Santa Clara Valley
CY 1999 PRESENTATIONS
JANUARY 20, 1999
Laser Refractive Surgery -- an Update
Terrance N. Clapham
The initial work on the excimer laser for refractive surgery began in 1986 at CooperVision. The founders of VISX acquired the rights to the project in 1988 and formed VISX. The intent was to create laser instrumentation and a market for refractive surgery for myopia, astigmatism, and hyperopia. The emphasis was to create the best technology for refractive surgery that would achieve the best clinical results.
Over the years three distinct product models and numerous upgrades and add-ons were developed. The first model was the VISX Twenty Twenty ?? system, which treated simple myopia and could treat corneal scars and dystrophys through a process known as Phototherapeutic Keratectomy (PTK). The second model was the VISX Twenty Twenty Model B ?? , which had several advances over the previous model, and added astigmatism capability. The third model was the VISX STAR ?? Laser System, which was a completely new, ground up design (including a new laser cavity) which was more reliable, smaller, and added hyperopia capability. After lengthy clinical trials in the U.S., PTK approval was granted in 1995, myopia in 1996, and hyperopia in 1998.
Over two million eyes have been treated with Laser Vision Correction since the technology became available. The clinical results have been steadily improving as the systems, algorithms, and pre-and post-operative care have improved. For myopia with astigmatism, studies have shown 95% of the patients with 20/40 or better vision, and 81% with 20/25 or better vision. For hyperopia, studies have shown 98% with 20/40 or better vision, and 85% with 20/25 or better vision. Studies are now being conducted for hyperopic astigmatism.
Terrance N. Clapham obtained his BSEE from Rochester Institute of Technology in 1971. He was recognized as 1998 RIT School of Engineering Alumni of the Year for his 26 years of work in Ophthalmic diagnostic instruments and laser treatment systems. In his 11 years at Coherent Medical he developed diagnostic instruments and ION lasers, CO2 lasers and YAG lasers for Ophthalmic surgery. As VP of R&D at CooperVision Laser Division for 4 years he developed YAG, ION, and Excimer medical products. He was co-founder of ICAL in 1983, which developed an Ophthalmic YAG laser that was sold to CooperVision. He was co-founder and VP of R&D of VISX, Inc. until December 1997, designing Excimer laser refractive surgery systems for vision correction. He is now a consultant to VISX.
FEBRUARY 17, 1999
Entrepreneurship in Medicine
Rebecca B. Robertson
Institutional Venture Partners
Institutional Venture Partners (IVP) is a privately held, professionally managed family of venture capital partnerships with over one billion dollars of invested capital. Investments are focussed on early stage companies that have the potential to be leaders in their respective industries. Rebecca Robertson will describe IVP's processes, expectations, and experiences in the life science industry with investments in medical devices, biotechnology, healthcare services, and heath care information technology.
IVP believes that the relationship between a company and its venture capital investors should be a close, long-term partnership, and strives to be a constructive, supportive and active partner. They work as partners with management providing valuable assistance in recruitment, technology evaluation, product and market strategies, organizational development, strategic planning and coordination of subsequent financing. In the past ten years, IVP has invested in 57 life science companies. Since its founding, IVP has actively invested in over 200 companies in life sciences, communications, software, and communications industries, which have resulted in almost 100 IPOs and successful acquisitions. Collectively, these companies employ more than 120,000 people with annual revenues of greater than $15 billion and have a combined market capitalization greater than $25 billion.
Rebecca B. Robertson is a Partner and Managing Director at Institutional Venture Partners, Menlo Park, California, where she emphasizes investments in the life sciences sector. She currently serves on the Boards of Directors of Elective Vascular Interventions, Intrepid BioMedical, Myocor, Inc., Thermage and Windy Hill Technology. Prior to joining IVP, Ms. Robertson had fifteen years of operating experience in the life sciences industry. She served as Senior Vice President at Chiron Diagnostics, a division of Chiron Corporation, where she had responsibility for the $200 million Critical Care business unit. In addition, Ms. Robertson was Vice President of Business Development where she led numerous deals in support of Chiron Diagnostics business objectives.
Before her position at Chiron, Ms. Robertson was a co-founder and Vice President at Egis and held senior management positions in operations and finance at Lifescan, Inc., a Johnson & Johnson Company. During her seven-year term at Lifescan, the company grew from an early stage venture-funded company to a worldwide market leader in diabetes diagnostics. Ms. Robertson holds a BS in Chemical Engineering from Cornell University
MARCH 17, 1999
Biological Bypasses: Angiogenesis for Cardiovascular Disease by Means of Gene Therapy and its Alternatives
John P. Cooke, MD, Ph.D.
Angiogenesis is the growth of new blood vessels. This process typically occurs in adults when their arteries become narrowed and obstructed by plaque (i.e. "hardening of the arteries" or arteriosclerosis). These "biological bypasses" are typically small threadlike vessels that branch out from the pre-existing blood vessels that have become narrowed or obstructed. Curiously, some individuals have robust angiogenesis in response to vascular occlusion, whereas others have little angiogenesis. The former individuals have fewer problems related to the arteriosclerotic disease of their arteries (for example, if the narrowing is in an artery supplying the heart muscle, individuals with robust angiogenesis will have less chest pain). We now understand the factors that regulate this biological process. With this understanding we can manipulate angiogenesis to have a therapeutic effect. However, there are still questions as to which growth factor (called VEGF) or combination of growth factors is optimal. In what form should the growth factor be administered (e.g. gene, protein, or small molecule)? How should the growth factor should be administered (intraveneously, intra-arterially, locally)? What should the duration of therapy be? In addition, there are potential adverse effects of angiogenic therapy that may need to be overcome. Nevertheless, angiogenic proteins and other agents that can enhance their action are leading to a brave new world of biological bypasses for patients suffering from coronary arterial disease (CAD) and peripheral arterial disease (PAD). Angiogenesis by means of gene therapy and its alternatives may eventually supplement and someday replace angioplastic techniques and bypass surgery.
John P. Cooke, MD, Ph.D., is Associate Professor of Medicine and Director of the Section of Vascular Medicine at Stanford. A nationally recognized figure in endothelial biology, he is equally well known for his clinical leadership in cardiovascular medicine. Dr. Cooke trained in cardiovascular medicine at the Mayo Clinic and obtained his Ph.D. in physiology there. Next he joined Harvard Medical School as an Assistant Professor of Medicine. Subsequently, he was recruited to head the program in Vascular Biology and Medicine at Stanford. Dr. Cooke has published over 100 articles on topics of vascular medicine and biology as well as a textbook in vascular medicine. He is a sought-after consultant to government and industry and has served on numerous national and international committees that deal with cardiovascular diseases, including those of the American Heart Association and the National Heart, Lung and Blood Institute.
APRIL 21, 1999
Radio Frequency Ablation of Soft Tissue
Eben Kermit, MSEE, CCE
Radio Frequency Ablation (RFA) is an emerging technology that has a bright future for the selective destruction of soft tissue. RFA evolved from a device familiar to any surgeon, the ElectroSurgical Unit (ESU), also referred to as the "Bovie", which uses high frequency electrical current to rapidly heat and desiccate tissue. A slightly modified application of this same electrical energy can be used in a thermal transfer process to selectively heat a volume of tissue, causing the destruction of cell membranes and proteins by elevated temperature.
Electrode development has produced the LeVeen Needle Electrode, a design incorporating a radial array of curved hook wire "tines" that emerge from a hollow delivery needle cannula. A 4-mm diameter outer needle contains an inner wire array that expands to 3.5 cm in diameter. The insertion path is quite small compared to the size of the "deployed" array that assumes a shape like the struts of an umbrella. The goal is to perform a minimally invasive procedure that creates a relatively large thermal lesion and minimizes trauma, complications and convalescence associated with conventional surgery.
In order to destroy the target tissue, a needle electrode array must be placed at the desired location within the body. Core biopsy and fine needle aspiration sampling are considered routine procedures performed with small diameter needles that are positioned with image guidance. These same insertion and imaging techniques are used to guide placement of the RFA electrode. RF energy is then passed between the active electrode element and a large surface return electrode pad located on the skin surface at a remote site. Thermal diffusion into the surrounding tissue from the "core" nearest the electrode allows complete heating of the area to create a spherical thermal lesion.
A description of the RFA system and its components will be presented. RFA is an emerging technology that complements current therapy and interventions. Early results are very encouraging and indeed can be used in some instances where conventional methods cannot be employed due to difficult local anatomy or patients too ill to withstand open surgery.
Eben Kermit has a long affiliation with IEEE/EMBS. He is a graduate of the University of California at Davis where he earned his BS degree in Biology. An MSEE was completed with an emphasis in Biomedical Engineering at California State University in Sacramento. Mr. Kermit has worked for more than 20 years as a Biomedical Engineer for hospitals and industry with a focus on both the use and design of medical systems and medical devices for monitoring and direct patient care. He is Senior Development Engineer at RadioTherapeutics Corporation.
MAY 19, 1999
Employing Telomere Biology to Treat Cancer and Diseases of the Elderly
Gregg B. Morin, Ph.D.
The ability of human cells to divide controls aspects of human aging and whether cells become cancerous. A tumor is a population of cells that have accumulated multiple insults or mutation events leading to uncontrolled cell division, which ultimately disrupts the function of critical tissues. Normal human cells when placed in culture will divide for a limited time, while cancerous cells will divide indefinitely. The finite lifespan of normal human cells is caused by their inability to fully copy the ends of their chromosomal DNA. The ends of chromosomes, termed telomeres, require an enzyme called telomerase for their maintenance. Although the critical gene for telomerase is present in essentially all cells, telomerase is not expressed in most human cells. Telomeres thus progressively shorten with each cell division, ultimately signaling a halt to cell division. Mutant cancer cells, in contrast, express telomerase thereby preventing telomere shortening and allowing them to divide forever in their normal state.
Telomerase is a special enzyme composed of both protein and RNA components recently identified by Geron. To study how cells become immortal we engineered normal human cells to express the critical protein component of telomerase. These cells now possess telomerase activity and maintain their telomere length. Furthermore, these cells divide indefinitely but remain functionally normal or non-cancerous. This experiment confirms the link between telomere structure and cellular lifespan. Moreover, it establishes that while telomerase expression is required for both normal and cancer cells to divide indefinitely, other changes are necessary for a cell to become cancerous.
Geron hopes to apply the expression of the telomerase protein component to extend the lifespan of key human cells and alleviate some age-related disorders. In addition, the broad expression of telomerase in cancer cells but not in normal cells indicates that telomerase inhibitors can "remortalize" tumors and therefore provide a potentially safe and universal approach to cancer therapy.
Dr. Gregg B. Morin is currently Director of Molecular Biology and Biochemistry at Geron Corporation in Menlo Park. He received a doctorate from the University of Colorado at Boulder in 1988 in Biochemistry. Dr. Morin's research throughout his career has been focussed on ribonuclear protein enzymes and telomeres - the molecular ends of eukaryotic chromosomes. In 1989, Dr. Morin was the first to observe the human activity of the enzyme telomerase, which is required to maintain the structure of telomeres. Recently, Dr. Morin has been a key contributor to efforts that cloned the protein component of telomerase and demonstrated that expression of telomerase in human cells resulted in elongated telomeres and indefinitely prolonged their lifespan while maintaining a normal youthful phenotype. He research efforts at Geron are aimed at finding inhibitors of telomerase for cancer therapeutics and to exploit telomerase expression for the treatment of age-related diseases.
JUNE 9, 1999
Evolution of a Non-invasive Glucose Monitoring System for People with Diabetes - Part II
Thomas E. Conn
Cygnus Therapeutic Systems, Inc.
Diabetes is a chronic disease characterized by the body's inability to maintain the proper amount of circulating glucose. Approximately seven million Americans have been diagnosed with diabetes, with as many as one hundred million worldwide. It is estimated that the complications arising from diabetes cost the U.S. health care system more than $45 billion in 1992. Results from the Diabetes Care and Complications Trial (DCCT) showed that more frequent self-testing of blood glucose and insulin administration could prevent many of the long-term complications of diabetes. Despite the clear, long-term advantages, the pain and inconvenience of present finger-stab methods, along with the fear of hypoglycemia has led to poor patient acceptance of a tight control regimen.
A painless, continuous and automatic glucose monitoring device, the GlucoWatch Biographer, has been developed with the potential to improve diabetes management by eliminating the barriers to frequent monitoring. Worn like a wristwatch, the device uses electroosmosis to extract glucose into a disposable AutoSensor/GelPad worn beneath the watch. The collected glucose triggers an electrochemical reaction with the reagents in the pad, causing an emission of electrons. A sensor measures the electrons, and the GlucoWatch electronics correlates the level of electron emission to the concentration of glucose in the patient's blood. Measurements are taken automatically and frequently, with past readings available at the push of a button.
The evolution of this device is tracked from early laboratory testing conducted on immobilized subjects over short periods of time through the portable module stage to the final watch format providing twelve hours of monitoring with up to three readings per hour. This update paper also presents the results of recent comprehensive clinical studies in controlled as well as home environments comparing Biographer results with whole blood measurements using laboratory methods. Finally, next steps forward and product timelines are discussed, considering FDA filing and review as well as commercial launch.
Thomas E. Conn joined Cygnus Therapeutic Systems in 1993 as a Cygnus Fellow, and was later appointed Director, Development Engineering for a newly formed division, Cygnus Diagnostics, and then Vice President, Product Development for the Diabetes Division. He is team leader for the Glucose Monitoring Program whose goal has been the development of a product making possible automatic, frequent and painless measurement of glucose for people with diabetes.
Mr. Conn has over 29 years of experience in the biomedical field involving design, development, manufacturing and program management.. He received his B.S. in Mechanical Engineering from the University of California, Berkeley and his M.S. in Applied Mechanics from Sacramento State University where he designed an aortic heart valve, later patented. Through the Stanford University Honors Program, he completed 24 units of graduate study toward a Ph.D. in Applied Mechanics. He holds four patents and has received five designer awards.
SEPTEMBER 15, 1999
Curing Cardiac Arrhythmia Using Microwave Ablation Technology
Dr. Dany Berube
Fidus Medical Technology
RF ablation has been the main technology used for ablation of certain cardiac rhythm disorders since the late 1980's. This method is very efficient when the arrhythmogenic region is small and located near the endocardial surface like for the Wolff-Parkinson-White syndrome. However, when the region to ablate is large and deep, like for ventricular tachycardia, or elongated, like for atrial flutter or atrial fibrillation, the efficiency of RF ablation decreases considerably. Microwave ablation can provide better penetration of energy in the tissue and a variety of applicators can be designed using different radiation patterns to meet the specific needs of these new applications. Dr. Berube will present the basic science behind microwave ablation technology for curing cardiac arrhythmia. Highlights of animal and clinical trials will be presented.
Dany Berube received the B. Eng. degree in physical engineering from Universit of Laval in Quebec City. He received the M. ScA. and Ph.D. degrees in biomedical engineering from the Biomedical Engineering Institute of cole Polytechnique de Montral. His research interests are in dielectric property measurements of biological tissues and in the design of microwave applicators and microwave generators used to perform microwave ablation of cardiac arrhythmia. Dr. Berube is now the Director of Applied Research at Fidus Medical Technology.
OCTOBER 20, 1999
Medical Applications of Electron Beam Tomography
David G. Hill, Ph. D
The talk will begin with a short history followed by a description of Electron Beam Tomography (EBT). This naturally leads to a comparison of EBT to conventional computed tomography (CT). EBT is optimized for the creation of cross-sectional images of the heart. Particular non-invasive applications such as measurement of coronary artery calcium, imaging of the arterial lumen, and measurement of the moving heart will be discussed. Finally, there will be a discussion of some of the potential applications of EBT technology.
David G. Hill is a high-energy physics graduate of Carnegie Mellon University. He than worked at Brookhaven National Laboratory and the University of Maryland in high-energy physics research. He became involved with medical imaging in 1976 as part of a design team for an early CT scanner with Pfizer Medical Systems, and joined Siemens Medical Systems in 1981 to establish a US group doing CT applications. Later he was also involved with MRI and PACS. In 1991 he was sent by Siemens to work with Imatron in further developing an Electron Beam Tomography scanner, and in 1998 joined Imatron as part of the marketing department.
NOVEMBER 17, 1999
Biological and Medical Applications
Dr. Raymond Mariella, Jr.
Lawrence Livermore National Laboratory
Over the last ten years, LLNL has been developing microtechnology for instrumentation with applications in national security, biomedical sciences, and the environment. In general, we operate in the "application-pull" mode, rather than the "technology-push" mode. This often means that we cannot pursue interesting subjects in microtechnology and especially, in nanotechnology. We have generally found that fabrication techniques in the "mesoscale" range (larger than "microscale") have been the most valuable to our applications, including flow cytometry, the polymerase chain reaction (for amplification of DNA sequences), gas chromatography, and electrophoresis. We include fabrication processes utilizing silicon, glass, and plastic, so that the integrated system or instrument delivers optimized performance. Negative feedback from end users is also important to our systems and instruments -- it occasionally happens that a design or function that is intrinsically appealing to the engineer may have to undergo major revision before it is acceptable in field performance.
Dr. Raymond Mariella received his BA from Rice University in 1969, with a triple major in Chemistry, Chemical Engineering, and Mathematics. He received his A.M. in 1970 and his Ph.D. in 1973, both from Harvard University in Physical Chemistry. He then spent two years as a Visiting Scientist in the Physics Dept. at MIT,. After one year as a Research Fellow at IBM Research Lab in San Jose, he spent ten years at the Materials Research Center of Allied Signal Corp., working in laser chemistry, surface chemistry, and molecular beam epitaxy. He came to LLNL in 1987, where he is Director of the Center for Microtechnology.