Leonard, Debra G. B. MD, PhD
Section Editor(s): KORN, DAVID MD; HEINIG, STEPHEN J. MA
I am currently prevented from practicing certain areas of my medical specialty, molecular genetic pathology, because of gene patent enforcements. I wanted to be a physician since I was 14 years old. My motivation was and remains the corny, simplistic statement: “I want to help people who are sick.” I spent four years in college, seven years in graduate school, and four years in residency and fellowship. My medical training is in pathology and my graduate training in molecular biology, and I have practiced molecular genetic pathology for the past ten years. Pathologists are the diagnostic detectives for clinicians who directly take care of patients. We are trained in clinical laboratory medicine and understand the appropriate use, performance, and interpretation of the tests that detect disease, predict outcomes, and direct therapies. My medical practice focuses on the appropriate use, performance, and interpretation of the tests that are based on molecular biology methods. This is not a research activity. It is the culmination of my medical training and the way I have chosen to help patients and fight disease as a physician.
I am outraged that anyone can control the use of medical information to the point that I cannot include the diagnosis of a disease in my medical practice. I can no longer perform testing for Canavan disease, Alzheimer's disease, and Charcot—Marie—Tooth Type 1A disease because of patent enforcement. Other physicians are prevented from testing for breast cancer genetic risk. Studies have demonstrated the negative impact of gene patents for hereditary hemochromatosis mutations on the number of testing laboratories, in that almost 30% of laboratory directors stopped or did not develop hemochromatosis testing due at least in part to the patent on the hemochromatosis genetic sequence.1 Limiting the practice of physicians, or even having the potential to limit the practice of physicians, by patent law is not in the best interest of the public health.
The patent system rewards inventors for creating or conceiving of something that is new, not obvious, and useful. However, the patent system does not allow inventors to patent things that are found in nature. Is the human genome not a part of nature? Those who patent genetic sequences and the correlation of genetic differences with the incidence or risk of a specific disease cleverly state that they are not patenting part of the human genome, since the patents claim only the cloned versions of the human sequence. However, when I need to look at the same patented sequence in a patient to provide a diagnosis for her genetic disease, I cannot. How do I explain to a patient that someone prevents me from looking at and characterizing a segment of her genome? The patient no longer has the ability to control her own body and the testing that can be done. How do I explain that I am not allowed by law to provide a test based on a part of her genome, a test that both the patient and her physician are asking me to perform, and that is necessary for diagnosis? Limiting the broad availability of medical testing is not in the best interest of the public health.
So what should be the rewards for those who expend time and money to discover the correlation between genetic variation and disease risk? When an invention is made, that invention has market value, and the goal of the inventor is usually to realize financial gain from the sale or use of the invention. This is a very different model from the motivations of medical scientists in the past, who sought to cure disease, obtain grant funding to continue their research, and be recognized for their scientific accomplishments. Now many academic medical scientists have changed to a model of research for financial gain. However, when the invention consists of demonstrating that a gene sequence is associated with a greater risk of disease, should the inventor (or, more likely, the inventor's institution) be allowed to control the use of that medical information? In many cases, control of specific genetic information limits the medical use of the information and impedes or prevents widespread research on the disease, the traditional pathway by which medical knowledge is advanced and shared. Limiting the use of medical information for research or medical practice is not in the best interest of the public health.
Should the financial rewards of the patent holders be removed to protect the use of genetic information for research and medical practice? Patents are meant to provide incentives for the downstream development of the invention, which carry with them financial rewards through either license agreements or direct use by the patent holder. There are three major downstream development pathways for genetic discoveries: diagnostics, therapeutics, and prevention. Certainly, the simplest, cheapest, and most rapidly implementable application for genetic discoveries is diagnostic testing. Diagnostic tests provide the ability to assess risk or identify the specific cause of disease symptoms that may be due to a variety of genetic or environmental factors. The second, much slower, and more expensive application for genetic information is drug development targeted at the metabolic pathways or cellular functions that are disturbed by the causative genetic alteration. Therapeutic drugs provide the ability to treat symptomatic patients with a disease caused by a specific genetic alteration. The third application, similar to the second, is the development of drugs to prevent disease onset. Preventive treatments allow individuals at risk for genetic diseases to lower their risks of developing disease symptoms and avoid the socioeconomic impact of loss of health.
Are patent protections and incentives needed for the development of these three downstream applications of genetic information? Certainly, the protection of the patent system is required to allow pharmaceutical companies to recoup their investment of years of time and hundreds of millions of dollars to bring a new drug to market. The pharmaceutical industry has a long track record of successfully negotiating cross-licenses for patents that allow access to protected information. I do not think the patent system should be altered with regard to drug development. If pharmaceutical companies do not develop drugs, there is not an alternative pathway to allow the development of and patient access to novel therapies. Patent protection for drug development is in the best interest of the public health.
Are patent protections and incentives needed for the development of diagnostic testing based on genetic information? Yes and no. There are two alternative pathways for the development of diagnostic tests: one leads to the production of commercially manufactured in vitro diagnostic test kits that can be sold across state lines, and the other leads to the development of clinical tests performed in the laboratory that developed the test. The commercial development of diagnostic test kits, like drug development, requires years of time and millions of dollars. Therefore, companies that produce diagnostic test kits require the same patent protections and incentives as the pharmaceutical industry because of the large financial burden required to bring the test kit through review by the Food and Drug Administration (FDA) and to produce it under current Good Manufacturing Practices. However, laboratories should not be required to use a test that has exclusive market rights for a specific disease if the test is not optimal. The availability of FDA-approved in vitro diagnostic test kits is in the best interest of the public health.
So what is the issue with gene patents in relationship to diagnostic testing? In contrast to downstream development of therapeutics, there is a second pathway for the development and performance of diagnostic tests based on genetic information that does not depend on the incentives or protections of the patent system once the discoveries are made. Physicians in laboratory medicine do not require the incentives of gene patents to develop and provide genetic tests based on the published medical and scientific literature. The regulations governing the laboratory development of diagnostic tests are different from those governing diagnostic test kit development by the in vitro diagnostic industry. Laboratory tests are developed under the guidelines provided in the Clinical Laboratory Improvement Act of 1988 (CLIA '88). Although the FDA continues to claim jurisdiction over laboratory-developed tests, the agency does not have jurisdiction over medical practice.
The need for allowing this type of laboratory-developed testing to continue freely is that diagnostic tests can be introduced in individual laboratories more quickly than commercial test kits can be developed and brought to market. We very rapidly translate new genetic knowledge into diagnostic tests for the benefit of patients without need for the incentives and protection of patents. Again, in a study of genetic testing for hereditary hemochromatosis, 60% of laboratories surveyed had implemented genetic testing before the gene patent was issued.1 The driving force for those in the clinical laboratory is the need of the patient, based on calls from clinicians to the laboratory requesting that a test be performed on their patients. We do not check whether a patent has been filed before deciding to develop a diagnostic test based on the published literature, nor do we have the negotiating skills or financial resources for cross-licensing of the patented information required for the diagnostic test. We struggle to make our laboratory break even financially, and work to justify the technical staff required for the testing we perform. Our motivation is the practice of medicine.
But hospital-associated laboratory physicians are not the only ones developing and performing tests in their laboratories to offer as a diagnostic testing service. This has become the business model for some companies whose goal is to be the exclusive provider of a testing service, and who are causing the vast majority of concerns. These companies identify patents needed for specific diagnostic tests before the patent even issues and negotiate an exclusive license for diagnostic testing based on the patent. Once the patent issues, the laboratories that have developed the medical need and use for the test and are already performing it are prevented from continuing to perform the test. A single provider of a health care service dominates the market. When this happens, there is no competition for the price of testing, the quality of service, the method used for testing, the further refinement of the test, or access for the uninsured or those with health care coverage requiring that testing be done under contract. A sole provider of a medical service is not in the best interest of the public health.
Many argue that those of us who are working to protect physicians from patent infringement lawsuits for the medical use of gene patent information are simply attempting to avoid paying patent holders and licensees their due. Many discussions between those who want gene patents strictly enforced and those who want access to genetic information for their medical practice in diagnostics focus on the definition of the physicians who develop genetic tests in clinical laboratories as a clinical service. Are we physicians or businesspersons? The patent holders and those with a business model of diagnostics declare that we are businesspersons. I am not a physician because I am interested in business. I want to practice medicine. Although the vast majority of the concerns surrounding gene patents center around those companies that base their business model on the control of genetic information and being the sole provider of a medical service, academic institutions are also at fault because they negotiate exclusive licenses for the performance of diagnostic tests based on their patents.2 These practices need to be changed.
I do not think there is as much controversy between diagnostic kit manufacturers and clinical laboratory physicians. On the one hand, the diagnostic industry wants to control diagnostic testing methods by mandating use of their test kits through patent enforcement in order to offset their costs of bringing a test kit to market. On the other hand, the clinical laboratory physicians need to provide clinical testing for their patients in a timely and cost-effective manner. Industry and clinical laboratory physicians need to work together. If a commercial test kit is available and performs well, the vast majority of laboratories will use the test kit rather than their laboratory-developed tests. The commercial kit offers convenience and a level of quality control of reagents and performance that is assured by the manufacturer. Use of a commercial test kit is generally easier and more efficient for the laboratory. So why not wait until a commercial test kit is available before performing testing? Laboratory developed tests can be made available more rapidly and very often are less expensive than commercial test kits. Also, the anticipated low volume of some testing cannot justify the time and expense of commercial test kit development. So laboratory developed testing fills a niche for early testing after gene discovery and for lower-volume testing. When commercial kits become available that are faster, easier, or require less technologist time, most laboratories will use the new test kits without the need for patent enforcement.
The goal is to allow the two systems for diagnostic testing to coexist, and even to develop partnerships between industry and laboratory physicians. The patent holders can focus on licensing for drug development and in vitro diagnostic test kit development for financial gain, while allowing laboratory physicians to focus on their medical practice and the rapid translation of genetic information into diagnostic tests. If necessary, the patent holder should take the approach of broadly licensing the patent to individual laboratories or institutions at a reasonable royalty rate to facilitate laboratory-developed testing. Once a test kit is available, laboratories are very likely to use the kit if it is accurate and has good performance characteristics. In my interactions with in vitro diagnostic test companies, industry wants to promote favorable interactions with their future customers, the laboratory physicians who will be the targeted users of their test kits. Diagnostic test companies and laboratories need to be partners, not competitors, and, on the whole, this has been my experience.
The drive to understand the human genome and its relationship to disease risk and causation has become a major focus of biomedical researchers and a future hope for physicians. The same drive to understand the relationship between human genome variation and disease risk, and to mine its commercial potential, has become the focus of the in vitro diagnostic, biotechnology, and pharmaceutical industries. Many argue that without the financial incentives offered by the patent system, the research would not be done, or would not be done as rapidly. Physician—scientists have long been motivated to look for the causes of disease without the incentives of financial rewards. Is the business model of medical discovery truly an advantage over the scientific model? In the past, physician—scientists sought scientific recognition for their discoveries, through publications and grant support. In the early days of genetic research, disease genes were not patented prior to publication and dissemination of the discovery. With the development of the biotechnology industry, the commercial potential of genetic discoveries has taken precedence over their scientific and medical value, even for the academic researcher. Today, genetic discoveries are patented to preserve the rights of investigators and their institutions to control access to and use of their discoveries, with financial rewards to both. The biomedical researcher has adopted the financial incentive model of industry.
In conclusion, the large financial gains to be made from gene patents are in therapeutics and diagnostic test kit development and sales. Allow laboratory physicians to continue to provide testing for patients, and, if necessary, mandate broad licensing at reasonable royalty rates for wide availability of testing services. The Genomic Research and Diagnostic Accessibility Act (H.R. 3967) introduced by Representative Lynn Rivers (D-Michigan) is aimed at just this goal. Those of us who are working to achieve protection for laboratory physicians are not out to derail the entire patent system. We only want to be able to practice medicine… all of it!