"The Pursuit of Noninvasive Glucose: "Hunting the Deceitful Turkey""
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The Pursuit of Noninvasive Glucose: “Hunting the Deceitful Turkey” By John L. Smith Fourth Edition: Revised and Expanded Parts Copyright 2015 by John L. Smith i Preface to the Fourth Edition I have learned a great deal about noninvasive glucose measurements in the ten years since I began the effort of writing about this subject. During that time, I have helped start and then close a noninvasive glucose company, consulted for more than thirty eager, hopeful inventers and entrepreneurs, and watched as almost all of those initially promising ideas were dashed on the rocks of reality. And in that time, I have seen the oldest, most discredited ideas investigated over again (breath, saliva, tears, sweat, etc.), and many millions of dollars invested and mostly wasted in this pursuit. I’ve seen brand new ideas tried, new twists added to some old technologies, and watched as a few diehards have continued to pursue the same technologies for more than twenty years. In one sense, it’s a continuing tribute to the spirit of innovation and dedication to help those who live with diabetes and the inconvenience and discomfort of daily glucose monitoring. In another, it indicates how little of the available information has either gotten to or been absorbed by those who choose this pursuit. I know there are some who either choose to disbelieve the experience contained in these pages, and others who, buoyed by the wellspring of hope, think they can do what their predecessors could not. For the benefit of all, I hope that the information updated in this fourth edition will help guide present and future adherents toward the goal we have all sought for so long—the noninvasive measurement of glucose for people with diabetes. PINPRICKS COULD SOON BE A THING OF THE PAST FOR DIABETICS! This headline has appeared more than fifty times during the interval between editions. Each new technology is reported, dominates the “alert-o-sphere” and the “blogosphere” for a day or two, and then is rarely heard again. And during that time, it has been joined by another frequent headline: i STUDIES SHOW EARLY STEPS TOWARD PASSIVE WEARABLE MONITORING OF GLUCOSE, HYDRATION, PULSE! And variants of it, such as: “Wristband to monitor your blood glucose;” “Bracelet to provide continuous glucose information;” and “New watch will do away with fingersticks.” This field was catapulted into national prominence by an announcement that there were new, serious players in the field: Apple, Google, Samsung, and Microsoft. Through 2012, any aspiring startup with an idea for noninvasive glucose had hoped for an acquisition by one of “big four” of glucose monitoring, LifeScan (J&J), Roche, Abbott, or Bayer. These companies were dealt a blow by the decrease in Medicare reimbursement in July of 2013 (from about 64 cents to about 21 cents per strip), and when the glory days of high profits for these companies ended, prospects for selling an invention to that group nosedived. But right on cue, as Wikipedia states: “On 16 January 2014 Google announced that, for the past 18 months, they had been working on a contact lens that could help people with diabetes by making it continually check their glucose levels. The idea was originally funded by the National Science Foundation and was first brought to Microsoft. The product was created by Brian Otis and Babak Parviz who were both members of the electrical engineering faculty at the University of Washington prior to working in Google’s secret lab, Google[x]. Google noted in their official announcement that scientists have long looked into how certain body fluids can help track glucose levels easier, but as tears are hard to collect and study, using them was never really an option. They also mentioned that the project is currently being discussed with the FDA while still noting that there is a lot more work left to do before the product can be released for general usage, which is said to happen in five years at best, and that they are looking for partners who would use the technology for the lens by developing apps ii that would make the measurements available to the wearers and their respective doctors. The partners would also be expected to use this research and technology to develop advanced medical and vision devices for future generations.” This announcement probably focused more attention on noninvasive glucose monitoring than any other in the history of this field. It was also the first public acknowledgement that the quest had been taken up by new crusaders, but clearly, the cell phone powers had long coveted the “health market.” Surely, said savvy observers, the long-rumored Apple Watch would include a glucose monitoring function.1 But in spite of Google Fit, Fitbits, Apple Healthkits, and dozens of other “wearable” health monitors, no reliable reports of noninvasive glucose measurements have yet appeared. This book has also served a useful purpose for those who would patent an idea in this field—instead of needing to describe in detail the dozens of failures in the field, references to editions of this book have appeared in many patents around the world.2 A popular illustration of the sequence of events for emerging technologies is known as “Gartner’s Hype Cycle” (http://www.gartner.com/technology/research/methodologies/hype-cycle.jsp): 1 One of the most cogent accounts of why this would not happen came from Yoni Heiser in his “ionApple” blog on February 26, 2014, entitled “Why the Apple iWatch won’t measure glucose “(http://www.networkworld.com/community/node/84894), with several quotes from this book. 2 There is a standing joke among inventors that preparing a patent application costs at least $1.00 for each word generated by a patent attorney, so anytime a reference with a comprehensive presentation of an area can be included, the cost to file an application decreases. iii There are many who feel that the correct version for noninvasive glucose measurements should be: A version was even created by Stephen Davies in 2014 for Digital Health (http://bionicly.com/digital-health-hype-cycle/):1 1 Throughout this edition, Internet links will be left live in the .pdf file published online. There is, however, no guarantee that they will all work as expected. iv After more than thirty years of looking into noninvasive glucose technologies, I have developed what may be an overly skeptical classification system for new ideas: 1. Holy cow, not this again! This technology has been investigated before (maybe five or ten times), and the investigators have always run up against the same roadblocks. 2. An old idea revived by researchers who think they have discovered that the earlier investigators “quit too soon,” or think they have a unique insight into why a multiply-investigated idea failed each time. 3. This is a new and possibly unique idea, but there is no scientific basis on which it could reasonably provide accurate glucose measurements. 4. This is something that has not been explored before, it has a reasonable basis in science and, there is no a priori reason why it could not yield glucose results. I live for these; a recent example of these was FoviOptics, where I came out of retirement to spend two years of my life (and gained a substantial long-term capital loss tax carryforward as a result of exercising options for founders’ stock) before learning why it did not work. The point is that it could have worked! 5. This will work! v To date, I have seen hundreds of ideas that fall into categories 1 and 2, quite a few that fit into category 3, and four or five in category 4. I am still waiting to hear of something in category 5. vi Foreword This is a compilation of experiences and investigations born of a combination of scientific curiosity, dedication to people affected by a chronic, life-threatening disease, and dogged determination to find a solution to the most difficult technical challenge I have encountered in my career. It is not, perhaps, as difficult or fraught with problems as realizing time travel or finding the final “grand unifying theory” of physics1, but it is the more tantalizing because it seemed for decades that the solution was always “just around the corner,” or at most, “just over the horizon.” I participated in evaluations of many of the technologies described here while employed at several companies directly or peripherally involved in glucose measurement, and consulted for the inventors or investors of many others. In the text, I will describe many of the technologies, their capabilities and (especially) their limitations for measuring glucose. I will articulate three very important “Laws of Noninvasive2 Glucose” (one with several subsections), and list tests which can be applied to spectroscopic and other techniques. Much of the description is technical, since it is the subtleties of the approaches that often lead to their failure. Nontechnical readers should still try to read through these—the conclusions are valid, some of the reasoning may be helpful, and there is certainly value in them as cautionary tales. Where companies have made a splash, or serve to illustrate the behaviors that were exhibited by many of those in this field, they will be described in some detail. In other cases, simple lists of the investigators will serve to illustrate how many times a similar approach has been attempted. Although I do not (yet) have diabetes, it has achieved epidemic proportions in this country, and will soon, as the standard of living rises elsewhere, be felt equally around 1 This is the long-sought system for reconciling General Relativity and quantum mechanics that caused Einstein so much heartache in his later years.