A New Project Could Fulfill a Promise

Just as cataloging the human genome provides a jumping-off point to develop genetic testing and molecular-based therapies, a similar effort is necessary on the cellular level. A detailed understanding of how human cells develop into specialized tissues will open the door to regenerative medicine, the therapeutic replacement of cells, tissues, and organs lost to disease. But a significant barrier to fulfilling the promise of regenerative medicine is the absence of a fully characterized, human cell catalog. Following on its collaboration with the Human Genome Project (HGP), the international biological community should focus on the human cell as its next strategic goal. A so-called Human Cell Project (HCP) could collect fully characterized human cell lines. This new resource--which would be unique with respect to the number and types of cells included, the degree to which these cells would be characterized, and the level of standardization at every data-collection step--would be available, restriction-free, to all researchers. The HGP's success spurred similar cataloging efforts for other cellular constituents, such as proteins and carbohydrates. The logical next step is to figure out how these molecular components fit together, not just in a test tube but in a living, functioning cell. Researchers are already asking these questions. The Alliance for Cellular Signaling,1 an international consortium, was established to study signaling networks, primarily in B lymphocytes and cardiac myocytes. International researchers have discussed forming a consortium to study existing human embryonic stem cell (ESC) lines.2 The HCP could provide an overall international framework for such work. Existing human cell collections are not uniformly characterized. The HCP's initial mandate would be to delineate the research framework, funding structure, and timeline for developing this catalog, which would be characterized as completely as possible under standardized conditions. The cells--which would include adult and embryonic stem, germ, and umbilical cord stem cells, taken from different tissues at various stages of development and differentiation--would be described under different conditions in terms of morphology, surface markers, genome-wide expression studies, and so on. Again, standardization must be a recurring theme for every step of data collection and analysis. A panel of scientists would determine the analyses and protocol types to be carried out as part of the research framework, and it would choose the cell types to be characterized at given time intervals. Cells could be grouped according to relative priority. It is likely that human stem cells and the cell lines used by the Alliance for Cellular Signaling, for example, would be given high priority. ESCs have generated considerable attention, because preliminary experiments suggest that they can be coaxed to develop into specific tissues. While ESCs undoubtedly will be of great medical benefit, other cell types also may prove useful in regenerative medicine. The HCP would provide the necessary tools to probe these kinds of questions. Conflicting ethical perspectives surround the use of human ESCs and, undoubtedly, any project that includes stem cell research will run into controversy. It is worth recalling, however, that researchers have faced similar controversies in the past and developed effective mechanisms to deal with them.3 By ensuring that cells are characterized under standardized and reproducible conditions, researchers could compare different cell lines and build on previous experiments. Mining existing data repositories does not help here. The HGP offers an example of how to organize a successful effort to drive scientific progress. Congress championed the HGP and provided a mandate for it; National Institutes of Health and US Department of Energy scientists were given key organizational and oversight roles, and the private sector stepped in as a collaborator. The proposed international HCP should follow a similar pattern. The NIH and its international partners would provide the HCP's funding structure and timeline. The genome project provides a starting point for planning. The HCP, as did the genome project before it, should allocate work among its international partners based on scientific interests and strengths. Countries that permit ESC work, for example, could undertake the bulk of this research. Furthermore, an organization such as the Human Genome Organisation [HUGO] could help coordinate the roles and responsibilities of the HCP's international partners. All HCP-generated data would be released into the public domain at regular intervals, and researchers would have access to cell lines. An important aim would be to establish a regulatory structure to ensure that all research is conducted according to ethical guidelines and established standards of open scientific exchange and public oversight. We are on the cusp of a major medical revolution, comparable in scope to the genetics revolution that unfolded over the past two decades. The HGP created a new paradigm in which medical treatment is based on an individual's genetic characteristics and that person's disease. Now, we need an international HCP to take us to the next level, a future in which a patient's own cells can be used to replace tissues lost to disease or, even better, to prevent their loss in the first place. Joseph G. Perpich heads a Bethesda, Md.-based consulting company specializing in science, education, and medicine. References 1. The Alliance for Cellular Signaling, "Overview of the Alliance for Cellular Signaling," Nature, 420:703-6, 2002. 2. E. Check, "Biologists seek blueprint for international stem-cell effort," Nature, 421:102, Jan. 9, 2003. 3. J. Perpich, "The recombinant DNA debate and bioterrorism," Chron High Educ, 5:B20, 2002.

A New Project Could Fulfill a Promise

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