Emile Zuckerkandl
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Émile Zuckerkandl (July 4, 1922 – November 9, 2013) was an Austrian-born French biologist considered one of the founders of the field of
molecular evolution Molecular evolution is the process of change in the sequence composition of cellular molecules such as DNA, RNA, and proteins across generations. The field of molecular evolution uses principles of evolutionary biology and population genetics ...
. He introduced, with Linus Pauling, the concept of the "
molecular clock The molecular clock is a figurative term for a technique that uses the mutation rate of biomolecules to deduce the time in prehistory when two or more life forms diverged. The biomolecular data used for such calculations are usually nucleo ...
", which enabled the
neutral theory of molecular evolution The neutral theory of molecular evolution holds that most evolutionary changes occur at the molecular level, and most of the variation within and between species are due to random genetic drift of mutant alleles that are selectively neutral. The ...
.


Life and work

Zuckerkandl was raised in
Vienna en, Viennese , iso_code = AT-9 , registration_plate = W , postal_code_type = Postal code , postal_code = , timezone = CET , utc_offset = +1 , timezone_DST ...
,
Austria Austria, , bar, Östareich officially the Republic of Austria, is a country in the southern part of Central Europe, lying in the Eastern Alps. It is a federation of nine states, one of which is the capital, Vienna, the most populous ...
in a household of intellectuals, but his family relocated in 1938 to Paris, and later Algiers, to escape the racial policy of Nazi Germany with respect to
Jews Jews ( he, יְהוּדִים, , ) or Jewish people are an ethnoreligious group and nation originating from the Israelites Israelite origins and kingdom: "The first act in the long drama of Jewish history is the age of the Israelites""The ...
. At the end of
World War II World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the vast majority of the world's countries—including all of the great powers—forming two opposing ...
, he spent one year at the University of Paris (
Sorbonne Sorbonne may refer to: * Sorbonne (building), historic building in Paris, which housed the University of Paris and is now shared among multiple universities. *the University of Paris (c. 1150 – 1970) *one of its components or linked institution, ...
), then came to the
United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territori ...
to study physiology—earning a master's degree in 1947 from the
University of Illinois The University of Illinois Urbana-Champaign (U of I, Illinois, University of Illinois, or UIUC) is a public land-grant research university in Illinois in the twin cities of Champaign and Urbana. It is the flagship institution of the Univer ...
, under C. Ladd Prosser—then returned to the Sorbonne to complete a Ph.D. in biology. Zuckerkandl developed a strong interest in molecular problems; his early research at a marine biology lab in
Roscoff Roscoff (; br, Rosko) is a commune in the Finistère département of Brittany in northwestern France. Roscoff is renowned for its picturesque architecture, labelled (small town of character) since 2009. Roscoff is also a traditional departure ...
emphasized the roles of copper oxidases and
hemocyanin Hemocyanins (also spelled haemocyanins and abbreviated Hc) are proteins that transport oxygen throughout the bodies of some invertebrate animals. These metalloproteins contain two copper atoms that reversibly bind a single oxygen molecule (O2) ...
in the molting cycles of crabs. In 1957, Zuckerkandl met renowned chemist Linus Pauling, who was becoming interested in molecular diseases and molecular evolution as an outgrowth of his activism on topics concerning nuclear power. They arranged a post-doctoral fellowship, and Zuckerkandl (now with his wife Jane) returned to the United States to work with Pauling at the
California Institute of Technology The California Institute of Technology (branded as Caltech or CIT)The university itself only spells its short form as "Caltech"; the institution considers other spellings such a"Cal Tech" and "CalTech" incorrect. The institute is also occasional ...
beginning in 1959. He was an atheist.


Linus Pauling and the molecular clock hypothesis

Zuckerkandl's first project under Pauling (working with graduate student Richard T. Jones) was the application of new protein identification techniques—a combination of
paper chromatography Paper chromatography is an analytical method used to separate coloured chemicals or substances. It is now primarily used as a teaching tool, having been replaced in the laboratory by other chromatography methods such as thin-layer chromatography ...
and electrophoresis that produced a two-dimensional pattern—to
hemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyt ...
. The peptide fragments of hemoglobin samples from different species, partially broken apart by
digestive enzyme Digestive enzymes are a group of enzymes that break down polymeric macromolecules into their smaller building blocks, in order to facilitate their absorption into the cells of the body. Digestive enzymes are found in the digestive tracts of anima ...
s, would produce unique patterns that could be used to estimate differences of protein structure. Zuckerkandl, Jones and Pauling published a comparison of several species' hemoglobin identification patterns in 1960, observing that the degree of dissimilarity of protein patterns corresponded approximately to the
phylogenetic In biology, phylogenetics (; from Greek φυλή/ φῦλον [] "tribe, clan, race", and wikt:γενετικός, γενετικός [] "origin, source, birth") is the study of the evolutionary history and relationships among or within groups o ...
distance between source species. However, the method was not conducive to quantitative comparisons, so Zuckerkandl began working on the determination of the actual
peptide sequence Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...
of the α and β chains of
human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, cultu ...
and
gorilla Gorillas are herbivorous, predominantly ground-dwelling great apes that inhabit the tropical forests of equatorial Africa. The genus ''Gorilla'' is divided into two species: the eastern gorilla and the western gorilla, and either four or fi ...
hemoglobin. In 1962, Pauling and Zuckerkandl published their first paper using the
molecular clock The molecular clock is a figurative term for a technique that uses the mutation rate of biomolecules to deduce the time in prehistory when two or more life forms diverged. The biomolecular data used for such calculations are usually nucleo ...
concept (though not yet by that name). Like a number subsequent collaborative papers, it was not peer-reviewed—it was an invited paper in honor of
Albert Szent-Györgyi Albert Imre Szent-Györgyi de Nagyrápolt ( hu, nagyrápolti Szent-Györgyi Albert Imre; September 16, 1893 – October 22, 1986) was a Hungarian biochemist who won the Nobel Prize in Physiology or Medicine in 1937. He is credited with fi ...
—and they intentionally took the opportunity to "say something outrageous". The paper used the number of differences in the α and β chains of hemoglobin to infer the time since the last
common ancestor Common descent is a concept in evolutionary biology applicable when one species is the ancestor of two or more species later in time. All living beings are in fact descendants of a unique ancestor commonly referred to as the last universal comm ...
for a number of species, calibrated based on
paleontological Paleontology (), also spelled palaeontology or palæontology, is the scientific study of life that existed prior to, and sometimes including, the start of the Holocene epoch (roughly 11,700 years before present). It includes the study of foss ...
evidence for humans and horses. Though the paper did not provide any explanation for why amino acid differences in a protein should accumulate at a uniform rate (the essential assumption of the molecular clock), it did show that the results were fairly consistent with those of paleontologists. During the succeeding years, Zuckerkandl worked to refine the molecular clock. In 1963, he and Pauling invented the term " semantides" for biological sequences—DNA, RNA, and polypeptides—that have evolutionary information and argued that such sequences could be the basis for constructing molecular phylogenies, suggesting that the "molecular clock" method might be useful for other semantides besides proteins. Emanuel Margoliash's first publication of sequence data for cytochrome c allowed comparison of the rates of molecular evolution for different proteins (cytochrome c seemed to evolve faster than hemoglobin), which Zuckerkandl discussed at a 1964 conference in
Bruges Bruges ( , nl, Brugge ) is the capital and largest city of the province of West Flanders in the Flemish Region of Belgium, in the northwest of the country, and the sixth-largest city of the country by population. The area of the whole city a ...
. Zuckerkandl also adjusted the mathematics of the "clock" to account for the observation that some positions in an amino acid sequence were more stable than others, and the likelihood of multiple substitutions at the same position. In September 1964, he attended the important Evolving Genes and Proteins symposium, where he and Pauling presented their most influential paper ("Evolutionary Divergence and Convergence in Proteins", published in the conference proceedings the next year). The paper, primarily Zuckerkandl's work, named the "evolutionary clock" and presented a derivation of its basic mathematical form. Though Zuckerkandl and Pauling saw the clock as compatible with
natural selection Natural selection is the differential survival and reproduction of individuals due to differences in phenotype. It is a key mechanism of evolution, the change in the heritable traits characteristic of a population over generations. Cha ...
, it would later become the basis of the
neutral theory of molecular evolution The neutral theory of molecular evolution holds that most evolutionary changes occur at the molecular level, and most of the variation within and between species are due to random genetic drift of mutant alleles that are selectively neutral. The ...
, in which
genetic drift Genetic drift, also known as allelic drift or the Wright effect, is the change in the frequency of an existing gene variant (allele) in a population due to random chance. Genetic drift may cause gene variants to disappear completely and there ...
rather than selection is the driving force of evolution at the molecular level.


Later work

In 1965, Zuckerkandl moved back to France to direct in Montpellier, th
"Centre de Recherche de Biochimie Macromoléculaire"
of the
Centre National de Recherche Scientifique The French National Centre for Scientific Research (french: link=no, Centre national de la recherche scientifique, CNRS) is the French state research organisation and is the largest fundamental science agency in Europe. In 2016, it employed 31,63 ...
. In 1971, he became the founding editor of the '' Journal of Molecular Evolution'', and in the late 1970s became President of the
Linus Pauling Institute The Linus Pauling Institute is a research institute located at the Oregon State University with a focus on health maintenance. The mission statement of the institute is to determine the functional roles of micronutrients and phytochemicals in pr ...
(then in 1992 of its successor, the Institute of Molecular Medical Sciences). His recent work includes criticism of
social constructionism Social constructionism is a theory in sociology, social ontology, and communication theory which proposes that certain ideas about physical reality arise from collaborative consensus, instead of pure observation of said reality. The theor ...
and
intelligent design Intelligent design (ID) is a pseudoscientific argument for the existence of God, presented by its proponents as "an evidence-based scientific theory about life's origins". Numbers 2006, p. 373; " Dcaptured headlines for its bold attempt to ...
.Emile Zuckerkandl, "Intelligent design and biological complexity", ''Gene'', Vol. 385 (2006), pp. 2-18


References

{{DEFAULTSORT:Zuckerkandl, Emile 1922 births 2013 deaths Scientists from Vienna American people of Austrian-Jewish descent Austrian biologists Austrian emigrants to the United States Austrian Jews Evolutionary biologists Jewish American scientists Jewish atheists American molecular biologists University of Paris alumni University of Illinois Urbana-Champaign alumni California Institute of Technology faculty