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New Insight into the “Fortuitous Error” that Led to the 2000 Nobel Prize in Chemistry

Seth C. Rasmussen

Department of Chemistry and Biochemistry, North Dakota State University, Fargo, ND, US

Accepted: 2020-08-18 | Published Online: 2020-08-23 | DOI: 10.36253/Substantia-973


In 2000, the Nobel Prize in Chemistry was awarded to Hideki Shirakawa, Alan G. MacDiarmid, and Alan J. Heeger “for the discovery and development of electrically conductive polymers.” While this award was in reference to their collaborative efforts on conducting polyacetylene in the mid-to-late 1970s, the narrative leading up to these efforts began in 1967 with the production of polyacetylene plastic films via what has been called a "fortuitous error." At the heart of this discovery were Shirakawa and a visiting Korean scientist, Hyung Chick Pyun. The current report provides background on Pyun and, for the first time, presents his version of the events leading to the discovery of polyacetylene films in order to provide new insight into this important historical event.

History of Research on Antisense Oligonucleotide Analogs

Jack S. Cohen

Chemistry Department, Ben Gurion University, Be’er Sheva, Israel

Accepted: 2020-08-11 | Published Online: 2020-08-23 | DOI: 10.36253/Substantia-964


In the search for novel therapeutics, antisense oligonucleotide (ASO) analogs have been a major focus of research for over 40 years.  They use the antisense strategy, namely they have a nucleic acid base sequence that is complementary to a portion of a specific mRNA that is produced in the cell, or to a viral RNA, in order to selectively inhibit gene expression. Oligonucleotides need to be chemically modified to stabilize them against hydrolysis by endogenous nucleases. Until now several phosphorothioate (PS) oligonucleotide analogs have been approved by the FDA for human use. This article seeks to provide a history of this subject to date.

Thermodynamics of Life

Marc Henry

Laboratoire de Chimie Moléculaire de l'Etat Solide, UMR 7140, Université de Strasbourg, France

Accepted: 2020-08-26 | Published Online: 2020-08-26 | DOI: 10.36253/Substantia-959


Biology is currently plagued by several fossil concepts that may be responsible for the current stagnation in medicine. Through a careful screening of the origins of thermodynamics, such fossils concepts have been identified: assumption that heat is a form of energy, assimilation of entropy to disorder, assimilation of death to states of maximum entropy, assimilation of ATP to the energy currency of living cells, non-recognition of entropy as a state function of the whole universe, belief that free energies are another kind of energy, self-referencing in the definition of life, ignorance of basic principles of quantum physics and more particularly of the importance of intrinsic spin, confusion between three different forms of reversibility, non-recognition that irreversibility is at the heart of living systems. After stowing of these concepts in the cabinet of useless and nasty notions, a fresh new look is proposed showing how life is deep-rooted trough the entropy concept in quantum physics on the one hand and in cosmology on the other hand. This suggests that life is not an emergent property of matter, but rather that it has always been a fundamental property of a universe filled with particles and fields. It is further proposed to dismiss the first (energy = heat + work) and third laws (entropy decreases to zero at zero Kelvin) of thermodynamics, retaining only the clear Boltzmann's definition of entropy in terms of multiplicity of microstates Ω, S = kB×Ln Ω, and the second law in its most general form applicable to any kind of macrostates: ∆Suniv ≥ 0. On this ground, clear definitions are proposed for life/death, healthiness/illness and for thermodynamic coupling. The whole unfolding of life in the universe: Big Bang → Light → Hydrogen → Stars → Atoms → Water → Planets → Metabolism → Lipids → RNA's → Viruses → Ribosome → Proteins → Bacteria → Eukaryote → Sex → Plants → Animals → Humans → Computers → Internet, may then be interpreted as a simple consequence of a single principle: ∆Suniv ≥ 0. We thus strongly urge biologists and physicians to change and adapt their ideas and vocabulary to the proposed reformulation for a better understanding of what is life and as a consequence for better health for living beings.

Capillary electrophores is and its basic principles in historical retrospect - 1 The early decades of the “Long Nineteenth Century”: The Voltaic pile, and the discovery of electrolysis, electrophoresis and electroosmosis

Ernst Kenndler,* Marek Minárik

Institute for Analytical Chemistry, Faculty of Chemistry, University of Vienna, Währigerstrasse 38, A 1090, Vienna, Austria

Accepted: 2020-08-30 | Published Online: 2020-08-31 | DOI: 10.36253/Substantia-1018


Here we set forth the first from a series of reports devoted to the history of capillary electrophoresis. In this opening part, we go more than two centuries back in time and revisit original discoveries of electrolysis, electrophoresis and electroosmosis. We emphasize the essential role of a brilliant invention of 1799 by Alessandro Volta, the Voltaic pile, basically the first battery delivering a constant-flow electricity, which has made all the scientific advances in the subsequent years and decades possible. We describe the experiments of William Nicholson and Anthony Carlisle revealing electrolytic decomposition of river water followed by enlightened investigations by Nicolas Gautherot, Ferdinand Frédéric Reuss and Robert Porrett that each independently and unaware of the works of the other uncovered the phenomena of electrophoresis and electroosmosis. We give not only a technical description and a chronological overview of the inventive experiments, but offer also some formidable details as well as circumstances surrounding some of the initial inventors and their observations. We conclude this time period, for which we coin the term "1st epoch of electrophoresis", with the same year 1914 as the astonishingly coincident period of the European history between the French revolution in 1789 and the begin of the First World War, termed the “Long 19th Century” by the British historian Eric Hobsbawm. We accentuate the surprising fact that over this entire cycle of 125 years no attempts were taken to utilize the findings and newly acquired knowledge to perform an electric driven separation of compounds from a mixture. In the field of electrophoresis and electroosmosis, it is rather the epoch of pure than of applied science.

Udagawa Youan (1798-1846), Pioneer of Chemistry Studies in Japan from Western Sources and his Successors

Yona Siderer

Edelstein Center for the History and Philosophy of Science, Technology and Medicine, the Hebrew University of Jerusalem, Israel

Accepted: 2020-09-14 | Published Online: 2020-09-14 | DOI: 10.36253/Substantia-963


This work presents chemistry studies of the Japanese scholar Udagawa Youan (1798-1846), specifically, his pioneering book Seimi Kaiso, introduction to Chemistry, and includes a short biography of Youan. The first aim of this work is to present Youan's contribution to Western chemistry in Japan. Youan studied many Western books and listed their authors. The new terms he invented for chemistry in Japanese influenced the development of chemistry writing and application in Japan. The seven books of Seimi Kaiso that were published during 1837-1847 and republished with annotation in Japanese in 1975 are discussed in this article.

The impact of Youan' terminology on the history chemistry writing in the nineteenth and twentieth centuries is discussed.  The conditions of knowledge transfer among Japanese and Western scholars were very different. Youan had severe difficulties facing the strict attitude of the Tokugawa authorities toward studying and distributing knowledge coming from foreign countries.  The later development of Japanese chemistry language and studies is also described.

Loren Eiseley’s Substitution

Bart Kahr

Department of Chemistry and Molecular Design Institute, New York University, New York City, NY 10003 USA

Accepted: 2020-10-26 | Published Online: 2020-10-26 | DOI: 10.36253/Substantia-1040


The anthropologist and acclaimed essayist, Loren Eiseley, in the midst of recounting a vision in the conclusion of a draft of a 1960 composition, “Creativity and Modern Science,” invoked Charles Darwin as the essay’s animating spirit. Eiseley modified his draft the next year and published it in no less than three of his subsequent books. The most striking differences between his draft and published texts is the substitution of Darwin in the final moments of the narrative with Francis Bacon, a barrister and philosopher who died nearly two centuries before the famous biologist was born. Here, is crafted a rationale for this unlikely switch, to the extent that the intent of another can be uncovered, by closely reading Eiseley’s psychologically charged work. Eiseley’s own struggles as both a scientist and an artist, identities respectively epitomized by Darwin and Bacon, reveal how and why the writer permitted his foremost heroes to be substituted, one for the other.

Darwin and Inequality

Enrico Bonatti

Columbia University, Lamont-Doherty Earth Observatory, Palisades NY 10964, USA

Istituto Scienze Marine CNR, Via P. Gobetti 101, 40129 Bologna, Italy

Accepted: 2020-11-23 | Published Online: 2020-11-23 | DOI: 10.36253/Substantia-1121


Charles Darwin during his travels on the Beagle noted the wretched primitive state of natives from Tierra del Fuego. He attributed it to their being egalitarians and to the absence of a leader among them.  The Gini Economic Index  suggests strong inequality today even among the richest, more developed countries.  This paper discusses whether equality and civilization are really incompatible, as Darwin seemed to imply.

The Eminent Russian – German Chemist Friedrich Konrad Beilstein (1838-1906) in the Literature between the 19th and 21st Centuries

Aleksander Sztejnberg

University of Opole, Oleska 48, 45-052 Opole, Poland

Accepted: 2020-12-01 | Published Online: 2020-12-01 | DOI: 10.36253/Substantia-1097


Friedrich Konrad Beilstein (1838-1906) was one of the most prominent chemists of the second half of the nineteenth century. His life and scientific achievements were described in the literature published between the 19th and 21st centuries in different countries. The purpose of this paper is to familiarize readers with the important events in the life of Beilstein and his research activities, in particular with selected results of his experimental studies. The names of authors of biographical notes or biographies about Beilstein, published in 1890-2018, and literature on his correspondence are given. In addition, a list of his publications is included.

Chemistry, Cyclophosphamide, Cancer Chemotherapy, and Serendipity: Sixty Years On

Gerald Zon

TriLink BioTechnologies, San Diego, California, 92121 U.S.A.

Accepted: 2020-12-03 | Published Online: 2020-12-04 | DOI: 10.36253/Substantia-1115


Cambridge Dictionary: serendipity | noun | the phenomenon of finding interesting or valuable things by chance.

The year 2019 marked the 60th anniversary of the approval of cyclophosphamide (CP) as an anticancer by the U.S. Food & Drug Administration in 1959 for the treatment of lymphoma. Between 1959 and 2019 there were ~50,000 publications listed in PubMed that have CP in the title and/or abstract, with these annual numbers showing a continual increase, and over 1,800 such articles in 2019 alone. The discovery of CP is a prime example of serendipity in science, which also applies to key elements of the metabolism and pharmacological basis for the specificity of the cytotoxicity of CP toward cancer cells. Phosphoramide mustard (PM), HO(H2N)P(O)N(CH2CH2Cl)2, the principal metabolite of CP with DNA alkylating activity, was synthesized and reported by Friedman and Seligman in 1954 prior to the discovery of CP. Interestingly, the original drug design premise for synthesizing PM, which was based on elevated phosphamidase enzyme activity in cancer cells proved to be incorrect. While this wrong premise also led to the synthesis of CP, as a six-membered ring cyclic phosphamidase-activated precursor of PM, the actual metabolic conversion of CP to PM was subsequently found to involve a surprisingly complex array of metabolites and metabolic pathways, all completely unrelated to phosphamidase. Although the molecular structure of CP has an asymmetrically substituted, i.e. chiral phosphorus center, the racemic mixture of the Rp and Sp enantiomers of CP was used throughout its initial investigations and subsequent clinical trials despite the involvement of an initial enzyme-mediated metabolic activation step, which could, in principle, be stereoselective for only one of the enantiomers of CP. Stereochemical investigations along those lines were eventually carried out, but the results did not warrant replacement of racemic CP with either enantiomer in the clinic. Amazingly, there are now ~4,000 structural congeners of PM listed in Chemical Abstracts, but none have led to an anticancer drug superior to CP. This account provides a synopsis of the key chemistry and stereochemistry investigations that comprise this story of CP, as a remarkable instance of serendipity in science, and my chance involvement in the unfolding of this fascinating story.