Re: Genetic engineering costs

From: Adrian Tymes (wingcat@pacbell.net)
Date: Tue Apr 22 2003 - 18:35:03 MDT

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    --- "Robert J. Bradbury" <bradbury@aeiveos.com> wrote:
    > On Tue, 22 Apr 2003, Adrian Tymes wrote:
    > > Out of curiosity, what are all the costs of
    > genetic
    > > engineering at this time? There is specialized
    > labor,
    > > of course, but even with widespread competition
    > (as a
    > > result of widespread training in the techniques),
    > this
    > > would still be skilled labor by modern standards,
    > and
    > > thus the cost of labor would still be a factor.
    > But
    > > what other costs are there, and how could one
    > minimize
    > > or eliminate them?
    >
    > One needs a certain amount of specialized machinery.
    > DNA synthesizers and sequencers & PCR apparatus to
    > amplify DNA for example -- these range from a few
    > thousand
    > to hundreds of thousands of dollars. Then one needs
    > very
    > high quality water purifiers and sterilizers.
    > Finally one
    > needs the reagents to perform the actual
    > "engineering" --
    > a small amount of a single restriction enzyme to cut
    > up a piece of DNA in a specific place may be a few
    > hundred dollars (and there are hundreds of different
    > kinds of restriction enzymes that one might need to
    > use).
    > Then there are the plastic consumables -- tubes or
    > plates
    > in which to grow you modified organisms.
    >
    > It isn't cheap.

    Hmm. Correct me if I'm wrong, please, but none of the
    above sounds fundamentally difficult to manufacture.
    Which means, in theory, if one had a large marget of
    would-be genetic engineers, one could set up efficient
    mass production of all of these components, especially
    the consumables and enzymes. The main reason they
    cost so much now is that the effort to set up initial
    manufacturing has to be amortized among a limited set
    of customers.

    In other words, it's the kind of problem that
    historically has naturally been solved as the skill
    base necessary to use this gets more and more widely
    disseminated, thus creating more customers for all of
    this. The problem is that it isn't cheap *right now*.
    Is this correct?

    If so, then it would seem one of the more efficient
    ways to solve the problem would be to document some
    simple examples of the type of engineering you'd like
    to make cheap - basically, recipes that others could
    follow - and give them away. This will, by itself,
    create the larger demand. It would take quite a lot
    of recipies to have noticable impact, though: a mere
    thousand extra customers, especially as a one-shot,
    would likely make little difference in the prices.
    But perhaps if one could then buy the machinery,
    consumables, etc. for these recipies in bulk - at bulk
    discount - then pass some of the savings along as a
    reseller to those interested in following the
    recipies? I believe this model has been successfully
    followed in certain other industries, ending when the
    recipies produced enough general-use customers that
    the manufacturers clued in and became their own bulk
    customers, or ossifying into distributor chains (as
    seen with, for instance, modern supermarkets).

    > > Might it not be simpler just to design a virus to
    > do
    > > this infection, but not replicate (beyond normal
    > > cell division, et cetera), then flood the body
    > with
    > > a lot of this virus?
    >
    > This involves placing the virus in a host which has
    > been
    > engineered to have the required additional
    > replication
    > machinery -- not simple (otherwise how do you get a
    > sufficient number of viruses?).

    Good point. One could, say, engineer or find a host
    optimized for replication of virii; this would be a
    significant cost, but one-time. Again, amortize over
    a number of different applications; stocks of this
    cell ("blank" - that is, ready for infection) could
    become one of the consumables in the above business
    model.

    > Then there is a
    > nasty
    > problem that you don't introduce any of the cells
    > that
    > are capable of replicating the virus.

    Typical virii are much smaller than typical cells, no?
    So, would it be possible to pass the solution,
    containing both virus and cells, through a filter with
    small enough pores that only the virus could fit
    through? You'd wind up with virus on one side, and
    virus plus cells on the other; discard the latter (or
    save for processing more batches) and use the former.

    > > One challenge would be how to make sure the
    > > virus does not needlessly overwrite the edit on a
    > cell
    > > that has already been modified, or at least that
    > such
    > > an overwrite would be harmless.
    >
    > Yes -- this is the "How many copies do you want
    > problem?".
    > There are some solutions for this in prokaryotic
    > cells
    > with bacterial viruses but I'm unaware of any that
    > function
    > within eukaryotic cells. With their much larger
    > size it
    > might be difficult for the regulatory proteins to
    > diffuse
    > sufficiently fast to perform the desired function
    > (of
    > regulating copy number).

    If limiting copies/overwrites would be difficult, then
    perhaps it might be easier to ensure that overwrites
    would be harmless? Say, design the virii such that,
    if one infects an already infected cell, it will
    merely knock out the previous copy and replace it.
    (Which is why I use the term "overwrite".)

    > I've thought about this for a long time and haven't
    > managed to come up
    > with a good solution (which is why I suggested
    > delivering single
    > pre-engineered secondary nuclei [biobots] outside of
    > the body). One can
    > always screen such cells to make sure you are
    > getting those with the
    > correct modifications. Inside the body it is much
    > more difficult to make
    > sure things are going as planned.

    True, but then you face the problem of integrating
    these secondary nuclei into existing cells, putting
    only one secondary nuclei into each cell instead of
    multiple in one cell and none in its neighbors, making
    sure they divide when they rest of the cell divides,
    et cetera. It seems, on first glance, that by the
    time you solve those problems you'd wind up with
    something very much like a non-self-reproducing virus
    anyway.



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