Advancing Laboratory Medicine through Innovation: A Tale of Six Inventors

In a recent issue of Science Translational Medicine (1), Yock and colleagues of Stanford University discuss the merits and challenges of developing a discipline of medical technology innovation. Innovation is defined as “inventiveness put to use”; a discovery that results in a commercial product or service. In this provocative article, the authors discuss two main streams of educational theory and practice that together form the basis for teaching innovation: design thinking and entrepreneurship education (Fig. 1). Design thinking focuses on identifying the opportunity and need, developing the idea to solve the problem, building the prototype, and testing the product, while entrepreneurship education provides an introduction to the skills and approaches required to take a product or a service and successfully commercialize it. The authors argue that medical technology innovation is the ideal environment for interdisciplinary team building combining physicians, engineers, scientists, and business professionals. Design thinking encompasses the creative roadmap toward innovation, including awareness of the opportunity or unsolved problem, an idea to fill the opportunity, development work to design and prototype the solution, and experimental testing as a reality check. Multiple cycles of ideas, prototyping, and testing may be required before a viable product emerges. Entrepreneurship assesses the feasibility of commercializing the product, including components of uniqueness (intellectual property) and market potential. Regulatory requirements and business strategy often suggest outcomes that may include in-house manufacturing, licensing, mergers/acquisitions, or an initial public offering (IPA). In laboratory medicine, numerous scientists and physicians have been able to successfully launch their inventions into the marketplace; inventions that changed the practice of medicine. Six of those inventors were invited to share their success stories with the readers of Clinical Chemistry. How did they do it? What influenced most their success? What were the major drivers for their pursuits? Did they have formal training in the innovation process? In addition, they were asked to score, in terms of relevance, 20 factors that influenced their endeavors (Fig. 2). Each of the 6 inventors highlighted here ranked 20 factors from irrelevant [Yock et al. (1)] to crucial [Lo et al. (10)]. For each factor, the median response is shown as a triangle with the range indicated as a line. There is no single recipe for success in innovation and there is a myriad of examples of highly successful entrepreneurs who have not taken a single course in entrepreneurship. I will summarize some of my own experiences as a scientist and innovator and comment on competencies that I acquired. I believe that the cornerstones to my apparent successes were my undergraduate degree in chemistry (1976) and my PhD in analytical chemistry (1979). This training made me an analytical biochemist, versatile in the art of quantitative measurements. These skills were complemented nicely with my postdoctoral training in clinical chemistry (1982–1984) and my medical degree (1986). My desire to return from Greece to Toronto as a professional was hampered by the Canadian immigration laws of that time, which stipulated that recruitment of foreign individuals must be sponsored by companies that needed unique skills. Although at that time I was concerned about working in industry, I had no choice but to accept a position as director of research and development of a small biotechnology company, CyberFluor, in 1986. CyberFluor was interested in developing highly sensitive nonisotopic immunological assays for clinically relevant analytes. At that time, I committed to a 2-year tenure, in exchange for landed immigrant status. I did not realize then that the 2 years I spent at CyberFluor were probably the most important of my career. Working in an industrial environment and overseeing eight PhD scientists, I had the advantage that the project/problem identification was already made for me. It was a very specific project, with a very specific target outcome; that is, to develop an instrument that could measure time-resolved fluorescence originating from lanthanide chelates (2). When I joined, I took on the challenge of working with engineers, programmers, physicists, and others to perfect the instrument prototype. At the same time I initiated a program to optimize the reagents through novel conjugation techniques (3,–,5). In the end, we put together a combination of instrument/reagents, a product that was marketed successfully in Canada and abroad. Without my realizing it at that time, my knowledge in Analytical Biotechnology and Laboratory Medicine was highly enriched with other skills of entrepreneurship, including intellectual property protection, technology transfer, marketing, production and quality control, fundraising, investor relations, and financing. I am not sure if I could have ever obtained such diverse training, in such a short time, in any university program. Despite my leaving industry in 1988 to return to academia, the knowledge that I acquired was invaluable and has followed me in my current career as a scientist. I did not cut ties with the company but, rather, I became the chair of their scientific advisory board. I established relationships between my new employer (University of Toronto and affiliated hospitals) and CyberFluor, which resulted in the continuation of my research in areas of interest to CyberFluor in exchange for research funds. A major boost was the fact that such contributions were matched dollar for dollar from provincial or federal sources. Over the following 20 years, matching funds have been the cornerstone of my research budget. When CyberFluor was acquired and eventually closed, I used my skills to identify other commercial sponsors that provided major funding for our research programs in exchange for intellectual property. My strengths in quantitative analytical biochemistry were adapted to solving other problems in laboratory medicine, such as identification and validation of diagnostic and prognostic biomarkers for various diseases, including cancer. This is a well-defined unmet clinical need with applicability to patient care. The clear biomedical question, with commercial potential, attracted many companies to work with us. My current academic employer has a very strong technology transfer office that facilitates discussions and signs deals with prospective collaborative companies. My deep understanding of what industry wants from us, and what we need from them, facilitated the development of successful relationships and attraction of substantial research money. Contrary to the view that companies may interfere with the freedom of research in academia, my experience has been the opposite. We have always defined our research and found companies with matching interest, not the other way around. More recently, we opened up new areas based on our core competencies in quantitative analytical chemistry. We apply mass spectrometry–based proteomic approaches for novel biomarker identification (6, 7). These programs are flourishing with both industrial as well as other funding, because they are attempting to address a very clearly defined clinical need. Hospitals are highly supportive of collaborative relationships with industry for many reasons, including overhead income, covering of patent costs by industry, licensing fees, and partial ownership of spin-off companies. Other benefits of industrial sponsors participating in academic research include training graduate and postdoctoral students in industrial environments and teaching them how these relationships can be initiated, sustained, and expanded. My own path to becoming an innovator was initiated by a series of uncoordinated steps early in my scientific career. Collaborations with industry can help sharpen the focus of one's research to identify problems that require solutions and lead to new products, attract new and matching funding, and train highly qualified personnel in academic and industrial environments, and can lead to licensing agreements, spin-off companies, patents, and generation of new income through licensing. As mentioned earlier, there is no single recipe to becoming a successful innovator and the route that I chose appears to best fit my own inspirations and desires. I hope that this commentary will be a case study for young clinical chemists who are seeking to become innovators in laboratory medicine. I spent the early part of my academic career at the University of Oxford but decided to return to my home city, Hong Kong, in 1997. This career move prompted me to consider exploring a new research direction. Two reports on tumor-associated genetic alterations in the plasma and serum of cancer patients at the end of 1996 (8, 9) inspired me and my coworkers to see if a fetus would also release its DNA into the plasma and serum of its pregnant mother. This work led to the discovery of the presence of cell-free fetal DNA in maternal plasma and serum (10). We were able to show that one could determine a variety of fetal genetic characteristics by maternal plasma/serum DNA analysis, and were granted our first patent on this technology. Initially, we focused on the detection of paternally inherited genetic sequences that were absent in the pregnant mother's genome, e.g. the Y chromosome of a male fetus or the RHD gene of a rhesus D-positive fetus. Such tests are now in use in a number of centers for the prenatal diagnosis of sex-linked diseases, congenital adrenal hyperplasia, and fetal RHD genotyping. We then embarked on the challenging task of attempting to detect a fetus with trisomy 21 by using maternal plasma. This task is very demanding technologically because fetal DNA represents only a minor proportion of the DNA present in maternal plasma (11). Over the next 10 years, we investigated multiple approaches to achieve this goal, including those based on plasma RNA analysis (12) and DNA methylation analysis (13). In 2007, we reported an approach based on single DNA molecule counting (14) and showed in 2008 that massively parallel sequencing was an effective way for implementing this concept (15). We recently completed a large-scale validation study that shows the robustness of this approach (16). We have just seen the launch of this technology in the US and are anticipating clinical adoption in a number of other countries in the near future. A number of factors have enhanced my ability to push forward in this field. First, my move from Oxford to Hong Kong had created an opportunity whereby I was more receptive to taking risks in my research direction than I might have been had I not moved my career from one continent to another, which is inherently risky in itself! The field of noninvasive prenatal diagnosis was filled with uncertainties at the end of the 1990s because decades of research had not resulted in a robust method for the isolation of fetal cells from maternal blood. The jump from targeting fetal cells to analyzing cell-free fetal DNA might be regarded by many as even riskier because many researchers did not believe that the new approach would yield precise fetal chromosome dosage information. Second, I am fortunate enough to be able to work with an excellent team, especially Rossa Chiu and Allen Chan, both within my department, and have collaborated with a dedicated team of obstetricians who have provided the clinical input and samples for the research. Third, I was able to gain access to new technologies at key time points in my career. The first such technology was real-time quantitative PCR, which was crucial for the accurate measurement of fetal DNA concentrations in maternal plasma (11). The understanding of these quantitative parameters had been essential for the subsequent development of trisomy 21 testing using plasma nucleic acids. The second such technology was mass spectrometry for nucleic acid analysis, which allowed us to show for the first time that plasma nucleic acids could be used for the direct elucidation of fetal chromosome dosage information (12, 13). The third such technology was massively parallel sequencing, which allowed us to realize a general and robust approach for detecting fetal chromosomal aneuploidies using molecular counting (15). I have also been fortunate to have access to the necessary funds for supporting my research. The Innovation and Technology Fund of the Hong Kong SAR Government and the Areas of Excellence Scheme of the University Grants Committee have provided the much-needed support for my work. A large donation from the Li Ka Shing Foundation in 2005 allowed the establishment of the Li Ka Shing Institute of Health Sciences and my appointment as the founding director. The Institute has provided state-of-the-art research facilities that have allowed my team to compete effectively. A good commercial partner has also been important for my efforts in realizing noninvasive prenatal diagnosis. A chance encounter with Charles Cantor, the Chief Scientific Officer of Sequenom, at a conference in Thailand in 2002, resulted in such a link. Since then, we have been collaborating both on the scientific (12, 14, 15) and the commercialization aspects of the technology. In summary, my research has been facilitated by the chance convergence of many favorable conditions. I hope that my story and those of other technological innovators might help the creation of institutional or funding infrastructures that would improve the odds of encountering such a convergence. This is the story of two disparate individuals who have forged separate, but similar, careers, often working together for years developing technology. One likes to sing and the other and The early of their but they share a for innovation. One of us to university the other the clinical laboratory as a and was into the as a medical in a and the of including before the of that a career would require led both of us to in clinical and chemistry We both our experience and found us as colleagues at the in the of the University of This by a clinical was unique in the as it was by the university and the of Health to and use new for use in It a and and a state-of-the-art and the commercial to clinical service in the medical It also had specific access to patent to patent For both of us, this experience was the basis of of our success as we that by can lead to We were with two major at the both of which were These were the by as the which a large in the from analysis toward and enhanced that was in and One of us in academic and the other on to work in the industry, as a director and of with the and then as a of research and development with the The experiences this invaluable developing new technology in It also a of the and necessary to develop a new technology and it to we were this time in the of and Laboratory Medicine at the University of in and a new of technology opened for both of us. We had both been developing a with and we a collaborative with the University of and a a we had our first with in with that facilitated and In there was information about the of in and we about these at able to and use was and we a of for the by our as clinical laboratory It became apparent that the work intellectual property that be This was by the fact that the University of had a for through its for Technology work of this especially if it is to be to gain support from the were as approaches to the Science Foundation clinical an this and of the funds to and the were through about the project, and help from colleagues who had for as We that it was important to be able to the benefits and the commercial of new technology if we were to in support for our work. A years had been and we were to our we spent many our to prospective that was in but we and eventually and a company together with the The company to become Technology and a successful company was this time we a team that numerous of our analysis and especially The small team we that and but we have that innovation a to ideas, to be to to patent first and to and to work in an freedom to new is The work on has resulted in US and to for the University of was the was the aspects of my including the development of and assays for of have already I will not to most of it I was a with a career as an undergraduate at I spent a to a as a professional but it did not work and I spent a on and on with the on I took and decided to to a graduate degree in chemistry. I was as a at the chemistry of the University of and then as a graduate in analytical chemistry the next I had to my was This experience was very and eventually I showed that generation of the very could not with laboratory was to develop and then my own I had a number of because postdoctoral were not in analytical chemistry. me but I a on clinical chemistry by then at that I to as the first postdoctoral in clinical chemistry with and and on a which I had to my own the of laboratory at I working with and then to and development in the This was successful to a and a laboratory team, and The work on with an unmet need. The assays for were for the clinical this was my was and not some of the other some of which and the release to the University of licensing by the only in technology and I through a together about the of how to the technology to the field. of information is very but I that it to become a product a or I not to form a company but to the technology. I also with my about of it might The development and licensing of allowed me to efforts in Laboratory Medicine in developing countries and to some and but this was that and was not the the which was developing and specific tests for the clinical of This of innovation used to be to clinical chemists who had to to the technology that was I the field. the of and such innovation in the general has become in the university I believe it can I a I years have of the university as a series of entrepreneurs together by a by of the University of at I believe innovation and entrepreneurship are of scientific efforts to solve unmet and new information about and the work can be are probably academic than general small or company than large in diagnostic I do not if there is one of characteristics or training that can lead to but I there is the ability to the for For the same of the who were invited to in this would have to the others if of me at University and and to the University of I commercialization a As an my first as an at the University of a to identify new technologies that might become important to our and University was a new research and the introduction of a the of by at the time a and was to that it led to and some based on and These in than the current of the art up with a business we from the University and with business that made for on of the product, the for a years, our first was a Technology from the to with fluorescence the from a we the prototype in PCR, and analysis to time In technology was to in most who the product the next The US a with to the and in the US first of a program that The first genetic tests to be were obtained on the in and were based on assays at and University in 1996 and as well as are now A focus on analysis resulted in in to commercial release of and the is now as the best genetic and the method of to licensing in the field. of was by analysis with using and analysis has become that it has time in the a diagnostic for in Technology is now a One third of its income as from the technologies mentioned I my academic laboratory at the University of has into one of and use of our In the end industry is by not scientific quality or in the field has instrument has been made in matching to the requirements of As an I to focus on to improve and analysis for assays based on As the stories of these inventors there is more than one path to their on one continent and moved to another, some only in while others also in industry, and only a had commercial and innovation The of the that led to their inventions for some but only for others (Fig. 2). that the in which they was crucial to their success because it provided the needed the the intellectual and the freedom to highly ranked was how to and the to determine the of The next two to and the inventors believe that if do not have a strong and if are not and the two most and needed to and the were highly ranked as We hope that these stories young scientists and in Laboratory Medicine to the established and and to technologies and with the hope of for

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.