Risks and rewards of pathology innovation: the academic pathology department as a business incubator.
Subject: Medical innovations (Analysis)
Pathologists (Practice)
Pathological laboratories (Innovations)
Pathological laboratories (Services)
Pathological laboratories (Human resource management)
Author: Weinstein, Ronald S.
Pub Date: 04/01/2009
Publication: Name: Archives of Pathology & Laboratory Medicine Publisher: College of American Pathologists Audience: Academic; Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2009 College of American Pathologists ISSN: 1543-2165
Issue: Date: April, 2009 Source Volume: 133 Source Issue: 4
Topic: Event Code: 200 Management dynamics; 360 Services information; 280 Personnel administration Computer Subject: Company personnel management
Geographic: Geographic Scope: United States Geographic Code: 1USA United States
Accession Number: 230246989
Full Text: Through spin-off businesses, the academic pathology department has a special role in creating the future for the field of pathology. This topic has not been discussed in any depth in the pathology literature.

Universities can recruit and mentor faculty members and nonprofessional employees who have the potential to start spin-off companies and who, thus, can make a difference through invention, creation, and commercialization of their ideas. (1,2) Strong leadership and a commitment to entrepreneurship are important in maintaining a departmental environment conducive to innovation. This article presents case studies of laboratory businesses emanating from The University of Arizona's Department of Pathology, which has had a strong track record in entrepreneurship for more than a quarter of a century.

THE TUCSON PATHOLOGY CLUSTER: SPIN-OFF OF LABORATORY COMPANIES BY THE ARIZONA HEALTH SCIENCES CENTER

The "Tucson Pathology Cluster" describes a group of independent companies with roots in the Department of Pathology at the Arizona Health Sciences Center and its University Medical Center in Tucson, Arizona. Academic principals in these companies were active contributors to an annual review series, Advances in Pathology and Laboratory Medicine, which I edited with Dr Ramzi Contran and others for years. I served as department head of pathology for 17 years in Arizona (1990-2007). Before that, I was chair of the Department of Pathology at Rush Medical College in Chicago, Illinois, for 15 years (1975-1990). During the 32 years I served as an academic pathology chair, I was personally engaged with start-up companies in positions ranging from CEO to scientific director. I had a bird's-eye view, from the dual perspective of a university insider and an entrepreneur, of some of the activities related to pathology department spin-off companies.

In this Futurescape presentation, I will describe 3 companies that were all spin-offs out of The University of Arizona's Pathology Department. Additional spin-offs of the Department of Pathology are not included for lack of space. For purposes of disclosure, I had no direct equity involvement in the first 2 companies, Sunquest Information Systems, Inc, and Ventana Medical Systems, Inc; I co-founded the third company, DMetrix, Inc, and do have equity in that company.

Sunquest Information Systems, Inc

Sunquest Information Systems, Inc, was actually one of the first spin-off companies of the new Arizona Health Science Center and its University Medical Center, in Tucson. The Arizona Health Sciences Center was created around 1966 to house Arizona's first and only College of Medicine. Sunquest Information Systems, Inc, was co-founded in 1979-1980 by James E. Peebles, BA, then director of Information Systems at The University of Arizona Health Sciences Center; Sidney Goldblatt, MD, a pathologist from Johnstown, Pennsylvania; and Robert Morrison, an engineer from Tucson, Arizona.

Mr Peebles was educated as a mathematician and, after earning a BA degree in mathematics from the University of Virginia (Charlottesville), he started his career in computers at the prestigious Applied Physics Laboratory at Johns Hopkins University in Baltimore, Maryland. By the time he was in his mid-20s, Mr Peebles had developed a reputation as a wunderkind in computers. The University of Arizona College of Medicine was founded in 1966. Jack M. Layton, MD, the founding Department of Pathology chair, was recruited from The University of Iowa (Iowa City). He was a gifted educator as well as a talented recruiter of outstanding faculty members. Also, to his credit, Dr Layton would prove to be a supporter of departmental entrepreneurship as well. One of Dr Layton's primary goals for the laboratory at the new university hospital was to have an automated laboratory information system when the hospital opened.

The founding dean of The University of Arizona College of Medicine, Merlin K. DuVal, MD, a surgeon recruited from the University of Oklahoma (Norman), wanted to create a university medical center that would eventually be entirely paperless. He envisioned a new hospital, our University Medical Center, that would leverage emerging computer technologies into a state-of-the-art clinical facility. Dean DuVal was a visionary in a number of ways.

Dean DuVal heard of Mr Peebles from other faculty members and personally assisted in recruiting him to Arizona. Mr Peebles' reputation was that of being the "best-of-breed" of young computer system integrators. Dean DuVal gave him the green light to build the laboratory information system of the future. Dr Layton was a key member of the search committee that recruited Mr Peebles and was instrumental in supporting the vision for information systems.

Initially, when the hospital opened in 1971, a commercial product, DECLab12, was purchased from Digital Equipment Corporation and installed. This product, although limited in functionality and hardware technology, supported the institution during the formative years.

Mr Peebles spent much of the late 1970s spearheading the creation of a more flexible hospital laboratory system for The University of Arizona's University Medical Center. As a matter of record, the new dean's vision resulted in a significant investment by the University Medical Center in developing a paperless laboratory system. As it evolved and was showcased, this laboratory system created quite a stir in the laboratory information system community of the late 1970s, resulting in visits from other early adopters of automated laboratory information systems.

Sunquest Information Systems, Inc, likely benefited from what today would be referred to as intellectual property related to the leading-edge laboratory information system that Mr Peebles and his staff, along with faculty members from the Department of Pathology, had created at the University Medical Center and later commercialized at Sunquest. (3,4) All of this was ethical, legitimate, and allowable in 1980. Today, The University of Arizona Office of Technology Transfer might get involved in spin-off activities involving such intellectual property. The Sunquest spin-off from the university occurred well before such technology transfer was regulated at Arizona's universities, and it was approved by appropriate University of Arizona authorities.

Recent interviews with some of the people involved with the spin-off of Sunquest Information Systems identified 2 pathologist faculty members from The University of Arizona's Pathology Department who had special roles in designing features of the information system that were subsequently recycled in the Sunquest laboratory information system product. Other than receiving some small consulting fees along the way, neither of the pathology faculty members apparently benefited financially from Sunquest in the form of equity in the company.

Sam Paplanus, MD, a pathologist recruited to The University of Arizona from Johns Hopkins Medical School, in Baltimore, Maryland, worked with Mr Peebles and his team in developing some of the specifications for the overall architecture of the University Medical Center laboratory information system. According to Kenneth J. Ryan, MD, Dr Paplanus had a role in creating some of the "physician friendly" features for the information system at the University Medical Center, including the design of the computer-physician interfaces. Dr Paplanus also developed a surgical pathology module that was not carried over to the Sunquest laboratory product but was successfully implemented at University Medical Center for many years.

Kenneth J. Ryan, MD, Director of the Microbiology Laboratory at the time of the Sunquest spin-off from University Medical Center, had a lot of input in the development of a highly innovative microbiology laboratory information system that Sunquest eventually emulated and marketed as a separate module of the Sunquest clinical laboratory information system. (3,4) This microbiology module became a popular feature of the Sunquest system. Mr Peebles worked with Dr Ryan, then a junior faculty member who had been recruited to Arizona in 1971, right after a stint in the US Army. This followed Dr Ryan's training as a microbiologist at the University of Washington in Seattle, Washington. Years later, Dr Ryan served as my vice chair of the Department of Pathology and the medical director of the University Medical Center Laboratories. He eventually rose to the position of interim dean of the College of Medicine. Dr Ryan is best known in the academic world as editor of Sherris Medical Microbiology: An Introduction to Infectious Diseases, the leading textbook in the microbiology field.

According to Dr Ryan, who I recently interviewed as part my preparation for this Futurescape presentation, 2 features of the Sunquest clinical laboratory system are traceable to a University Medical Center laboratory information system development project he worked on in the 1970s. (3-6) These features were incorporated into a Sunquest product after Mr Peebles left the University Medical Center to become president and chief executive officer of Sunquest Information Systems, in 1980.

One of Dr Ryan's innovations was the introduction of single keystrokes to control specific functions, a novel concept for laboratory information systems in those days. (3,4) Dr Ryan's second innovation involved directly transferring results from the microbiology analytical machines into databases and patient reports. (5,6) Until that time, microbiology results from automated instruments were recorded on paper and then reentered into reports. Mr Peebles and Dr Ryan directly linked analytical machines to their laboratory information system at the University Medical Center. Dr Ryan, as the first laboratory microbiologist hired at the University Medical Center, signed out most of the microbiology laboratory reports himself in those days. He observed that 99% of the data coming from the automated instruments was identical to what went into his written laboratory reports. The exceptions were cases in which diagnostic information and antibiotic susceptibility information were inconsistent. Dr Ryan set up a computer matrix for comparing diagnostic and susceptibility information coming from the automated instruments. Discrepant findings that needed further analysis were flagged by the computer system for review by the laboratory microbiologist. (5,6) This is an example of an early clinical decision-support system that worked.

While an employee at the University Medical Center, Mr Peebles began to develop a laboratory information system to replace the existing DECLab12 system, using techniques and design concepts that were later used to develop the commercialized Sunquest system. He then left the University Medical Center, later followed by several members of his information system group, to work full time at Sunquest. In some measure, the Sunquest information system was a clone of the University Medical Center laboratory information system.

Academic activities of the personnel at The University of Arizona helped to put its University Medical Center's state-of-the-art laboratory information system on the map and catalyzed the creation, and some of the subsequent successes, of this spin-off company. (5,6) Of course, memories of this fade with time. Today, new employees at Sunquest are often unaware of the university origins of their company.

Back in the 1970s, Mr Peebles and Dr Ryan presented their work on the microbiology laboratory module, built for University Medical Center, at national meetings and then, by invitation, at other hospitals and universities. Their work together was published in the early pathology informatics literature. (3-6) These presentations and publications initially led to invitations to share the technology with other institutions and then encouragement to commercialize the system. As Mr Peebles tells the story today, the first customer for Sunquest's laboratory information system product was the Hershey Medical Center in Hershey, Pennsylvania, where the laboratory department was chaired by Dr Arthur Krieg. At that time, Dr Krieg was a nationally recognized laboratory information system user and a proponent of continued automation of the laboratory. He had published extensively and was considered an authority in this area. Hershey Medical Center had an early laboratory system, similar to the DECLab12 product that was installed in Arizona. Recognizing the limitations of the existing systems and technology, Dr Krieg and his staff had developed an extensive specification for the "laboratory system of the future," which provided for considerable flexibility and growth as compared with existing products at that time. There is no doubt that Hershey Medical Center and Dr Krieg took a huge risk by contracting with a new and unknown company in Tucson, Arizona, to develop a system to meet their specifications. Dr Krieg had visited the site of the system at Arizona and, in retrospect, was impressed by what Mr Peebles had accomplished. The success of the development and the installation of the system at Hershey were keys to the future success of Sunquest. Other early adopters of the Sunquest system included the Lahey Clinic, Burlington, Massachusetts (Dr Sandy Kurtz); Moses Cone Hospital, Greensboro, North Carolina (Dr Charlie Hassell); and Peninsula General Medical Center, Salisbury, Maryland (Dr Neil Carey), all of whom contributed significant input to the continued improvement of the system, which benefited everyone.

Dr Goldblatt, for whom I have great respect, is a talented businessman with long-standing interests in pathology informatics and education (he directed the pathology residency training program at the Johnstown Hospital in Johnstown, Pennsylvania, for years). He had been working on solutions in medical informatics since 1963 and had directed projects in cytology automation while head of comparative cytology at the National Cancer Institute in Bethesda, Maryland, which is part of the National Institutes of Health. (7) Dr Goldblatt and his staff were early users of the DECLab12 system initially installed at Arizona in 1971 and hosted a visit to the site by Mr Peebles during their selection process for a new laboratory system.

Mr Peebles, Mr Morrison, and Dr Goldblatt entered into a business arrangement and cofounded Sunquest. The early growth of the company was financed largely from sales of systems. In approximately 1986, as Mr Peebles tells the story, Dr Goldblatt bought out the Peebles and Morrison interests in Sunquest. Fortunately for Tucson, Arizona, Dr Goldblatt did not relocate the company to Johnstown, Pennsylvania but, instead, ran the company by commuting between Johnstown, Pennsylvania, and Tucson, Arizona. As a historical footnote, the name of the company, Sunquest, was suggested by Mr Peebles' wife, who first saw the name Sunquest on the outdoor sign of an apartment complex in Tucson, Arizona, and liked it (J. E. Peebles, personal communication, May 2008).

Today, Sunquest Information Systems is still headquartered in Tucson, Arizona, in a large, modern building in a commercial real estate complex that includes the sizeable American College of Radiology headquarters. According to their Web page, Sunquest Information Systems, Inc, has more than 700 employees with more than 300 staffers involved in research and development. The company has a portfolio of industry-leading, best-of-breed diagnostic solutions for laboratory, radiology, and pharmacy. Sunquest's industry share is more than 20% of US hospitals, including more than 1000 US hospitals and commercial laboratories. Currently, Sunquest Information Systems is owned by Vista Equity Partners of San Francisco, California, a private firm with more than $2 billion of committed capital under management. Our University Medical Center uses Sunquest systems.

Old-timers in our Pathology Department fondly remember Mr Peebles and the Sunquest spin-off story and still keep in touch with him. After Mr Peebles left Sunquest, he founded another successful company in Tucson, Arizona, called MIDAS+, a health care technology firm that provides software tools to support the care-management process. The company is now called ACS Healthcare Solutions, MIDAS+ Division (Tucson, Arizona). The University of Arizona and the University Medical Center became separate nonprofit corporations around 1984.

In Tucson, Arizona, we count Sunquest Information Systems, Inc, as a spin-off company of the Department of Pathology of The University of Arizona College of Medicine. Dr Goldblatt, who is not on The University of Arizona faculty, became chief executive officer of Sunquest in 1986 and kept the company in Tucson, Arizona. He was chair of pathology at the hospital in Johnstown, Pennsylvania, for many years.

The establishment of what evolved into a large laboratory information system company in Tucson, Arizona, has had significant benefits for the Tucson, Arizona, pathology community, as well as for The University of Arizona, in many ways:

1. Sunquest has expanded the pool of workers in the information system industry in Tucson, Arizona.

2. Sunquest has expanded the local job market for computer workers, system trainers, information system sales personnel, and management.

3. Sunquest has indirectly stimulated some of the rapid growth of computer sciences at our university.

4. Academic pathologists at The University of Arizona have been sideline observers to the success of Sunquest and have seen firsthand how some laboratory information products, developed initially at the university, such as Dr Ryan's microbiology module, can be successfully commercialized.

5. The University of Arizona faculty and staff have had opportunities to provide input into improvements of the Sunquest Laboratory system on an ongoing basis for many years.

6. As a practical matter, through the years, the Department of Pathology and the University Medical Center have recruited talented information system personnel away from Sunquest.

Today, Arizona's University Medical Center remains a loyal Sunquest customer. We like the "made here" feeling that goes along with having a local vendor.

Also, Sunquest training sessions, which are very good, are just across town for us. Many pathologists from across the United States and from around the world come to Tucson, Arizona, for Sunquest training sessions. This has certainly increased the visibility of Tucson, Arizona, in the pathology world. It has also promoted the idea that Tucson, Arizona, is a friendly home for laboratory product companies. Each laboratory company that succeeds in this environment encourages others to follow its lead.

Ventana Medical Systems, Inc

The second spin-off company of the Department of Pathology at The University of Arizona was founded by a faculty member in the department, Thomas M. Grogan, MD. Dr Grogan, a talented hematopathologist, is one of the finest physicians I know. Ventana Medical Systems, Inc, which Dr Grogan founded in 1985, is heralded as a tremendous success story for biotechnology transfer at The University of Arizona, as well as for the biomedical industry in Arizona. Ironically, Dr Grogan tells horror stories about the university's lack of support for his new business venture, early on, for what became Ventana Medical Systems, Inc. The early days were tough, in part because the university lacked good policies for technology transfer in the mid-1980s. Dr Grogan, figuratively speaking, ran into brick walls and took his lumps trying to get Ventana off the ground. The record shows that Dr Grogan, as a pioneer and visionary and a doctor capable of great persistence, helped to write the rules for technology transfer in Arizona. Dr Grogan displays missionary zeal when it comes to patient care. He simply would not accept obstacles to his dream of automating immunohistochemistry stainers to provide better and quicker laboratory services, especially for his lymphoma and leukemia patients. (8,9) Arizona certainly owes Dr Grogan a debt of gratitude. Today, decades later, this is now widely acknowledged in many circles.

What evolved into Ventana Medical Systems, Inc, started out as a company with a different name and was spunout of The University of Arizona 4 or 5 years before I came to Arizona as the Pathology Department chair, in 1990, replacing an interim chair, Dr George Ray. I chaired The University of Arizona Department of Pathology during much of the time that Ventana was growing from a relatively young start-up company into a major international laboratory device and reagent company in Tucson, Arizona. Today, some 10000 patients a day, worldwide, are diagnosed using Ventana systems. Ventana has a base of more than 5000 installed machines and more than 70% (T. M. Grogan, written communication, September 2008) of the world market share in automated immunohistochemistry. The evolution of Ventana into a major medical device and reagent company was interesting to observe from the perspective of the home academic department of this spin-off company.

What kind of faculty member spins off a company like Ventana? As a faculty member, Dr Grogan has been an international leader in diagnostic hematopathology for many years. His clinical research, in collaborations with Thomas P. Miller, MD, a hematologist-oncologist, and the Southwest Oncology Group (San Antonio, Texas), produced important papers on lymphoma classifications and lymphoma clinical trials; some of these papers were published in very prestigious journals, including the New England Journal of Medicine. Dr Grogan also actively participated in important basic-science research. For example, his research with William T. Bellamy, PhD, an associate professor of pathology, on the expression of vascular endothelial growth factor in lymphomas, is widely cited in the literature.

During the early stages of the development of Ventana, Dr Grogan had hands-on management of the company. (8,9) This involved a remarkable balancing act because he retained all of his service, teaching, and research responsibilities at The University of Arizona throughout the early start-up phases of the company. Later, during the time-consuming process of taking the company public and, then, during the recent acquisition of Ventana by the giant Swiss pharmaceutical company, Roche Pharmaceuticals (Basel, Switzerland), Dr Grogan remained an active part-time faculty member in the College of Medicine's Department of Pathology. Even today, despite his packed schedule as a senior vice president at Ventana, Dr Grogan still makes himself available at the university to help out with difficult clinical cases and to provide guidance on research strategies.

As seen from the outside, for Dr Grogan, Ventana has never been about money, nearly as much as it has been about improving and expanding patient care. My impression is that Dr Grogan is most excited about the recent acquisition of Ventana by Roche because it means that Ventana will have the opportunity to expand and to bring leading-edge patient care to many millions of additional patients around the globe. Although Dr Grogan's vision is global, his primary interest is patient-centric health care.

Roche acquired Ventana Medical Systems, Inc, for $3.4 billion in 2008. This relatively high valuation represents a confluence of the pharmaceutical and pathology industries, because, in part, of their shared commitment to patient-centric care. These industries share a new vision of an expanded global market for laboratory diagnostic technologies married to customization of clinical pathways for the treatment of individual patients.

From a College of American Pathologists' Futurescape perspective, the Ventana-Roche corporate strategy may be especially worth noting because it may have a bearing on the globalization of laboratory services in the decades ahead. The corporate strategy that helped to drive up the value of the Roche-Ventana deal to $3.4 billion provokes thought. The company has focused its attention on global demographics, showing that 4% of the world's population lives in the United States and another 5% of the world's population lives in the European Union. The remaining 91% of the world's population represents potential new markets for the company's patient-centric, targeted, therapy-related, diagnostic and therapeutic products (T. M. Grogan, written communication, September 2008). For example, the market for HER2/neu testing and therapies becomes much larger with this global perspective. The development of Ventana's customer base for its key technology, automated immunohistochemistry, may be roughly plotted along the lines of the "S-curves of innovation," which were described at last year's Futurescape meeting. (1)

DMetrix, Inc

The third spin-off company of The University of Arizona Department of Pathology, DMetrix, Inc, is at an early stage in its evolution. For purposes of disclosure, I am one of the cofounders of DMetrix as well as one of the coin-ventors of its enabling technology, its miniaturized array microscope digital-imaging device.

DMetrix, Inc, represents the convergence of interdisciplinary interests, including 3 areas in which The University of Arizona excels: optics, laboratory innovation, and telemedicine/telepathology (Figure 1). The University of Arizona's College of Optical Sciences (Tucson) is widely regarded as being tops in its field. Optical sciences and astronomy are large enterprises at The University of Arizona. For example, many newspapers and Web sites currently have many articles about the Phoenix Mars Lander spacecraft, which recently landed on the planet Mars, in May 2008. A robot on Mars is now analyzing Martian soil for signs of ice and life. The principal investigator for the project, Peter Smith, PhD, is on our faculty at The University of Arizona in Tucson. Some remarkable analytic devices on the Phoenix Mars Lander were also developed at The University of Arizona.

[FIGURE 1 OMITTED]

In the medical imaging arena, Peter Bartels, PhD, a distinguished scientist with joint appointments in optical sciences and pathology, is a world leader in the area of computer machine vision for laboratory diagnostic applications. For the aforementioned reasons and many others, Tucson, Arizona, markets itself as "Optics Valley."

Telemedicine is yet another area of excellence at the Arizona Health Sciences Center. A banner hanging from a light post on the university mall, outside the office of The University of Arizona president reads, "#1 Telemedicine Program in the World." Arizona is very proud of its telemedicine program. The Arizona Telemedicine Program is regarded as one of The University of Arizona's premier programs and has been involved in technology transfer activities at the university. In early telemedicine activities at The University of Arizona, the Department of Pathology took the lead and has been offering telepathology services since 1992. This antedates the establishment of the Arizona Telemedicine Program by 4 years. This Arizona telepathology service has diagnosed more than 3500 patients to date and is still active. When the Arizona Telemedicine Program was initially funded in 1996 by the state legislature, the then-new statewide, multispecialty telemedicine program was administratively housed in the Department of Pathology. I was appointed its director but retained my position as pathology chair as well.

Today, the Arizona Telemedicine Program is one of the largest multispecialty telemedicine programs in the United States. Telemedicine services are provided at dozens of rural sites, in 61 subspecialties of pediatrics, medicine, surgery, psychiatry, radiology, pathology, and others. More than 700 000 cases have been handled to date (www. telemedicine.arizona.edu). The Arizona Telemedicine Program has received 10 national and international awards.

Personally, I have been interested in telepathology, a subspecialty of telemedicine, since my days as a pathology resident in Boston at the Massachusetts General Hospital in the late 1960s. The predecessor of telepathology was the so-called television microscopy. Telepathology has only recently entered its rapid growth phase, illustrating that medical imaging technologies can take decades to mature and to begin to enter into mainstream medical practice. (1,10,11)

In 1986, my group at Rush Medical College in Chicago, Illinois, introduced the term telepathology to replace the term television microscopy and designed, built, and tested the first robotic telepathology system. (10) Since then, robotic microscopes have been installed in many countries, benefiting tens of thousands of patients. (11)

Virtual slide telepathology can be traced to the late 1980s and early 1990s. This topic has been discussed elsewhere. (11-13) Because of our interest in telepathology, in 2000, in Arizona, the optical science researchers and our pathologists began to consider reengineering light microscopy to bring the field of digital microscopy into the 21st century. We discussed our concept of a laboratory industry in which traditional light microscopy might be replaced by highly automated digital-imaging machines. (11) Video monitors would replace glass-lens eyepieces as the viewing devices of choice. Looking at the new field of virtual slide telepathology, we speculated that, to take laboratories fully digital, the laboratory industry would need a scanner that would have a throughput of a virtual slide of 1 minute or less. (12-14) At the time, we thought we might eventually want to reduce slide scan times to 10 to 15 seconds, enabling us to image multiple planes digitally in a histopathology section.

"Reinventing" light microscopy, instead of working around the constraints imposed by the limitations of single light-axis optics, as other vendors were doing, made sense to us. (12,13) The designs of light microscopes until the 21st century were built around the needs of human observers. The eyepieces of the microscopes were positioned at eye level, the focus knobs were positioned just above a desktop, and stage controls for moving a glass slide on a microscope stage were conveniently arranged for positioning glass slides with human fingers. Human ergonomics were a significant design concern and often one of the measures of the suitability of the instrument.

When the Arizona design team began brainstorming about next-generation light microscope designs, we realized that human ergonomic factors would be less important in the future. The design team postulated that pathologists might no longer be looking through eyepieces. This was liberating for the design team because they were freed of the ergonomic constraints imposed on conventional light microscope designers by the prior need to make light microscopes user friendly.

Our faculty member, Dr Bartels, came up with the idea of using an array of tiny microscopes to digitize histopathology slides. Achieving this would require miniaturization of the optics and massive parallel processing of digital information. I suggested that we use planar arrays of precision lenses (ie, lenslet arrays), separated by multi-channel spacers, to create lenslet array ensembles that would constitute the optics for the system. Professor Roland V. Shack, PhD, of our College of Optical Sciences, proposed that the lenslet arrays be monolithic and fabricated from single sheets of optical-grade plastic or glass. Chen Liang, PhD, senior optical scientist at DMetrix, designed the aspheric lens systems that allowed for extreme miniaturization of the lenses that could be tightly packed into the DMetrix lenslet array ensemble (Figure 2). Michael R. Descour, PhD, was responsible for integrating the optical, electrical, and mechanical components of the DMetrix DX-40 Ultrarapid Virtual Slide Scanner. (12-14) James C. Wyant, PhD, dean of The University of Arizona College of Optical Sciences, continues to give thoughtful advice to DMetrix, Inc.

By the year 2005, DMetrix had succeeded in designing, fabricating, and commercializing such an instrument.12 This involved perfecting fabrication methods for producing monolithic arrays of lenses; developing a novel, high-performance, 25-megapixel sensor camera; developing a new multilight-emitting diode illumination system; developing a novel slide delivery system; and developing the software that would support massive, parallel processing of data.13 Virtually none of the components of the DMetrix virtual slide scanners were off-the-shelf products.

The first commercial DMetrix DX-40 Ultrarapid Virtual Slide Scanner became operational at The University of Arizona's Department of Pathology in 2005 and is still in use today. The first scanner is still used for research and education. (12)

DMetrix owns much of the intellectual property for array microscopy. To date, 16 US patents have been issued to The University of Arizona or DMetrix, Inc. (14) Another 14 US patents are in the pipeline. DMetrix scanners have been purchased by US government agencies, universities, the Cleveland Clinic, Massachusetts General Hospital, M. D. Anderson Cancer Center, a major cancer center in Europe, and others.

[FIGURE 2 OMITTED]

Currently, the DMetrix system uses an 80-miniaturized microscope array (Figure 2). Histopathology slides are scanned by passing the lenslet array ensemble, with a sensor directly on top of the array, along the long axis of a glass histopathology slide. The digital images produced with this system are often indistinguishable from those produced with other commercial, virtual slide-scanning systems.

At The University of Arizona and its affiliated hospitals, we have two DMetrix DX-40 virtual slide scanners, with two more on the way. Virtual slide telepathology has changed the way we do business. We have several successful applications. We use DMetrix virtual slides for clinical services, including a multisite quality assurance program. We also use virtual slides for second opinions, subspecialty consultations, and same-day laboratory services. For example, in Tucson, Arizona, we have 2 university hospitals located 6 miles apart; 1 is relatively small and has 1 pathologist on site, whereas the other hospital has many pathologists on site during a work day. The surgical pathology quality-assurance cases from the smaller hospital are routinely scanned into virtual slides using the DMetrix DX-40 system and then reviewed at the larger institution at the regularly scheduled, afternoon quality-assurance conference. Staff pathologists have reviewed more than 300 of these quality-assurance cases by viewing DMetrix virtual slides at a distance. The diagnostic accuracy is very high. This quality-assurance conference reduces the sense of isolation for the pathologist at the smaller hospital, while enabling our residents at the larger hospital to see more interesting cases. Everyone seems satisfied with the quality of the virtual slide images. As another example, DMetrix virtual slides have essentially replaced conventional light microscopy in our courses for medical students at The University of Arizona College of Medicine.15

LESSONS LEARNED

Academic department-incubated start-up companies can provide a pathology department with valuable opportunities to stay abreast of advances in the field. These companies can also provide talented faculty members and staff with incentives to stay within the university system. I believe that the spinning off of companies is generally a good thing for an academic pathology department. Business-oriented faculty and staff provide the department with invaluable and unique links to future realities for the laboratory industry. Such activities are to be encouraged, as long as they do not interfere with day jobs and are not a conflict of interest.

The Department of Pathology at The University of Arizona College of Medicine has embraced an entrepreneurial mentality for many decades. As a result, in return for relatively modest investments, The University of Arizona and the State of Arizona are reaping large rewards. It is noteworthy that while this was ongoing, National Institutes of Health funding and other federal funding for research in our Department of Pathology increased significantly. Often the pathology department faculty entrepreneurs were also among the most successful pathology faculty members when it came to competing for federal grants. Faculty activities in the business arena often seemed to actually catalyze the rate of progress of the same faculty member's research team at the university, not distract from it. This was impressive and can be replicated as success stories in other academic pathology departments.

At The University of Arizona, we showed that an academic pathology department can serve as an incubator for new companies across a wide spectrum of business categories, several of which are described in this presentation. We also found that these extracurricular faculty and staff activities did not necessarily distract from traditional academic responsibilities of other department members. In our experience, the majority of pathology faculty members were remarkably disinterested in being entrepreneurs, and some individuals even preferred not to participate in entrepreneurial activities going on in their own department. They didn't seem to mind them either. Uninvolved department members often regarded the entrepreneurial activities as "being of another world," even as they worked with the faculty-entrepreneurs shoulder to shoulder during their shared education, service, and research activities in house.

At the end of the day, what have we learned about individual entrepreneurship? What is the profile of a pathology department entrepreneur? What do these entrepreneurs have in common, if anything?

In general, I would characterize the pathology department entrepreneurs as multitaskers, who leverage their passion for their profession, their intelligence, their creativity, and their persistence into an entrepreneurial strategy for pursuing their dreams and ambitions, which are beyond the usual scope of the traditional academic missions of research, teaching, and service. It seems to me that fame and wealth tend to be relatively low on their list of priorities. On the other hand, some pathology department-based entrepreneurs can become addicted to the frenzy of start-up activities and maintain their involvement in such endeavors by founding a series of companies over time. Personally, I found start-ups to be fascinating. Generally, the highs can outweigh the lows by a healthy margin.

Finally, I would end this speech by suggesting that The University of Arizona experience with pathology entrepreneurship might serve as a model for other academic pathology departments, especially those departments with an interest in expanding the influence of academic pathology on the future of pathology and laboratory medicine. It's a special opportunity for our academic pathology departments to shine in the public limelight!

References

(1.) Weinstein RS. The S-curve framework: predicting the future of anatomic pathology. Arch Pathol Lab Med. 2008;132(5):739-742.

(2.) Weinstein RS, Lopez AM, Barker GP, et al. The innovative bundling of teleradiology, telepathology and teleoncology services. IBM Syst J. 2007;46(1):6984.

(3.) Peebles JE, Ryan KJ. A Microbiology Information System. In: O'Neill, JT, ed. Proceedings: The Fourth Annual Symposium on Computer Applications in Medical Care. Long Beach, CA: Institute of Electrical and Electronics Engineers Computer Society; 1 980:534-538.

(4.) Ryan KJ, Peebles JE. On-line entry of routine and AutoMicrobic system bacteriology results. In: Tilton RC, ed. Rapid Methods and Automation in Microbiology. Washington, DC: American Society for Microbiology; 1 982:23-27.

(5.) Ryan KJ. The computer in microbiology: future applications in test performance and reporting. Ann N Y Acad Sci. 1984;428:243-250.

(6.) Ryan KJ, Peebles JE. A turnkey MUMPS-DEC microbiology system. In: Pearson AC, ed. Proceedings: Second International Workshop on Computers in Microbiology. Leicester, England: University of Leicester Press; 1985.

(7.) Goldblatt SA. Design of the laboratory information system. In: Weinstein RS, ed. Advances in Pathology and Laboratory Medicine. Vol 6. St Louis, MO: Mosby Co; 1993:37-62.

(8.) Grogan TM, Casey T, Miller P, Rangel CS, Nunnery D, Nagle R. Automation of immunohistochemistry. In: Weinstein RS, ed. Advances in Pathology and Lab oratory Medicine. Vol 6. St Louis, MO: Mosby Co; 1993:253-283.

(9.) Grogan TM, Rangel C, Rimsza L, et al. Kinetic-mode, automated double-labeled immunohistochemistry and in situ hybridization in diagnostic pathology. In: Weinstein RS, ed. Advances in Pathology and Laboratory Medicine. Vol 8. St Louis, MO: Mosby Co; 1995:79-100.

(10.) Weinstein RS, Bloom KJ, Rozek LS. Telepathology and the networking of pathology diagnostic services. Arch Path Lab Med. 1987;111(7):646-652.

(11.) Kayser K, Molnar B, Weinstein RS. Digital Pathology Virtual Slide Technology in Tissue-based Diagnosis, Research and Education. Berlin, Germany: VSV Interdisciplinary Medical Publishing; 2006:1-193.

(12.) Weinstein RS, Descour MR, Liang C, et al. An array microscope for ultra-rapid virtual slide processing and telepathology: design, fabrication, and validation study. Hum Pathol. 2004;35(11):1303-1314.

(13.) Weinstein RS, Descour MR, Liang C, et al. Reinvention of light microscopy: array microscopy and ultrarapidly scanned virtual slides for diagnostic pathology and medical education. In: Virtual Microscopy and Virtual Slides in Teaching, Diagnosis and Research. London, England: CRC Press; 2005:9-35.

(14.) Weinstein RS, Descour MR, Liang C, Bartels PR, Stack RV, inventors; The Arizona Board of Regents on Behalf of The University of Arizona, assignee. Miniaturized microscope array digital slide scanner. US patent 7,184,610 B2. February 27, 2007.

(15.) Weinstein RS. Time for a reality check. Arch Pathol Lab Med. 2008;132(5): 777-780.

Ronald S. Weinstein, MD

Accepted for publication October 31, 2008.

From the Department of Pathology, Arizona Telemedicine Program, The University of Arizona College of Medicine, Tucson.

Dr Weinstein is cofounder of, and has equity in, DMetrix, Inc, Tucson, Arizona.

Presented in part at the College of American Pathologists Futurescape of Pathology Conference, Rosemont, Illinois, June 7-8, 2008.

Reprints: Ronald S. Weinstein, MD, Department of Pathology, The University of Arizona College of Medicine, 1501 N Campbell Ave, Tucson, AZ 85724-5043 (e-mail: ronaldw@u.arizona.edu).
Gale Copyright: Copyright 2009 Gale, Cengage Learning. All rights reserved.