This article examines the factual events surrounding the development of two human cell lines infected with variants of the human T lymphotropic virus type-1 (HTLV-1). Further, this article will review and discuss the National Institutes of Health (NIH) policy under which the NIH applied for patents on these two cells lines. One patents covering one of these two cell lines was issued on March 14, 1995 by the U.S. Patent and Trademark Office (USPTO), while the patent application covering the second cell line was abandoned by the NIH in September 1994.
Also, this article will examine current issues regarding the sharing of benefits between industry and host country sources of biological material, within the context of patenting, licensing, and development of new products to enhance public health. These issues include determining the appropriate use of patents as a means to protect rights and transfer technologies to the private sector for the development of new diagnostic and therapeutic agents. The National Institute of Health
The fundamental mission of the National Institutes of Health (NIH) is to conduct and support biomedical research in order to create knowledge that can be used to advance the health of people the world over. Composed of 24 separate Institutes, Centers, and Divisions, the NIH has a budget of almost $12 billion for 1996. A principal concern of the NIH is to invest wisely the tax dollars entrusted to it to help prevent, detect, diagnose, and treat disease and disability.
More than eighty percent of the NIH investment is made through grants and contracts supporting research and training in more than 1,700 research institutions throughout the U.S. and abroad. About ten percent of the remainder of the NIH budget is spent on research conducted in NIH's own laboratories.
Increasingly, the capacity to capitalize on scientific opportunities and to capture the potential of new discoveries will depend on the scientific interaction on a global scale among biomedical and behavioral researchers, technicians, and laboratories. The growing interdependence of the world's scientific community is accompanied by developments that present new challenges and opportunities. Thus, it is incumbent upon all scientists throughout the world to work together and share knowledge about their discoveries.
Also, just as important, in order to carry out its mission, the NIH must transfer information, materials, and intellectual property rights to industrial partners who make the drug and medical devices needed to care for the sick and the disabled. It is a statutory responsibility of the NIH to ensure that research results make their way "from the bench of the bedside."
The considerable anticipated health benefits from NIH-supported research depend in large part on the ability and willingness of both biomedical researchers to work together and create new knowledge and the private sector to commercialize new ideas, techniques and products. The "PNG Patent"
The National Institute of Neurological Diseases and Stroke (NINDS), an institute of the NIH, has had a long-term commitment to surveillance of neurological and infectious diseases in the Western Pacific region for the more than thirty years. With the discovery of the first human retro-viruses (HTLV-1), the Laboratory of Central Nervous System Studies began to test blood samples in 1983 from remote populations all over the world to search for occurrences of HTLV-1 infection. The laboratory found suggestive evidence for the existence of HTLV-1 in samples from Melanesia, but lacked virological evidence.
Beginning in 1985, scientists in the laboratory began a collaboration with Dr. Carol Jenkins of the PNG Institute of Medical Research, who had worked closely with a group of native Papua New Guineans called the Hagahai. With the consent of the Hagahai and the PNG government, Dr. Jenkins collected blood samples from the Hagahai people and sent them to the laboratory for analysis. These samples showed definite signs of HTLV-1 infection. Later, Dr. Jenkins collected additional blood samples from the Hagahai in order to isolate the HTLV-1.
From one of the infected Hagahai, a cell line was developed which was used to determine the genetic sequence of the virus. This showed that the virus in the PNG sample was a genetically distinct variant of HTLV-1 found elsewhere in the world. The laboratory sought out other blood samples from all over the Western Pacific region, including the Solomon Islands where they found another population infected with another distinct strain of HTLV-1. In neither the case of the PNG nor the Solomon Islands samples did the investigators clone the genes of the human blood donors; they cloned only the genes of the two viruses.
In an effort to make widely available the discoveries of the two viruses, the following NIH policy at the time, the NIH field patent applications in 1990 and 1991 on the two cell lines infected with the HTLV-1 variants. Patenting the cell lines would make possible later development of vaccines or other methods to prevent the type of fulminant leukemia that occasionally strikes elderly persons infected with this virus.
The application for the Solomon Islands cell line was withdrawn in 1994 by NIH, because it appeared that the demand for commercial products that might be produced from this cell line was low. However, the patent on the PNG cell lines was not withdrawn at the request of Dr. Jenkins, a co-inventor on the patent, who had pledged to the Hagahai that she would give the group her share of any royalties to be realized from the parent. The PNG cell line was granted a patent by the U.S. Patent and Trademark Office in March 1995. Nonetheless, there has been no commercial interest in the patent, and it was not expected that either of these two cell lines will be commercialized. Patents and the NIH
NIH has a statutory responsibility to transfer technology to the private sector to ensure that new products are developed for the public health. Generally, NIH seeks patent protection on biomedical technology where a patent is necessary to ensure investment by the private sector in further research and development of the technology to accomplish this goal. NIH may also seek patent protection on selected research tools to facilitate their licensing to the private sector.
The primary intent of the patenting process is not to accrue economic benefits to NIH. Rather, the intents is to clarify commercial rights, so the development of useful products. Current NIH policy is to generally not seek patents on biological materials unless (1) there are reasonable prospects that they can be developed into useful products, and (2) patent protection is necessary for private sector participation in the development process. In accordance with a long-standing tradition of academic freedom, NIH research results are published freely. Publication of research is not significantly delayed for the purpose of obtaining patentable subject matter. NIH's Commitment to Protect Cultural and Biological Diversity
The NIH recognizes that special circumstances arise when natural resources are involved or are being investigated. Natural resources normally refer to plants and other nonvertebrate organisms. Furthermore, these natural resources can often be found in biodiversity-rich developing countries, where the lack of scientific infrastructure has hampered the ability of those countries to discover the full potential of those resources. Following are two example of the types of policies that the NIH has initiated in the last few years to address these special circumstances. Although not entirely relevant to the recent controversy regarding the patented cell line, they do demonstrate the commitment that NIH has shown towards the sharing of benefits and the transfer of scientific and technologic skills with source countries and indigenous people.
Beginning in the early 1990s, the National Cancer Institute (NCI) of the NIH began to formulate policies aimed at promoting collaboration with, and compensation of, countries participating in NCI's natural product drug discovery programs. Over the years, these policies have been refined and developed, following the input of source country representatives, intellectual property experts, and multilateral organizations. The policy document, known as a letter of Collection (LOC), has formed the basis for formal agreements with organizations or agencies in sixteen countries, and negotiations are proceeding with several other countries. The terms of the LOC normally provide for the provision of test result, and senior scientists are invited to NCI laboratories to participate actively in determining the goals of the program and explore the scope for expanded collaboration. Qualified junior scientists are also invited to train for up to one year and carry out joint research projects on topic of mutual interest, usually related to the exploration of the compound from the source country.
In the long term, the NCI LOC requires any licensee of an NCI-patented drug to negotiate acceptable terms of compensation, e.g. percentage of royalties accrued from the sale of the drug, directly with the appropriate organization or government agency in the source country. Furthermore, NCI collaborates with the source country in developing adequate supplies of the source raw material, either through sustainable harvest or cultivation, and will require a licensee to seek, as its first source of supply, the raw material produced in the source country.
Also, in 1991, the NIH, the National Science Foundation (NSF), and the U.S. agency for International Development (USAID) sponsored a workshop on "Drug Development, Biological Diversity, and Economic Growth" which first explored the interdependent issues of biodiversity conservation, pharmaceutical development, and cultural diversity. Representatives from U.S. government agencies, pharmaceutical companies, developing country organizations and governments, and indigenous group met to share their perspectives on their interlocking needs and concerns. The meeting resulted in the development of a list of critical observations to help provide a sound basis for future efforts to conserve biological diversity through mutual understanding and cooperation between developed and developing countries and the effective integration of government and private-sector activities. The general principles emphasized equal partnership, cooperation and fair compensation, as well as the maintenance of biodiversity and traditional knowledge. The principles recognized that traditional helpers and indigenous peoples have valuable knowledge and important analytical and observation capabilities. Finally, the meeting participants agreed that efforts to develop drug from natural products should address diseases and health problems see in developing countries.
In the following year, the NIH, NSF, and USAID announced a new program that incorporated these general principles in an effort to conserve biodiversity, discover new sources of pharmaceuticals, and promote sustainable development in biodiversity-rich countries. Administered by the Fogarty International Center of the NIH, the International Cooperative Biodiversity Groups (ICBG) Program has made five awards to consortia of university, pharmaceutical companies, non-governmental organizations, and developing country organizations and universities to collect and record biodiversity and to screen plants and insects for bioactive compounds. As a condition of award, each consortium was required to develop contractual agreements for the equitable distribution of benefits and compensation to all those who contribute to product development. Each agreement is unique. Some require that a set percentage of royalties be returned to the host community through a trust fund; others call for training opportunities, equipment donations, or up-front payments. The Role of International Cooperation in Biomedical Research
International collaboration is crucial to the conduct of biomedical research in an age where disease knows no boundaries, Increasingly, the ability to meet new public health challenges depends on scientific interaction on a global scale. The NIH participates in numerous other research projects in the Southeast Asia/Western Pacific region. The benefit to American scientists of conducting research in the Western Pacific region is access to the biological diversity specific to the region - not merely humans, but also plants, animals, inserts and other organisms that carry or are susceptible to disease. In the majority of these cases, NIH investigators work alongside researchers in regional research institutions, such as the Institute of Medical Research (IMR) in Goroka, PNG, Benefits to scientists in the region are the great, if not greater, than what accrues to American scientists. These include access to American technology, NIH or other funding, and cross-fertilization of ideas. Furthermore, the research is often of direct relevance to the public health needs of the host country.
The NIH is committed to working with scientists from all parts of the world in order to promote long-term scientific cooperation and enable scientists worldwide to benefit from the sharing of expertise, information and specialized resources. Only through global coordination and international cooperation can the world hope to address such universal threats as epidemic disease, environmental degradation, unsustainable population growth, and famine. Article copyright Cultural Survival, Inc.
