Life in the Lab -- Proof of Concept (Long) Part 2
Tue, 11 May 1999 21:37:09 EDT

In this third part I will finish providing the evidence that demonstrates
that Fox has synthesized life in the lab.

As I've stated before, however, none of this would invalidate the fact that
Fox's protocells are alive. So at this point we should now examine the
evidence that should establish this. In his symposium to the Pope and his
scientific staff, Fox listed a number of protophysiological properties of
proteinoid microsphere protocells: electrotactism (the ability to sense an
electrical field), protometabolism (the ability to perform catalytic
reactions), aggregation (the ability to collect into colonies), protomobility
(the ability to move more or less at will), osmosis (the ability to absorb
material from the environment), permselectivity (the ability to selectively
pass materials across a semi-permiable barrier), fission (the ability to
break about into smaller functional units), protoreproduction (the ability to
create functional copies), conjugation (the ability to join and pass material
directly to another), protocommunication (the ability to pass information to
another) and excitability (the ability to generate and utilize energy,
especially electrical fields). Some research that establishes these
properties includes:

Masinovsky Z, Lozovaya GI, Sivash AA, Drasner M. "Porphyrin-proteinoid
complexes as models of prebiotic photosensitizers." _BioSystems_ 1989;
22(4):305-10 [This paper demonstrates that complexes of porphyrins like heme
and proteinoids are able to catalyze photochemical reactions, even when
biosynthetic porphyrin precursors were used.]

Vaughan G, Przybylski AT, Fox SW. "Thermal proteinoids as
excitability-inducing materials." _BioSystems 1987; 20(3); 219-23 [This
paper demonstrates that the portion of a mixed proteinoid-lipid microsphere
that the electrical activity of an excitable protocell is caused by the
proteinoids and not the lipids.]

Przybylski AT. "Excitable cell made of thermal proteinoids." _BioSystems_
1985; 17(4):281-8 [This paper demonstrates that proteinoid microsphere
protocells can have electrical properties such electrical polarization across
the membrane, electrical discharges, current-voltage characteristics,
negative resistence and even certain light characteristics.]

Matsuno K. "Electrical excitability of proteinoid microspheres composed of
basic and acidic proteinoids." _BioSystems_ 1984; 17(1):11-4

Przybylski AT, Stratten WP, Syren RM, Fox SW. "Membrane, action, and
oscillatory potentials in simulated protocells." _Naturwissenschaften_ 1982
December; 69(12):561-3 [This paper demonstrates that protocells have the
property of electrical potential.]

Matsuno K. "Self-sustaining multiplication and reproduction of microsystems
in protobiogenesis." _BioSystems_ 1981; 14(2):163-70 [This paper
demonstrates that not only can protocells reproduce, they can sustain it
through several generations.]

Ishima Y, Przybylski AT, Fox SW. "Electrical membrane phenomena in spherules
from proteinoid and lecithin." _BioSystems_ 1981; 13(4):243-51 [This paper
demonstrates that ceratin types of protocells exhibit electrical phenomena
resembling membrane and action potentials in natural excitable cells.]

Bahn PR, Fox SW. "Models for protocellular photophosphorylation."
_BioSystems_ 1981; 14(1):3-14 [This paper demonstrates that certain types of
protocells can convert light energy into chemical energy.]

Brooke S, Fox SW. "Compartmentalization in proteinoid microspheres."
_BioSystems_ 1977 June; 9(1):1-22 [This paper demonstrates that certain types
of protocells can create internal compartments that can pass materials
between them.]

Hsu LL, Fox SW. "Interactions between diverse proteinoids and microspheres
in simulation of primordial evolution." _BioSystems_ 1976 July; 8(2):89-101
[This paper demonstrates that protocells can absorb and utilize a variety of
proteinoids with different catalytic functions, both from their environment
and from other protocells.]

Fox SW, Hsu L, Brooke S, Nakashima T, Lacey JC Jr. "Experimental models of
communication at the molecular and microsystemic levels." _Int J Neurosci_
1972 April; 3(4):183-92 [This paper discusses the ability of microspheres to
associate, form junctions and pass endomicroparticles back and forth as a
model for intercellular communication.]

Fox SW, McCauley RJ, Montgomery P, Fukushima T, Harada K, Windsor CR.
"Membrane-like properties in microsystems assembled from synthetic
protein-like polymer." In Snell F, Wolken J, Iverson GJ, Lam J, eds.,
_Physical Principles of Biological Membranes_. New York:Gordon & Breach
(1969) pg. 417-30 [This paper explains how proteinoids have amphiphilic
properties that allow them to form biological membranes.]

For additional references, see Fox and Dose 1977.

Also in his symposium, Fox listed a number of protobiochemical properties of
proteinoid microsphere protocells: esterolysis (the ability to break ester
bonds), phosphatation (the ability to remove phosphate groups from
biomolecules), decarboxylation (the ability to remove CO2 groups from
biomolecules), peroxidation (the ability to use hydrogen peroxide to perfom
oxidation-reduction reactions), synthesis (the ability to create biomolecules
-- specifically peptides and polynucleotides using phosphate groups or ATP)
and photodecarboxylation (the ability to remove CO2 groups from biomolecules
using light energy). Some research that establishes these properties

Nakashima T, Fox SW. "Formation of peptides from amino acids by single or
multiple additions of ATP to suspensions of nucleoproteinoid microparticles."
_BioSystems_ 1981; 14(2):151-61 [The paper demonstrates that microspheres
made from lysine-rich proteinoids and acidic proteinoids can in the presence
of ATP synthesize small peptides and high-molecular-weight fractions of
substituted proteinoids.]

Nakashima T, Fox SW. "Synthesis of peptides from amino acids and ATP with
lysine-rich proteinoid." _Journal of Molecular Biology_ 1980 May;
15(2):161-8 [This paper demonstrates that an aqueous solution of lysine-rich
proteinoids can synthesis peptides from free amino acids and either ATP or

Lacey JC Jr, Stephens DP, Fox SW. "Selective formation of microparticles by
homopolyribonucleotides and proteinoids rich in individual amino acids."
_BioSystems_ 1979 March; 11(1):1-7

Lacey JC Jr, Yuki A, Fox SW. "Coprecipitation of thermal lysine-rich
proteinoids with polyribonucleotides." _BioSystems_ 1979 March; 11(1):9-17

Ryan JW, Fox SW. "Activation of glycine by ATP, a divalent cation, and
proteinoid microspheres." _Current Models in Biology_ 1973 December;

Junck JR, Fox SW. "Synthesis of oligonucleotides by proteinoid microspheres
acting on ATP." _Naturwissenschaften_. 1973 September; 60(9):425-7 [This
paper demonstrates that proteinoid microspheres can make small

Nakashima T, Fox SW. "Selective condensation of aminoacyl adenylates by
nucleoproteinoid microparticles (prebiotic-lysine-model system-genetic
code)." _Proceedings of the National Academy of Sciences USA_ 1972 January;
69(1):106-8 [This paper demonstrates that microspheres made from lysine-rich
proteinoids and polynucleotides can synthesize polymers of amino acids
cojugated with adenylates, which could serve as the bridge between
proteinaceous information and genetic information.]

Osterberg R, Orgel LE. "Polyphosphate and trimetaphosphate formation under
potentially prebiotic conditions." _Journal of Molecular Evolution_. 1972;

Wood A, Hardebeck HG. "Light enhanced decarboxylations by proteinoids." In
Rohlfing DL and Oparin AI, eds., _Molecular Evolution_. New York:Plenum
Press (1972) pg. 233-45

Rohlfing DL, Fox SW. "Catalytic activities of thermal polyanhydro-amino
acids." _Advances in Catalysis_ 1969; 20:373-418

Fox SW, Wang C-T. "Melanocyte-stimulating hormone activity on thermal
properties of amino acids." _Science_ 1968; 160:547-8 [This paper
demonstrates that proteinoids made from mixtures of amino acids that contain
the residues found in the active site of melanocyte-stimulating hormone
possess specific hormonal activity themselves.]

Hardebeck HG, Krampitz G, Wulf L. "Decarboxylation of pyruvic acid in
aqueous solutions by thermal proteinoids." _Archives of Biochemistry and
Biophysiology_. 1968; 123:72-81 [This paper demonstrates that acidic
proteinoids can remove carbon from pyruvate and convert it into acetate.]

Karmpitz G, Baars-Diehl S, Haas W, Nakashima T. "Aminotransferase activity
of thermal polylysine." _Experientia_. 1968; 24:140-2 [This paper
demonstrates that lysine-rich proteinoids can transfer amino groups between
pyruvate and alanine and between alpha-ketoglutarate and glutamate.]

Oshima T. "The catalytic hydrolysis of phosphate ester bonds by thermal
polymers of amino acids." _Archives of Biochemistry and Biophysiology_.
1968; 126:478-85

Rohlfing DL. "The catalytic decarboxylation of oxaloacetic acid by thermally
prepared poly-aminoacids." _Archives of Biochemistry and Biophysiology_.
1967; 118:468-74 [This paper demonstrates that basic proteinoids can remove
carbon from oxaloacetate and convert it to pyruvate.]

Usdin VR, Mitz MA, Killos PJ. "Inhibition and reactivation of the catalytic
activity of a thermal-amino acid copolymer." _Archives of Biochemistry and
Biophysiology_ 1967; 122:258-61 [This paper demonstrates that catalytic
proteinoids have very good enzyme-like behavior.]

Fox SW, Krampitz G. "The catalytic decomposition of glucose in aqueous
solution by thermal proteinoids." _Nature_. 1964; 203:1362-4

For additional references, see Fox and Dose 1977.

So, what conclusions can we draw from all this research? 1) Proteinoids have
amphiphilic properties (both polar and nonpolar character in the same
molecule but in different places); the microspheres they form are stable and
durable, have Gram-negative or Gram-positive character depending upon
composition, respond to osmotic gradients, form structured boundaries,
contain ultrastructures, are capapble of selective passage of molecules
through the boundary and are able to associate, form junctions and transfer
informational molecules between themselves. These are the properties of
cells, so proteinoid microspheres are cellular. See Fox and Dose 1977 for
more details.

2) Proteinoids possess a variety of enzyme-like catalytic activity; the
microspheres they form are able to integrate these individual activities to
form simple pathways that can breakdown molecules for energy, store the
energy in the form of other molecules, then use this energy to synthesize
macromolecules. These are the basic properties of metabolism, so proteinoid
microspheres possess metabolism. See Fox and Dose 1977 for more details.

3) Proteinoid microspheres are able to undergo fission and can bud off
microparticles that then grow into microspheres. Microspheres also have the
ability to propogate through these methods. These are the properties of
reproduction, so proteinoid microspheres are capable of reproduction. See
Fox and Dose 1977 for more details.

4) Proteinoid microspheres display the ability to control their movements,
which would be necessary for them to avoid danger or seek out concentrations
of proteinoid to grow and reproduce. This along with their ability to
respond to osmotic pressure suggests that they can react to external stimuli.
See Fox and Dose 1977 for more details.

Modern cells are cellular structures that possess an integrated metabolic
system, reproduce and respond to external stimuli; according to the
conclusions outlined above, proteinoid microspheres are also cellular
structures that possess an integrated metabolic system, reproduce and respond
to external stimuli. As such, it is valid to label proteinoid microspheres
as (proto)cells. (The qualifier recognizes that they are not modern cells,
but that they were probably the first original cells and that modern cells
could have evolved from them.)

The basic characteristics of life are cellularity, metabolism, reproduction
and response to external stimuli; according to the conclusions outlined above
proteinoid microspheres possess these basic characteristics. As such it is
valid to say that proteinoid microsphere protocells are alive.

However, proteinoid microspheres are not made from biotic processes, but from
abiotic processes, taking advantage of the ability of amino acids and
proteinoids to selectively self-assemble into nonrandom functional
structures. Furthermore, these abiotic processes can be reproduced in the
lab. Therefore, it is valid to say that proteinoid microsphere protocells
are living systems that have been abiotically synthesized in the lab.

So while I may have failed to prove that the consensus of the biological
community is that Fox synthesized life in the lab, I believe I have shown
that he in fact did exactly that.

Kevin L. O'Brien