampede to commercialize optical technologies for medicine, Gellermann and McClane have corralled a large herd of novel devices and applications. At the Center for Biomedical Optics, the duo and their colleagues develop new optical instruments that will be used for non-invasive assessment and therapeutic treatment of cancers and other diseases. "Mooo."
Like many innovations, the Center's devices have roots in the adage "necessity is the mother of invention", and Paul Bernstein, M.D., Ph.D., is a very proud parent. At the University of Utah's Moran Eye Center, Dr. Bernstein has been studying age-related macular degeneration (AMD), the leading cause of blindness in the western world. About 1.7 million people in the US alone have AMD, and more than 30 percent of the population over age 70 will be impaired or blinded by the disease.
"When I joined the U's faculty, I had been looking at nutritional factors and vitamins that might be helpful in preventing AMD," said Bernstein. "Epidemiology suggested that people who have large intakes of certain carotenoids are protected against AMD, but the best available way to test people for carotenoids, a psycho-physical test called heterochromatic flicker photometry, was non-quantitative, subjective and very unreliable. I needed an accurate, repeatable, and non-invasive way to measure carotenoids in the eye."
In walked Robert McClane from the Dixon Laser Institute, looking for new university collaborations and interesting problems to solve with lasers.
"Robert told me about their work in Raman laser spectroscopy," said Bernstein, "and not knowing much about lasers, I did a little homework on Raman and thought, 'Hey, this technology just might work'. He and I and Werner got together and decided that we should try some studies." Five years, $1 million, and many prototypes later, they've got a product, a company, and a wide-open market. "Mooo."
SPECTRAVISION
Remember when your grandmother said, "No dessert until you eat your spinach, it's good for your eyes"? Turns out she was right. You've probably heard about B-carotene, a carotenoid most closely associated with carrots. Less known are the 600 or so other carotenoids found in nature, about 18 of which are found in the human body. All of these carotenoid molecules are anti-oxidants and produced only by plants. Like other anti-oxidants such as vitamins C and E, they play important roles in protecting our eyes and tissues from "reactive oxidative species."
The problem is exemplified by sun exposure. When ultraviolet (UV) light hits human tissue, it reacts with normal oxygen molecules, producing radical oxygen molecules like "oxygen singlets"--a particularly nasty type of "reactive oxidative species." These singlets are like little bombs in the presence of cell wall lipids. Fortunately, anti-oxidants react with singlets and other oxygen radicals to quench and diffuse their destructive capacity, and carotenoids are particularly good at this.
When you were a kid, did you ever focus sunlight through a magnifying glass to start fires or sizzle ants? Nope, me neither, but this is roughly what's happening at the back of your eyes on a sunny day. Imagine all of the oxygen singlets being produced in that tiny spot of focused light; without carotenoids, your eyes would probably be toast. Thankfully, two carotenoid molecules--lutein and zeaxanthin--are intensely concentrated right in the center of that focal spot--the macula lutea. In fact, this is the highest concentration of carotenoids anywhere in the body, with levels 100 to 1,000 times greater than the skin.
"We've been able to develop one of our main technologies, Raman Spectroscopy, into a hand-held device that gives us a really accurate and non-invasive way to measure carotenoids," said Gellermann. "The science is pretty complicated, of course, but resonant Raman scattering is observed when laser light changes frequency as it hits and scatters from carotenoid molecules. The frequency changes correlate with the natural vibrational frequencies of the molecule, and we can detect and read these Raman spectrums as a unique "fingerprint" to identify the molecules. The intensity of the Raman signal is directly proportional to the concentration of the molecules, so we've got qualitative and quantitative detection."
For eyes and age-related macular degeneration, the measurement of carotenoids could be a valuable diagnostic and interventional tool for the prevention of AMD. The disease is not considered to be reversible, but Bernstein believes its progress could be halted or even prevented with changes in diet.
"Although our clinical trials are just beginning," said Bernstein, "the results are very encouraging. Our goal is to have this as an early diagnostic test to identify people that might be at risk for AMD long before they develop symptoms. If we are able to catch them early through carotenoid screening, we expect that patients will be able to modify their diets or take supplements so that long term they will have much lower risk of developing AMD. I've been very gratified at the patient interest in this technology. Most everyone wants to be measured and wants to know what the measurements mean."
Let's see...18,000 ophthalmologists and 34,000 optometrists at an average price of about $15,000 per laser scanning machine...chugga-chugga-ka-ching...$790 million; not a bad market for just the United States. And that's just what Steve Ingleby, VP of Marketing at National Laser Corp. in Salt Lake City thought. Gellermann, McClane, Bernstein and National Laser created a joint venture in 1997 called Spectratek to commercialize the carotenoid detection instruments for ophthalmic markets.
"We're pretty excited about the market opportunities in front of Spectratek," said Ingleby with a Cheshire grin. "Biophotonics is hot, and for AMD, we're addressing a growing and graying market. Since we were already in the medical laser business, we saw a good fit with the work at the University of Utah and negotiated a licensing deal that included the U as an equity participant. For the ophthalmic carotenoid detector--and yes, we're working on a branding name for it--we're about 9 months or so from market and will probably be looking at a significant capital raise fairly soon."
CAROTENOID SKIN CANCER DETECTION
The money won't be used just for Spectratek's ophthalmic device, however. There's more to this story than meets the eye.
Imagine you've got a funny little mole on your neck. It's frightful to consider, but you think, "Hmmm, could be skin cancer." That mole might have only a 1-to-2-percent chance of being cancerous, but it will be 100 percent deadly if it's malignant and goes untreated. You have two options: cross your fingers and pray, or chop it out and then cross your fingers and pray. You'll know after two or three uneasy days if it was cancerous, but did they get it all?
Enter a Spectratek laser device at your local physician's office. A pen-sized light probe is placed against the skin for 10 seconds and--bing!--a small computer spits out a cancer probability diagnosis based on 2 million people who went the chop and pray route. If surgery is needed, the same device can be used during the procedure to ensure right then and there that no "dirty margins" were saved for a rainy day.
Now, imagine a similar laser probe tucked inside an endoscope that can quickly scan almost any questionable tissue in the cervix, prostate, lungs, mouth, or colon. An elegant, least-invasive method to scan for cancer. The technology? Carotenoid detection.
According to Gellermann, "Once we knew we could measure carotenoids, we started looking around for other ways to apply the technology where there would be large markets. There are five carotenoids in the skin--different molecules than the two found in the retina--and we wondered if we could adapt the eye laser to directly read the carotenoid levels in skin. The only way to do this now is with HPLC techniques that require 10 square centimeters of skin for a carotenoid reading."
Similar to the reactive oxidative species produced by UV exposure, many cancers produce just about the same effect through fast and highly oxidative metabolic processes. The cancer cranks out oxygen radicals that react with and deplete local carotenoids, thereby forming a distinct boundary between healthy and cancerous tissue that can be (theoretically) detected and mapped by carotenoid levels.
This isn't rocket science or brain surgery. It's better.
It's better because carotenoids are thought to prevent--and in some instances, reverse--cancer. In the human cervix, prostate, lung and colon, high carotenoid levels have already been linked to the prevention of cancers. But there's a long road of clinical testing and development ahead before any of the Center's devices will be diagnosing cancer.
"Actually, the technology development is pretty far along right now," said Gellermann. “Sure, we'll look at internal tissues in the near future, but our first tissue target has been skin, and for this our device works quite well. We can already get good readings. What we need to do now is build up our database with clinically relevant information. We don't know yet how genetic, environmental, and dietary variables come into play here, but we have great clinical facilities and research partners who are working on this."
Correlations between skin carotenoid readings and skin cancers are now being explored on another side of the University of Utah campus, at the Melanoma Clinic of the Huntsman Cancer Institute, where a dedicated Raman measurement facility has been installed. According to the Skin Cancer Foundation, approximately 1 million new cases are reported in the US each year from the two most common types of skin cancer alone.
"In the West, and particularly in Utah, skin cancer is epidemic," said Ingleby. "In the US, there are more than 65,000 family physicians and 9,000 dermatologists who need a diagnostic device like this. We (Spectratek) have just recently licensed this newer technology from the University for use in medical applications. Even though diagnosing cancer this way is some years off and still speculative, we have a growing number of holistic MD's in the U.S. who could use the device right now as an indicator of oxidative stress and overall health. We're probably less than a year away from launching this type of product."
NEUTRACEUTICAL LEGITIMACY
So it's not just about skin cancer. There's a whole secondary market for carotenoid measurement in skin related to neutraceuticals. In fact, the market is so strong that Gellermann and McClane formed their own university spin-off called NutriScan just to address the non-medical applications for carotenoid measurement in skin. Nutriscan, Inc. is in the process of commercializing the Center's carotenoid detection technology for the promotion of nutritional supplements.
"The neutraceutical and supplement industry is just loaded with scams and unsubstantiated claims about how good one anti-oxidant supplement or another is," said Sheryl Hohle, the President of Utah-based BioCatalogia and commercialization consultant to Gellermann's Center of Excellence. "Utah is pretty much the neutraceutical capital of the world, and Werner's technology is really going to shake things up, because now that we can directly measure anti-oxidants in the skin, companies will have to provide efficacy data with their product or no one will buy it. Consumers want to know that what they're taking works, and health food stores will almost have to have these machines to attract and retain customers."
Back in the basement of the Dixon Laser Institute, I couldn't resist the temptation to test out the skin-measurement device. One of the team's technology inventors, Dr. Igor Ermakov, a post-doc from the General Physics Institute in Moscow, placed the probe on my hand for 10 seconds and took a reading.
"13,452," he scolded me in a thick Russian accent. "Not too good. You haven't been eating your vegetables, have you? Or maybe you smoke?" Thanks, Grandma.
No cancer sticks for me, but I confess to the low veggie intake. "Start drinking V-8," McClane told me. "My diet has changed substantially since we started doing this, and I've raised my carotenoid levels quite a lot. Lycopene is by far the most abundant carotenoid in skin, and processed tomatoes are just loaded with lycopene. The Italians got a good thing going, but I don't think all that wine is keeping their cancer levels so low. It's the spaghetti sauce." (Check out wwwlycopene.org for more info.)
"Obviously, we didn't discover the importance of carotenoids," added McClane. "People have been working in this area for 2S years. What we have done is apply an enabling technology to make something that was already very interesting suddenly clinically viable and useful in a number of markets. This isn't pie-in-the-sky stuff from the ivory tower of academia. What we have works and people need it." He laughed. "I guess we've become academic capitalists."
National Laser will likely manufacture the devices in Salt Lake City for Spectratek and NutriScan, but the founding partners of Spectratek (Bernstein, Gellermann, McClane, Ingleby, and John Parberry) recognize the value and pipeline a big multi-national marketing partner could bring to the table.
"We’re weighing our options right now," said Ingleby. "We'll certainly consider a strategic relationship with the likes of a Zeiss or a Bausch & Lomb or an Alcon, but we can move faster right now without them."
McClane agreed emphatically. "A few big companies were hot on us, and it was memo after memo and we would meet and memo and meet again...One year later we're still sending memos. Nothing moves fast in a big company. Our experience suggests that they would rather have us work out the technology bugs, remove some of the development risk, and then pay more for it later--a lot more!--after we've built value into the technology. We think we're getting pretty good at this and already have more technologies and applications on the drawing board than we have time to develop.
"Thankfully, funding from the Center of Excellence program helps us take the early development risk and get these technologies patented and up to the point where a company can take them into production and onto the market. We've got three other major developments underway right now, and with a little luck, we're going to repeat this commercialization cycle again and again and again."
On and on and on until the cash cows come home.
Randy Block is president of The Gamut Technology Group, a Utah consulting firm that helps clients with technology development and commercialization, market research and analysis, and strategic planning.
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