MYTH 7

THAT FRIEDRICH WÖHLER’S SYNTHESIS OF UREA IN 1828 DESTROYED VITALISM AND GAVE RISE TO ORGANIC CHEMISTRY

Peter J. Ramberg

The Wöhler synthesis is of great historical significance because for the first time an organic compound was produced from inorganic reactants. This finding went against the mainstream theory of that time called vitalism which stated that organic matter possessed a special force or vital force inherent to all things living. For this reason a sharp boundary existed between organic and inorganic compounds.

—Wikipedia, “Wöhler Synthesis” (2014)

In the early nineteenth century … many scientists subscribed to a belief that compounds obtained from living sources possessed a special “vital force” that inorganic compounds lacked. This notion, called vitalism, stipulated that it should be impossible to convert inorganic compounds into organic compounds without the introduction of an outside vital force. Vitalism was dealt a serious blow in 1828 when German chemist Friedrich Wöhler demonstrated the conversion of ammonium cyanate (a known inorganic salt) into urea, a known organic compound found in urine.

Over the decades that followed, other examples were found, and the concept of vitalism was gradually rejected. The downfall of vitalism shattered the original distinction between organic and inorganic compounds.

—David Klein, Organic Chemistry (2012)

In 1828, Friedrich Wöhler (1800–1882) published a short article in which he described the unexpected formation of urea from ammonium cyanate. The appearance of urea as a product was entirely unexpected, because theory predicted that cyanic acid and ammonia should produce a compound with the properties of a salt. Urea was not a salt, and it did not possess any of the properties expected for cyanates.1 In the article, Wöhler repeatedly noted the novelty of the artificial synthesis, but he and his mentor, the well-known Swedish chemist Jöns Jakob Berzelius (1779–1848), were most intrigued by the formation of a nonsalt from a salt, and that ammonium cyanate and urea had the same elemental composition. Neither Wöhler nor Berzelius commented, as the epigraphs might suggest, on how the synthesis influenced the doctrine of vitalism, but within a few decades, chemists came to regard Wöhler’s experiment as an “epochal” discovery that would mark both the death of vitalism and the birth of organic chemistry as a subdiscipline of chemistry. The myth has proved remarkably enduring—a survey of modern organic chemistry textbooks has revealed that 90 percent of them mention some version of the Wöhler myth.²

The urea myth can be conveniently condensed into three components: (1) that Wöhler synthesized urea from the elements, (2) that the synthesis unified organic and inorganic chemistry under the same laws, and (3) that the synthesis destroyed, or at least weakened, the idea of a “vital force” in living organisms. As historians have extensively documented, however, each of these three parts is highly problematic. First, Wöhler’s synthesis could be, and was, rejected as artificial, because there may have been a residual “vital force” in his starting materials. Second, well before the urea synthesis, chemists had operated under the assumption, promoted by Berzelius, that organic and inorganic chemistry should follow the same laws of chemical combination. Third, “vitalism” was not a single theory but a variety of related ideas about the nature of life that continued well after Wöhler’s synthesis in both chemical and biological contexts.

Inorganic Starting Materials?

For more than a century after Wöhler’s synthesis, chemists and historians generally assumed that the synthesis was in fact “from the elements,” and therefore completely artificial. In 1944, the chemist-historian Douglas McKie (1896–1967) argued that Wöhler’s synthesis could never have sounded the “death-knell” for vitalism because his starting materials were actually derived from organic sources, and he had therefore not made urea directly from the elements. McKie concluded that “those who believe Wöhler drove vitalism out of organic chemistry will believe anything.” According to McKie, the first total synthesis from the elements was achieved by Hermann Kolbe (1818–1885), who successfully made acetic acid from coal in 1845.3 Until the mid-1960s, historians and chemists debated whether Wöhler had completed a “total” synthesis, but by 1970 it seemed clear that it was extremely difficult to establish whether or not Wöhler had made urea directly “from the elements.”⁴ The ambiguity surrounding the definition of “artificial” synthesis does not necessarily refute this component of the myth, but neither does it provide much support for it.

Unified Chemistry?

In the first decades of the nineteenth century, chemists were unclear about the nature of organic compounds and uncertain about whether they could be made artificially. This uncertainty does not mean, however, that chemists were without methods for investigating organic compounds as chemicals following the laws of chemical combination. Already in the 1780s Antoine Lavoisier (1743–1794) had demonstrated that compounds isolated from living things consisted mostly of the elements carbon, hydrogen, and oxygen. In the first decades of the nineteenth century, chemistry was strongly influenced by the newly discovered phenomenon of current electricity and the new theory of atomism developed by John Dalton (1766–1844). These two developments led Berzelius to his theory of electrochemical dualism, in which inorganic compounds consisted of positively and negatively charged pieces held together by electrostatic attraction. Berzelius’s theory worked well for inorganic compounds, and because they existed in a wide variety of simple combinations of many different elements, it was thought that the composition itself caused the chemical properties of the compound. But this theoretical framework did not seem to hold for organic compounds. Because carbon, hydrogen, and oxygen could combine to form so many different compounds, it appeared that composition alone could not account for the properties of each compound.

Despite these difficulties, chemists largely agreed that organic and inorganic compounds would follow definite laws of chemical combination. During the 1810s, for example, Michel Eugène Chevreul (1786–1889) closely studied the chemistry of naturally occurring fats and oils.5 Chevreul separated animal fats into distinct compounds and determined that they had a definite composition, and that each fat consisted of a combination of glycerin with three large-molecular-weight fatty acids. Highly admired at the time, Chevreul showed that fats, like inorganic compounds, were subject to systematic chemical analysis and obeyed definite laws of chemical combination.⁶

Also in the 1810s, Berzelius became the champion of Daltonian atomism, consolidating the principles by which atomic combining proportions could be calculated. Berzelius had long thought that organic and inorganic chemistry should follow the same laws of combination, and in 1814 he turned explicitly toward organic chemistry, writing the following:

It is evident that the existence of determinate proportions in inorganic bodies leads to the conclusion that they exist also in organic bodies; but as the composition of organic bodies differs essentially from that of those which are inorganic, it is clear that an essential modification must exist in the application of these laws to these two different classes of bodies.⁷

To show that organic compounds followed consistent laws of chemical combination, Berzelius developed techniques to determine the proportion of carbon, oxygen, and hydrogen atoms in pure organic compounds, finding that each consistently gave the same proportion of elements. He concluded that organic compounds could be interpreted in terms of the atomic theory and had definite measurable combining proportions, as did inorganic compounds.8

In his comprehensive and influential book Essay on the Theory of Chemical Proportions (1819), Berzelius argued simply that the combining proportions of the elements in organic compounds were more complex than were those in inorganic compounds.⁹ Believing that inorganic chemistry could serve as an analogy for understanding the composition of organic compounds, Berzelius argued that his law of electrochemical dualism should also apply to organic compounds.¹⁰ The principal stumbling block for the synthesis of organic compounds was therefore not ignorance of a different kind of chemical force that held organic compounds together but the complexity of the “arrangement” of atoms in the molecule.

The Demise of Vitalism?

In most versions of the myth, vitalism is assumed to be a theory that supposes the existence of a mystical, nonmaterial entity that is present in living things but absent in inorganic systems—a “rational soul” that is responsible for maintaining the complex systems found in living organisms. This is certainly one version of vitalism, defended, for example, by Georg Ernst Stahl (1659–1734) early in the eighteenth century. But Stahl’s version of vitalism is one extreme on a continuum of ideas about the nature of life. At the opposite extreme lay a pure materialism, in which living things are envisioned as complicated machines governed solely by physical and chemical laws. This completely “anti-vitalistic” position was already well established by the mid-eighteenth century, held most famously by Julien Offray de La Mettrie (1709–1751) in his book Man a Machine (1748).11

Other natural philosophers staked out different conceptions of vitalism. Albrecht von Haller (1708–1777) and Xavier Bichat (1771–1802), for example, rejected the concept of vitalism as an external nonmaterial entity, suggesting instead that living things possessed certain kinds of forces, analogous to Newtonian gravitational attraction, which could be characterized and studied but whose ultimate nature remained unknown. Johann Friedrich Blumenbach (1752–1840) and Johann Christian Reil (1759–1813) developed yet another version of vitalism, called “vital materialism,” in which the vital force was not an independent entity but something that emerged from the complex interaction of the chemical and physical components of the organism.¹² Although living systems were governed by chemical and physical laws, they were more than simply the sum of their parts. These examples show that vitalism was not a single, comprehensive theory but a variety of theories about biological systems.

Berzelius himself had developed a version of vital materialism as early as 1806, which he incorporated into the section on organic chemistry in the 1827 edition of his textbook; he never substantially revised the entry in subsequent editions.¹³ Similarly, Justus von Liebig (1803–1873) described vital force in Animal Chemistry (1842) as “a peculiar property, which is possessed by certain material bodies, and becomes sensible when their elementary particles are combined in a certain arrangement or form.”¹⁴ This force, analogous to gravity or electricity, arose from the complexity of the system. Because the synthesis of a single compound could have had little effect on vitalistic theories about an organized system, it should not be surprising that Wöhler and Berzelius failed to discuss the impact of the synthesis of urea on vitalism in their correspondence and that early textbooks on organic chemistry did not mention Wöhler or the urea synthesis.¹⁵

Among biologists, vitalism continued to wax and wane. In the 1890s, Hans Driesch (1867–1941) suggested the existence of an explicitly nonmaterial factor he named “entelechy,” which directed the growth of the organism; and during the 1920s, Nobel Laureate Hans Spemann (1869–1941) developed a sophisticated holistic theory of embryonic development that was commonly mistaken by his contemporaries as vitalistic.16 The modern concepts of “emergent structures” and “self-organization” to explain such diverse phenomena as biological systems, the origin of life, intelligence, as well as economic systems and galaxy formation, are themselves reincarnations of vital materialism.¹⁷

Even the increasing success of chemists in making organic compounds did not completely eliminate the gap between organic and inorganic compounds. In 1848, Louis Pasteur (1822–1895) suggested that molecules of tartaric acid could exist in left- or right-handed asymmetric forms, leading to the conclusion that many compounds isolated from living things consisted of only one of these two forms. Attempts to create them artificially resulted in both forms without preference. In his famous 1860 lecture “On the Asymmetry of Natural Organic Products,” Pasteur declared that the presence of asymmetry was “perhaps the only well marked line of demarcation that we can at present draw between the chemistry of dead nature and the chemistry of living nature.”¹⁸ According to Pasteur, asymmetric molecules could be produced only by “asymmetric forces,” a view closely related both to his conviction that alcoholic fermentation was a vital and not a chemical process, and to his later attempts to disprove spontaneous generation (see Myth 15).¹⁹

In 1898, the British chemist Frances Japp (1848–1928) argued explicitly that asymmetry at the molecular level required a nonmaterial cause:

At the moment when life first arose, a directive force came into play—a force of precisely the same character as that which enables the intelligent operator, by the exercise of his Will, to select one crystallized enantiomorph and reject its asymmetric opposite.20

In 1894, Emil Fischer (1852–1919) suggested an unequivocally chemical and mechanistic view of fermentation and enzyme action, in which the source of biological asymmetry was the asymmetry already present in the enzymes that fit asymmetric molecules like a lock and key. Japp deftly countered Fischer by noting that even if this mechanistic interpretation were true, it still left unexplained the origin of asymmetry. Indeed, the origin of molecular asymmetry remains an unsolved problem today.

Reasons for Endurance

Like other myths in this volume, the Wöhler myth shows no signs of fading away, because it serves several specific purposes. For organic chemists, it provides a hero who accomplished a specific datable task that assumed great significance. The myth became widespread after Wöhler’s death in 1882, in part to validate the theoretical autonomy of organic chemistry as a discipline that no longer required concepts from either biology or physics, and in part because German chemists wished to place the origins of the powerful German chemical community, in which synthesis played a central role, squarely in their own country.²¹ For biologists, the myth’s simplistic image of vitalism provides a convenient foil for depicting how physiologists adopted the rigorous mechanistic and quantitative methods of chemistry and physics in the process of making biology more “scientific” by ridding it of “pseudoscientific” entities such as vital forces.²²