Re: God...Sort Of -- Protein Chemistry B
Mon, 9 Aug 1999 14:33:56 EDT

Greetings to One and All:

Here is the second part of my seventh response to Steve; we now move from
what constitutes a polypeptide/protein to whether proteinoids are true
polypeptides/proteins. Throughout I will use thermal protein instead of
proteinoid and I will use polypeptide and protein interchangeably.

> In fact Yockey says that "There is a chasm between the proteinoid spheres
> of Fox and the simplest protein":
> "...proteinoids are a heterogeneous mixture of sequences of racemic amino
> acids that cannot fold to produce an active protein....

The first part of this sentence is true, but the second part is false; the
two parts are in fact a non sequitor. Thermal proteins can fold to produce
active proteins. This is verified by the fact that thermal proteins loose
their activity when subjected to agents or conditions that denature modern
proteins, then regain their activity when the agents are removed or the
conditions reversed. This is a diagnostic characteristic of proteins.

> a serious difficulty
> in the hypothesis that proteinoids were precursors of true proteins.

Actually, the model did not claim that thermal proteins evolved into modern
proteins. The model instead claims that polynucleotides would be made using
thermal proteins as templates, then polypeptides would be made from the
polynucleotides. Under such a process, chances are excellent that branched
thermal proteins would be ignored, or the main peptide chain would be copied
while the branch points are ignored, or the branches would be copied as
separate peptide chains. In any event, only unbranched polynucleotides would
most likely be produced, and so only unbranched polypeptides would then be
produced. On top of that, the thermal proteins that would catalyze the
synthesis of polypeptides from polynucleotides are known to create
alpha-peptide bonds almost exclusively, and there is research that shows that
proteinous amino acids have the strongest affinity for polynucleotide
sequences. If the thermal protein peptide synthetases also have a preference
for L-amino acids, then even if thermal proteins are not real proteins but
merely proteinoids, they could still produce real proteins abiotically.

> There is
> a chasm between the proteinoid spheres of Fox and the simplest protein."
> (Yockey H.P., "Information Theory and Molecular Biology", 1992, p270)

In point of fact, Yockey is simply unfamiliar with the research that refutes
his claim. See Sidney Fox and Klaus Dose, _Molecular Evolution and the
Origin of Life_, Revised Edition, Marcel Dekker Publisher, 1977 for more

> KO>In fact, Chemical Abstracts, the authoritative word in chemistry on
> >nomenclature, categorizes proteinoids as proteins, under the subheading
> >thermal.
> Interestingly, when I searched the Chemical Abstracts Service (CAS)
> database at for " proteinoid" and
> "proteinoids" it returned "no documents found" errors. Maybe it's there
> somewhere? Perhaps Kevin can check and confirm this?

Steve's subtle suggestion of deception is noted, but what Steve searched was
not a database; it was the service homepage, where one can purchase access to
the databases. The search engine Steve used does not search the databases,
but the webpages that make up the site. As such, it is no surprise that he
was unable to find any references to proteinoids. He would have to purchase
access to be able to search the databases themselves.

When I searched the CAS databases through the company I work for, I found
both proteinoid and thermal protein under Chemical Substances, and I found
numerous abstracts that used both terms. In fact, as Fox points out, one can
quickly become conservant with thermal protein research simply by reading
these abstracts.

> But even if "proteinoid" is listed in a Chemical Abstracts Service, that
> not surprising because Fox *invented* the term " thermal protein" as a
> name for proteinoids (see below)....

Unfortunately, Yockey does not claim (as Steve implies) that Fox invented the
term thermal protein; Yockey only claims that Fox started using it in 1980.
In point of fact, the term thermal protein was invented by CAS and used in
place of proteinoid. Fox did not invent the term; he simply adopted it.

Here is the history: Fox first proposed the term proteinoid in 1967;
Chemical Abstracts accepted the term as legitimate and started using it as a
subheading in their indexes. In 1972, Chemical Abstracts, in response to the
growing evidence of the clear proteinous features possessed by proteinoids,
unilaterally dropped the designation proteinoid and adopted the subheading
protein, thermal instead. Fox seemed reluctant to use it, probably because
he feared that proteinoids would be confused with modern proteins, which he
wanted to avoid. Even so, he himself started using the term sporadically in
1980, then adopted it fully by 1984, though he was still being careful to
distinguish them from modern proteins. The fact that in later publications
he even dropped the prefix thermal indicates how much even he was willing to
accept that proteinoids were true proteins, just not modern proteins.

> ...and once it is being used in the
> biochemistry literature a Chemical Abstracts service would have to include
> it, and where else to include "thermal protein" but under "proteins,
> thermal"?

As I explained above, CAS invented the term for use by scientists in place of
proteinoid. They invented a term they believed was more accurate than
proteinoid. And while others started using the term as soon as it was
availablem Fox did not start using the term (according to Yockey) until some
eight years later, and even then he used it sporadically (again according to
Yockey), as if he himself was not totally convinced the term was right.

Chemical Abstracts does not adopt terms as subheadings in its indexes simply
because they are being used by scientists, but only if they believe the term
is both legitimate and descriptive of a unique substance or process.. That's
why they are recognized as having final authority over chemical nomenclature.

> Originally Fox made it quite clear that "proteinoids are not proteins" and
> "the very name indicates that they are not proteins". But he has over the
> years he has gradually blurred the definitions so that what started off as
> "not proteins" in 1976 had become "informed protein" by 1986:

Two points: First of all, what Steve does not seem to know, probably because
Yockey doesn't mention it, is that what Fox has said was that proteinoids are
not **modern** proteins. See below for more details. It should also be
pointed out that above quotations were made in 1984, not 1976 as Steve
claims. In other words, those quotations are later clarifications to avoid
confusion, not initial statements of perceived fact. Unfortunately, both
Yockey and Steve have fallen for the same confusion, namely that prebiotic
should be identical to modern proteins.

Secondly, Steve's implication is that Fox was engaging in unethical behavior
by "gradually blurring the definitions". In point of fact, Fox's own opinion
of just how truly protein-like his thermal proteins were changed over the
years as he and others learned more about them. While he started out
cautiously, eventually the evidence mounted to the point where even he could
no longer deny that proteinoids were true proteins, just not modern proteins.

But then that's how science works: new evidence creates new points of view.

> "The description of the resemblance of thermal proteinoids to proteins has
> fluctuated in time since they were first prepared. In 1975 proteinoids
> artificial proteins (Fox, 1975). Yet in two publications in 1976, Fox
> (Fox, 1976a) that proteinoids are not proteins, reiterating the assertion
> (Fox, 1976b) in his comment on the work of Temussi et al. (1976), (see
> Temussi's reply, 1976).

Fox has made clear that proteinoids are not modern proteins, but are
nonetheless definitely polypeptides, and probably even a form of true
protein. The following quote comes from the revised edition of the book he
co-authored with Dose, but it appeared in the ealier, 1972, edition as well,
and was originally published in 1967. As such, it predates all of Yockey's
references: "A definition of proteinoids ... is 'macromolecular preparations
of mean molecular weights in the thousands containing most of the twenty
amino acids found in protein hydrolyzates. Although these polymers have
other properties of contemporary protein as well, identity with the latter is
not a necessary inference.'" While Fox is being suitably cautious to avoid
claiming more than he can support with evidence (though evidence would
increase dramatically between 1967 and 1972), it is clear from this quote
that when Fox would later say things like, "Proteinoids are not proteins,"
what he meant was that they were not **contemporary** (ie, modern) proteins,
though they share the same characteristics of modern proteins. Yockey was
probably unaware of this definition, but if he wasn't (and he apparently had
read both the 1972 and the 1977 editions of the Fox and Dose book) then he is
misquoting Fox by citing out of context.

> In 1980 they were thermal proteins (Fox &
> Nakashima, 1980). They became 'protein-like polymers' in 1981
> (Hartmann, Brand & Dose, 1981). By 1984 they had again become
> 'thermal proteins (Fox, 1984a), but in another publication that year
> (1984b), Fox states, `Proteinoids are in the main much like proteins, but
> the very name indicates that they are not proteins...'

Based on the above quote, it is quite clear that Fox meant that the name
proteinoid indicates they are not **modern** proteins, but as he points out
they are still a form of true protein.

> However, by 1986,
> Fox writes (Fox, 1986), 'Biomacromolecular information emerged at the
> stage of nonrandom thermal reactions of sets of amino acids to yield
> informed protein '." (Yockey H.P., 1992, p270)
> So having "proteinoids" classed as "proteins, thermal" under Chemical
> Abstracts, seems more a triumph for Fox's facility in inventing new names
> than it does for the scientific merits of his case!

Steve is simply wrong here. CAS invented the term thermal protein in
response to mounting evidence that established that proteinoids were enough
like proteins to be catagorized as proteins. Fox himself was reluctant to
adopt this term until he became comfortable with the idea of referring to
them as actual proteins, something that (according to Yockey) did not occur
irreversibly until 1986, some 14 years after CAS made the change. If Fox
really had his way, CAS would still be calling them proteinoids.

> >MB>So Fox and collaborators called the structures
> >>"proteinoids," then went on to show that the proteinoids had some
> >>interesting properties, including modest catalytic abilities, that were
> >>reminiscent of real proteins.
> KO>Fox called them proteinoids to distinguish them from modern
> >proteins; nonetheless they are real proteins.
> See Yockey's quote above where Fox himself once admitted that
> "proteinoids are not proteins" and " the very name indicates that they are
> not proteins".

See above where I show that Yockey left out statements by Fox establishing
that he meant proteinoids are not **modern** proteins, but are still proteins

> The ending "-oid" means only "something *resembling* a (specified)
> object" ( My emphasis).

Yes, they resemble modern proteins, but they are not modern proteins. They
are, however, true proteins in that they are polymers of amino acids linked
together by the peptide bond in specific sequences that create specific
functions; they are simply created by thermal processes rather than biotic

> If "proteinoids" were "real proteins" why would they need to be
> called "proteinoids to distinguish them from modern proteins"?

Because modern proteins do not set the standard for what constitutes a true
protein. As I explained earlier, a true protein is simply a polypeptide
chain; ie, a polymer of amino acids linked by the peptide bond in a specific
sequence that imparts a specific function. That modern proteins are made
only of a specific group of 20 L-amino acids and form only the alpha-peptide
bond in unbranched polymers is the result of evolution, not some chemical
law. By calling thermal proteins proteinoids Fox hoped to distinguish them
sufficienty from modern proteins to avoid misunderstandings about their
nature or their evolutionary role.

> >MB>The scientific community has remained deeply skeptical of these
> >>experiments.
> KO>This is a logical fallacy called a sweeping generalization. Most
> >scientists have never even heard of these experiments (but then most
> >have barely heard of any origin of life experiment).
> Kevin is here being pedantic. Clearly Behe is talking primarily about that
> part of "the scientific community" which deals with the origin of life....

Steve is again putting words into Behe's mouth in an attempt to justify what
is in fact a lousy and factually inaccurate argument. Behe didn't say "The
abiogenic community" or "Those members of the scientific community who do
orgin of life experiments" or even "Chemical evolutionists". No, Behe said
"The scientific community", without qualification. Rather than try to divine
what Behe meant as Steve is doing, I prefer to take Behe at his word: he
meant all scientists; the entire scientific community.

> ...although the rest of "the scientific community", to the extent it
> about the origin of life at all, would take its cue from what the origin
> life subset of "the scientific community" thought about Fox's proteinoid
> experiments.

This is demonstrably untrue. There are many non-abiogenecists who, having
read the literature, are convinced that the proteinoid microsphere is the
best current model for the protocell, despite the opinions of abiogenecists
who oppose the protein-first point of view. An example is the review by H
Follmann in _Naturwissenschaften_ ("Deoxyribonucleotide synthesis and the
emergence of DNA in molecular evolution", 1982, 69, 75-81). There are just
as many who are not convinced, but very few say it is because of what other
abiogenecists say.

> KO>That who are familiar with proteinoids are skeptical about any form
> >of abiogenic scenario, though very few question the evidence.
> See above. This confirms what Behe said above about: "The scientific
> community has remained deeply skeptical of these experiments."

Steve is being willfully dense again. Behe was talking specifically about
proteinoid microsphere research; my comment states that many
non-abiogenecists who are skeptical of proteinoid microspheres are in fact
skeptical of ALL abiogenesis research. In other words, they question any
origin of life scenario regardless; they do not single out proteinoid
microspheres for greater skepticism.

> KO>Among those who do research in abiogenesis skepticism is based
> >either on a bias in favor of genetic material as the determinator of life
> >or on certain misconceptions such as the belief that the first functional
> >macromolecules had to be a result of random polymerization formations,
> >or both.
> This is too simplistic. Shapiro is a "protein-first" advocate and he is
> sceptical of Fox's proteinoids, suggesting they have no more relevance to
> the origin of life than a shadow image of a dog cast on a wall by a
> fingers has any relevance to real dogs:

And as I have shown in previous responses, Shapiro has some serious
misconceptions of proteinoid microsphere research and its history. Plus,
Shapiro promotes his own protein-first scenario, so I would not expect him to
be sympathetic of a rival model.

> "One simple alternative is to presume that the properties of the
> microspheres are less significant than claimed. Suppose, for example, that
> our monkey had typed a sentence containing more numbers than letters,
> rather than a phrase from Shakespeare. It would be nonrandom but
> unimportant, indicating only that he had a preference for the upper part
> the keyboard. Similarly, the various properties shown by the microspheres-
> division, weak catalytic activity, a double-layered border, electrical
> signals, and the rest-may be somewhat general properties of microscopic
> particles of a certain size and unrelated, or only slightly related, to the
> actual processes of life.

This is demonstrably untrue. The catalytic activity can be traced directly
back to the thermal proteins themselves; the double-layer boundary is a
direct result of the amphiphilic character of the thermal proteins
themselves, as are the electrical signals; in fact, the vast majority of
properties can be traced either directly back to the thermal proteins or are
emergent properties that appeared when the thermal proteins associated. Only
a very few may be caused by physical processes due to size, but there is no
experimental support for such a conclusion, whereas there is strong
experimental support for the conclusion that even these few are due directly
to the properties and functions of thermal proteins. Since "the actual
processes of life" are governed largely, if not solely, by proteins, the fact
that protocellular processes are governed by thermal proteins should be
strong evidence that protocells made of thermal proteins are in fact alive.
I do not have Shapiro's book, but I would be willing to guess that the
"alternative" Shapiro is referring to is the claim that protocells have life.

> During my childhood, I learned that I could make the
> shadow of a dog with my hand. I needed only to point my thumb out, bend
> in my index finger, and hold my hand before a light to produce the image
> a dog's head on the wall. I could enhance the effect by moving my pinky
> while making barking noises. But this form was not a dog, nor could it
> become one; it was merely shadow play. In the same way, the properties of
> the microspheres, while entertaining, may be merely shadow play."
> (Shapiro R., 1986, p200).

The key word here is may. If in fact all the properties of thermal
protocells were due simply to physical processes common to all microparticles
of a certain size regardless of composition (as Shapiro suggests) then his
analogy would be correct. In point of fact, however, not only do we know
that the properties of thermal protocells are based on functional thermal
proteins, we also know that microparticles of the same size made out of other
materials (such as lipid vesicles) display few or none of the same
properties, so size is not the issue. So Shapiro's analogy is incorrect.

A better analogy would be a spring-driven, gear-and-flywheel controled pocket
watch versus a battery-powered, quartz-crystal driven, microchip controled,
liquid crystal displayed wrist chronometer. Like thermal protocells versus
modern cells, a pocket watch can tell time just as easily and nearly as
accurately as a wrist chronometer, and its parts perform the same functions
as the parts of a chronometer, even though the parts do not have the same
structural nature.

> KO>I therefore find it significant that no other scenario has the same
> >degree of experimental continuity, the same degree of environmental and
> >evolutionary relevance, and the same degree of success at producing
> >living protocellular structures that the proteinoid model has had
> First, "the proteinoid model" has had *no* "success at producing living
> protocellular structures"! If it did, Fox would not have had to keep doing
> the experiment. He would be able to use his original proteinoids to
> offspring!

This is a strawman objection. As I have explained in previous posts, thermal
protocells make excellent bacteria chow, so it is nearly impossible to keep
them long term while also doing experiments on them. However, Fox has in
fact been able to produce multiple generations of thermal protocells from an
initial batch, sometimes making it out to the sixth generation before
bacteria finally get too numerous to continue the experiments. At that point
"the experiment" needs to be repeated in order to get a fresh stock of
protocells. You have the same trouble with cell culture. Unless you keep
the cultures sterile (which is difficult and inevitably fails), bacteria
eventually kill all the cells and you have to collect more from whatever
source you got them from in the first place.

> Second, to say that "no other scenario has the same degree of experimental
> continuity...environmental and evolutionary relevance, and...success" as
> "the proteinoid model" is not saying much! As Klaus Dose, a collaborator
> with Fox in proteinoid experiments has admitted, "*all*...experiments in
> the field either end in stalemate or in a confession of ignorance.":

I've already dealt with this claim. Dose was being overly conservative, but
he was specifically referring to gene-first scenarios like the RNA world. At
the time he wrote that, he still believed that thermal protocells were the
best model for the protocell. Dose's opinion, however, is in the minority.
Other collaborators of Fox are still far more confident of the experimental
results. And in the sense that he is also somewhat critical of thermal
protocell research, he is also wrong. Thermal protocells are living
structures and no one else has yet ever been able to duplicate that feat.

> And Behe points out below that what limited success the proteinoid
> scenario has had owes more to "investigator involvement" than to
> unintelligent natural causes.

See below for a detailed answer. In essence, Fox and his colleagues could
never have accomplished anything if it was impossible for thermal proteins or
protocells to be formed naturally by abiotic processes.

> Indeed, as Thaxton, et. al., point out, "most so-called prebiotic
> experiments actually owe their success to the crucial but illegitimate
> of the investigator":
> "Over the years a slowly emerging line or boundary has appeared which
> shows observationally the limits of what can be expected from matter and
> energy left to themselves, and what can be accomplished only through what
> Michael Polanyi has called "a profoundly informative intervention.". When
> it is acknowledged that most so-called prebiotic simulation experiments
> actually owe their success to the crucial but illegitimate role of the
> investigator, a new and fresh phase of the experimental approach to life's
> origin can then be entered. Until then however, the literature of chemical
> evolution will probably continue to be dominated by reports of experiments
> in which the investigator, like a metabolizing Maxwell Demon, will have
> performed work on the system through intelligent, exogenous intervention.
> Such work establishes experimental boundary conditions, and imposes
> intelligent influence/control over a supposedly "prebiotic" earth. As long
> as this informative interference of the investigator is ignored, the
> of prebiotic simulation will be fostered. We would predict that this
> will prove to be a barrier to solving the mystery of life's origin."
> (Thaxton C.B., et. al., 1992, p185).

I see alot of philosophical mumbo-jumbo here, but no concrete objections
based on experimental evidence. The fact is, Thaxton et al. are
philosphically opposed to any concept of naturalist, materialist explanation
of the origin of life. This talk of the "informative interference of the
investigator" is simply their excuse for rejecting any experimental evidence
without having to demonstrate why it is invalid. What they ignore is that
the "informative interference of the investigator" is not the equivolent
god-like powers. Researchers can only manipulate conditions, they cannot
create new physiochemical laws. If prebiotic processesses and mechanisms
simply could not exist because the physiochemical laws did not permit them to
exist, then no amount of "informative interference of the investigator" could
create a successful experiment regardless of how conditions were manipulated.
The fact that simulated prebiotic experiments are successful is because the
physiochemical laws permit prebiotic prossesses and mechanisms to exist, not
because of any "informative interference of the investigator".

> KO>As with our imaginary baker, a heavy odor of investigator
> >>involvement hangs over proteinoids. The special circumstance needed
> >>to make them-hot, dry conditions (putatively representing rare spots
> >>such as volcano rims)....
> KO>Incorrect; such spots were more likely to be quite numerous, even
> >common.
> The simple test of this would be to "such spots" today and see if
> proteinoids were forming. If protenoids were naturally occurring
> phenomena, and the conditions needed to produce them were "quite
> numerous, even common", they proteinoids themselves should also be
> "quite numerous, even common".

And so would be bacteria, which would eat the proteinoids so fast we would
never detect them.

> >MB>...with exact amounts of already-purified amino acids
> >>weighed out in advance casts dark shadows over the relevance of the
> >>experiments.
> KO>The amino acids don't need to be purified or of the alpha
> >or even of the L stereospecificity, and proteinoids have been
> >made from a wide variety of amino acid mixture proportions, including
> >found in meteorites, lunar soil samples and in simulated origin of life
> >experiments such as Miller-Urey.
> If Kevin is saying that the output of a Miller-Urey type chemical
> experiment with its minor traces of amino acids and major amounts of
> "goo" can be fed as is into the input of a Fox type proteinoid experiment,
> and proteinoids are formed, I would request him to post the reference(s).

Since I did not mention the word goo, I believe it is safe to conclude that I
am not saying that. What I am saying is that if you take all the amino acids
produced in a Miller-Urey type experiment, including all the beta-amino acids
and the nonproteinous amino acids, mix them together in the same proportions
as they are produced in the experiment, then heat them, you get thermal
proteins. To my knowledge, no one has yet taken the raw product of a
Miller-Urey type experiment -- insoluble material and all -- and used it
directly to make thermal proteins, but such an experiment has been simulated
by producing thermal proteins with mixtures of amino acids containing various
amounts of a wide variety of organic, inorganic, soluble and insoluble
material. So far, no mixture has failed to produce thermal proteins.

Besides, there are easier ways to make amino acids without also making
insoluble material. For example, Fox demonstrated that heating an aqueous
mixture of formaldehyde and ammonia at 180 C for 8 hours produces a dry
material that, when rehydrated, hydrolyzes into amino acids and other
compounds of biological significance. The amino acids include the three most
common -- glycine, alanine and aspartate -- but can also include serine,
proline, valine, leucine, isoleucine and phenylalanine. Glycine is generally
the most abundant, but alanine can range from approximately 7-30% and
aspartate can range from approximately 5-25%, and aspartate can out-produce
alanine. An example of a published result yielded 57% glycine, 12% valine,
10% aspartate, 9% alanine, 8% serine and 4% leucine. This mixture in turn
produced thermal proteins.

So one needn't rely on a Miller-Urey type experiment to get amino acids.

> And again, if it was proteinoids can be made naturally from a wide range
> naturally occurring phenomena, and are "living" and therefore produce
> offspring, the proteinoids themselves should be plentiful. So where are
> they?

Being eaten by all the bacteria that would be living in the same places where
the proteinoids would be made.

> KO>And in fact no scientist has questioned the relevance
> >of proteinoid microspheres simply on the basis of experimental protocol.
> See my posts where the "scientists" Shapiro, Yockey, and Thaxton, et. al.
> have "questioned the relevance of proteinoid microspheres".

Except that Shapiro, Yockey and Thaxton et al. do not question the relevance
of proteinoid microspheres on the basis of experimental protocol, but for
philisophical reasons; Shapiro most likely on the basis of rejecting the idea
that thermal protocells are alive, Yockey on the basis of rejecting the
concept of self-organization and Thaxton et al. on the basis of rejecting any
form of materialist explanation.

> >MB>Worse, because proteinoids are not really proteins, the
> >>considerable problem of producing authentic proteins remains.
> KO>As I have already pointed out, there is no problem because they are
> >real proteins.
> See above. Even Fox has not said that "proteinoids are not proteins" and
> "Proteinoids...the very name indicates that they are not proteins".

And as I pointed out, Yockey neglected to mention that Fox himself stated
that he meant that proteinoids are not **modern** proteins, but they still
are real proteins.

> Indeed,
> if "proteinoids" were "real proteins" then why are they called

As I have already explained, to distinguish them from modern proteins, and to
indicate their status as the prebiotic progenetors of modern proteins. This
is why thermal protein is more appropriate than proteinoid.

Kevin L. O'Brien