Life in the Lab -- Fox Symposium (Long)
Sun, 2 May 1999 14:59:43 EDT

Greetings to one and all:

Here is the text version of the symposium; it is really a shame I could not
reproduce the photos, but you can see them at
<>. My own
comments are offset by "{}'s", to distinguish them from the Editor's own
comments. Incidentally, I do not completely agree with Fox's comments
concerning determinism, but I hope people will not be distracted by his
philosophical beliefs from his scientific work.


My Scientific Discussions of Evolution for the Pope and His Scientists

[Editor's note: The following is a transcript of the presentation by Dr.
Sidney Fox on May 15 at the Harbinger symposium, "Religion & Science: The
Best of Enemies - the Worse of Friends," with an introduction of Dr. Fox by
Dr. Sheldon Gottlieb, one the project's directors.]


by Sheldon Gottlieb

questions about who they are, where did they come from, what purpose, if any,
do they have on this planet, and what happens to them, if anything other than
decay and recycling, after they die. Over the past few weeks we have
explored aspects of these questions from the religious, scientific, and
philosophic points of view.

Tonight we are going to explore one of the more fascinating aspects of the
subject of where do we come from, from the point of view of how life on this
planet originated--how life came into being from non-life; how inanimate
organic molecules self-organized into animate cells. One thing that will make
tonight so exciting is a video tape that you will see, one that has not yet
been shown to the rest of the scientific world, one that is being prepared
for presentation before a scientific audience, in which you will see the
phenomenon of living cells forming before your eyes.

A few months back, Pope John Paul II, came out with what many people consider
-- at least for the Vatican -- an historic statement concerning the Roman
Catholic Church's view on accepting evolution as a scientific theory.

Before the Papacy makes such a historic statement, it tends to study the
issues very carefully. The Pope did not want to have the church make the same
mistake with evolution that it had made with Galileo and Giordano Bruno.

There is no doubt in my mind that one of the great influences on the Pope was
the work of the man we are going to be privileged to hear tonight, Dr. Sidney

Dr. Sidney Fox is a native of Los Angeles, who received his B.A. degree from
the University of California at Los Angeles (UCLA) and his Ph.D. from the
California Institute of Technology. The chairman of his Ph.D. dissertation
was the famous evolutionary biologist and geneticist, Thomas Hunt Morgan, who
personally taught young Sid aspects of evolution.

Dr. Fox has a long and very distinguished career involving several
universities. From 1943 to1956 he was at Iowa State University, where he rose
through the academic ranks to become full professor in 1947. From 1949 to
1955 he was the head of the Chemistry Section of the Iowa Agricultural
Experiment Station. From 1955 to 1961 he was director and professor of the
Oceanographic Institute of Florida State University.

At the behest of the National Aeronautic and Space Administration (NASA) Dr.
Fox served as director of the Institute of Bioscience at Florida State
University from 1961 to 1964. And from 1964 to 1989 he was professor and
director of the Institute of Molecular and Cellular Evolution at the
University of Miami in Coral Gables, Florida.

Dr. Fox's first formal retirement was in 1977. Following his second
retirement in 1989, Sid departed Miami to become Distinguished Research
Professor in the Department of Plant Biology at Southern Illinois University
in Carbondale, Illinois. In 1993, the University of South Alabama was
fortunate to attract Sid, where he is now Distinguished Research Scientist in
the Department of Marine Sciences.

Sid has published numerous papers and books in the field of amino acid
sequencing and evolutionary biology. In fact, way back in the ancient days of
1945, Sid was a pioneer of amino acid sequence determination. Sid was also
the first to synthesize a protein by heating amino acids under conditions
found here on planet earth. Also, he was the first to show that these new
thermal proteins, when placed in water, would self-organize into a living
cell. More recently, he has demonstrated that this first protocell is also a
protonerve cell.

As a result of this historic work, people like Linus Pauling and Albert Szent
Gyorgyi, both Nobel Laureates, gave credit to Sid for pioneering the field of
molecular evolution. As a result of his monumental discovery of thermal
proteins and their self-organization into protocells and that these
protocells exhibit virtually all of the properties associated with life, Sid
was invited to lecture widely throughout the world. Even Pope John Paul II
and his advisors, on at least three separate occasions, invited Sid to the
Vatican to explain his work on the synthesis of cellular life in a test tube.

Dr. Fox has served on numerous national and international scientific boards
and has been the recipient of numerous honors.

It is with great pleasure and honor that I present to you one of the truly
great biologists of this century, my friend and colleague, Dr. Sidney Fox.


My Scientific Discussion of Evolution for the Pope and His Scientists

Sidney W. Fox, Ph.D.

On reading the open letter of October 1996 of Pope John Paul II to the
Pontifical Academy of Sciences (The Scientist May 12, 1997), I am struck by
his concern about "the subject of the origin of life and its evolution." This
shifts the emphasis from evolution only to papal mention of origin of life,
and its interdigitation with subsequent evolution.

My own contact with this question was to present for the first time a
scientific theory of origins to the Pope and the papal scientists as derived
from repeatable experiments. These occurred in 1984, 1985, and 1990, when I
was a guest of three groups in Rome, the trips being supported by Academia
Lincei, IBM, and the National Foundation for Cancer Research.

Why was Pope John Paul II interested in what I might say? I can think of
three main answers. The first is that, like anyone else, he is curious about
where he came from, or to put the question in its most ancient time frame,
what did he come from? Secondly, the Pope recognizes that, with forward
extrapolation, synthesis of primitive life in the lab is a natural equivalent
of Genesis in the Bible; as Pope he must therefore prepare for new arguments.
The third explanation is one I received in Rome from many scientists of
several faiths who surround and advise Pope John Paul II. This answer,
related to the second one, is that Pope John Paul II wants not to repeat the
mistake of the predecessor church who had excommunicated Galileo.

My round-trip to Rome from Miami was paid three times, each time to answer a
major question. I shook hands with the Pope on the first occasion in 1984.
After his stroll in the audience, he retired to the chairman's table at which
sat several of the organizing scientists. While I had special discussions
with the scientists after my presentations, the Pope, as I was informed, held
his own subsequent discussions with them. This indirect process was thorough
enough that, as I believe, Pope John Paul II and his associated scientists
have a far better grasp and more up-to-date awareness of natural genesis than
the funded scientists whom I know on this side of the Atlantic. There are
signs also that the most up-to-date awareness in the subject can be found
near Rome, in Padova, and Trieste especially. For me, these enjoyable
sessions relating research generously supported by NASA and others in 1960 to
1992 came twenty years after an earlier unpleasant and dramatic introduction
to the science-religion interface. In that 1963 encounter, I was on an
American Chemical Society lecture tour, speaking on how our group had
recently learned to make a kind of protein under terrestrial conditions that
existed before there were cells on Earth to make protein. In Colorado, on my
tour, I encountered a well-known professor of chemistry. I had respect for
this man through having read his papers on analysis of proteins. I found in
Colorado that he did not have respect for me and my claim to having made
protein-like molecules under conditions of the Earth. In the middle of my
lecture he rose in the audience and announced emotionally, "Only God can make
a protein!" He had to be led from the audience by a companion so the meeting
could continue. He evidently belonged to the 40 percent of scientists who
cling to some form of theistic religion.

In the first of my three lectures for the papal group, we considered
self-organization of matter into living beings. This process had been
predicted by the French Catholic scientist, Louis Pasteur, in an 1864 debate
in the
Sorbonne on what was then called spontaneous generation, Pasteur asked: "Can
matter organize itself? In other words are there beings that can come into
the world without parents, without ancestors? That is the
question to be resolved."

Figure 1. Cells from thermal protein. These figures are seen in a 1975 book
on Genetics by Winchester, fifth edition, 1000X. Laboratory protocells on
left. Staphylococcus aureus on right.

{The point here is that protocells are both the same size as a modern
bacteria and by external morphology indistinct from them as well.}

Similar pictures have appeared in hundreds of textbooks in U.S. and abroad.

Figure 2. Original cellular genesis in retracement taped by Mr. Randall
Grubbs. A large chunk of thermal protein (1000x) is contacted by warm 1.0%
sodium chloride solution. On cooling, protocells stream forth in less than
two minutes.

{This photo is taken from a video that was made showing microspheres forming
from thermal proteinoids.}

The right kind of matter to organize itself is known now as thermal protein,
protein made from amino acids on Earth by heat. This was first suggested
from the work of Alfonso Herrera of Mexico City in his laboratory of
Plasmogeny, where he showed in 1924 to 1942 how to make amino acids and
sulfobes, a kind of cell, under terrestrial conditions. This synthesis has
much more geological plausibility than that of the amino acids of Harold Urey
and Stanley Miller, which are produced in assumed atmospheres in closed
flasks, and which are much better known due to publicity.

{Two comments here. First, Fox is not saying that the Urey/Miller experiment
has no validity, but he is saying that amino acids can be made by thermal
processes **under current atmospheric conditions**. In other words, a
strongly reducing atmosphere as predicted by Urey and Miller may not have
been necessary to make amino acids, then proteinoids, then protocells.
Second, Fox's comment about publicity may help explain why his protocells are
far less well known than Urey and Miller's amino acids. Urey and Miller (or
their university) publicized the results, whereas Fox and his colleagues (or
his university) did not.}

The thermal amino acids also fit into a single thermal continuity. The second
step toward a cell after amino acids is the formation of protein. This is
where we came in, in a context of protein, not thinking at that time of this
as a stage of life's origin. As a young professor of protein chemistry, I
wanted to know if it were possible that amino acids such as had been produced
by Herrera, and later by Miller, could yield proteins on the primitive Earth
even before there were living cells to make protein. So we tried heating
amino acids, even though heat was known to decompose amino acids.

Figure 3. Heated amino acid mixture, sans glutamic and aspartic acid, on
left. Heated mixture containing glutamic and aspartic acid, on the right.

We learned that we could avoid the decomposition if we included in the
mixture to be heated a sufficient proportion of one or both of two amino
acids: aspartic acid and/or glutamic acid. The results of indiscriminate
heating is seen as a dark tarry mass in Figure 3. When only a small
proportion of these two amino acids is included we get an amber-colored
product. For years we thought the amber component contaminated the kind of
white product that professional polymer chemists obtain, such as in
styrofoam. In 1979, Dr. Klaus Dose and associates of Mainz, Germany, showed
that the amber color was due to flavin, formed by heating amino acids
together. We then remembered that flavins are significant in energy
metabolism of all cells; indeed riboflavin is standard in the human diet and
even in supplements in the drugstore. The experiments indicate that flavin
was there from the beginning.

{This in fact a recurring theme in abiogenesis: the ease and persistence
with which certain key biomolecules are made, regardless of the precise
method used to synthesize them.}

The main product of heating the amino acids is protein, so listed under
protein, subheading thermal, by Chemical Abstracts since 1972. The
nomenclature came into existence a year after a special report on existence
of characteristics common to protein and to thermal proteins was published in
Chemical and Engineering News.

The expectation of protein chemists, which we shared, is that thermal
protein, then called proteinoid, would be randomly disordered. What the
experiments and analyses showed is almost the opposite.

Figure 4. Nonrandom peptides from heated glutamic acid, glycine, and tyrosine
on top, from glutamic acid, alanine, and tyrosine below, and analyzed on
HPLC. Each is highly reproducible.

{The photos show HPLC chromatographs, each with a number of tall, narrow,
separate peaks above a horizontal baseline.}

In Figure 4 we see analyses of products of heating three amino acids
together. In the top the three amino acids are glutamic acid, glycine, and
tyrosine. These were separated on what is known as an HPLC apparatus. If the
products were random, we should observe a low-lying horizontal line. {That's
because no one peptide would be made in a large enough quantity to be
separately detectable from all the other peptides.} The nearly vertical
lines are individual thermal peptides, or thermal proteins. They represent
individual peptides. This nonrandom result is highly reproducible. If we
replace the amino acid glycine-G by another one, alanine-A, we get a similar
product that is perceptibly different. However, each of these analytical
pictures is highly reproducible.

{What Fox means is that if you use the same amino acids in the same
proportions you get virtually the same identical proteinoids every time. You
**do not** get different peptides everytime you do the experiment.}

The third lecture in Rome (1990) concerned restating that the arrangement of
amino acids in thermal polymers is and was orderly. After the papers
emphasizing that amino acides can order themselves with high precision when
heated, the Polish chairman expressed interest in seeing that DNA and RNA
were unnecessary. More recently than 1990, the leading investigators in the
RNA-first and DNA-first hypotheses acknowledged the uselessness of their
approaches. Francis Crick, famous for the DNA double helix for example,
stated in 1994, "The point about DNA is that it goes back not to the origin
of life." By 1993, a number of RNA-first investigators, for example James
Ferris, had made similar statements for RNA not being primary.

{So it would seem that even among rival researchers the fact of Fox's results
are beginning to have an influence.}

In each case the amino acids determine their own arrangements. No outside
agent such as RNA or DNA makes any difference during a heating process, as
the late Cyril Ponnamperuma showed in 1990. The possibilities with DNA and
RNA were the scheduled subject of my second paper for the papal scientists on
the visit to Rome in 1985. The papal scientists had arranged this as a debate
with a collegial friend from California, who at that time postulated nucleic
acids as arising first. He gave his talk in the morning, and left at noon to
visit someone elsewhere in Italy. As a result, the scheduled debate did not
follow my lecture in the afternoon. There was no debate then, as there is
none now.

{This last comment is hyperbole, but Fox's point is that his colleague never
pursued the issue even after the conference. Even among professional
scientists there can be the strong tendency to ignore a debate than admit to
being wrong.}

When brought into contact with water, all tested thermal polymers of amino
acids, without exception, have been found to organize themselves into cells,
as described in the 1984 meeting.

Figure 5. Growth of laboratory protocells from warm solution of 1% sodium
chloride at 60 Celius. Growth of cells can be followed at 1000X to numerous
units of size programmed by the individual polymer. Entire sequence requires
90 seconds.

Figure 5 illustrates both natural genesis and GROWTH.

{These photos were taken from the video mentioned earlier. Incidentally, 90
minutes is about the time many unicellular organisms take to reach full
growth before reproducing.}

Figure 6 is from Lehninger's 1975 textbook of Biochemistry. One sees one of
four known modes of REPRODUCTION of the protocell, that of budding as in

{And these daughter protocells will themselves grow to maturity, then
reproduce. Several generations can be observed to pass in a single day, as
with many unicellular organisms.}

Figure 7. X1000 upper right hand. Proteinoid microspheres from which the
interior has been leached. Duble layers left behind are durable. Lower left,
beginning of diffusion. Upper left, sliced Bacillus cereus.

In Figure 7 are several sliced microspheres. They have infrastructure
resembling that of natural cells. In the right hand micrograph are protocells
in water. The interior material has leached through the double-layered
boundary, which is itself very durable. In the lower left is shown how the
beginning of diffusion outward occurs. For comparison in the upper left is a
sliced modern bacterium, Bacillus cereus.

{You get the same result when you leach the contents of a red blood cell out,
leaving behind the plasma membrane (which is called a "ghost"). While not a
real plasma membrane, the microsphere boundary serves the same purpose, has
the same structure and is just a durable, strong evidence that microspheres
are true cells, if not fully modern.}

The list of the properties of these protocells as presented to the Pope in
the first meeting are in Table 1. At the bottom of the list you will notice
excitability. We had just begun to study the kind of RESPONSIVENESS to
stimuli that is followed by implanting microelectrodes into microspheres as
if they were nerve cells. By displaying growth, metabolism, reproduction, and
response to stimuli, the microspheres meet definitions of life in some
textbooks and in Webster's Dictionary.

{The American Heritage Dictionary as well.}

Table 1. Salient Properties of Proteinoid Microspheres

Synthetic, with P-O-P or ATP
For peptides
For polynucleotides

Protometabolic (Catalytic)

{I will explain what these terms mean in my essay.}

Figure 8 compares an action potential of the crayfish receptor neuron to an
action potention in one of our microspheres. {They are virtually identical.}
In trains of electrical spiking action potentials are beginning to have a
bedside flavor for a cardiology ward. Dr. Yoshio Ishima of the Tokyo Medical
School studied those displaying regular rhythm and said he could not
distinguish some from the recording of a heart. Hundreds of types of
microspheres made from thermal protein all exhibit electrical activity. The
principal ways in which the laboratory protocell meets the
definition of life in the dictionary are in displaying growth, metabolism,
reproduction and responsiveness in cells made by synthesis. By the process of
cellular engineering, we can do a more meaningful job of arriving at a
definition of life than by describing behavior of modern cells. This is a
theme in a recent book titled Defining Life edited by Professor Martino
Rizzotti of Padova, Italy, 1996.

In Figure 9 is a comparison of microfossils and laboratory microspheres, from
T. Berra's Evolution and the Myth of Creationism (Standford University Press,

{The point of which is that these microfossils may just help prove that
proteinoid microspheres were the first primitive life to emerge on the earth.}

One relationship of this work to religion lies in its providing a natural
description of Genesis. The Bible has supplied, for most people, answers to
questions that everyone asks. I think it was beautifully written for its
time. More than half of all scientists now prefer to explain genesis by
evolution rather than by revelation. Some of the scientific uncertainities in
the transmutation of species are overcome by retracing the primary conversion
of inanimate to animate as I have done here and to the Pope and to members of
the pontifical academies. The results are in hundreds of textbooks, and I am
informed that thousands of high-school students have repeated the main
experiments, in the vein of a most fundamental requirement of science:
repeatability. Our beautiful Bible is not up-to-date. It does not mention
microscopes or cells. Accordingly, it could not in its time honor
evolutionary theory, which is now a natural sequence from molecules to cells
to plants and animals, all in a synthetic direction.

At this point we leave the experiments to focus on interpretations, which are
more variable. Here we can cite Einstein (Clark, 1971) and in his wake Linus
Pauling and others. Although others have called him an agnostic or an
atheist, Einstein regarded himself in his later years as a disciple of Cosmic
Religion. He did not attend church or synagogue, but he made frequent
reference to a deterministic God, by which he clearly meant nature. There is
no doubt that he regarded nature with reverence. Determinism is common to
Einstein's view of science and to divine determinism. However, Einstein's
emphasis on determinism was opposed by most of the developers of the quantum
theory, a theory that he initiated. As I see it, our experimental results
support Einstein that everything is determined, the beginning as well as the
end. Einstein believed in a God who was, however, Spinoza's God. But
Spinoza's God was natural, not supernatural.

A Catholic leader of Einstein's time, Bishop Fulton Sheen, represented the
opposing point of view. In the early 1930s, Sheen said of an article written
by Einstein that it was the sheerest kind of "stupidity and nonsense. There
is only one fault with his (Einstein's) cosmical religion; he put an extra
letter in the word -- the letters 's'" To Einstein, what was cosmic was to
Sheen comical. Einstein focused on as fact what we find as a common principle
in both science and religion: determinism. Einstein did not regard
determinism as divine determinism, but due only to natural forces. In 1929 he
said: "Everything is determined, the beginning as well as the end, by forces
over which we have no control. It is determined for the insects as well as
the star. Human beings, vegetables, or cosmic dust, we all dance to a
mysterious tune intoned in the distance by an invisible piper." In this
statement, Einstein appears not only as a scientist but as a philosopher and
a poet.

{Not to mention an advocate of intelligent design, only for him it would have
been natural intelligence -- the intelligence of nature -- not supernatural

Einstein also said: "I believe in Spinoza's God who reveals himself in the
oderly harmony of what exists, not in a God who concerns himself with fates
and actions of human beings."

The words the famous philosopher, Benedict Spinoza, used to define God
(Ethics, 1677) were: "By God I understand a being absolutely infinite, that
is, a substance consisting of infinite attributes, each of which expresses
eternal and infinite essence."

In the 1600's, Spinoza could not involve chemistry as we know it to specify
"substance," because chemistry was yet in its alchemy days; amino acids were
unknown. I would like to be able to ask Spinoza if he would accept an
updating of his definition in which God is a family of substance (as has been
described) consisting of "infinite attributes." Or would he rather refer to a
single type of substance, thermal protein, from which infinite attributes
seem to flow? Certainly, we can see that what is new since Spinoza's time is
the cell as the sine qua non of all life, and the use of experimental
synthetic retracement to answer biological questions. And we propose to
replace Spinoza's undesignated "substance" by a family of substances of
defined constitution in a modern way, the amino acids, or perhaps by thermal
protein, which is itself already an article of biomedical research and
industry. In this offshoot, thermal proteins are a subject of more than one
hundred patents (Bahn and Fox, 1996) since 1990.

{And it would seem that Fox is an advocate of intelligent design as well, but
again the intelligence of nature through its agent the thermal proteinoid.}


While our experiments agree with Einstein's interpretations in the main, he
was a hard determinist, whereas the experiments lead me to a kind of soft
determinism. This thinking results from the belief that if Einstein had known
of thermal protein, he would have anticipated that thermal protein would be a
single substance.

If we honor thermal protein as the original progenitor, we must recognize
that it is not a single substance but rather a family of closely related
substances. This permits the act of selection. Some would cite this fact as a
basis for free will. Another interpretation, however, is that the whole range
of thermal proteins in one batch is determined. Since the substance thermal
protein is several substances, "free will" and determinism may both be rooted
in thermal protein.

The base in the whole picture is still molecular determinism, which is a kind
of molecular religion that extends into Einstein's cosmic religion. The same
May 12 issue of The Scientist in which the Pope's open letter is reprinted
contains a response of Dr. David S. Thaler which includes the statement that
"the next Galileo may be a microbiologist." In his letter the
Pope states that "theories considering the mind as emerging from the forces
of living matter...are incompatible with the truth about man." The fact that
the cells made from thermal protein behave as neurons indicates that this
problem exists now.

Finding thermal proteins was the product not of the usual hypothesis. It was
a testing of terrestrial conditions and substances. The experimenter did not
ask the experiments to check on hypothetical products; rather the experiments
talked to the obsever.

The development from thermal protein as mother substance is a rediscovered
advance. It calls to mind the rediscovered science of genetics. Gregor Mendel
published the results that are the basis of genetics in 1845. In the 1870's
and 1880's this advance was covered up by others. The rediscovery did not
occur util 1900, after Mendel's death.

In the case of protobiogenesis, the initial discovery reached a plane of
completion by 1971. The finding into the background lasted from the middle
70s until the middle 90s. In this subject the answer of the 1960's to 1970's
was subjugated to a presumed field that placed RNA-first and DNA-first center
stage and inadvertently covered up the earlier thermal


To initiate the discussion, Dr. Gottlieb asked the audience "Based on what
you heard tonight, how many of you now think that a living organism, a
protocell, has been synthesized artificially in a test tube from inanimate
material?" Approximately half the audience raised their hands.

The remainder of the audience divided their responses between the next two
questions: "How many of you do not think that a living organism, protocell,
was synthesized artifically in a test tube?" and "How many of you are
uncertain as to whether a living organism, protocell, was synthesized
artificially in a test tube?"

The discussion ensued from there and covered a variety of subjects including
determinism and free will.

The Harbinger symposium, "Religion & Science," was funded by a grant from the
Alabama Humanities Foundation, a state program of the National Endowment for
the Humanities.