The Questions of Developmental Biology

Phenotype Manipulation
This technology also means that we may someday have the ability to genetically modify
our bodies (and the bodies of our children). The ability to insert new genes into a fertilized egg
and the ability to produce human embryonic stem cells have caused concern that the human
genome could be manipulated. Some people look forward to the time when genetic diseases
might be treated by gene therapy, "fixing" the deleterious gene in germ cells and thereby
eliminating it from subsequent generations as well. Other people (and in some cases, the same
people) worry that this ability to manipulate germ line genes will result in misguided attempts to
enhance human physical or mental abilities.
There is relatively little concern about genetic therapy being applied to somatic cells.
This type of gene therapy is currently being tested at several medical centers. In such cases, a
stem cell (such as a blood stem cell) is cultured, given the new gene, and reinserted into the body
(Anderson 1998; Gage 1998; Ye et al. 1999). This procedure is akin to standard medical
treatment wherein the individual is treated. Germ line gene therapy, in contrast, would seek to
eliminate "bad" genes from the population.
When would germ line genetic manipulation be justified? Wivel and Walters (1993) see
two possible cases. First, such manipulation may be justified when both parents are afflicted with
a recessive autosomal disorder, so that 100% of their offspring would be expected to have it. This
is an exceptionally rare situation. More common is the case in which both parents are
heterozygotes for a recessive genetic disorder. These parents have a 75% chance of having a
phenotypically normal child, and screening can be carried out during pregnancy, followed by
selective abortion if the fetus is found to be homozygous for the mutant allele. Germ line genetic
modification is seen as an alternative to screening and selective abortion. Wivel and Walters view
such monogenic deficiency diseases as Lesch-Nyhan syndrome, Tay-Sachs disease, and
metachromatic leukodystrophy as candidates for this type of genetic therapy.
The arguments against germ line gene therapy come from several sources. Danks (1994)
can see very little medical good coming from germ line gene therapy. First, he finds that there are
very few candidates for such a procedure. The case of two homozygous parents is extraordinarily
rare. Moreover, in the case of the two heterozygous parents, the procedures that would be used
for germ line therapy would include in vitro fertilization, a technique that discards several viable
embryos and is seen by many as equivalent to abortion. Indeed, the same techniques used to
identify the affected offspring of two heterozygous parents would also be able to identify those
embryos that are not at risk. "Are we to propose discarding those ova that are shown to be
unaffected in order to correct an affected one and reimplant it? Surely one should discard the
affected and reimplant one of the unaffected."
Danks also argues against the view that germ line gene therapy would result in the
correction of genetic disease in future generations. It might even lead to more mutations. No one
can target a gene to a particular location in the egg nucleus. So a new gene added to a cell could
become inserted within a normal gene and mutate it. To achieve heritable correction, it will be
necessary to achieve replacement of the defective gene by the inserted gene, and this has not yet
been done. Zanjani and Anderson (1999) have proposed that somatic gene therapy in utero might
be a worthwhile alternative to germ line gene therapy.