Human Cene Therapy 
Patients with serious genetic diseases have little other hope at present 
for alleviation of their medical problems. Arguments that genetic 
engineering might someday be misused do not justify the needless 
perpetuation of human suffering that would result from _ unneces- 
sary delay in the clinical application of this potentially powerful 
therapeutic procedure. 
GERM LINE GENE THERAPY 
The second level of genetic engineering, gene therapy of germ line 
cells, would require a major advance in our present state of knowl- 
edge. It would require that we learn how to insert a gene not only 
into the appropriate cells of the patient’s body, but also how to 
introduce it into the germ line of the patient in such a way that it 
would be transmitted to offspring and would be functional in the 
correct way in the correct cells in the offspring. Based on the small 
amount of information now available from animal studies, the step 
from correction of a disorder in somatic cells to correction of the 
germ line would be difficult. 
Cenn Line Therapy in Animals 
Germ line transmission and expression of inserted genes in mice has 
been obtained by several laboratories but with a technique that is 
not acceptable for use in human patients, namely, the physical micro- 
injection of fertilized eggs. Microinjection into tissue culture cells 
has been used for a number of years and has the advantage of high 
efficiency (up to one cell in five injected can be permanently trans- 
fected). However, the distinct disadvantage is that only one cell at 
a time can be injected. Transfection of a large number (like 10 6 ) of 
blood-forming stem cells is not feasible. 
Microinjection has been used with considerable success in trans- 
ferring genes into mouse zygotes. DNA can be microinjected into one 
of the two pronuclei of a recently fertilized mouse egg. This egg can 
then be placed into the oviduct of a pseudopregnant female where 
it can develop into a normal mouse carrying the exogenous DNA in 
every cell of its body including its germ cells. Consequently, the 
injected DNA can be transmitted to offspring in a normal Mendelian 
manner. Mice carrying an exogenous gene in their genome are called 
‘transgenic’. 
It is this technique that was used to partially correct a mouse with 
a defect in its growth hormone production (Hammer et al., 1984). 
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Recombinant DNA Research, Volume 12 
