Re: Life in the Lab -- Proof of Concept (Long) Part 1

Moorad Alexanian (
Tue, 11 May 1999 09:25:26 -0400

Dear Kevin,

I have partially read you long message and must say that I am impressed with
your honesty and desire to find the truth. May I suggest that in addition to
searching for those who support Fox's contention, you must also search for
known, reputable scientists who are critical of Fox's work. This is not an
issue of science vs. creationism. This is a purely scientific question.

Take care,


-----Original Message-----
From: <>
To: <>;
Date: Tuesday, May 11, 1999 8:29 AM
Subject: Life in the Lab -- Proof of Concept (Long) Part 1

>In this second part I will describe the research that provides the basis
>the consensus among biologists that life has been synthesized in the lab.
>The references I will provide will by no means be complete, but they should
>be enough to not only verify the veracity of my claim, but to also provide
>anyone the basis for doing their own more extensive literature search.
>as I explained in the first part, while the significance this breakthrough
>has for abiogenesis in general or the origin of life on earth is not yet
>fully determined, it does serve as proof of concept that life can be
>abiotically from simpler chemicals.
>As I also pointed out in the first part, however, I have none of the types
>references that would be most convincing to certain key people. I wish I
>did, to be perfectly frank. It would have been wonderful to have been able
>to report that _Nature_, _Science_ and _Scientific American_ all ran news
>reports and major articles describing how scientists in some lab had
>announced that they had synthesized life, or to provide references to _New
>York Times_, _Newsweek_ and _Time_ articles with screaming headlines like
>"ARTIFICIAL LIFE MADE IN LAB". Neither can I provide the kinds of
>that Brian asked for, even though I looked for them. Outside of
>popularizations, as far as I know no biologist or chemist has claimed in
>textbooks, reference books or journal articles that life has been
>in the lab, even though that is the general consensus. The reason of
>is very simple: most scientists are cautious about making bold claims and
>even more cautious about accepting them. What I have found, however, are
>books and articles like the one authored by Fox that Brian quoted from,
>seem to endorse the consensus without actually stating it or claiming that
>is true. If one reads between the lines the endorcement is obvious, but
>make any explicit claims.
>For example, Albert L. Lehninger describes Fox's work in the 1970 edition
>his textbook _Biochemistry_ on pages 782 to 785. Though Lehninger never
>quite states that they are alive, it is clear from his theoretical
>that even as early as the late Sixties Fox's proteinoid microspheres were
>being recognized as possibly being alive. I was taught about Fox's
>protocells in my undergraduate biochemistry classes in the early Eighties;
>professors accepted that they were at least technically alive. Stephen F.
>Mason, a chemist, reported in his book _Chemical Evolution_
>Press (1991)] that Fox's proteinoids could form microspheres that had
>"proto-cellular attributes" (pg. 244) such as reproduction and enzymatic
>activity (pg. 251); his discussion is matter-of-fact and distinctly
>uncritical, though he does not himself claim that the microspheres are
>genuinely alive. In his book _Evolution and the Myth of Creationism_
>M. Berra (a biologist) all but agrees with Fox that his microspheres are
>alive (pg. 75). And so on. Again, no one that I could find actually comes
>right out and says that Fox synthesized living cells in his lab, but nearly
>all who discuss it appear to accept it.
>So why do I claim that there is a consensus among biologists that life has
>been synthesized in the lab, if I cannot produce even one citation that
>supports such a claim? That in and of itself is an interesting story. I
>shall try to be brief.
>Early last year, I was approached by Sheldon Gottlieb, a retired biologist
>formerly of the University of Southern Alabama, to join his team that was
>working on writing a response to _The Creation Hypothesis_, edited by J. P.
>Moreland [Downers Grove, IL:InterVarsity Press (1994)]. He specifically
>wanted me to critique the chapter "Information and the Origin of Life" by
>Walter L. Bradley (an engineer and materials scientist) and Charles B.
>Thaxton (a chemist). After reading the chapter I declined, not because I
>found their arguments unassailable (they had in fact made a number of
>fundamental biochemical errors), but because their position was ultimately
>based on information theory, something I knew nothing about. I informed
>Gottlieb of this and included the statement, "Even if in the next three
>months [the time before his writing deadline] I could manage to create life
>in the lab, it would be no serious objection to their basic argument." He
>responded, in part, to say that Fox had in fact succeeded in making life in
>the lab.
>At the time I was familiar with Fox's work and I had read some of his early
>papers, but all I remembered were his proteinoids. So I told Dr. Gottlieb
>that Fox's proteinoids were simply random polymers of amino acids without
>catalytic activity and that they did not constitute living organisms. He
>responded by reminding me that they formed microspheres, then informing me
>that the microspheres had catalytic activity, that they could reproduce,
>could convert light into usable chemical energy and they could react to
>external stimuli. He concluded by saying that the general consensus among
>biologists was that Fox's microspheres were alive and could be considered
>true protocells.
>What he said sounded fantastic to me, so I simply responded by advising him
>not to do a biological refutation of the chapter, but to get someone who
>information theory, preferably a biological theorist. He thanked me for my
>advice and we have not been in touch since. However, what he said about
>intrigued me, so I began to pursue it. I started by contacting all the
>biologists I knew to ask them what they thought of Fox's work. I have to
>admit that most of them were even less familiar with it than I was, but
>those who did know of it they agreed that Fox had synthesized life in the
>lab. Every one of them, without dissent. That in and of itself made me
>leery, so I broadened my scope to include textbook authors and college
>professor that I did not know. This time nearly everyone whom I contacted
>was familiar with Fox's work. There were a handfull that were unimpressed
>and preferred the theories advanced by those who advocated the primacy of
>nucleic acids over amino acids as the intitial abiotic carriers of
>information, or the metabolic theories of Morowitz, but the majority
>virtually without reservation that Fox's microspheres were living
>At this point most of you may be expecting me to reproduce a list of these
>people to satisfy Brian's request, but I will not for two reasons. First
>all, most of these people refused to allow me to do so, saying that they do
>not want to get involved in a debate with creationists. Secondly, however,
>these were personal correspondences, not publications, so it would be
>impossible for anyone to independently verify the truth of my claims
>contacting my correspondents directly. I want to keep these people
>and I'm afraid I would alienate them if they each received a dozen requests
>for verification.
>Besides, as I explained in an earlier post, what matters is not how many
>people claim that life has been synthesized in the lab, but whether their
>claim can be supported by the scientific evidence. Hence late last year I
>started doing an intense literature search for all papers on protocells,
>proteinoid microspheres and Fox's work. It is by no means finished, and I
>have only begun to read all this literature, but what I have so far
>discovered convinces me that the consensus among biologists is correct.
>To start off, let me give a list of books and review articles, then I'll
>on to the critical references. First the books:
>Sidney Fox. _The Emergence of Life: Darwinian Evolution From the Inside_.
>New York:Basic Books (1988) ISBN: 0465019250
>Sidney W. Fox and Klaus Dose. _Molecular Evolution and the Origin of
>Revised Edition. New York:M. Dekker (1977) ISBN: 0824766199
>Duane L. Rohlfing and A. I. Oparin, editors. _Molecular Evolution:
>Prebiological and Biological_. New York:Plenum Press (1972)
>Sidney W. Fox, editor. _The Origins of Prebiological Systems and Their
>Molecular Matrices_. New York:Academic Press (1965)
>The first is the one Brian quoted from in his post; I have not seen it, but
>from what I have heard of it, it sounds like a popularization. As such a
>more scientifically rigorous book (that I have seen) would be the second
>of which there is also an earlier edition (1972). It contains a general
>discussion of the question of whether protonoid microsphere protcells are
>actually a primitive synthetic organism or simply represent plausible
>evolutionary precursor (pg. 250-2). The general conclusion was, first of
>all, "that proteinoid microspheres are *not* contemporary organisms
>in original]." Secondly: "The essential defensible statement is that the
>proteinoid microsphere is a plausible, or the most plausible, model for the
>evolutionary precusor of the contemporary cell." Then later they said, "A
>perhaps fuller assertion of the same kind is one that a proliferative (page
>214) protoorganism has been synthesized in the laboratory." Fox and Dose
>were confident that the experiments that had been done up to that time
>"demonstrated that some of the evolutionary gap between the primordial and
>contemporary cell has been bridged." In the summary of their chapter
>"Interpreting Experiments: Proteinoid Microsystems" (pg. 241-67) they
> "The unit of contemporary life is the cell. The unit of primitive life,
>back-extrapolation, was the protocell." And in a flowchart of the
>stages of molecular evolution and the origin of life (pg. 350) they label
>formation of protoproteinous cells as the beginning of primitive life (in
>same chart they label the development of internal synthesis of coded
>macromolecules as the onset of contemporary cellular life). All of this
>would indicate that Fox and Dose accept that proteinoid microsphere
>protocells are living systems, even if they qualify that acceptance with
>terms as "proto-" and "primitive". From this general discussion, however,
>they use those terms to avoid the mistaken impression that protocells are
>indistinguishable from modern contemporary cells.
>The third and the fourth books are worth a look if as much for a historical
>perspective as for scientific information. The third is a volume
>commemorating the sixtieth birthday of Sidney W. Fox, the fourth contains
>proceedings of the second of a series of meetings on the origin of life.
>These books should be available through interlibrary loan if they are not
>your local library system.
>The review articles (including letters and "editorials") follow. (Some of
>these I haven't read yet, so I cannot vouch for their relevence.)
>Fox SW. "My Scientific Discussions of Evolution for the Pope and His
>Scientists." _The Harbinger_ 1997 May-June; 15(15):1. Accessible at
><> [In
>paper, Fox openly claims that he indeed created a living cellular system in
>his lab, though again he is careful to explain that it is not a modern
>cellular system.]
>Fox SW. "Thermal synthesis of amino acids and the origin of life."
>_Geochimica et Cosmochimica Acta_ 1996; 59:1213-4
>Pappelis A, Fox SW. "Thermal peptides as the initial genetic system." In
>Chela-Flores J and Raulin F, eds, _Chemical Evolution: Physics of the
>and Evolution of Life_. Dordrecht:Kluwer Academic Publishers (1996) pg.
>Fox SW, Bahn PR, Pappelis A, Yu B. "Experimental retracement of
>origin of an excitable cell: Was it predictable?" In Chela-Flores J and
>Raulin F, eds, _Chemical Evolution: Physics of the Origin and Evolution of
>Life_. Dordrecht:Kluwer Academic Publishers (1996) pg. 21-32
>Pappelis A, Fox SW. "Domain protolife: protocells and metaprotocells
>thermal protein matrices." In Ponnamperuma C and Chela-Flores J, eds,
>_Chemical Evolution: Structure and Model of the First Cell_.
>Dordrecht:Kluwer Academic Publishers (1995) pg. 129-32
>Fox SW, Bahn PR, Dose K, Harada K, Hsu L, Ishima Y, Jungck J, Kendrick J,
>Krampitz G, Lacey JC Jr, Matsuno K, Melius P, Middlebrook M, Nakashima T,
>Pappelis A, Pol A, Rohlfing DH, Vegotsky A, Waehneldt TV, Wax H, Yu B.
>"Experimental retracement of the origins of the protocell: It was also a
>protoneuron." In Ponnamperuma C and Chela-Flores J, eds, _Chemical
>Evolution: Structure and Model of the First Cell_. Dordrecht:Kluwer
>Academic Publishers (1995) pg. 17-36
>Pappelis A, Fox SW. "Domain protolife: The protocell theory." In
>BF, Kurganov BI, Kritsky MS and Gladilin KL, eds, _Evolutionary
>and Related Areas Physicochemical Biology_. Moscow:Bach Institute of
>Biochemistry and ANKO (1995) pg. 151-9
>Pappelis A, Fox SW, Papagiannis MD. "Protocell and metaprotocells of the
>Protolife Kingdom." _Illinois State Academy of Science_ 1993;
>Fox SW. "Synthesis of life in the lab? Defining a protoliving system."
>_Quarterly Review of Biology_ 1991 June; 66(2):181-5 [In this paper, Fox
>again argues that proteinoid microsphere protocells are representatives of
>"(_proto_) living organisms" (pg. 182) and he continues to use the
>"proto-" and "primitive". However, he also more freely refers to his
>protocells as "organisms" and "cells" without qualifiers, and he asserts
>(pg. 181): "The 'synthesis' of an organism in the lab holds special
>significance as an affirmation of cell analysis....Such verification is an
>extension to cellular science from organic which synthesis
>bioorganic compounds is a traditional confirmation of the analysis by
>chemists of the chemical structure of a natural compound." This is also
>my knowledge) the first time he specifies the criteria he will use to
>that his protocells are alive: metabolism, cellularity, reproduction and
>growth, and response to external stimuli. He even quotes critics who admit
>that (except for the lack of a genetic system) they would willingly accept
>that his protocells are alive because they demonstrate metabolism, growth
>reproduction. Even so, he still does not come right out and claim that he
>synthesized life in the lab. I therefore believe that this paper
>a transition in his thinking based on the accumulating evidence from his
>cautious position in 1977 to his bolder claims in 1997.]
>Fox SW. "Molecular selection and natural selection." _Quarterly Review of
>Biology_ 1986 September; 61(3):375-86
>Fox SW. "Self-sequencing of amino acids and origins of polyfunctional
>protocells." _Orig Life_ 1984; 14(1-4):485-8 [This article discusses the
>information content of proteinoid microsphere protocells.]
>Fox SW, Nakashima T, Przyblyski A, Syren RM. "The updated experimental
>proteinoid model." _International Journal of Quantum Chemistry_ 1982; QBS
>Fox SW. "How many theories for the origin of (proto)life?" in Srinivasan
>ed., _Biomolecular Structure, Conformation, Function and Evolution_.
>Oxford:Pergamon Press (1981) pg. 643-6
>Fox SW. "A model for protocellular coordination of nucleic acid and
>synthesis." in Kageyama M, Nakamura K, Oshima T, Uchida T, eds., _Science
>and Scientists_. Tokyo:Japan Science Society Press (1981) pg. 39-45
>Fox SW. "From inanimate matter to living systems." _American Biology
>Teacher_ 1981; 43(3):127-35, 140
>Matsuno K. "Material self-assembly as a physiochemical process."
>_BioSystems_ 1981; 13:237-41
>Fox SW. "Life from an orderly cosmos." _Naturwissenschaften_ 1980
>67(12):576-81 [This article ties in the nonrandomness of thermal
>with the order seen in the universe and discusses how this is a reflection
>the second law of thermaldynamics "on a cosmic scale".]
>Fox SW. "Metabolic microspheres: origins and evolution."
>_Naturwissenschaften_ 1980 August; 67(8):378-83 [This article discusses the
>catalytic activity of proteinoid microspheres as a model for the evolution
>Fox SW, Nakashima T. "The assembly and properties of protobiological
>structures: the beginnings of cellular peptide synthesis." _Biosystems_
>1980; 12(3-4):155-66 [The research that forms the basis for this proposal
>in Nakashima T, Fox SW. "Synthesis of peptides from amino acids and ATP
>lysine-rich proteinoid." _Journal of Molecular Evolution_ 1980 May;
>Fox SW. "The origins of behavior in macromolecules and protocells."
>_Comparative Biochemistry and Physiology_ 1980; 67B:423-36
>Fox SW. "Organic microstructures and terrestrial protocells."
>_Naturwissenschaften_ 1977 July; 64(7):380-1
>Fox SW. "Bioorganic chemistry and the emergence of the first cell." In
>Tamelan EE, ed., _Bioorganic Chemistry_. New York:Academic Press (1977)
>Fox SW. "The evolutionary significance of phase-separated microsystems."
>_Orig Life_ 1976 January; 7(1):49-68 [This article discusses how proteinoid
>microspheres can serve as a models for the cell and the protocell.]
>Fox SW> "Stereomolecular interactions and microsystems in experimental
>protobiogenesis." _BioSystems_ 1975 July; 7(10):22-36
>Fox SW. "Looking forward to the present." _Biosystems_ 1975 March;
>Fox SW. "Origins of biological information and the genetic code." _Mol
>Biochem_ 1974 April 15; 3(2):129-42
>Fox SW, Jungck JR, Nakashima T. "From proteinoid microsphere to
>cell: formation of internucleotide and peptide bonds by proteinoid
>particles." _Orig Life_ 1974 January-April; 5(1):227-37
>Fox SW. "The proteinoid theory of the origin of life and competing ideas."
>_American Biology Teacher_ 1974; 36:161-72, 181
>Fox SW. "Origin of the cell: experiments and premises."
>_Naturwissenschaften_ 1973 August; 60(8):359-68
>Fox SW. "Molecular evolution to the first cells." _Pure Appl Chem_ 1973;
>Hsu LL, Brooke S, Fox SW. "Conjugation of proteinoid microspheres: a
>of primordial communication." _Current Models in Biology_ 1971; 4:12-25
>Fox SW. "Self-ordered polymers and propagative cell-like systems."
>_Naturwissenschaften_ 1969 January; 56(1):1-9
>Fox SW. "Spontaneous generation, the origin of life, and self assembly."
>_Current Models in Biology_ 1968 November-December; 2(5):235-40
>Now something I'm sure you've noticed is that Fox is the sole author on the
>vast majority of these papers and a coauthor on all of them save one. The
>reason, however, is quite simple. Of all the candidates for synthesized
>in the lab, including self-replicating molecules and enzymatic RNA
>the one with the strongest case are the proteinoid microspheres. Other
>people have investigated them, and I will discuss their work shortly, but
>made the major effort; in fact, he devoted virtually the whole of the last
>years of his career to trying to understand them and their implications for
>life in general and abiogenesis in particular. As the acknowledged expert,
>it should be no surprise that he wrote the majority of the papers dealing
>with them.
>What might be a surprise is why so few have followed up on his research.
>reason may involve a combination of three factors. The first is that Fox
>his colleagues seemed to investigate them so thoroughly that many
>may feel that there is little new to discover. There is also the fact that
>certain experiments need only be replicated so many times before everyone
>comes to believe the results are real and so stop replicating them simply
>verify their reality. Since the general biological consensus is that
>proteinoid microsphere protocells are alive, there is little need for
>to continue to verify that. Instead, most of the people who investigate
>do so to try to find medical or industrial uses for them, not to understand
>them or abiogenesis.
>The second factor is that, while most of his colleagues appear to have
>accepted that his protocells were alive, as Brian has pointed out most of
>them did not accept that they had much of anything to do with abiogenesis
>the origin of life on earth. They were investigating their own ideas, so
>they were rivals -- friendly, cooperative rivals who valued and respected
>each others' work, but rivals nonetheless. As a result, they probably
>convinced succeeding generations of biologists that Fox's protocells were
>little more than an interesting sideline or even a complete deadend. Fox
>himself has pointed this out, with regard to the RNA-first and DNA-first
>concepts. And why would anyone investigate a deadend when they could
>more fruitful avenues? (In point of fact, I do not believe that Fox's
>protocells are a deadend, but that is a different topic from the one we are
>currently discussing. Besides, more of the current generation of
>appear to be abandoning the genetic-code-first concepts for the
>concept of thermal proteinoids.)
>The third factor is somewhat like the second. Nearly all of Fox's
>are dead now, and unfortunately with them went their own concepts, for much
>the same reasons as for Fox's protocells. Their critique of each others'
>work as having little or no relevence to abiogenesis may have worked too
>well, so that most contemporary biologists have largely rejected their
>specific concepts in favor of more exotic ideas. However, it is
>that whereas many seem now to be concentrating on protocells composed
>of amphiphilic molecules, they still accept the fundamental precepts
>established by Fox: the first life must be cellular; information in the
>of proteins and metabolism preceeded a genetic code; and the key
>must be capable of self-assembly.
>This should not, however, be misconstrued to believe that no one is
>investigating proteinoid microsphere protocells in terms of abiogenesis.
>Southern Illinois University in Carbondale is the Thermal Protein Study
>( headed by Aristotel Pappelis and Donald Ugent.
>Also, Duane L. Rohlfing of the University of Southern Carolina continues to
>do research in proteinoids. The names of additional researchers can be
>which is a publication and abstract listing for the 1994 American Chemical
>Society Symposium on the Origin of Life. They include such scientists as
>C. Steven Sikes of the University of Southern Alabama;
>K- Harada of Shoin Women's University, Japan;
>Klaus Dose of Gutenberg University, Germany;
>Paul Melius of Auburn University, Alabama;
>Koichiro Matsuno of the Nagaoka University of Technology, Japan;
>Peter R. Bahn of Bahn Biotechnology Co.;
>R.M. Ottenbrite of the Virginia Commonwealth University;
>Alexander T. Pol of the College of Engineering, University of Miami;
>R. Rosen of Dalhousie University, Halifax, Nova Scotia; and
>Etsuo Kokufuta of the Institute of Applied Biochemistry, University of
>Tsukuba, Japan
>I will post the third and last part when I know this one has propogated.