The Unknown Force of Life

There is an eternal quest to answer this very question- What is the Nature of Life? There exists a prevalent philosophy which states that living organisms are fundamentally and inherently different from non-living matter because of the existence of some non-physical factor, some kind of distinct fluid or spirit which distinguishes living entities from non-living ones. Aristotle used the term entelechy for drawing a line between living and non-living entities. 3^rd Century Greek Anatomist Galen advocated that these spirits are essential for life. This view was widely accepted by ancient scientists, philosophers and the common people alike, as it was evident that there is a clear distinction between the matter of the organism and a certain sense of inner activity. This ancient school of thought was brought back to life during the Renaissance, a sort of scientific and cultural revolution between the medieval and modern times which was marked by the revival of focus on art and beginning of modern science. The nature of life, the property of being alive had always been a jigsaw puzzle for both philosophers and scientists. Descartes’s explanation was that an organism is nothing but a machine. He extended mechanistic theories to biological systems, something unprecedented for his time as biology wasn’t really considered a science like physics, chemistry or mathematics. Descartes termed animals and human bodies as automata which meant that it differed from a mechanical machine only in terms of its degree of complexity. There was fierce opposition towards extension of a mechanistic approach to biology as it could not explain concepts of movement, perception or free will which are essential to life. French philosopher Henri Bergson theorized the existence of an élan vital or an “impulse of life” which overcomes the resistance of inert matter in formulation of living bodies. An eminent French embryologist Hans Driesch revisited the Aristotelian philosophy and reemphasized the presence of an entelechy, an entity responsible for controlling organic processes.

It was a common postulate amongst physiological chemists of the nineteenth century that organic compounds are products of vital activity and therefore can only be formed in living organisms. Berzelius argued that chemistry can explain all reactions occurring even within living organism and that organic and inorganic processes differed merely in terms of complexity as put forth by Descartes. He believed that there indeed was a “vital force” but he stated that there was no such exclusivity to this force which made it the sole property of living matter, it was just that under the current circumstances it only existed in living organisms. Liebig, a contemporary of Berzelius, carried out extensive studies on chemical reactions occurring in plants and animals and reached a similar conclusion that a vital force was necessary because certain phenomena lacked a chemical explanation. The concept of vital force introduced by Berzelius and Liebig was not supposed to undermine a mechanistic explanation of biological phenomenon, rather just like motion of planets, moons and stars are governed by an invisible force called the gravitational force, analogously the movement and other acts of life are governed by an invisible force known originally as Lebenskraft or vis vitalis or simply Vital Force.

Let us take the example of fermentation, a simple chemical process which should be easily interpretable whether it is taking place inside a living organism or in a test tube. Schwann and Pasteur claimed that fermentation was an activity of living organisms and that it cannot be reduced to mere laboratory chemistry. Schwann, quite ironically, put forth the idea that cells simply make up a special environment in which ordinary matter exists in different concentrations. Pasteur by contrast described and demonstrated that fermentation was irreducibly a vital process which was in stark contrast to the theories put forward by people like Berzelius, Liebig and other chemists who believed that fermentation resulted from chemical agents and catalysts within cells.

While fermentation was a great victory for the vitalists, artificial synthesis of urea was for the rationalists. Urea is the major organic compound excreted by the kidneys. It was first extracted from urine by Hilaire-Marin Rouelle. In his 1828 paper titled Über künstliche bildung des Harnstoffs, i.e., ‘On the artificial formation of Urea’, Wöhler’s showed how his investigation had given him unexpected results. When he reacted ammonium chloride with potassium cyanate by heating the mixture, he got potassium chloride, an expected product and ammonium cyanate, also an expected product. But when he further heated the mixture, a new compound was formed. He tried to obtain the same compound by reacting various compounds like cyanic acid and ammonia, silver cyanate and ammonium chloride, lead cyanate and ammonia and mercury cyanate and cyanotic ammonia.

Wöhler discovered the properties of this new compound and found a peculiar similarity with that of urea. This similarity led him to perform comparative experiments with pure urea isolated from urine and the former crystallized unknown new compound. The results showed that both were identical compounds. Urea is nothing but a rearranged form of ammonium cyanate. This was Wöhler’s Eureka moment- he had pioneered the formation of an organic compound out of an inorganic compound in vitro. He was so overwhelmed that he wrote to his friend and teacher in Sweden, Jacob Berzelius stating that he couldn’t stop himself from telling him that he (Wöhler) had produced urea requiring neither kidneys nor any animal for that matter and that it was by no chemical means any different from urea of the urine which he had produced himself.

Although Wöhler gave artificial in vitro synthesis of urea, the mechanism for formation of urea in vivo remained unknown for another century. Schultzen and Nencki independently speculated that amino acids upon degradation give two cyanate groups, which then combine with ammonia produced from proteins to generate urea. Krebs and Henseleit studied the formation of urea in animals. In their experiments they discovered a surprising fact that if the medium used to incubate liver slices contained both ammonia and d-ornithine, then the yield of urea increased exponentially. They deduced that a cyclic process occurs in which a molecule each of ornithine, ammonia and CO₂ to form citrulline. Aspartate was then added to citrulline to form arginine which was then hydrolyzed to form urea with regeneration of ornithine.