Re: Fw: Origin's: Yockey's book

Glenn Morton (grmorton@waymark.net)
Mon, 12 Jan 1998 22:16:42 -0600

At 10:14 PM 1/9/98 -0500, Dr. Fred Phelps wrote:

>What did I miss while I was overseas? Did someone show that "useful
>functional molecules" are being created in laboratories? I'm sure you
>(Glenn) can summarize that paper faster than I can find, read, and
>understand it.

I am sure others can do better on this topic than I. What I will describe
has been going on for several years. And I will end with a post from one of
the researchers in the field who goes by the moniker, "non-woof' on
talk.origins.

What is happening is that biopolymers can be made with random orientations,
and then reproduced (with a lot of mutation). Selection is then carried out
on those molecules for some type of functionality (cutting a dye molecule,
an RNA cutting a DNA, enzymatic activity whatever.) Those molecules that
show even the slightest predisposition to perform the desired trick are
isolated, and then copied (once again with a lot of mutation allowed). Then
the selection is repeated only this time the bar is a little higher. The
molecules must be able to do the trick in a shorter time (use less energy,
etc) than the first generation. Those molecules that pass the test are then
copied with mutation. this is repeated over and over. they are finding
that most functionalities they look for are found in a given vat of 10^14
molecules. Some functionalities are found at a lower frequences
10^-15---10^-18.

Anyway, it appears that lots and lots of functionalities can be found at
considerably lower frequencies than anti-evolutionists often claim. One
will find the claim that the odds of randomly selecting a molecule to do
thus and such is 1 in 10^300 or something like that. This appears to be
erroneous and that is what the 330,000 ways to say "If I pick my nose, I
will get warts" was designed to show.

Here are some of the results.

Gerald Joyce wrote

"Andrew Ellington and Jack W. Szostak "used small organic dyes as the target.
They screened 10^13 random-sequence RNAs and found molecules that bound tightly
and specifically to each of the dyes.
"Recently they repeated this experiment using random-sequence DNAs and
arrived at an entirely different set of dye-binding molecules.
...
"That observation reveals an important truth about directed evolution
(and indeed, about evolution in general): the forms selected are not
necessarily the best answers to a problem in some ideal sense, only the best
answers to arise in the evolutionary history of a particular
macromolecule."~Gerald F. Joyce, "Directed Evolution," Scientific America,
Dec. 1992, p. 94-95.

A novel trait was found by one of these experiments.

"In a recent experiment, Joyce was trying to get his ribozymes to do without
one of these reproductive enzymes when a few of his molecules struck out on
their own. 'All of a sudden something quite a bit smaller than the parent
ribozymes popped up,' Joyce says. 'Through subsequent generations it got a
little bigger, then a little smaller, kind of shifting around in size. But
each time it got better and better at replicating.' He dubbed this
free-spirited, pint-size RNA the 'minimonster,' or less charitably, 'the
beast.'
"The thing Joyce immediately wanted to know was how his wayward new
molecule was replicating. Could the minimonster somehow be doing without
enzymes and primers altoghether? If so, Joyce and his colleagues really had
something on their hands. As substance that reproduces itself by itself for
its own purpose--that's a pretty good description of being alive. Was their
minimonster a brand-new example of what nature had first accomplished all
those billions of years ago? Were they seeing the sponaneous flowering of
life?
"Well not exactly, 'We found out that it did require the two enzymes,'
says Joyce. "So it wasn't self-sustaining.' But although the molecule still
needed the enzymes, it eventually dispensed with both the primers that allow
the enzymes to go to work. The minimonster had figured out a way to
accomplish that part of the reproductive process itself. It wasn't alive, but
is sure was heading in that direction."~Peter Radetsky, "Speeding Through
Evolution", Discover, May, 1994, p. 87

A molecule to bind to thrombin, Bock et al describe their molecule:

"We synthesized a pool of ~10^13 96 mer oligodeoxyribonucleotides that share
18-nucleotide binding sites for polymerase chain reaction (PCR primers at
their 5' and 3' termini and also contain 60-nucleotide randomly generated
sequences."
Louis C. Bock et al, "Selection of Single-stranded DNA Molecules that Bind
and Inhibit Human Thrombin," Nature 355(1992), p. 564

They then applied the selection process described above. There are 10^36
possible sequences of a 60 unit long nucleotide. If as creationists often
claim, that only one of these sequences would work, they would be expected
to have to produce 10^36 / 10^13 batches before they would find that one
workable sequence. This is 10^23 batches. The earth is only 10^17 seconds
old so this is about 1 million batches per second for the entire history of
the earth. The creationist argument would predict that they would not find
a Thrombin binder. Yet they did. They write:

"Our findings show that a population of ~10^13 molecules of 96 mer
single-stranded DNA can be selected for apatamers that bind human thrombin,
a protein with no known nucleic acid-binding function."~Louis C. Bock et al,
"Selection of Single-stranded DNA Molecules that Bind and Inhibit Human
Thrombin," Nature 355(1992), p. 566

The above is a novel function produced by molecular selection.

Bartel and Szostak, "Isolation of New ribozymes from a Large Pool of Random
Sequences," Science 261(1993):1411-1418, studied the ability to find a
ribozyme to catalyze two other RNA molecules. They write on p. 1411

" An iterative in vitro selection procedure was used to isolate a new class
of catalytic RNAs (ribozymes) from a large pool of random-sequence RNA
molecuels...In vitro evolution of the population of new ribozymes led to
improvement of hte average ligation activity and the emergence of ribozymes
with reaction rates 7 million times faster than the uncatalyzed reaction."

Now the following was taken off of Talk.Origins and is from Andrew
Ellington, mentioned above by Joyce.

"Next five to ten years. Joyce actually has some pretty tough
criteria for 'life' (as opposed to moi, who tends to equate
it with self-replication): he really wants the little
buggers to be able to change form and function in order to
better utilize their environment. So, I would guess when
there is an RNA molecule that can reform itself from monomers
(no easy task, but ligases are down to <100 bases, so hey ho)
can evolve to respond to, say, cytidine deprivation (this
will be easy; Q-beta expts. can already do this) that most
of the criteria for 'life' (except for a shell, see other
post o' (TM-Acker) mine) will be met. There, if you waded
through all the internal asides you have come out the other
end with only a headache to show for it.
"I sometimes wonder how the C'ists are going to take it when
this in fact happens. The trail between prebiotic muck and
organisms is quickly becoming populated. As in the always-
being-written FAQ (yes, it is really almost done; "*"
indicates not yet experimentally shown):

(1) Nucleotides can be synthesized prebiotically
(2) Oligonucleotides can be synthesized prebiotically
(3) Oligonucleotides can ligate and autocatalytically
template their own replication
*(4) Oligonucleotides can catalyze (as well as template)
ligations.
*(5) Oligonucleotides can grow into polynucleotides
(6) Polynucleotides have amazing catalytic properties,
and can replicate themselves very efficiently (* for the
last half of this sentence)

Most work is currently being done to flesh out (6) (be on the
lookout for work from the Szostak lab: amazing stuff coming
down the pike), including most of the work Joyce is talking
about. The "missing links" of (4) and (5) are also being
pursued, I think primarily by Leslie Orgel and von Kiedrowski
(still; I know I always use them as references for (3)).

Making it all work together (i.e., starting from discharge
experiments ala Miller and working to (6), above) is still
way too advanced for me to even contemplate -- which means,
in the great scheme of things, 20-40 years (just think, it's
only a little over 30 years since we knew the structure of
DNA!).

Non-woof

other articles on this:

Jon Lorsch and Jack W. Szostak, "In vitro Evolution of new Ribozymes with
Polynucleotide Kinase activity," Nature 371(1994):31-36

Ronald R. Breaker and Gerald F. Joyce, "Inventing and Improving Ribozyme
Function: Rational design vs. Iterative selection Methods," Trends In
Biology Tech. July 1994, p. 268-275

Charles Wilson and Jack W. Szostak, "In vitro Evolution of a Self-Alkylating
Ribozyme," Nature 374(1995), p. 777-782

glenn

Adam, Apes, and Anthropology: Finding the Soul of Fossil Man

and

Foundation, Fall and Flood
http://www.isource.net/~grmorton/dmd.htm