The Importance of Sugars in Jacques Loeb (1916)
Until the end of the nineteenth century, most speculation about the origins of life was often fragmentary and philosophical. Sometimes it amounted to an idea expressed in a single paragraph within an article, or a fleeting intuition in part of a chapter in a book whose main subject was not the question of origins. Also, with a few exceptions, it was not yet really possible to conceptualize the physico-chemical mechanisms that might have contributed to the emergence of primitive forms of life, quite simply because of the limitations imposed by the knowledge available at the time.
This was so much the case that one might even sometimes feel a certain tenderness toward the apparent naïveté of the hypotheses discussed at the time, or toward the ferocity of debates over points that seem of little interest to us today.1.When this happens, it is important for today’s observer to keep in mind that this may be the very attitude future observers will have toward our own current speculations, which they may judge naïve in the light of new knowledge accumulated in the future.
As a result, we are still very far from being able to propose experimental work, and even further from successfully carrying out such experiments. Yet certain intuitions were already emerging concerning the primitive conditions of the Earth, the metabolism of the first organisms, or the possible mechanisms of organic synthesis.
Jacques Loeb and the Mechanistic Program
The book we will discuss here illustrates this wonderfully. Its title is The Organism as a Whole from a Physico-Chemical Viewpoint2.Jacques Loeb. The Organism as a Whole from a Physicochemical Viewpoint. New York: G. P. Putnam’s Sons, 1916, 379 pages. The book is available to read on the Internet Archive: https://archive.org/details/organismaswholef00loebrich/page/n3/mode/2up. It was published in August 1916 by the German-born American biologist Jacques (born Isaac) Loeb (1859–1924).
Loeb was then one of the major representatives of the so-called “mechanistic” program in biology, as opposed to the “vitalist” current, seeking to reduce vital phenomena to measurable physico-chemical processes. His work on tropism, artificial fertilization, and the “forced movements” of organisms formed part of a broader ambition: to show that life requires no vital principle distinct from ordinary matter.
In this work by Jacques Loeb, dating from 1916, the mechanisms behind the origin of life are only briefly alluded to across a few pages of a book whose subject is much broader. His ideas are nevertheless far from uninteresting, particularly in Chapter II, entitled: “The Specific Difference between Living and Dead Matter and the Question of the Origin of Life”3.The Specific Difference between Living and Dead Matter and the Question of the Origin of Life, pages 14 to 39, i.e. 26 pages..
Sugar as the Chemical Basis for the Construction of Life
In 1862, Louis Pasteur demonstrated the growth of brewer’s yeast and other fungi in a sterile solution containing 100 grams of water, 10 grams of crystallized sugar, 0.2 to 0.5 grams of ammonium tartrate, and 0.1 grams of ash from calcined yeast4.Louis Pasteur (1862). “Mémoire sur les corpuscules organisés qui existent dans l’atmosphère, examen de la doctrine des génération spontanées”, Annales de chimie et de physique, 3rd series, volume LXIV, page 106. The article is available to read on Gallica: https://gallica.bnf.fr/ark:/12148/bpt6k34805g/f105.item. He had thus shown that proteins or decomposing organic matter were not necessary for the appearance of new organisms.
For Jacques Loeb, this solution proved that sugars and a source of nitrogen — in the case above, in the form of ammonium tartrate — could serve as the basis for the synthesis of the main molecules necessary for life. To this he added that phosphates were required for the synthesis of nucleins. Loeb specified that organic acids could be formed from sugars and that, when combined with ammonia, these formed amino acids, which he called the “building stones” of proteins. According to him, “it is thus obvious that the synthesis of living matter centres around the sugar molecule”5.“It is thus obvious that the synthesis of living matter centres around the sugar molecule” (page 16)..
Where could this sugar come from, “which is a constituent of the majority of culture media and which seems a prerequisite for the synthesis of proteins in living organisms?”6.“Where then should the sugar come from, which is a constituent of the majority of culture media and which seems a prerequisite for the synthesis of proteins in living organisms?”.
This emphasis on sugars as the chemical foundation of life nevertheless reflects the still very incomplete state of biochemical knowledge at the beginning of the twentieth century. For example, the role of nucleic acids remained poorly understood, and the idea that they were the molecular support of biological information would only truly emerge in the middle of the century.
The Rejection of a Chlorophyll-Based Origin and Winogradsky’s Work
Chlorophyll might have seemed well suited, since plants use it to synthesize sugar from sunlight and the carbon dioxide contained in the air. But Jacques Loeb immediately dismissed this possibility: according to him, chlorophyll seemed more likely to be a product of life than the reverse7.“[…] it seems more natural to conceive of chlorophyll as a part or a product of living organisms rather than the reverse.” (page 16).
At the end of the nineteenth century, a Russian researcher, Sergei Winogradsky (1856–1953), discovered bacteria capable of forming the specific constituents of living matter from inorganic matter8.Sergei Winogradsky (1904). “Die Nitrifikation,” Handbuch der technischen Mykologie, Volume 3, pages 132–181 (50 pages). The article is available to read, in German, on the Internet Archive: https://archive.org/details/handbuchdertechn03lafauoft/page/132/mode/2up.
This observation seemed crucial to Jacques Loeb, who considered that all the organic matter such organisms needed for their growth could “exist on the planet before the appearance of life”9.“From this medium, which […] contains only constituents which could exist on the planet before the appearance of life, the nitrifying bacteria were able to form sugars, fatty acids, proteins, and the other specific constituents of living matter.” (page 17), that is, without depending on pre-existing organic matter produced by plants.
In addition to the “classical” oxidation of organic molecules — including sugars, but not only sugars — one could add, thanks to Winogradsky’s work, the oxidation of ammonia into nitrite (NH3 → NO2), the oxidation of nitrite into nitrate (NO3 → NO2), and the oxidation of hydrogen sulfide into sulfur (H2S → S), then into sulfate (S → SO4), as energetic metabolisms, drawing their sugars and starch from carbonates in solution or from CO2 in the air, “without the aid of chlorophyll”10.“These bacteria can only develop if CO2 from the air is admitted or when carbonates are present. For these organisms the CO2 cannot be replaced by glucose, urea, or other organic substances. Such bacteria must therefore possess the power of producing sugar and starch from CO2 without the aid of chlorophyll.” (page 20). He wrote:
“We may, therefore, consider it an established fact that there are a number of organisms which could have lived on this planet at a time when only mineral constituents, such as phosphates (PO4), K, Mg, SO4, CO2, and O2 besides NH3, or SH2, existed. This would lead us to consider it possible that the first organisms on this planet may have belonged to that world of micro-organisms which was discovered by Winogradsky. If we can conceive of this group of organisms as producing sugar, which in fact they do, they could have served as a basis for the development of other forms which require organic material for their development.”11.“We may, therefore, consider it an established fact that there are a number of organisms which could have lived on this planet at a time when only mineral constituents, such as phosphates, K, Mg, SO4, CO2, and O2 besides NH3, or SH2, existed. This would lead us to consider it possible that the first organisms on this planet may have belonged to that world of micro-organisms which was discovered by Winogradsky.If we can conceive of this group of organisms as producing sugar, which in fact they do, they could have served as a basis for the development of other forms which require organic material for their development.” (page 20).
The Decisive Role of Autocatalysis
According to Jacques Loeb, if living matter appeared, and continues to appear, from non-living matter, “it should one day be possible to discover synthetic enzymes which are capable of forming molecules of their own kind from a simple nutritive solution”12.“[…] it should one day be possible to discover synthetic enzymes which are capable of forming molecules of their own kind from a simple nutritive solution.” (page 38).
Jacques Loeb took up the suggestion made in 1898 by the Dutch chemist Jacobus van’t Hoff (1852–1911), according to whom it should be possible, with catabolic enzymes, to reverse the process and catalyze anabolic reactions from the products of the catabolic reaction13.Jacobus H. van’t Hoff (1898). “Über die zunehmende Bedeutung der anorganischen Chemie”, Zeitschrift für anorganische Chemie, Volume 18, Issue 1, pages 1–13 (13 pages). DOI: https://doi.org/10.1002/zaac.18980180102 .
That same year, in 1898, Arthur Croft Hill (1863–1947), a physician at the Royal Institute in London, discovered that enzyme-catalyzed hydrolysis did indeed seem to be reversible. By adding the enzyme maltase from yeast to a 40% glucose solution, Croft Hill apparently obtained an appreciable quantity of what he believed to be maltose14.Arthur Croft Hill (1898). “Reversible zymohydrolysis”, Journal of the Chemical Society, Transactions, Volume 73, pages 634–658 (25 pages). DOI: https://doi.org/10.1039/CT8987300634.
Three years later, Oskar Emmerling (1853–1933) was able to show that this was not maltose, but an isomer, isomaltose15.Oskar Emmerling (1901). “Synthetische Wirkung der Hefenmaltase”, Berichte der deutschen chemischen Gesellschaft, Volume 34, Issue 1 (Januar-April 1901), pages 600–605 (6 pages). DOI: https://doi.org/10.1002/cber.19010340199. Edward Frankland Armstrong (1878–1945), verifying Emmerling’s results in 1905, added the interesting fact that the enzyme maltase could not hydrolyze isomaltose16.Edward Frankland Armstrong (1905). “Studies on Enzyme Action.—VII. The Synthetic Action of Acids contrasted with that of Enzymes. Synthesis of Maltose and Isomaltose”, Proceedings of the Royal Society of London, Series B (Biological Sciences), Volume 76, no. 513 (9 November 1905), pages 592–599 (8 pages). The article is available to read on JSTOR: https://www.jstor.org/stable/80012.
Jacques Loeb then formulated a hypothesis already defended by Leonard Troland (1889–1932)17.We will soon devote a dedicated article to the very interesting work of Leonard Troland. two years earlier18.Leonard Thompson Troland (1914). “The Chemical Origin and Regulation of Life”, The Monist, Volume 24, no. 1 (January 1914), pages 92–134 (43 pages). The article is available to read on JSTOR: http://www.jstor.org/stable/27900476 — We will soon devote a dedicated article to the very interesting work of Leonard Troland., although he apparently had no prior knowledge of that work:
“This would lead to the idea that the enzymes in the cell also synthetize molecules of their own kind, or that, in other words, the synthetic processes in the cell are of the nature of autocatalysis.”19.“This would lead to the idea that the enzymes in the cell also synthetize molecules of their own kind, or that, in other words, the synthetic processes in the cell are of the nature of autocatalysis.” (see the footnote at the bottom of page 29).
Behind this idea of autocatalysis, a fundamental problem in theories of the origin of life was already taking shape: how can a chemical system acquire the capacity to reproduce itself and maintain its own organization? Long before contemporary models of autocatalytic networks, Jacques Loeb seemed to glimpse, like some of his contemporaries, the possibility of a continuity between chemical catalysis and biological reproduction.
Louis Pasteur, His Results, and Primitive Conditions
Criticizing overly general interpretations of Louis Pasteur’s results concerning the impossibility of spontaneous generation in the sugar solution mentioned above, he wrote:
“It is at least not inconceivable that in an earlier period of the earth’s history radioactivity, electrical discharges, and possibly also the action of volcanoes might have furnished the combination of circumstances under which living matter might have been formed.”20.“It is at least not inconceivable that in an earlier period of the earth’s history radioactivity, electrical discharges, and possibly also the action of volcanoes might have furnished the combination of circumstances under which living matter might have been formed.” (page 39).
In Jacques Loeb’s work, then, Louis Pasteur’s findings do not definitively close the question of the origin of life; rather, they reformulate its experimental conditions. The spontaneous generation of complex organisms is rejected, but the gradual emergence of organized chemical systems remains conceivable.
A Fundamental Distinction between Structures and Synthetic Chemical Processes
Jacques Loeb closed his chapter on the distinction between living and inert matter — and, incidentally, on the origin of life — by putting into perspective the work begun in 186721.Moritz Traube (1867). “Experimente zur Theorie der Zellenbildung und Endosmose”, Archiv für Anatomie, Physiologie und wissenschaftliche Medicin, Volume 87, pages 87–128 (42 pages). https://archive.org/details/archivfranatom1867berl/page/87/mode/1up by Moritz Traube (1826–1894), which Stéphane Leduc (1853–1939) would call “synthetic biology” in 190722.Stéphane Leduc. Théorie physico-chimique de la vie et générations spontanées, Paris, A. Poinat, 1910, 202 pages. https://archive.org/details/thoriephysicoc00leduuoft/page/n10/mode/1up, while Alfonso Herrera (1868–1942) preferred the term “plasmogeny.”[od_sitenode]Alfonso Luis Herrera. Nociones de Biologı́a, Imprenta de la Secretaria de Fomento, Mexico, 1903.[/od_sidenote]
Such work was multiplying at the time. It used what we would today call “chemical gardens” to reproduce mineral structures, often made of ferrocyanide salts, whose forms resembled those found in plants and other living organisms.
In the final paragraph of this second chapter, Jacques Loeb emphasized the “overwhelming difficulties” involved even in imagining the possibility of synthesizing proteins from CO2 and a source of nitrogen. Clearly, beyond the chemical aspect, the physical counterpart — that is, the production of a defined cellular structure — seemed to him less insurmountable:
“Attempts have repeatedly been made to imitate the structures in the cell and of living organisms by colloidal precipitates. It is needless to point out that such precipitates are of importance only for the study of the origin of structures in the living, but that they are not otherwise an imitation of the living since they are lacking the characteristic synthetic chemical processes.”23.“Attempts have repeatedly been made to imitate the structures in the cell and of living organisms by colloidal precipitates. It is needless to point out that such precipitates are of importance only for the study of the origin of structures in the living, but that they are not otherwise an imitation of the living since they are lacking the characteristic synthetic chemical processes.” (page 39).
Conclusion
To be sure, Jacques Loeb’s reflections remain very far removed from contemporary models of prebiotic chemistry. Nevertheless, they bear witness to an important transformation of the conceptual framework: the origin of life gradually ceased to be conceived as an essentially philosophical or religious — even metaphysical — problem, and became an experimental problem involving precise physico-chemical mechanisms that still had to be determined.
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