Cambridge the Mecca at the Start

My PhD task, with Theo on ADH, was to characterize the subunit size, composition, and primary structure of the enzyme. A big challenge at the time when no enzyme that size had been characterized, isozyme complexity was far from realized, and the subunit size was not unanimously agreed upon. I started with this at Karolinska Institutet in the fall of 1963, as Theo's last PhD student. I did my PhD studies part-time, at the same time as I continued my medical studies, following the general...

Growing Up

At home, in Palestine, there were only three of us father, mother, and myself. I always envied my schoolmates who were surrounded by large families. During their youth, my parents joined the Zionist Blau-Weiss organization, which was motivated by an idealistic desire to build a new-old homeland for the Jewish people. In 1923, they decided to fulfil their dream and left Germany to settle in Eretz-Israel (Land of Israel, as the Jewish population called Palestine). The idea of moving to an...

Programmed Death at Supracellular Level Bystanders Organoptosis

There are some indications that apoptotic signal(s) can be transmitted from an apoptotic cell to neighbor cells (so-called bystander effect'') (for reviews, see Refs. 180,181 ). This may be used as a line of antiviral defense when an infected cell organize a death area'' around itself inducing suicide of nearby cells that are the most probable targets for the virus during expansion of the infection. I have suggested that H2O2 produced by the apoptotic cell and released to the intercellular...

War Important Projects of Butenandt

What was the content of the papers labeled ''Geheime Reichssacheri' I presume that it were war important research projects, which should not be left to the enemy, because they would help the enemy or compromise the German reseachers. Such projects start small. They have precursors. They grow. In this context the war important projects of Butenandt will be analyzed. Before I begin, I will quote extensively a lecture Butenandt gave on January 23, 1941, at the high point of German military...

Development of Protein Sequence Analysis

The general breakthroughs of those days in the 1960s were structural analysis - by X-ray crystallography centering on Perutz's and Kendrew's work on globins - and by chemical sequence analysis centering on Sanger's and collaborator's start with peptide hormones and enzymes. All these authorities' work is well-known. Sanger's sequencing techniques, first in protein chemistry and then in DNA sequencing, gave him two Nobel Prizes, the only one to get the Nobel Prize in the same subject twice...

My Happy Days with Lac Repressor in a Dark World

Institut f r Genetik der Universit t zu K ln Weyertal 121, D- 50931 K ln, Germany I never considered that I would be seventy years old, and that my laboratory would disappear. This is going to happen soon. So the moment was perfect when I was asked to write an autobiographical chapter for this series. Private life and science are intertwined and cannot be clearly separated as so many autobiographies of scientists demonstrate. This is also true in my case. In science one does not write about...

Another View Opportunisms and Power Hunger

I have so far described Butenandt as if his opportunism was the price he had to pay to make scientific research. The scientific letter exchange'' which I was allowed to read suggested such a point of view. But is this the entire truth Only after I had left the Archive I realised that the private letter exchange which did not interest me was not the only other form of letter exchange. There must have been a letter exchange with state agencies of all types, with firms, like Schering or IG-Farben....

Phenoptosis Programmed Death of Organism

On the face of it, death of an organism should be considered to be a result of a lethal pathology of no biological sense. However, this may not be the case if the organism in question is a member of a kin, community, or population of other individuals. Here, altruistic death of individuals may appear to be useful for a superorganismal unit, being a mechanism of adaptation of the group of organisms to a changing environment, just as was suggested by Weismann (see above). From this point of view,...

Mass Spectrometry

As obvious from my recollections above, I have followed two separate, long-term developments in protein chemistry. One is the wet chemistry part, with protein chemistry and analysis, ranging from early manual methods, via sequencers, to cloning and mutagenesis, separations, X-ray crystallography NMR, and into the present proteomics. The other is the in silico'' branch, with interpretations, functional assignments, comparisons, molecular modeling, and bioinformatics. Both these fields continue...

Experiments with DNA Polymerase from E coli

In the late 1960s a detailed knowledge of the mode of action of DNA polymerase from E. coli (later known as DNA polymerase 1) was available. This was almost entirely due to the monumental work carried out in Arthur Kornberg's laboratory at Stanford. A number of properties of the enzyme made it, however, unlikely that this enzyme alone could account for the replication of DNA in vivo. Among the problems was that the enzyme could not initiate the synthesis of new DNA chains but only extend chains...

Von Verschuer Excellent Scientist and Outspoken Antisemite

In the thirties von Verschuer was highly respected internationally for his scientific work. I mention as evidence that the Rockefeller Foundation funded his research on twins in the KWI for Anthropology in Berlin-Dahlem from 1932 to 1935 (2). In 1939 von Verschuer, a speaker at the International Congress of Genetics in Edinburgh, was invited to give a talk on twin research before the Royal Society. His paper appeared after the war had begun in the Proceedings of the Royal Society (3). Von...

Protometer A Glagolev and S Bibikov

Photoreception was the first biological function postulated for bacteriorhodopsin by Oesterhelt and Stoeckenius 94 . Such a suggestion was based upon the facts that (i) Halobacteria, where bacteriorhodopsin was discovered, possess a phototaxis, and (ii) visual rhodopsin is a key component of the animal photoreceptor system. However, later the authors changed their mind assuming that it is the light-dependent A 2h+ generation that is the function of bacteriorhodopsin. Works of mine and some...

Correlation with 3 D Structures

I have collaborated with excellent crystallographers. Indeed, this is a necessity for meaningful interpretations of biochemical analyses and for the real understanding of protein structures. Theo saw this connection, too. Much like he initially sent me to Cambridge to pick up the biochemical methods, he made the then emerging crystallographic star in Sweden, Carl-Ivar Branden, interested in ADH. Carl had already been on a postdoc to Cambridge and started at his home lab in Uppsala to embark on...

Dark Side of Science in Difficult Times

Institut f r Genetik der Universit t zu K ln Weyertal 121, D- 50931 K ln, Germany Twenty five years ago I began to investigate the past of Human Genetics in Nazi Germany. When in 1984 I published my book ''T dliche Wissenschaft' 1 it was greeted with silence in Germany. The Max-Planck-Gesellschaft (MPG) and the Deutsche Forschungsgemeinschaft (DFG) pretended that this was not part of their past. This is changing slowly. The President of the MPG, Hubert Markl, founded a committee which is to...

Regulation of the Mitochondrial Branched Chain 2 Oxoacid Dehydrogenase Complex BCDH Complex by Reversible

Earlier studies by Bowden, Connelly, Harper, Benevenga, and Wohlhueter had suggested the existence of enzyme complexes catalysing the oxidative decarboxylation of the branched chain 2 -oxoacids formed by the deamination of leucine, isoleucine, and valine 71,72 . It seemed likely that the BCDH complex would be related in structure and operation to the PDH complex. Reed and colleagues first reported on the bovine kidney branched chain 2-oxoacid dehydrogenase complex in 1978. P.J. Parker (a new...

Perspectives

For the perspectives, how do I expect the development of protein chemistry for the next generation Of course, this is hopeless to predict, much like the present stage was outside all our science fiction grasps when I started. But it does perhaps not take too much imagination now to see at least some of the start of the future developments. Thus, for the future, I believe very much in 1. 1-molecule analysis sensitivity at this level or there about is expected. Fluorescence correlation...

Idea Becomes True

After his return to Sweden, Pehr Edman applied for and was awarded a vacant associate professorship at the University of Lund. He continued to work there on the use of phenylisothiocyanate for sequence analysis. For a while, we find him working also on other problems in protein chemistry. So, in 1948 he designed the first clock operated chromatographic fraction collector. He also undertook some studies on separation of chymo-tryptic peptides by partition chromatography on starch, 8To support...

Can it Happen Again

Abderhalden was a pure biochemist, but most of those using his method were medical, clinical biochemists. Such researchers often work during the day with patients in a hospital, and their experiments are confined to the afternoon or more likely the night. The senior author of research papers may be the director of a hospital. Clearly the universe of science is rather different from that of patients, who prefer to hear an optimistic diagnosis rather than the simple truth. It is difficult enough...

The Soros Foundation

In 1992-1993, economic crisis defeated Russia. In some months, inflation was as high as 300 . All the funds to buy scientific journals, chemicals, and equipment were exhausted. In many groups in my Institute, experiments ceased and in the evening the Institute building looked wistful, all its windows dark. The help came quite unexpectedly. In November, 1992, I visited Professor H. Michel in Frankfurt. A conversation after my talk was suddenly interrupted by an urgent call from the USA. It was...

Samurai Law of Biology

Discoveries of programmed death mechanisms on subcellular (mitoptosis), cellular (apoptosis), supracellular (death of cells -bystanders, and organoptosis), and even organismal (pheno-ptosis) levels allowed me to put forward a general principle which I called the Samurai law'' of biology. It can be formulated briefly as following It is better to die than to be wrong '' or, in more detail Any biological system from organelle to organism possesses a program of self-elimination. This suicide...

Chemiosmotic Hypothesis Peter Mitchell

One of the attractive features of the adenine hypothesis of energy coupling was that it did not require any high energy intermediates of respiratory chain electron carriers since ATP was presumed to be immediately formed from ADP and phosphate. A search for such intermediates was performed in many laboratories in the late 1950s and 60s. Results proved to be quite negative and initiated numerous confusions. Independently from Blumenfeld and Temkin, a quite new hypothesis, called chemiosmotic,...

Three Laws of Bioenergetics

Discovery of the Sodium World allowed the filling of a significant gap in our knowledge concerning cellular energetics based on the Mitchellian H+ cycle scheme. This is why I have decided to formulate some general bioenergetic principles of universal applicability to living cells. In 1992, I published a paper in Eur. J. Biochem. called The laws of cell energetics'' 145 . The first law was presented as follows The living cell avoids direct utilization of external energy sources in the...

Weizmann Institute of Science

Early in 1949, Hemed members were gradually transferred from Rehovot to other camps, and the scientific activities at the Weizmann Institute returned to normal. I received an extended leave of absence from the Army, which enabled me to complete my master's thesis. In June 1949, Bergmann invited me to join him in the Weizmann Institute as his PhD student. I gladly accepted. Professor Chaim Weizmann, the first President of the State of Israel and the Zionist statesman, championed the idea of...

Some Other Duties

In this context, I should mention some other activities which also consumed my energy for a long period of time. This is, first of all my editorial activity. For 14 years I was a member of the FEBS Letters editorial board. During this time, I handled 2235 papers. I calculated that this work took almost one year of my life. I am very proud that since 1988, when I joined the FEBS Letters Editorial Board, the percentage of the Russian papers strongly increased and this journal is now the most...

Von Verschuer et al Back to Normal Academic Life

Von Verschuer was a founding member of the Mainz Academy in 1950. In 1951 he became professor of Human Genetics at the University of Miinster. In 1954 he became dean of the medical faculty. In 1956 he gave an invited talk at the international congress of genetics in Tokyo and Kyoto on 'Tuberculosis and cancer in twins' (44). In the same year his Italian colleague Luigi Gedda gave a talk where he called von Verschuer a 'Master and Example' (45). Von Verschuer received several other honours (see...

The Last Ten Years Before my Retirement in Cologne 19881997

During the last ten years before my retirement, I concentrated my research on the lac system of E. coll. We showed that operator-Lac repressor-operator looping can be quantitized with gel shift experiments 52 . My student Stefan Oehler demonstrated that two such loops can be formed with 01 one with 02 and the other with 03. Thus, only when 02 and 03 are destroyed, repression goes down 70-fold. When 02 or 03 are destroyed, it goes down twofold 35 . Stefan Oehler by chance also isolated a mutant...

Unique MAP2 Species in Human Neuroblastoma Cells

While this work on the tubulin binding sites for MAPs was in progress, we had begun a new line of investigation on the role of MAPs and laminin in the differentiation of human neuroblas-toma cells. My interest in human neuroblastoma was stimulated during my frequent visits to The Children's Hospital of Philadelphia. Human neuroblastoma is one of the most common solid tumors in children. It is of presumed neuronal crest origin and can occasionally undergo maturation into a more differentiated...

Mitochondria and ROS in Apoptosis Mitochondrial Suicide Mitoptosis

In 1996, an event occurred which initiated quite a new wave of mitochondrial research. Kroemer and coworkers in France reported 167 that in the mitochondrial intermembrane space a protein is hidden which causes apoptosis when released from mitochondria to the cytosol. The novel protein was called Apoptosis-Inducing Factor (AIF). It proved to be a FAD-containing enzyme resembling plant dehydroascorbate reductase also localized in the intermembrane space 168 . AIF was found to activate a DNAse...

Chemistry in Freiburg and Munich

I began to study chemistry at the University of Freiburg. Here everything was solid and slow. I heard that Munich was much better. My parents financed three half-years there with the money inherited from Charles Hill. There I took first the lab course of quantitative inorganic analytical chemistry. My first experiment was to determine Mg++ as MgNH4PO4. It took a full day to do so. This I did and in the late afternoon I presented my results to the postdoc running the lab. Wrong.'' he said. I did...

Mengele in Auschwitz

I begin by citing how three witnesses saw the activities of Mengele in Auschwitz. Nyiszli, Mengele's slave assistant, testified before a Jewish committee half a year after his liberation (20). His statement is the most direct description of the horror I arrived on May 22,1944 from the ghetto of Aknaszlatina together with 26 colleagues to Auschwitz. We were all medical doctors in public service (Kreis rzte). After the selection, I was on the right side. They sent me to Buna, where 14,000...

Fifty Years of Biochemistry as Enjoyed by a Medical Biochemist Motivated by an Interest in Diabetes

Nuffield Department of Clinical Biochemistry, Clinical Laboratory Sciences, Radcliffe Infirmary, Oxford OX2 6HE, UK My interest in medicine was first aroused when, as a boy, I experienced surgery (tonsillectomy), and succumbed to most of the infectious diseases of childhood. I have recollections of being given a junior version of a stethoscope to play with at the age of six or seven or thereabouts but I have no recollection of how much of a nuisance it was or what happened to it Presumably, I...

Mystery of Alkaliphilism

The studies described in the preceding section contributed to verification of the chemiosmotic hypothesis and extended it in such a way that A xh+ proved to be not only a transient between oxidation and phosphorylation but also convertible and transportable energy currency buffered in bacteria by the Na+ K+ gradients. However, an exception clearly inconsistent with the chemiosmotic scheme was still waiting for explanation. I mean the life under alkaline conditions. Some bacteria can survive at...

Butenandt and National Socialism

Not only Mengele, but also von Verschuer was a product of National Socialism. How did Butenandt see the National Socialists How did his view change in 1933 when they got power and then in the years until their defeat How did he see them as president of the Max-Planck Gesellschaft (MPG) in the Federal Republic of Germany Before I will try to present the view of Butenandt, I will quote from two letters written to him by his teacher, Nobel Prize winner Adolf Windaus. It is revealing that...

The Silence of Von Verschuer and his Colleagues Scientists and Historians

After the war von Verschuer and almost all his colleagues in human genetics remained silent about the past until their deaths. None of them ever wrote an article or a book about the past. At best they said or wrote a very few sentences. And the scientific institutions like the Max-Planck-Gesellschaft or the Deutsche Forschungsgemeinschaft were silent too. They were uninterested in the dark sides of their past. The brief remarks on the past by those geneticists active in Nazi Germany are worth...

Extended Mitochondria as Intracellular Electric Cables

The electric conductance of the media on both sides of a biological membrane is always very high whereas the transmembrane conductance can be extremely low. This means that A , if produced by a A xH+ generator molecule inlaid in this membrane, cannot avoid fast irradiation over the membrane surface. As to ApH, it also must irradiate quickly due to the high rate of H+ diffusion in water and the high concentration of mobile pH buffers which cause a further increase in the rate of H+ movement....

Project II Genetic Differences among Jews Gypsies and Others in Resistance to Infectious Diseases

On 16 November 1944 von Verschuer gave an invited talk at the Academy of Sciences in Berlin on 'The effect of genes and parasites in the human body'. The abstract of his talk, but not the talk itself, was deposited at the Archive of the Academy of Sciences 28 . The abstract concludes as follows 'The task of future research involves analysis of all those infectious diseases where parts of the defence mechanism are genetically determined. Individuals with a particular defect in this defence...

Surface Glycoproteins

Mary Catherine Susy Glick, a sabbatical visitor from The Children's Hospital of Philadelphia CHOP , had begun, in 1971, a completely new line of research on the glycoproteins from surface membranes of neuroblastoma cells. Together with Yosef Kimhi, we examined the composition of surface membrane glycopeptides isolated from different clones of mouse neuro-blastoma cells. Our results demonstrated that there appeared to be a positive correlation between the capacity to differentiate...

Reversible Phosphorylation in the PDH Complex 19711975

In 1969 Linn, Pettit, and Reed 31 showed that mammalian pyruvate dehydrogenase complexes PDH are regulated by reversible phosphorylation, phosphorylation being inactivating. This discovery, which was confirmed in due course by Wieland and Siess 32 , and in my own laboratory in collaboration with Coore, Denton, and Martin 33 , was clearly of substantial potential -importance in relation to the concept of a Glucose Fatty Acid Cycle and to Denton's interest in the regulation of fatty acid...

New Duties

Although I had been teaching and administrating earlier, this had been far from a major occupation. Suddenly, one duty after the other fell upon my shoulders and it is unavoidable to mention them in a chapter of personal recollections. For the period 1966-1979 the main part of my time was occupied by administration and scientific evaluation. The fact that our research still was alive must be attributed to my gifted co-workers and students. Even if we were several persons, who shared the...

The Nobel Prizes

The great prestige of the academy is to a large extent due to its role in selecting Nobel laureates. The Nobel Foundation is taking care of the endowment and organizes the awarding ceremony but independent institutions select the laureates. The prizes in physics and chemistry are decided by the academy after considerations in the Nobel committees. The academy also selects the prize winner in economics to the memory of Alfred Nobel. The Nobel Committee of Chemistry. The members of the Nobel...

The Invention of Polymer Science

The most important feature of the working model for globular proteins that was imprinted on my mind was the fact that proteins are macromolecules - a fact as old as protein chemistry itself, generally accepted for 100 years or more. I was reminded of this just recently, when a contradictory historical opinion emerged 9 . On 19 April 1999 an International Historic Chemical Landmark'' was designated at the University of Freiburg in Germany, under the joint auspices of the Gesellschaft Deutscher...

Is there a Bottom Line

Von Verschuer's scientific record and his scientific career are deeply disturbing. Equally disturbing is the disinterest of his colleagues in this past. A scientific community which is unable to face its own crimes, and which prefers to look constantly away, works towards its own destruction. It is late but not too late. Von Verschuer was the director of a KW Institute and thus belongs to the history of the MPG. The documents which I present show unambiguously that von Verschuer considered...

Automation Must Come

In 1957 Pehr Edman accepted an offer as Director of Research at the newly established St. Vincent's School of Medical Research in Melbourne where he would remain for 15 years and became an Australian citizen. The reasons for his leaving Sweden were rather complex. Pehr Edman's time at the biochemistry department in Lund had not been altogether happy, possibly because of personal frictions. Also, his scientific endeavor was apart from the mainstream scientific aims of the department. Few were...

Bacteriorhodopsin W Stoeckenius and E Racker

In January of 1973, I had a talk at a Bioenergetics conference organized by David Green in the New York Academy of Sciences. After the talk, somebody approached me saying that he has interesting information. This was Walter Stoeckenius, an electron microscopist involved in studies on membrane ultrastructure. We came to his room in the Americana Hotel where Stoeckenius put many figures on the table and bed. After an hour of conversation, it became clear for me that my new acquaintance had...

Phageinduced tRNA

Early studies of RNA synthesis in E. coli cells showed that after infection with a T-even bacteriophage, there was a rapid incorporation of 32P-orthophosphate into RNA. While most of the labeled RNA synthesized after infection was phage-specific mRNA, it was noticed by Sol Spiegelman and his colleagues that some eight percent were found as a low molecular weight RNA fraction. Because of this finding, we attempted to characterize this 4S RNA fraction and determine whether it has amino acid...

Uppsala 19611966

The professor of medical and physiological chemistry in Uppsala, Gunnar Blix, was due to retire in 1961 and there was a lack of senior investigators in the department. Therefore, my friend Lennart Roden, who lived in Stockholm, held the position as docent associate professor and commuted to Uppsala. Lennart saw a possibility of getting me to Uppsala and convinced Gunnar Blix that he should propose an established inves-tigatorship of ophthalmic biochemistry in the Swedish Medical Research...

Behind the Fraud

It is worth noting that Abderhalden was a convinced eugenicist. Given that his main scientific activity was based on self-deception and fraud, it is interesting that between 1922 and 1935 he edited a journal about ethics Ethik . He wrote a textbook of biochemistry that appeared in 28 editions between 1906 and 1948 and was translated into four languages. He was president of the Leopoldina Academy from 1931 to 1950. After 1933, the notes membership ended'' or membership extinguished'' were...

Letters Exchanged between Butenandt and Von Verschuer September 1944September 1945

How did the collaboration von Verschuer-Butenandt-Hillmann get started The simplest explanation is that Von Verschuer told his neighbor Butenandt, their villas in Dahlem were next to each other, of his project. Perhaps they met for lunch in the Harnack-house closeby. Then Butenandt may have told von Verschuer, that he had a collaborator, Hillmann, who was an expert in the test of defense enzymes. In the first letter of Von Verschuer Berlin to Butenandt T bingen , collaboration is mentioned as...

Membrane Potential Revealed by Penetrating Ions

Elucidation of the protonophorous mechanism of uncoupling directly confirmed one of the crucial postulates of the chemi-osmotic hypothesis. The next piece of evidence in favor of this concept was obtained when we tested Mitchell's assumption that respiratory and photosynthetic electron carriers, as well as membranous ATPases, generate transmembrane difference in electric potentials A 63,66 . To this end, we decided to find artificial ions penetrating through biomembranes. By definition,...

From Weismann to Apoptosis

More than 120 years ago, the great German biologist August Weismann put forward a paradoxical idea that death due to aging was invented by evolution as an adaptive mechanism. For the first time, this concept was presented in his lecture to a meeting of the Association of German Naturalists in September, 1881. The hypothesis was published in German 1882 and then in English l889 . Weismann wrote There cannot be the least doubt, that the higher organisms, as they are now constructed, contain...

Cohn and Edsall

My undergraduate thesis in chemistry and my PhD thesis in physical chemistry both focussed on the mechanism of interaction of small molecules in the gaseous state - on combustion in a burner flame, in the case of my PhD dissertation. The Tanford-Pease theory of burning velocity'' was briefly in the limelight, before more elegant theories took its place 1 . My first exposure to proteins and a huge transition from what I had been doing at Princeton came when I went to Harvard, to the medical...

Birth of an Idea

Let us start with some historical remarks. Traditionally, proteins were regarded as biocolloids in the 19th century and few people supposed that any protein preparation contained identical molecules. At the end of the 19th century, Olof Hammarsten in Uppsala isolated fibrinogen out of horse4 plasma 4 . This clotting protein was one of the first proteins to be isolated in pure form it appeared to be a homogeneous component on the basis of being almost completely transformed into fibrin by...

Back in Stockholm 19541958

When Does Torticollis Improve

From now on Ulla concentrated on finishing her MD while I went back to the Chemistry Department to continue my graduate studies interwoven with some medical courses. My further work took two directions. First, Bertil Jacobson wanted to pursue his idea that DNA and hyaluronan surrounded themselves with large icelike hydration shells and to prove this by X-ray diffraction. He built X-ray cameras to record the amorphous diffractograms from water solutions of these polymers and I did the...

Molecular Evolution Development from Early Diagonals over the Atlas Issues to Bioinformatics

Tomas Bergman Proteomik

With the availability of primary structures in the 1960s, I, like many others, started to do comparisons. Gradually, they grew more and more sophisticated, and these developments have formed part of my life, much like the chemical protein analyses have. Once I had the first ADH primary structure horse EE form , and small parts of some others yeast, the horse ES form and a human and a rat form , two things became apparent 1 the isoforms were closely related and constituted an isozyme family, and...

Interaction with Industry

Although as a principle I have tried to keep my activities within the academic world, it has sometimes been necessary to act also in the commercial area. As mentioned above I had a lot of experience from scientific collaboration with colleagues employed at the drug company Pharmacia. The introduction of hyaluronan in eye surgery around 1980 created a dramatic boost for Pharmacia, which was both positive and negative. On the positive side was the increase in research and development, on the...

Genetic Basis for Antibody Diversity

It was not possible in the 1960s to be involved with immunoglo-bulins without being aware that there was a more important unsolved problem than that of molecular shape. At that time it was still generally believed that the general axiom of protein chemistry, that amino sequence uniquely determines three-dimensional structure and thereby function, did not apply to antibodies - it was thought implausible that the huge number of distinct immunological specificities that were known to exist could...

Science Takes Hold

Moses Kunitz Princeton

After the matriculation examination, Pehr Edman decided to study medicine and therefore applied to the Karolinska Institutet in Stockholm, a medical school. He started his medical studies in 1935 and received a bachelor of medicine degree in 1938. He graduated as a physician in 1946. During his studies at the Karolinska Institutet, he joined a socialist political organization, Clarte.3 Several Swedish intellectuals, politicians, and artists were its members. Tage Erlander, who later became...

Project I Genetic Defects in Families and Twins

On December 16,1942, two weeks before Mengele turned up at the Berlin-Dahlem Institute, Himmler had given the general order that all Gypsies, with the exception of a very few racially pure families, ought to be transferred to Auschwitz. A detailed order was given on January 29,1943. Before, most German Gypsies had been held in various camps. The Gypsies had been an object of study for students and post-docs of von Verschuer and Fischer. In particular Dr Georg Wagner, a graduate student working...

End of Journey

In the early 1970s, Pehr Edman accepted an offer to be Director of the Department of Protein Chemistry I of the Max Planck Institut fur Biochemie in Martinsried, near Munich. He and his wife Agnes Henschen moved there in 1972. During the last years of his life, he continued his work on the sequenator with the main objective of improving the yields. He was of the opinion that high repetitive yields are crucial in stepwise sequencing and that all efforts must be directed toward this goal. The...

The First Ten Years in Cologne 19681977

In the morning of April 18, 1968, I arrived in Cologne airport with my wife Barbara, a cat in a box, and two pieces of luggage. In the afternoon, I gave my first lecture on bacterial genetics in front of five students. Barbara, the cat, and I stayed in the guest room on the sixth floor of the institute, until we found a beautiful apartment in an old house in the center of Cologne. I still live in this place. To return to Germany was not easy. This country haunted me. Directly after my return, I...

Pehr Victor Edman The Solitary Genius

Primary Protein Structure

Karolinska Institutet, Fogdevreten 2A, Stockholm, SE-171 77, Sweden One of the main problems in protein chemistry half a century ago was how to efficiently elucidate the sequence of amino acids in proteins. With laborious methods, only small protein structures had so far been resolved. For insulin, the most famous example, the sequence of its 51 amino acid residues took a decade to unravel. Entertaining the thought of establishing the amino acid sequences for protein molecules with hundreds or...

Service on General Medical and Dental Councils

In the period from 1967 until my move to Oxford in 1975, I had represented the University of Bristol Medical School on the General Medical Council GMC . I also served on the General Dental Council but had relatively less to contribute as my knowledge of dentistry was minimal. The GMC had two roles - it was responsible for maintaining standards in medical education and ensuring up-to-date curricula in medical schools and it was responsible for maintaining standards in medical practice i.e. it...

Edman The Person

Helena Edman Henschen

I believe that most people who met Pehr Edman for the first time got the impression of a courteous, kind but also reclusive man with a hint of shyness. There was, in his personality, a certain aloofness, which people who did not know him may mistakenly have taken for snobbishness. People who came closer to him could fully appreciate other qualities generosity, warmth, humor, and sympathy. 15Many scientists have asked me why Pehr Edman never got the Nobel Prize. Considering the importance of his...

AN Belozersky Bioenergetics a Department in MSU and a Branch of Biological Sciences

I liked Mitchell's hypothesis since it gave a chance to explain the mechanism of the thermoregulatory uncoupling as well as other numerous cases when respiration occurs without phosphorylation. However, I proceeded to its verification only five years after its publication. Such a delay was due, first of all, to that I tried to exhaust possibilities of an alternative adenine hypothesis. Moreover, the period between 1960 and 1965 was overcrowded by events only indirectly related to science or...

The Student Year SE Severin and VA Engelhardt

In the second year, I joined the famous seminar at the Department of Biochemistry chaired by the Head of the Department Professor Sergey Eugenyevich Severin and Professor Vladimir Alexandrovich Engelhardt. The latter name is well known in the West because of his two most famous discoveries, namely, oxidative phosphorylation early 1930s and ATPase activity of myosin middle 1940s . On the other hand, S.E. Severin was less popular abroad although in the USSR his contribution was well recognized he...

Chemistry Department 19511953

Hjalmar Holmgren was seriously ill with cancer at the time when Bandi left Sweden, and he died a few months later. His research group dissolved. A virologist working in Holmgren's laboratory had a friend in the Chemistry Department, Bertil Jacobson, and suggested that I should move to him. At this time the Chemistry Department had moved to the Solna campus and to a completely new building. I started there in the fall of 1951. The Chemistry Department was divided into two sections headed by...

Student Years at the University of Copenhagen

Herman Kalckar 1950

I liked very much my time as a student at the University of Copenhagen. There was a good and relaxed atmosphere. We were very few less than 10 biochemistry students all together at all levels. We had good teachers both at the practical courses and at the lectures, and they were excellent scientists too. One of our teachers in plant physiology Poul Larsen had just found a plant hormone that stimulated the growth of dicotyledones. The compound was isolated and given to our teacher in organic...

Solvation Energy and Phosphate Compounds of High and Low Energy

The concept of energy-rich and energy-poor phosphate compounds was formalized by Lipmann in 1941 46 . On the basis of the knowledge available at that time, Lipmann proposed that the energy that could be derived from the hydrolysis of a phosphate compound would be determined solely by the chemical nature of the bond that links the phosphate residue to the rest of the molecule. In this early work, the possibility that some energy might be derived from the interaction of reac-tant and product with...

Origins

I was born in Saxony, in Halle-an-der-Saale, in 1921, although my father and mother actually lived in the big city of Leipzig, 45 km away. My mother was in fact a Leipzig girl my father, though born in Poland of Jewish parents , had lived in Leipzig for a decade or more and had a thriving business there. Our family moved to England in 1930 and my father lived in England until he died in 1971. Why was I born in Halle It probably reflects nothing more than a shortage of maternity beds in Leipzig...

With Howard Rickenberg in Bloomington Indiana 19631964

In order to reach Bloomington, Indiana, I took a ship that went from Holland to New York. From New York I took the night train to Chicago and from there a train to Bloomington. It was snowing when I arrived. There was no train station. Howard Rickenberg met me at the train. I thought I had ended somewhere in the desert. Howard drove me to the guest house of the university. Visits in the rooms were strictly forbidden. My neighbor was a lady who warned me about the red network, which was active...

Heidelberg

Aristides Pacheco Leao was a distinguished neurophysiologist with an international reputation for the discovery of spreading depression. He was both the president of the Brazilian Academy of Sciences and one of the leading scientists of the Biophysics Institute. In August 1969 Aristides quietly suggested that Regina and I should leave the country for one or two years. He had heard unsettling rumors about us and felt we should leave while things cooled down and possible misunderstandings could...

The Wenner Gren Foundations

In the fall of 1992 I received a phone call from a colleague in Stockholm, who unofficially asked if I would consider to become Science Secretary of the Wenner-Gren Foundations WGS . It was in the middle of my term as president of the academy and I could hardly think of any further duties. I would only accept if the assignment was postponed until 1994. I then got an official invitation to talk to the chairman of the board, Jan Wallander, a former director of one of the major banks in Sweden. We...

Experiments with Penicillin

In a period during the German occupation of Denmark, all lectures were abandoned at the University of Copenhagen. A close friend of mine, Rolf Brodersen, suggested therefore that I in this period performed experimental work together with him at the University Institute of General Pathology where he had a job. At the institute the professor K. A. Jensen, but not the chemist of the same name had managed to isolate a sample of a mould that apparently produced penicillin. He and his assistant...

Conclusion

Half a century ago, biochemistry was regarded as being a bit esoteric and of limited interest for the society. The family of biochemists was so relatively small that almost all in the field knew each other, or at least knew of each other. Looking back over the many years, it is overwhelming to recognize the enormous development of biochemistry in this period. It has been a greatly awarding intellectual experience and a great privilege to have had the opportunity to try to follow this progress....

Historical Perspective

I turn now very briefly to our more serious project of writing a history of proteins the book was completed early in 2001 and published later that year. I should acknowledge at the start our indebtedness to Walter Gratzer's active promotion of the project. Walter recommended it to Oxford University Press he tried valiantly to get us to appeal to the ''popular science'' market -a genre where he himself has been so skilful. He is even the person who proposed the essence of the book's title he...

Protonophores Efim Liberman

Keeping in mind the mechanism of thermoregulatory uncoupling, I started with a program of verification of that part of the chemiosmotic theory that deals with uncouplers. The program in question was initiated by my visit to a workshop on oxida-tive phosphorylation organized by L. Wojtczak just after the Warsaw FEBS Meeting in April, 1966. Here, for the first time, I met Peter Mitchell. I was very much impressed by his personality in spite of the fact that he absolutely failed to Britton Chance...

Experimental Histology 19491951

After my first year at the Karolinska Institute, I was asked by Professor Hjalmar Holmgren to be an unpaid instructor of histology. This was a common way at the time to recruit graduate students. Hjalmar Holmgren held a personal chair of experimental histology. His main contribution had been the identification of heparin in mast cells, but he was also very interested in the regulation of the daily rhythm as mirrored in the biochemical processes in the liver. He was a young energetic man, coming...

In the Watson Gilbert Group 19651968

The three years I spent in the Watson-Gilbert group were the most productive in my life. I had just one goal to isolate Lac repressor. This was dangerous. If I failed, that was it. If somebody else succeeded, and many tried, that was it, too. It was an all or none gamble. The same was true for Wally. He was a physicist. At the time I joined the group he was still teaching theoretical physics at Harvard. In the group were about six to ten graduate students and two postdocs. The principle was...

Neuroblastoma Laminin Binding Proteins

Laminin, the major glycoprotein of basement membrane, is known to promote cell adhesion, growth, migration, and neurite outgrowth. I have, therefore, examined the involvement of laminin in the differentiation of cultured neuroblastoma cells. Together with Nira Garty and Ilana Bushkin-Harav, we have noticed that the differentiation of human neuroblastoma cells is accompanied by increased adhesion to laminin. The major binding site in laminin, mediating cell attachment, was then identified as...

Back in Copenhagen

In those years there was a growing excitement about enzyme reactions involving DNA and other 2-deoxyribose compounds. In 1950 Herman Kalckar together with E. Hoff-Jorgensen and Walter MacNutt, an American research fellow, had found that extracts of Lactobacillus helveticus contained an enzyme that catalyzed the exchange of purines and pyrimidines between 22-deoxyribosides without the intervention of phosphorolysis, i.e. by a trans-N-glycosidase reaction. Kalckar and Morris Friedkin had also...

Research and Graduate Students 19661980

The biological role of connective tissue polysaccharide networks continued to be my own main interest until 1980. However, as should be clear from the previous chapter, there was little time left for me to be at the lab bench even if I was assisted by very efficient technicians. Much of the work was carried out together with guest scientists and many of the concepts had already been formulated. Instead, the new ideas and research lines came from my students and successively from their students....

Von Verschuer Director and Mengele Former Postdoc Now Guest and Collaborator in the Berlin Kaiser Wilhelm Institute for

Mengele Documents

In October 1942 von Verschuer became director of the Kaiser Wilhelm Institute of Anthropology in Berlin-Dahlem, and so successor of his teacher Eugen Fischer. Among the scientists who came with him from Frankfurt to Berlin was Dr Ayres de Azevedo, a Portuguese post-doc. Azevedo had come to vanVerschuer' s lab in Frankfurt in July 1941. He stayed with von Verschuer in Berlin until August 1943. He analysed the sera of twins for differences in their blood groups. The bottom line of his research...

Eastman Professor at Oxford

For the year 1977-1978,1 accepted an invitation to be the George Eastman visiting professor at Oxford. This position was established in 1930 through the philanthropy of the American manufacturer, George Eastman. It was limited to American citizens, creating a kind of inverse of Rhodes scholarships. Rhodes scholars have often been viewed in England as visitors from a relatively backward former British colony, coming to Oxford for a taste of culture and scholarship the Eastman professorship...

Subunits and Allosterism

And then quite by chance I even became involved with molecular biology,'' the pinnacle of the bright new look of biological research. After the DNA double helix molecular biology'' had moved to the top of the league in terms of relevance to the ultimate secrets of life. But proteins remained very much a part of the story. How many polypeptide chains How big are they Are they all alike How are they linked These questions were fundamental to an understanding of immunoglobulins, as seen in Figure...

Macromolecules Theoretical Research with JG Kirkwood

Changeux Jean Pierre

I was still of course a physical chemist. My two-year stint at a medical school did nothing to alter my identity. My research interest in proteins was undoubtedly unusual for the typical physical chemist in a chemistry department, whose undergraduate classes held a mixture of aspiring industrial chemists and chemical engineers, but when it came to what the research was about, it was clearly the physical chemistry of proteins -the physical state of protein molecules, the thermodynamics of their...