Re: Life in the Lab -- Fox and the Nobel Prize
Fri, 14 May 1999 00:50:53 EDT

In a message dated 5/13/99 3:07:27 AM Mountain Daylight Time, writes:

> The proteinoid-sphere-first model seems awkward in that it requires
> that at some point in evolution the process of making the sphere via
> polymerization changes to a process in which the cell is made via
> DNA.

Not as awkward as trying to use naked protogenes to make cells. The best
scenario I've seen for a gene-first approach assumes that simple chemicals
lead to nucleotides that produced polynucleotides that lead to catalytic RNA
that eventually started producing cells. The first two steps -- simple
chemicals to nucleotides; formation of nonrandom polynucleotides -- are
supported by experimental evidence, but the third step -- the "evolution" of
nonrandom polynucleotides into catalytic (proto)RNA -- is not. All the work
that I've seen on catalytic RNA involves using biotic material; I have yet to
see any research that shows that abiotically synthesized nonrandom
polynucleotides possess catalytic activity, or that noncatalytic nonrandom
polynucleotides can be converted to catalytic (proto)RNA. This represents a
major discontinuity in this scenario.

The next even larger discontinuity comes in with the next "step", the
formation of protocells from catalytic (proto)RNA. To my knowledge there is
no experimental evidence demonstrating that catalytic RNA have the ability to
synthesize catalytic polypeptides or replicate their own catalytic function
in new polynucleotides. Or for that matter that they possess any catalytic
activity that would be necessary to form a cell. They have certainly not
been demonstrated to form cells on their own. How did they acquire these
activities? How did they coordinate them so as to start forming cells? How
did they "come to know" (anthropomorphically speaking) that they should be
creating cells? Did they create cells with protein-based membranes or
lipid-based membranes? If the latter, how did they start synthesizing
amphiphilic lipids (which is something modern genes cannot do)?

In other words, there are a whole host of unanswered questions attached to
this scenario, with almost no research to suggest any answers. Nor has the
genes-first research of the last couple of decades produced any answers.
This may be one reason why Crick and others have been forced to abandon a
genes-first approach. This is not to say that answers will never be found.
But it does suggest that the overall scenario may be wrong, especially since
the protein-first scenario has been far more successful.

> Does Fox go into this?

Indeed he does. The basic scenario goes like this: simple chemicals (water,
carbon dioxide, formaldehyde, cyanide, methane, ammonia, phosphate) form
amino acids, purines, pyrimidines, nucleosides, nucleoside triphosphates
(e.g., ATP) and nucleotides (as well as sugars and hydrocarbons); amino acids
form nonrandom polypeptides that possess catalytic capabilities, including
the ability to synthesize more polypeptides and polynucleotides (using
polypeptides as templates); these nonrandom catalytic polypeptides form
microspheres that also possess catalytic capacity as well as biological
membranes; polynucleotides formed abiotically or by microspheres (using
polypeptides as templates) combine with polypeptides to form nucleoprotein
microspheres that possess ribosomal activity, allowing them to use
polynucleotides as templates to synthesize proteins. Add to this the natural
pigment possessed by all microspheres that allows them to capture light
energy and use it to manufacture nucleoside triphosphates like ATP, which can
in turn be used to make polynucleotides.

None of this speculative; each and every one of these steps has been
experimentally demonstrated, so in fact it has also been experimentally
demonstrated that proteinoid microspheres from inception possess most of the
properties that are necessary for a modern cell to exist. Add to this the
powerful advantages of having a cell over naked genes, and you have a
situation that practically demands that cells came first. From there it is
simply a matter of selection to coaxe protocells into producing a system in
which catalytic activity and information storage are divided between two
different types of macromolecules (proteins and DNA/RNA, respectively). The
entire process is continuous, with no gaps (except in experimental evidence)
and no major unanswered questions (though some details are still missing).

For more information you might want to read _Molecular Evolution and the
Origin of Life_, Revised Edition, by Sidney W. Fox and Klaus Dose, pg.
241-267 (Marcel Dekker Inc., New York, 1977).

Kevin L. O'Brien