Religion & Science
May 27, 1997
[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
From the dawn of recorded history we know that human beings have been asking 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 Fox.
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.
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.
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.
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. 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 in included we get an amber-colored product. For years we thought the amber component contaminated the kinf 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.
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.
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. 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.
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.
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.
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.
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 yeast.
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.
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.
Table 1. Salient Properties of Proteinoid Microspheres
Figure 8 compares an action potential of the crayfish receptor neuron to an action potention in one of our microspheres. 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, 1990)
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.
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.
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 18645. In 1970 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 initiial 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 proteins-first.
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.
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