RE: EVOLUTION: Germline engineering

From: Robert J. Bradbury (bradbury@aeiveos.com)
Date: Fri Nov 29 2002 - 16:07:23 MST


On Fri, 29 Nov 2002, Ramez Naam wrote:

> I think this is a great question. However, I must point out that
> modifying the genome of an adult organism is not going to have nearly
> as profound an effect as modifying the genome of an embryo.

Well, it depends on what kind of modifications you want to make.
The problem from a bioethics standpoint is that modifying the genome
of an embryo violates the principle of "informed consent".

> The genes we have, in many cases, have their most profound effect on
> us during our developmental phases - as embryos, newborns, children,
> adolescents, etc... The later in life you intervene, the less of an
> impact you will have.

Why? Cannot lizards regrow their tails, lobsters claws, etc.?
The flexibility for significant self-modification can be programmed
into the genome.

> In an earlier version of this thread I used the example of homeobox
> genes in the fruit fly. We can manipulate these in an embryo and in
> so doing give the adult fruit fly an extra pair of wings or legs or
> whatever.

But the examples I cite above seem to suggest there is no reason
one couldn't do these things in adult organisms. A good example
that could be done with "current" technology would be a bone marrow
transplant of ones own stem cells with the CCR5 gene knocked out.
Voila -- you have your own immune system back with a significantly
higher resistance to HIV. A fairly significant improvement in
ones phenotype.

> However, if you were to try making this same genetic change to an
> adult fruit fly, I predict you would get a result far different (and
> probably far more lethal) than you get by making the change in an
> embryo.

Predict based on what? There are thousands or tens of thousands
of changes that could be made to genomes that would produce
embryonic or developmental lethality (I posted a pointer to
a paper months ago on just how often development is lethal
due to "natural" mutations or developmental failures). There
is nothing to suggest that genomes cannot be programmed for
significant changes (tadpole to frog, catapillar to butterfly, etc.)

> So, to my mind, adult gene therapy will never catch up with embryonic
> genetic engineering in terms of its effects. To match embryonic
> genetic engineering you're going to need something like molecular
> nanotechnology, and we've already seen how bullish I am on that. :)

Yes, but I don't believe you saw my talks at Extro-3 or Extro-4
and you haven't read my current business plan. [several :-)]

Here is the question to ask yourself. Can we with near term technology
(say this decade) develop the ability to add a "secondary nucleus"
to cells in an adult human body?

I believe the answer to that question is yes, either through the
use of engineered bacteria or liposomes. If it can be done then
one has the ability to augment the natural human genome with
hundreds to thousands of genes. That isn't an "insignificant"
patch.

That's not the same as ripping out the installed genome and replacing
it. My current thinking is that that will require real MNT
(as you point out) -- but "patches" of the magnitude I think
are feasible will allow you to get a significant part of the
way to that eventual goal.

Robert



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