Recombinant DNA Advisory Committee - 5/30-31/91 
is thought to be the most appropriate model. Mice are the most appropriate model to look 
at transplant efficiency because of the ability to engineer all sorts of genetic markers in them. 
And despite the desire to do more primate models, they are a scarce resource and not 
generally available for use in this research. 
Dr. Ledley then went on to discuss why an exogenous marker is needed when a heterologous 
transplant is being proposed. He said all other forms of assays do not possess the specificity 
and sensitivity exhibited by the provirus PCR assay and therefore it has extreme advantage 
over in situ hybridization, HLA antigen testing and DNA polymorphism assays. He noted that 
the provirus PCR assay is extraordinarily sensitive and possesses the advantage of being able 
to have the same marker in every patient, thus allowing for good quantitative comparisons 
between patients. 
Dr. Ledley then introduced Dr. George Ferry to discuss the patient selection procedures, 
which is central to the ethics issues surrounding the proposal. 
Dr. Ferry noted that the major problem faced with children is that the majority of acute liver 
disease and liver failure is in very young children where the availability of organ donors is the 
poorest. He said this protocol had been set up to use children with acute fulminant liver 
failure who were not expected to live longer than a few days or a week or two at most who 
would be eligible for liver transplantation if such a donor organ became available. In this age 
range survival in infants and young children is less than 10% as a rule and that it is difficult 
to ascertain which patient, if transplanted, would survive and which would die. Further, he 
noted that young infants with metabolic defects and fulminant necrosis and liver failure are 
at incredible risk for early and severe brain damage with subsequent death early on or a 
lifetime of total handicaps and inability to function as an adult. These patients are also 
transplantable, however even by a month of age some have already suffered so much brain 
damage they're no longer eligible for transplantation. 
Dr. Ferry said that all the clinicians dealing with liver disease are encouraged with the 
prospects of transplantation, despite the drawbacks of high cost for transplant procedures as 
well as the 80-90 percent survival rate in moderately ill patients. However, he felt that there 
was a need to develop a process whereby a patient will not be faced with a lifetime of 
cyclosporine use with its inherent toxicity and that this was a major drawback to liver 
transplant. 
Dr. Ferry concluded his remarks by noting that despite the fact that the effectiveness of these 
cells decreases over time, he felt that did not detract from the significance of doing 
hepatocellular transplantation in that even in patients with fulminant failure and necrosis it 
could buy as much as a month's time with functioning hepatocytes, therefore allowing more 
time to obtain a transplant donor organ. 
Dr. McGarrity then called on Dr. Mclvor to begin the review. Dr. Mclvor noted that he had 
also been a primary reviewer for the HGTS meeting in April. He said he would only cover 
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