Henri Moissan, a prestigious chemist

Way followed by Moissan in the field of inorganic chemistry. Isolation of fluorine and its developments. Artificial diamond production by simultaneous actions of high pressures and high temperatures. Arc electric furnaces, and powerful models enabling temperatures up to 3000 degrees C. High pressures obtained by fast cooling of iron-carbon alloys melted at high temperature. Numerous distinctions from foreign Chemical Societies, of which the Nobel Prize.     

From apprenticeship to Nobel Prize: Henri Moissan's fabulous destiny

Born in Paris on September 28, 1852, son of an eastern railways' employee and of a dressmaker, Henri Moissan's secondary schooling in Meaux did not allow him to get access to the sesame diploma "baccalauréat" (GCE). In 1869, he did obtain a special certificate of secondary schooling so that he could become an apprentice in watch making. That could have been the end of the story, but dreadful event for France appeared to have beneficial effects for Moissan. Under the threat of the Prussian army, Moissan's family took refuge near Paris. This gave the young Henri the opportunity to register as a student for the second-class pharmacy diploma, which did not need, at the time, the GCE. Moissan became then a trainee in pharmacy in 1871. Meanwhile, he followed the special schooling of "Ecole de chimie" founded by E. Frémy, and then joined the laboratory of Dehérain at the Museum, where he worked in plant physiology. He finally obtained the famous "baccalauréat" (GCE) and could register as a student in first-class pharmacy. He became a pharmacist as well as a doctor in sciences. In 1883, Moissan was named professor at the school of pharmacy in Paris. In 1886, he isolated fluorine by electrolysis of fluorhydric acid, in the presence of potassium fluoride, at a low temperature. He then studied diamond synthesis and gave a start to high temperature chemistry, designing his famous furnace. These findings and many others allowed Moissan to rise to membership in many learned academies around the world. Crowning achievement, Moissan won the Nobel Prize in 1906. A man of culture, collector of autographs and paintings, he died in 1907. Nothing of that would have been possible if there had not been a second-class pharmacist diploma. The history of Henri Moissan is one of a rise from apprenticeship to the Nobel Prize.     

Halogens: discoveries of pharmacists

The discovery of four halogens is due to pharmacists. Chlorine was isolated by Carl Wilhem Scheele, a Swedish who was first an assistant to a pharmacist, then a pharmacist himself. Bernard Courtois, a pharmacist under the First Empire, the son of a saltpetre worker isolated iodine in I811, after a modification of the ancestral production protocol of potassium nitrate, which is the major component of the gunpowder: he replaced wood ashes by varech ashes which are less expensive. Antoine Jer?me Balard was still an assistant in chemistry and physics when he discovered bromine in the residues of the salt marshes. He became soon after a pharmacist and started a famous career as then he became Professor in the College de France and General Inspector of Higher Education. The last halogen: fluorine was isolated by Henri Moissan who received the Nobel Prize of Chemistry. The discovery will be the subject of our next communication.     

Maximilian Ehrenstein (1899-1968)--life and work

The pharmacist, chemist and food analyst Maximilian Ehrenstein prepared his doctoral thesis at the Georg-August-University G?ttingen under the supervision of the later Nobel Prize winner Adolf Windaus. He has been a postdoctoral fellow with the two later Nobel Prize winners Paul Karrer at Zurich and Heinrich Wieland at Munich and worked in Berlin with Carl Mannich to obtain his habilitation for pharmaceutical chemistry. After his emigration to the United States he prepared the ground for the development of oral active progestational hormones, which finally led to the anti-baby pill by Carl Djerassi. He received the honorary doctorates from the Free University of Berlin (Dr. rer. nat. h. c.) and the University of Hamburg (Dr. med. h. c.).     

Electron transfer reactions: from electrons to drugs

Electron transfer reactions have been at the heart of great advances in organic and inorganic chemistry and biology since the early work in 1954 by H. Taube (Nobel Chemistry Prize in 1983) and R. Marcus (Nobel Chemistry Prize in 1991). In organic chemistry, a new kind of chain substitution reaction with paramagnetic species was defined and identified as S(RN)1 (substitution, radial-nucleophilic, unimolecular). In our laboratory, choosing more or less complex molecules which possess electron-withdrawing groups and correctly disposed alkylation sites has enabled us to extend this concept to the heterocyclic (S(RN)1 HET) and quinonic (S(RN)1 QUI) series. These studies led us to prepare, under mild operating conditions, highly branched molecules hard to obtain via other pathways and which possess high pharmacological activity in various fields. We have discovered new reaction mechanisms such as LD-S(RN)1 (long-distance S(RN)1) E(RC)1 (elimination radical chain, unimolecular), bis-S(RN)1 and poly-S(RN)1. Moreover, we have developed a new technology using microwaves which increases the interest of electron transfer reactions in medicinal chemistry for drugs synthesis.     

Muller’s Nobel lecture on dose–response for ionizing radiation: ideology or science?

In his Nobel Prize Lecture of December 12, 1946, Hermann J. Muller argued that the dose–response for radiation-induced germ cell mutations was linear and that there was “no escape from the conclusion that there is no threshold”. However, assessment of correspondence between Muller and Curt Stern 1 month prior to his Nobel Prize Lecture reveals that Muller knew the results and implications of a recently completed study at the University of Rochester under the direction of Stern, which directly contradicted his Nobel Prize Lecture. This finding is of historical importance since Muller’s Nobel Lecture gained considerable international attention and is a turning point in the acceptance of the linearity model in risk assessment for germ cell mutations and carcinogens.     

The contributions of Paul Ehrlich to pharmacology: a tribute on the occasion of the centenary of his Nobel Prize

On the centenary of Paul Ehrlich's Nobel Prize, this German researcher deserves to be remembered as a pioneer in a large number of scientific disciplines. As a result of his enthusiasm and scientific abilities, dedication, and contacts with other scientists of his time, he was able to make countless contributions in fields as diverse as histology, haematology, immunology, oncology, microbiology and pharmacology, among others. Although the Swedish award was meant to recognize the standardization of the manufacture of antidiphtheria serum, it was the discovery of arsphenamine (Salvarsan) for the treatment of syphilis which won him wider international acclaim. From a pharmacological perspective, Ehrlich's outstanding contributions include dissemination of the 'magic bullet' concept for the synthesis of antibacterials, introduction of concepts such as chemoreceptor and chemotherapy, and linking the chemical structure of compounds to their pharmacological activity. These achievements took place within the framework he established for the transition from experimental pharmacology to therapeutic pharmacology. He introduced a modern research system based on the synthesis of multiple chemical structures for pharmacological screening in animal models of disease states. These contributions were undoubtedly decisive in propitiating the wider development of antibiotics decades later. For these reasons, it is fitting to mark the 100th anniversary of the Nobel Prize awarded to this great scientist by commemorating the importance of his contributions to the advance of pharmacology.     

A brief philatelic evocation of Louis Pasteur and of his disciples

Philately is an important source of knowledge on numerous items. Evocation of Louis Pasteur's as well as his disciples life and works throughout stamp collection is a perfect example of this. Born in D?le in 1822, he spent his youth in Arbois. It is at the Ecole normale supérieure that he performed his work on cristals which led him to establish molecular dissymetry principles. Later, he studied of the fermentation process, he searched the reason of wines' disease and the means to prevent it (i.e. pasteurisation), he solved the problem of the silkworm disease and discovered agents of numerous infectious diseases. He demonstrated scientifically the vaccination principle. In 1885 he tried with success the first human antirabic vaccination. Three years later, the Pasteur Institute was inaugurated. After his death, his works survived in numerous institutes all over the world. Many pasteurians received the Nobel Prize.     

A new therapy with bortezomib, an oncologic medicinal product of the year 2004

Proteasome-mediated proteolysis is a mechanism for mediating important regulatory proteins within the cell. Proteins that have been targeted for degradation by the proteasome are convalently tagged with a poly-ubiquitin protein chain prior to be recognized by the 19S subunit of proteasome. This degradation system controls the expression of a wide variety of cellular targets including tumor suppressors such as p53, inhibitor of nuclear factor NFkappaB, cyclin-dependent kinase inhibitors such as p21 and p27. Because of these functions, the proteasome has become a new target for cancer treatment. The potent and selective proteasome inhibitor, PS-341 or Velcade was approved in the United States and launched in may 2003 for the treatment of multiple myeloma patients who have received at least two prior therapies. On April 2004, the European commission granted marketing authorization for Velcade with the same indication. The same year 2004, the Nobel Prize in chemistry was awarded to three researchers "for the discovery of ubitiquin-mediated protein degradation", a regulated process by which proteins are cleaved into peptides inside cells.     

Prostaglandins, bioassay and inflammation

The formation of the British Pharmacological Society coincided almost exactly with a series of ground-breaking studies that ushered in an entirely new field of research--that of lipid mediator pharmacology. For many years following their chemical characterisation, lipids were considered only to be of dietary or structural importance. From the 1930s, all this changed--slowly at first and then more dramatically in the 1970s and 1980s with the emergence of the prostaglandins (PGs), the first intercellular mediators to be clearly derived from lipids, in a dynamic on-demand system. The PGs exhibit a wide range of biological activities that are still being evaluated and their properties underlie the action of one of the world's all-time favourite medicines, aspirin, as well as its more modern congeners. This paper traces the development of the PG field, with particular emphasis on the skillfull utilisation of the twin techniques of bioassay and analytical chemistry by U.K. and Swedish scientists, and the intellectual interplay between them that led to the award of a joint Nobel Prize to the principal researchers in the PG field, half a century after the first discovery of these astonishingly versatile mediators.     

The electric furnace of Henri Moissan at one hundred years: connection with the electric furnace, the solar furnace, the plasma furnace?]

The trace of Henri Moissan's pioneer work 100 years ago is clearly evidenced by an overview of achievements in high temperature devices; 1987: "Le four électrique" by Henri Moissan; 1948-1952: "High temperature heating in a cavity rotary kiln using focusing of solar radiation" by Félix Trombe; 1962: "The cavity rotary kiln using focused solar radiation jointly with a plasma gun" by Marc Fo?x; 1970: "The rotary kiln with two plasma guns and arc transfer" by Marc Fo?x; 1984: "The plasma furnace" by Electricité de France (EDF) at Renardières; 1997: "The plasma furnace" by the Atomic Energy Center (CEA) at Cadarache, the VULCANO program. The first part of this contribution is devoted to Henri Moissan. Re-reading his early book on the electric furnace, especially the first chapter and the sections on silica, carbon vapor and experiments performed in casting molten metal--the conclusions are outstanding--provides modern readers with an amazing insight into future developments. The last two parts are devoted to Félix Trombe and Marc Fo?x, tracing the evolution of high temperature cavity processus leading to the solar furnace and the present day plasma furnace at the CEA. Focus is placed on research conducted by the French National Center for Scientific Research (CNRS) with the solar and plasma furnaces at Odeillo. The relationships with Henri Moissan's early work are amazing, offering a well deserved homage to this pioneer researcher.     

Stephen Neidle on cancer therapy and G-quadruplex inhibitors. Interview by Joanna De Souza

Stephen Neidle was educated at Imperial College, London, where he graduated in chemistry and then proceeded to do a PhD in crystallography. After a period as an ICI Fellow, he joined the Biophysics Department at King's College, which ignited his interest in nucleic acid structural studies. He was appointed as one of the first Cancer Research Campaign Career Development Awardees, becoming a Life Fellow on moving to the Institute of Cancer Research. He was appointed to the Chair of Biophysics at the Institute of Cancer Research in 1990, and moved to the new Chair of Chemical Biology at the School of Pharmacy in the University of London in 2002, where he also directs the Cancer Research UK Biomolecular Structure Group. He is currently Chairman of the Chemical Biology Forum of the Royal Society of Chemistry, which is involved in developing the interface between chemistry and the life sciences. He will shortly assume the Directorship of the newly-established Centre for Cancer Medicines at the School. Stephen Neidle has received several awards for his work on drug-nucleic acid recognition and drug design, including the 2000 prize of the Biological and Medicinal Chemistry Sector of the Royal Society of Chemistry, and its 2002 Interdisciplinary Award. He was the 2004 Paul Ehrlich Lecturer of the French Societé de Chimie Therapeutique, and was recently awarded the 2004 Aventis Prize in Medicinal Chemistry.     

Pharmacist Theodor Salzer (1833-1900) and the discovery of bisphosphonates

Herbert Fleisch, the father of the therapeutic use of bisphosphonates in modern medicine, repeatedly stated in his numerous reviews that bisphosphonates were first synthesized 1865 in Germany by the Russian chemist Menschutkin. He was wrong on two counts. Had Menschutkin synthesized bisphosphonates, as he was a student of Wurtz at the time of the "synthesis", the birthplace of the substances would have been France and not Germany; but he did not. By reacting phosphorous acid with acetyl-chloride he obtained derivatives of pyro-phosphorous and pyro-phosphoric acids (P-O-P backbone) and not bisphosphonates (P-C-P backbone). The discovery of the first bisphosphonate occurred indeed in Germany but some thirty years later and not without some drama. First 1894 the pharmacist Theodor Salzer (1833-1900) described an impurity contained in commercially available phosphoric acid but failed to identify it as acetodiphosphoric acid, a bisphosphonate. 1896, an undergraduate student, Hans von Baeyer working in Munich at the Royal Academy of Sciences in the chemical laboratory of his father Adolf (the 1905 Nobel Prize laureate and discoverer of the barbiturates) synthesized an unknown substance which his famous father summarily rejected as some "Dreck" or impurity. Only due to the tenacity of young Hans work on the matter was continued and the paper describing the synthesis published a year later. The correctness of the chemical structure of the compound as assumed by von Baeyer (and his Ph.D. supervisor Hofmann) was confirmed 1901 by Heidepriem, a Ph.D. student of Hofmann. This short report attempts to shed some light on the life of the lesser known pharmacists and chemists involved in the synthesis of the first bisphosphonate, focusing on Salzer, Heidepriem and von Baeyer.     

Utilization of a transferred arc-plasma rotating furnace to melt and found oxide mixtures at around 2000 degrees C (presentation of the film VULCANO)]

Unless security measures are taken, a hypothetical accident resulting from the loss of the cooling circuit in a pressurized water nuclear reactor could cause the heart of the reactor to melt forming a bath, called the corium, mainly composed of uranium, zirconium and iron oxides as well as the structural steel. This type of situation would be similar to the Three Mile Island accident in 1979. In order to limit the consequences of such an accident, the Atomic Energy Commission has implemented a large study program [1] to improve our understanding of corium behavior and determine solutions to stabilize it and avoid its propagation outside the unit. The VULCANO installation was designed in order to perform the trials using real materials which are indispensable to study all the phenomena involved. A film on the VULCANO trials was presented at the Henri Moissan commemorative session organized by the French National Academy of Pharmacy. The rotating furnace used to melt and found the mixture simulating the corium is a direct descendant of the pioneer work by Henri Moissan. An electrical arc is directed at the center of the load to melt which is maintained against the walls by centrifugal force. After six high-temperature trials performed with compositions without uranium oxide, the first trial with real corium showed that the magma spread rather well, a result which is quite favorable for cooling.     

Prostacyclin analogues: prevention of cardiovascular diseases

Prostacyclin (PGI(2)) inhibits platelet aggregation and vasoconstriction. PGI(2) synthase (PGIS), a catalyst of PGI(2) formation from prostaglandin H2, is widely distributed and predominantly found in vascular endothelial and smooth muscle cells. Vane et al. first discovered PGI(2) in 1976, for which they received the Nobel Prize in medicine and physiology in 1982. However, the later discovery of nitric oxide (NO), which also resulted in a Nobel Prize for the scientists involved, led to less attention being focused on PGI(2). The reason for this is somewhat perplexing and may have been due to the lack of information on how to correctly use PGI(2). Current findings suggest that researchers concentrated too much effort on the therapeutic effects of PGI(2), while largely ignoring the potential for preventative effects. In addition, PGI(2) was shown to be effective against diseases in some studies but was without effect in others. The present paper contains a review of PGI(2) and PGIS, in addition to an examination of the relationship between PGIS gene mutations and cardiovascular diseases. PGI(2) analogues that can be used in the prevention of cardiovascular diseases are also discussed.     

The diamond saga: from Moissan to the present day

Diamond synthesis by Moissan brought about fierce controversies and harsh criticisms. Our purpose is not to settle the debate but to show that many criticisms were not as rigorous as it could be expected from scientific arguments. We will briefly describe how diamond synthesis developed towards methods that make Moissan's work appears as quite reasonable. The paper concludes with a tribute to Moissan, Hannay and Burton who opened the way towards modern diamond synthesis and the predicted revolution of the semiconducting diamond.     

Review of chemical and radiotoxicological properties of polonium for internal contamination purposes

The discovery of polonium (Po) was first published in July, 1898 by P. Curie and M. Curie. It was the first element to be discovered by the radiochemical method. Polonium can be considered as a famous but neglected element: only a few studies of polonium chemistry have been published, mostly between 1950 and 1990. The recent (2006) event in which (210)Po evidently was used as a poison to kill A. Litvinenko has raised new interest in polonium. 2011 being the 100th anniversary of the Marie Curie Nobel Prize in Chemistry, the aim of this review is to look at the several aspects of polonium linked to its chemical properties and its radiotoxicity, including (i) its radiochemistry and interaction with matter; (ii) its main sources and uses; (iii) its physicochemical properties; (iv) its main analytical methods; (v) its background exposure risk in water, food, and other environmental media; (vi) its biokinetics and distribution following inhalation, ingestion, and wound contamination; (vii) its dosimetry; and (viii) treatments available (decorporation) in case of internal contamination.     

Nobel prize recognizes industrial scientists'' contribution to pharmacology and medicine

The award of the 1988 Nobel Prize for Physiology or Medicine to three industrial scientists is a long overdue recognition of the major contributions of drug development to modern medicine. It is no longer necessary for patients to suffer the pain of angina, stomach ulcers and gout; new drugs that have been developed by Nobel laureates Sir James Black, Gertrude Elion and George Hitchings have allowed these very common conditions to be alleviated or cured. Zidovudine (AZT) was the first drug to offer hope to AIDS victims. The following tributes to these scientists are not confined to the retrospective — Jim Black continues to actively research new pharmacological targets; Trudy Elion is presidential appointee on the National Cancer Advisory Board and chairs the Chemotherapy of Malaria Steering Committee of the WHO/World Bank/UNPP special programme in tropical diseases; George Hitchings continues to work as a Consultant at Burroughs Wellcome.     

医学院校《生物化学与分子生物学》教学中的科学创新教育

生物化学与分子生物学是医学院校最重要的专业基础课之一。该文以最近20年诺贝尔医学或生理奖项和化学奖为例,论述了生物化学与分子生物学是生命医学领域最前沿的学科,生物化学与分子生物学老师在教学中肩负着培养创造性思维与高层次生物医学创新人才的责任。文章从教师必须具备科学创新意识、激发学生学习生物化学与分子生物学兴趣、建立创新教学模式和加强创新实践教学等四个方面,探讨了在医学院校生物化学与分子生物学教学中进行科学创新教育的方法。