Re: Count sheep, anyone?

Brian T. Greuel (bgreuel@epix.net)
Fri, 07 Mar 1997 21:43:13 -0500

Loren Haarsma wrote:

> A colleague of mine suggested a variation on this. Although it is not
> possible now, it may soon be possible to identify, and in certain cases
> activate, the control genes for developing certain specific kinds of
> tissue and organs. (More would need to be known about the external
> biochemical developmental cues as well.) Suppose this "cloning"
> procedure could be modified so that, instead of re-setting the *entire*
> embryonic developmental program, only a certain portion of it were
> activated by activating specific control genes. This could, in theory,
> be done simultaneously with implanting the donor nucleus into the
> enucleated egg. Now, instead of growing a whole embryo, you are
> growing only a portion of an embryo, producing a specific type of tissue.
> (Again, this is not possible yet, but I suspect it will be in a decade
> or two.) Would someone like to critique the moral status of *this* type
> of procedure?

My only "moral" problem with this is that it would lead to a waste of
human resources. Human eggs are not exactly available in unlimited
quantities. You have to collect them from a hormonally-induced woman by
suctioning them from mature ovarian follicles, usually with the aid of a
laparoscope--a somewhat uncomfortable procedure for the woman that
yields at most perhaps 5 or 6 eggs in a single isolation procedure.
Even in vitro fertilization of isolated human eggs is usually not100%
efficient, in part because of a failure of some eggs to mature properly
during the hormone treatments. The efficiency of enucleation and
nuclear transfer would be far less than that achieved for in vitro
fertilization because of the great potential for damage to the eggs.
But assuming that the nuclear transfers were successful and the
manipulated "semi-embryos" began to grow in culture, then what are you
going to do? Are you going to transfer them to the uterus of a
hormonally prepared "mother" to serve as a host for what you hope will
be a new organ? Never mind the scientific obstacles that must be
overcome, do you really think this type of approach is going to solve
the problem of shortages in donor organs?

There are other avenues of investigation that I think will be more
fruitful in solving this crisis. Perhaps the most promising will be to
genetically alter another mammalian species such as the pig so that its
organs will no longer be seen as foreign within a human host. Continued
progress in organ/tissue culture may also lead to the production of
"spare organs" in culture. Breakthroughs in regeneration research may
one day lead to the ability to repair severed spinal cords or
diseased/damaged organ tissues by simply inducing regrowth of the organ
or part of an organ within the patient.

Another strategy might be to isolate a human embryonic stem cell line
which could be genetically manipulated in culture and/or subjected to
various treatments (different growth factors, hormones, extracellular
matrices, etc.) that would push it down specific developmental pathways
in culture. Mouse embryonic stem cell lines, for example, will form
cardiac muscle tissue under certain culture conditions and it actually
contracts rhythmically in the culture dish! Current research is aimed
at inducing these cell lines to develop into a number of different
tissues "upon command." Performing such procedures with a human
embryonic stem cell line does raise some serious ethical issues,
however, because the development of such a cell line would involve the
sacrifice of at least one cleavage-stage human embryo. Once
established, however, the embryonic stem cell line would provide a
virtually unlimited supply of undifferentiated human cells that,
theoretically, could develop into any organ or tissue of the human
body. Personally I don't favor the development of a human embryonic
stem cell line for the reason mentioned above and because the potential
for abuse of this resource is just too great.

Brian Greuel