Along the lines of
cloning, chimera, and dangers, I was just reading the article entitled
"Synthetic Life" in the May 2004 issue of Scientific American. (www.sciam.com) The idea behind "synthetic
biology" is described also at MIT's www.syntheticbiology.org:
Synthetic biology refers to both (a) the
design and fabrication of biological components and systems that do not
already exist in the natural world and (b) the re-design and fabrication of
existing biological systems.
Under the
Documents tab on this website, the Slides from the 11/20/02 seminar provide a
coarse overview. (Any programmer will appreciate the pseudocode on slide
7.) The document "Recombineering: Homologous Recombination-Mediated DNA
Engineering in E.coli" supplies a surprisingly step-by-step
description of one method of building augmented/altered functions into
organisms. It might be retitled "How to Recombineer E. Coli in Your
Spare Time for Fun and Profit".
Certainly the
Sci-Am article points out that the current level of ability in synthetic biology
falls far short of being an ability to engineer in an reliably predictable
manner. The current approach seems to focus on finding those codings of chunks
of DNA that will reliably encode some particular function - those that are
context-independent. Along these lines, the goal is to create a
canonical set of such parts, called "BioBricks", which can be utilized for
adding predictable sets of functions to organisms at will. MIT has a list of the
current set of such canonical parts, called the "MIT Registry of Standard
Biological Parts" at http://parts.mit.edu/.
The presumed
context-independence, though, does not stretch far. On p. 3 of the Sci-Am
article:
One way to deal with the complexity added by the cells' native
genome is to dodge it: the genetic device can be sequestered on its own
loop of DNA, separate from the chromosome of the organism. Physical
separation is only half the solution, however, because there are no
wires in cells. Life runs on "wetware," with many protein signals simply
floating randomly from one part to another. "So if I have one inverter
over here made out of proteins and DNA," Endy explains, "a protein
signal meant for that part will also act on any other instance of that
inverter anywhere else in the cell," whether it lies on the artificial
loop or on the natural chromosome. |
One way to prevent crossed signals
is to avoid using the same part twice. Weiss has taken this approach in
constructing a "Goldilocks" genetic circuit, one that lights up when a
target chemical is present but only when the concentration is not too
high and not too low. Tucked inside its various parts are four
inverters, each of which responds to a different protein signal. But
this strategy makes it much more difficult to design parts that are
truly interchangeable and can be rearranged.
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This seems to me
to go back to Judith's recent quote from the intro to AS: "Can we design
systems which are proof against a principle of function change?". If we
could indeed have a canonical set of context-independent parts, then this would
seem to be immediately possible. However, it seems to me that if such
context-independence is mostly wishful thinking, then "proof against function
change" requires an entirely different approach, where the intended
organization of multiple functions cannot rest on serial accretion of functions,
but rather a simultaneous interdependence among 'parts' - an impredicative
organization. This would be a very different kind of engineering
task.
Alternatively, one
might use mitochondria as examples of how to achieve some greater degree of
context-independence within a cell: rather than conceiving 'parts' as
canonical chunks of DNA, one builds mitochondria-like 'modules' which
provide some greater degree of chemical and functional separation. At some
point, this approach will break down too, as the desire to concatenate functions
result in unwanted side-effects as signals pass from module to module. (Also,
the burden on the cell of such concatenation must at some point become
excessive.) So, eventually, the kind of impredicative engineering I mention
above would seem to me to be required eventually for this approach
too.
Although I can
appreciate the spirit behind synthetic biology, I have to say it strikes me
as fraught with the potential to wreak unbelievable havoc on the world,
either through intentional misapplication or through unforeseen functional
relations occurring between a modified organism and some ecosystem into which it
mistakenly contaminates.
Regards,
Tim
Ayten Aydin wrote:
I am wondering, even it may not be directly related to your
post, what your father was thinking and you&others in the list are
thinking about the cloning, in terms of both biological and cultural
anthropology. On the ethical side, if successful, an authority with all the
means at hand, could produce uniform individuals to gradually replace the
diversity at large, as one point. The other is whether physiologically
cloned individual (i) will have the ability to cope with the requirements of
higher more and more complex realms such as biological, neurological
(including all brain functions), passional, intuitional, spiritual; (ii) if so
will they develop in line with the abilities of the original from which
they sprung out or split in the process ???
I discussed issues like cloning and genetically modifying
organisms with him often. Regarding cloning in particular and genetic
modification in general, he felt that science which is proceeding
from the limited theoretical premise of mechanism would naturally
generate endless side effects. Even a Rosennean theoretic premise would not be
able to eliminate side effects, but the scientists would be able to do some
complexity analysis going IN (in preparation), and the results of that
analysis might be enough to scare the hell out of them enough to scrap the
whole idea. At least they would see the dangers.
The kind of tinkering they are doing with complex systems, when
they really don't understand complexity at all, is extremely dangerous and I
think they mostly don't see the danger. But when we break apart a complex
system like an atom, we are unleashing forces that are otherwise
stabilized in our environment and that is obviously going to have side
effects. Can you imagine what would be some of the results if science figures
out how to "genetically modify" atoms? Would some new form of matter be
compatible with this universe? This is the kind of thing I write fiction
about!
In cloning, we have already discussed the fact that the
mitochondria in the donor egg are not replaced with the mitochondria of the
organism to be cloned, so there is a chimerical element introduced, right
there, from day one. There are going to be consequences from that. Side
effects. It may be that every single cell in the body of the cloned individual
has subtle immune consequences due to the fact that there are really two
separate individuals present in every single cell of the body. Cells
apparently have certain immuno-capabilities within the cell walls to regulate
internal activity in limited ways, according to the preliminary research I did
on the subject.
However, my father's views on genetically modified
organisms were very mixed. He thought that certain types of genetic
engineering were extremely useful: engineering an inoffensive bacterium
to produce some needed antibiotic or engineering human cell lines (in a
lab setting) to produce a vaccine, for example rather than using
animal based production techniques as is currently done. But he also felt
that knowing when it is safe to tinker with genetic
modifications required wisdom and science is notorious for its lack of
wisdom. The "test-planting" of GM crops in open fields, for example, is just
plain stupid in my opinion. These organisms are not naturally designed to
"stay where we put them" an no one has addressed genetically engineering that
out! Pollen is airborne and the side effects are already being detected, even
with the limited amount of such GM crop testing currently in progress in this
country. Certified organic crops, in several cases, are already showing
the presence of genetic material that can only have come from airborne
pollen released by GM crops in another location. This is worse than second
hand smoke inhalation, by far. Deliberately implanting food crops with genes
for artificial pesticides? Sheesh! It's a guarantee that natural ecosystems
are going to incorporate all of this stuff into wild and other "unintended"
gene pools, at which point the interactions are off the scale into infinity.
That's just plain common sense, methinks.
I'm hearing all sorts of ominous reports that using these GM
crops as feed in raising food animals is causing nasty side effects, including
unexplained miscarriages and deaths; that most species of farm
animals can detect (!)(How???) which feed is genetically modified and
when given a choice, they avoid the GM feed completely; and that some of these
transgenic genes are finding their way into fetuses of pregnant animals, etc,
etc... I'm not sure as yet how solid such reports are scientifically, so
I'm looking into that, but the sheer volume of such reports from so many
different sources tends to add weight to the reports' veracity, in my
eyes.
It was all of this that made my father stop short
of writing down what he had developed, conceptually, on the
notion of creating a living system artificially. He was sure such
information would be misused and abused. Given all of what science
does not know about these systems that we are tinkering with in various ways,
it certainly seems that we ought to err on the side of caution. I personally
believe laws ought to prevent these kinds of open tests in farm fields, among
other things. But the laws haven't caught up with the technologies yet. This
is one reason why I've chosen to work to get my father's
theoretical ideas "out there" and accessible-- the relational quality of
an organization-based theoretical foundation, which is one description
of Rosennean Complexity Theory, would automatically guarantee these
genetic engineers that what they're doing is going to have unforeseeable side
effects in unforeseeable directions.
Judith
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