Recombinant DNA Advisory Committee - 12/1-2/94 
communication to investigators is critical about the need for and type of information to be obtained from 
autopsy. 
Dr. Straus noted that autopsy is particularly problematic in the clinical setting. He was concerned with the 
lack of cooperation by investigators in reporting complete data regarding safety and efficacy, perhaps due to 
competitive pressure. Dr. Walters inquired if any serious adverse event was not reported. Dr. Straus 
responded that no such instances have been documented. Dr. Motulsky noted the importance of 
communication between the investigator and the pathologist who perform the autopsy. The investigator should 
inform the pathologist about the type of scientific information sought, the tissue to preserve, and appropriate 
procedures for tissue preservation. Dr. Motulsky said that this 5% autopsy rate observed for gene transfer 
studies is below the national average of between 5 and 10%. Dr. Wivel said that the national average could be 
as high as 15 to 20%. To correct the problem of inconsistent reporting, Dr. Ross suggested that the 
questionnaire sent to investigators should be expanded. 
In response to Ms. Meyers’s concern about the low autopsy rate, Dr. French Anderson (University of Southern 
California) stated that for Dr. Steven Rosenberg’s protocol #8810-001, extensive and extremely careful 
autopsies were conducted on all the deceased patients which resulted in greater research costs. In Dr. 
Rosenberg’s study, there was no evidence that the transgene had spread to any unintended site or evidence of 
any replication competent retrovirus (RCR). In the absence of adverse effects, costly autopsies for all patients 
in gene transfer studies are not justified. Autopsy alone is unlikely to uncover any serious adverse effects. Ms. 
Meyers noted that Dr. Rosenberg failed to report the autopsy information described by Dr. Anderson. 
Mr. Capron stated that in the early stages of gene therapy development, negative results may be as valuable as 
positive information in documenting the lack of untoward effects. It is the very reason to demand autopsy. 
NIH and sponsoring companies should provide the funding necessary to gather such data in order to assure 
the safety of the nascent scientific technology. In response to Dr. Anderson’s statement regarding the cost of 
autopsy, Dr. Straus said that an added cost of between $10,000 and $20,000 for autopsy is inconsequential 
compared to the total cost of developing a new gene therapy protocol 
Dr. Walters remarked that he was not aware that autopsies had been conducted on the first gene transfer 
protocol #8810-001. Dr. Anderson responded that the results were presented in a simple statement in a paper 
published in the New England Journal of Medicine. Dr. Miller commented it is preferable that the autopsy 
data be published in a more extensive format. Dr. Anderson said that he cannot defend his colleagues in 
terms of publication of their data. Dr. Miller said the data cannot be considered as part of the literature 
unless it is peer-reviewed and published. Dr. Anderson said that he would urge the RAC to encourage Drs. 
Rosenberg and Blaese to publish their results. 
Ms. Wilson noted that the importance of inclusion of autopsy information had been reiterated in the cover 
letter that was sent out to investigators. Dr. Motulsky said that a brief narrative report from the investigators 
rather than just filling out the report may be more informative. 
Report on Gene Marking-Dr. Parkman 
Dr. Parkman stated that he was encouraged by the results of the gene marking studies. There have been 4 
substantial publications in major medical journals from these marking studies. The RAC should consider 
whether the data that have been generated should be used to reevaluate ongoing studies and/or make 
recommendations regarding the study design of ongoing and future studies. For example, the data clearly 
demonstrate that there is no evidence of tumor-specific migration of tumor infiltrating lymphocytes (TIL). 
The RAC should consider: (1) whether they should review any future TIL studies; and (2) whether the 
currently open protocols should be revised to focus on clearly defined scientific objectives. Dr. Parkman stated 
that one of the most important questions that has been answered by the bone marrow transplantation/gene 
marking studies is the aggregate data about human stem cell development. This data is an excellent example 
of the unexpected (yet valuable) information that can be obtained from these studies. Although these 
experiments were designed to determine the origin of disease relapse, this unexpected knowledge about stem 
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Recombinant DNA Research, Volume 20 
