after expansion and vector marking ex vivo. These data, which 
have been published (11), have shown that the marking of the 
TIL cells with the NEO vector does not change the phenotype of 
the cells, does not result in horizontal infection, and was 
successful in tracking the fate of the marked cells. 
Subsequent clinical investigations carried out by the NIH have 
shown that the same marking vector, when carrying the 
adenosinedeaminase gene (ADA) , may result in a conversion of 
the phenotype of immuno incompetence to immunocompetence in 
severe combined immunodeficiency patients and results in no 
other adverse effects. This same series of marking vectors 
has been studied in over 1500 mice, 21 primates (32 monkey 
years) , and over 70 human patient months and has shown no 
adverse effect. Twenty-one monkeys infused with the LNL6 
marked autologous marrow have remained without problems for 
2.5 to 5 years. No reverse transcriptase assays have been 
positive after infusion of the marked marrow in primates or 
man. Four animals, which were exposed to a replication 
competent variant of the LNL6 vector, have remained negative 
for N2 virus 2-3 year after exposure. No leukemias, 
lymphomas, solid tumors, or other problems have been 
identified as late complications in these experiments which 
have utilized safety modified viruses which are replication 
incompetent, involve single transductions, and are not 
contaminated with replication competent before virus. The NIH 
group has recently reported the occurrence of thymic lymphomas 
in 3 of 11 monkeys who were infected with a virus preparation 
which was purposely contaminated with a replication competent 
retrovirus (see Appendix F) . All authorities agree that the 
complication of lymphoma is attributable to the presence of 
the proliferating helper virus and perhaps also to the 
practice these workers followed of transducing the producer 
cell lines used to generate the virus multiple times to raise 
viral titres. The then director of the NIH, Dr. James 
Wyngaarden, has concluded in an official analysis of this 
issue, that the LNL6 retroviral vector poses no health hazard 
and is suitable for use in human subjects as well as in 
laboratory work (13, 14) (see Appendix B) . 
Our own data have indicated that 3% of the progenitors, 
measurable by in vitro colony assay, after vector exposure, 
contain the marking vector. Similar data has been developed 
in other laboratories. We have assessed the efficiency of 
transduction of the safety modified retroviruses LNL-6 and 
GINA into normal and leukemic hematopoietic cells. Three to 
ten percent of normal progenitor cells, which can be measured 
by the existing in vitro culture assays, integrate these 
viruses. Ten to thirty percent of leukemia cells integrate 
these viruses. The in vitro growth of the normal and leukemia 
cells is not reduced by exposure to the viruses. Our in vitro 
data has suggested that the two viruses, LNL-6 and GINA, which 
differs only in small stretches of neutral sequences 
introduced for marking which are detectable by PCR, transduce 
Recombinant DNA Research, Volume 15 
