Thirty-five years ago we produced a poliovirus vaccine in cultured normal human cells and demonstrated its efficacy and safety in children. This was the first human biological ever produced in a normal human cell population. The major advantages of using a normal human diploid cell strain over the primary monkey kidney cells then used were safety and standardization. A normal human cell strain derived from a single tissue can be cryogenically preserved, extensively tested, and then used as the substrate for the production hundreds of millions of vaccine doses. This cannot be done with a primary cell population. Today, hundreds of millions of people worldwide have benefited from vaccines produced in cultured normal human cells. For example, all of the rubella vaccine used in the Western Hemisphere is produced in my human diploid cell strain WI-38.
Because biological systems could not be patented in 1962, I brought a law suit against the NIH and the United States Department of Health, Education and Welfare who claimed title to WI38. After six years of litigation, a settlement was reached confirming my position that legal title to self-reproducing biological systems should be vested in those whose intellectual property rights provide value to the system.
Because some essential molecules needed to benefit humans will probably only be capable of manufacture in human cells, it is inevitable that human cells or tissues will be used increasingly for the production of human biologicals. The direct use of more human organs and tissues is also inevitable when cultural barriers fall as a result of the realization that the use of human tissue, that would otherwise be discarded, can be defended on the basis that it could be used to save or better another human life.

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The International Institute for the Advancement of Medicine (IIAM) was established in 1986as a non-profit research tissue bank. IIAM is a division of the Pennsylvania Regional Tissue and Transplant Bank (PRTB), whose purpose as a not-for-profit organization is to obtain, process and distribute human tissues for transplantation, medical/scientific research, education and the advancement of medicine. As the research division of PRTB, IIAM facilitates the distribution of non-transplantable human organs and tissues for biomedical research, education and development.
I will describe the organization and operation of IIAM, including the requirements for tissue and the application process. Legal and ethical considerations, financial support, our resource network and our customer base will be covered. Potential commercial use of human tissue is an area of concern, legally and ethically, and will be discussed as well.
IIAM is a truly international organization, with a branch in Leicester, England that has been in operation for over two years. I will describe some of the obstacles that were encountered and lessons that were learned in setting up that research tissue bank for human tissue.
Future developments include the development of a cell biology laboratory within IIAM, in which primary human cells from various organs and tissues will be isolated, characterized and distributed for research.

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In order to investigate Gardner's syndrome at the cellular level, we attempted to culture fibroma cells obtained from a patient with Gardner's syndrome and then partially characterized the cultured cells. The patient who was a 21-year-old male had a huge soft tissue mass on his back. This soft tissue mass had been removed surgically and a small piece was used for cell culture. The tissue was minced with surgical scalpels before being treated with collagenase and then cultured in plastic culture flasks. The cells formed collagen fibers which stained red with Sirius red F3BA in vitro. The collagen fiber formation was also confirmed with data obtained from amino acid analysis showing hydroxyproline formation in the hydrolysate of the cells. In chromosome analysis, three of fifteen metaphases of the cultured cells revealed a deletion of chromosome 5, although all metaphases of the primary fibroma from the patient showed a normal human karyotype.

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We have established a number of human cell lines, which have been deposited in the Japanese Cancer Research Resources Bank (JCRB). For the convenience of users of these cell lines, we characterized the p53 gene status of these cell lines using a yeast functional assay (functional analysis of separated alleles in yeast: FASAY). The cell lines described here are as follows: 11 hepatoma,2 hepatoblastoma,2 in vitro immortalized hepatocyte, a cholangiocarcinoma,5 in vitro immortalized fibroblast,2 osteosarcoma, a chondrosarcoma, an ovarian teratocarcinoma and a colon cancer cell lines. Out of 26 cell lines,15 cell lines had mutations of the p53 gene, and other 10 cell lines had no mutation in the p53 gene. The remaining one cell line, PA-1, had both the normal and the mutant p53 alleles. There was significant relationship between the p53mutation and tumorigenicity of the cells transplanted into nude mice. All the liver cell lines with the mutant p53 were tumorigenic, but the liver cell lines with the wild-type p53 were not always tumorigenic. A cyclin dependent kinase inhibitor, p21, which can be transactivated by the wildtype p53 protein, was expressed in all the liver cell lines with the wild-type p53. On the other hand, among 8 liver cell lines with the mutant p53,3 lines expressed p21 but other 5 lines did not.

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