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Tim, Judith
Thank you for your very informative and educative posts. It
seems that to be on the safe side we should not be outsiders to what is going on
in this field, certainly including the GM that is already in practice and
rapidly spreading all over the world in the name of combatting the hunger. In
this venture, side effects are deliberately overlooked by policy makers as the
alternative is considered to letting people to die of
hunger. It is already a great dilemma in the field of GM, let aside the cloning,
for organ or the whole human being.
I wonder, how we,
non-biologists, can defend future generations from these likely
ill doings. Who are informing the people, at the bottom line? I gather,
Scientific American has a very limited readership. I have a subscription, but
copies arrive here (Italy) very sporadically. When I see an article of a public
interest, I do some informing around me. But the people tend to ignore things
belonging to tomorrow! There must be more effective and incisive system of
alert. Something useful is moving in Italy on the GM. At least the vendors put
by law a label on their products indicating the origin of the food they
sell and if it is GM or not. I wonder how these things are handled in the USA.
Usually the rest of the world blindly follow what happens in the USA good or
bad.
My best,
Ayten
----- Original Message -----
Sent: Monday, May 03, 2004 6:55 PM
Subject: Re: Cloning
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.
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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. |
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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