Sir Hans Adolf Krebs (1900 – 1981) – Part 2

  • DOI: 10.1002/chemv.202000121
  • Author: Klaus RothORCID iD
  • Published Date: 01 December 2020
  • Source / Publisher: Chemie in unserer Zeit/Wiley-VCH
  • Copyright: Wiley-VCH GmbH
thumbnail image: Sir Hans Adolf Krebs (1900 – 1981) – Part 2

Hans Krebs discovered the citric acid cycle (or "Krebs cycle") and the urea cycle and received the Nobel Prize in Physiology or Medicine in 1953. In this part, we look at his life from 1933 to 1981.




4. Short Outline of Krebs' Life between July 1933 and 1981

After being forced to leave Germany in 1933, Hans Krebs seamlessly and unwaveringly began his scientific research in Cambridge, UK. His work remained centered on a seemingly simple question: How do cells break down nutrients and what intermediate products are produced?


In 1937, he discovered the citric acid cycle [14] at the University of Sheffield, UK. Like the formation of urea, this is a catalytic reaction cycle in which the acetic acid that arises from the breakdown of all nutrients is broken down into carbon dioxide and water. This discovery made him world-famous and he was awarded the Nobel Prize for Physiology and Medicine for it in 1953.


His private life in Sheffield was also harmonious. They were "nineteen happy years", particularly with his marriage to Margaret Fieldhouse in 1938 and the births of their three children, Paul Stephen (born 1939), Helen Margaret (born 1942), and John Richard (born 1945). Later, he was called to Oxford and became Vice-Chancellor of the university there. After his retirement from Oxford in 1974, he moved his entire research group to Radcliffe Infirmary in Oxford, working there until his death in 1981.


Krebs earned many honors, becoming a Fellow of the Royal Society in 1947, receiving the 1953 Nobel Prize for Physiology and Medicine (with Fritz Lipman), and receiving a knighthood from Elizabeth II in 1958. In Germany, he was made an honorary citizen of his hometown of Hildesheim in 1966 and received honorary doctorates from the Universities of Berlin, Freiburg, Göttingen, and Hannover.




5. Timeline from April 5, 1932, to July 1933

The timeline below presents the critical phase of Hans Krebs’ life between April 1932 and July 1933. Events in his personal life (orange) are shown interspersed with historical events (blue).


April 10, 1932

With 53 % of the vote, General von Hindenburg defeats Adolf Hitler in the election for President of the German Reich.


April 13, 1932
With an emergency decree for the "Protection of State Authority", Chancellor Heinrich Brüning bans the paramilitary organizations SA and SS.


April 28, 1932
Hans Krebs investigates urea formation in a rat liver tissue section after adding citrulline (see Part 1, Chapter 2.5) contributed by Professor Ackermann from Würzburg. Krebs observes substantial urea formation. This is the last piece of the puzzle for understanding the catalytic urea cycle.


April 30, 1932

Publication of the first memorandum about Hans Krebs’ investigations of urea formation in animal tissue [7].


June 1, 1932
President von Hindenburg appoints former Center Party politician Franz von Papen to replace the resigning Brüning. The SA and SS bans are lifted.


June 13, 1932
Krebs is invited by Otto Meyerhof to give a lecture at the Kaiser Wilhelm Institute for Medical Research in Heidelberg (see Part 1, Chapter 2.5).


June 14, 1932
Comprehensive publication of the urea cycle [3] (see Part 1, Chapter 2.5).


July 31, 1932
In the Reichstag election, the NSDAP attains 37.3 %, but an end to this growth rate is foreseeable. (In his journal, Goebbels writes, "We will not attain an absolute majority in this way! We must take another path.")


August 13, 1932

In a speech, President Hindenburg refuses to transfer his power to Adolf Hitler.


November 6, 1932
In the Reichstag election, the NSDAP share of the vote drops to 33.1 %. Regardless, the Communists and the Right together maintain a majority blockade.


December 16, 1932
Invited by Max Planck to lecture at the Kaiser Wilhelm Society’s "Dahlem Medical Soiree" at the Harnackhaus in Berlin (see Part 1, Chapter 3).


January 30, 1933
The NSDAP becomes the most powerful party in Germany. Hitler is elected Chancellor in a coalition with the German National People’s Party and the Stahlhelmbund ("The Steel Helmet", a First World War veteran's organization also operating as a paramilitary organization). The NSDAP talks about seizing power.


February 1, 1933
Dissolution of the Reichstag.


January 31, 1933
Comparison of different yeast strains. The Fürstenberg yeast used in Freiburg proves to be superior to the yeast used by Warburg in Berlin.


February 1, 1933
Investigation of urea formation by dipeptides, such as glycyl-leucine and alanyl-glycine. The result: "Peptides slower than amino acids", meaning that urea is not formed directly from peptides, but from the amino acids released when they are hydrolyzed.


February 17, 1933
Göring instructs the police in Prussia to work with the SA, SS, and Stahlhelm, "in which circles the most important powers for maintaining the state are represented, to reach the best agreement."


February 22, 1933
The SA and SS are deployed as auxiliary police in Prussia.


February 27, 1933
Burning of the Reichstag. Hysteria after the fire facilitates abolition of all fundamental rights laid out in the Weimar Constitution.


February 28, 1933

Emergency decree "for the protection of the people and the state" suspends the most important fundamental rights. Communist Party delegates are arrested and communist and social democratic newspapers are banned.


March 5, 1933
The NSDAP attains 43.9 % of the vote in the Reichstag election. Together with other right-wing parties, they now have the majority.


March 21, 1933
Goebbels stages the opening of the new Reichstag as a "reconciliation of the old and the young Germany" ("Potsdam Day"). Social Democrats and Communists are not invited.


March 23, 1933
The Enabling Act was enacted by a 2/3 majority, 81 KPD (Communist Party of Germany) delegates are unlawfully not invited, 26 SPD (Social Democratic Party of Germany) delegates have already been arrested or fled. The Center and Liberal Parties consent, only the few remaining Social Democrats vote against the complete disempowerment of the parliament.


April 1, 1933
Nationwide call for a boycott of Jewish businesses.


April 7, 1933
The "Law for the Restoration of the Professional Civil Service" sees the first appearance of antisemitism in a law: “§3: Officials who are of non-Arian descent are to be retired. Section 1 is not in effect for officials … who fought during the World War at the front for the German Reich, … or whose fathers or sons were killed in the World War.”


April 6, 1933
Investigation of the deamination of glutamic acid to ketoglutaric acid in kidney tissue from dogs.


April 10, 1933
Investigation of ammonia formation in rat kidneys. Result: no ammonia is formed.


April 11, 1933
Continuation of the previous day's research, but on kidney tissue from guinea pigs.

This ends the portion of the laboratory notebook written in Germany.


April 12, 1933

Immediate suspension of Hans Krebs by the Dean of the Medical Faculty, surgeon E. Rehn. This same Dean praised Krebs at the end of 1932 as an outstanding scientist, whom the University of Freiburg should regard with pride.

In explanation, a letter from the Minister of Education is included, which states: "The Minister of the Interior has decided that all members of the Jewish race (regardless of their religion) who are employed in the civil service or educational facilities will be suspended until a further decision is made. All academic instructors and assistants in this category are to be informed that they are immediately suspended." Among Krebs' documents are some results (including invoices) for elemental analyses issued on the same day, which were forwarded to him.


April 13, 1933
On the first day of his involuntary suspension, Krebs cycles 15 km from Freiburg to St. Peter, located in the southern Black Forest, in order to spend the next eight days preparing a series of manuscripts for publication.


April 18, 1933
Notice of termination. Krebs is surprised by the impersonal and abrasive tone of the letter, because he knows the administrator quite well. He and the administrator’s son had recently completed a research project and published the results together [15].


April 22, 1933
Krebs had asked Albert Szent-Györgi for a sample of ascorbic acid for his experiments. Szent-Györgi had agreed to this and also advocated for Krebs in Cambridge. He wrote:

"If you really want to go to Cambridge, it would be good if you would write to Hopkins to assure him that you would be satisfied with even the most modest living. There are no major positions free there, and perhaps they will not dare to offer you a minor position. Please also ask Hopkins, if you would like to go to Cambridge, to give you the opportunity to do it. If you do not feel comfortable doing this, please draw upon my encouragement."


April 24, 1933
Krebs does not wait to be told a second time. He writes on the same day:

"Most honored Professor,

today Mr. Szent-Györgi wrote to me that your great kindness may make it possible for me to work in your laboratory in Cambridge. The letter from Mr. Szent-Györgi gives me the courage to contact you with the request that you take me on there.

Because I am Jewish, I have lost not only my position, but also all possibility to work in Germany. The government has already forbidden me to do any work in the laboratory, even though I will continue to receive my salary for a few more weeks. I would consider myself highly fortunate if I could continue my work with you. It naturally goes without saying that I would be satisfied with even the most modest circumstances, if I could continue my scientific activities in any way.

Would it be agreeable to you if I were to travel to Cambridge in the near future to discuss this question with you in person? Because I am forced to be on vacation, I have time to travel, and it would be a great pleasure to introduce myself to you and to personally thank you for your friendly disposition.

With my greatest veneration and thankfulness, I remain your highly respectful

Krebs"


April 26, 1933
Another offer of help comes to Krebs from his mentor Otto Warburg in Berlin:

"…If you lose your position, I could likely hire you here as a scientific guest and give you an apartment, a study, and about 250 Marks a month. However, England seems to me to be safer and more promising for you. Here, we don’t know what all is to come (although nothing has happened yet in Dahlem).

Best wishes,

your Otto Warburg"


April 29, 1933
In the meantime, Hopkins replies from Cambridge:

"I admire your work so much that I absolutely wish to help you. If it turns out that the necessary financial means are available, I would be happy to offer you a position in my laboratory…"


May 1, 1933
"Day of National Work" is proclaimed a legal holiday by the Nazis, of all people. With this, Hitler meets an old demand of the labor unions. By the next day, the unions would come to realize how underhanded Hitler's trick was.


May 2, 1933
Occupation of labor union offices by the SA and SS. Labor union officials are arrested and assets are seized. The Freiburg student newspaper publishes a manifesto of the "German student body", which is posted all over the university. The Vice-Chancellor of the University, anatomist von Möllendorff, orders the immediate removal of the posters from university property.


May 10, 1933
The national socialist mass organization "German Labor Front (Deutsche Arbeitsfront, DAF)" is founded and replaces the labor unions. Public burning of "un-german" writings in 50 cities. A planned book burning in Freiburg is canceled due to rain [16].


May 21, 1933
Submission of the manuscript entitled "Further Investigations of the Degradation of Amino Acids in Animals", which summarizes experiments for the clarification of the high consumption of ammonia in the presence of glutamate in rabbit and guinea pig livers. This also includes the experiment described on the last page of his laboratory notebook. The nature of the product remained unclear. Krebs gives the reason for the lack of a structural characterization in a single sentence ("The question of which nitrogen compounds are formed from the added ammonia and the amino acids, particularly the glutamic acid in unpoisoned kidney cells, remains unanswered because I had to abandon the work"). He is only able to complete this work later, in Cambridge [17,18].


June 14, 1933
A farewell letter arrives from his father:

"My dear Hans!

Before you leave German soil, I wish to send you my most sincere regards and wishes. I hope you get even more recognition and luck abroad than you have so far obtained in your homeland!

I hope that we will not see each other less often than before, whether in England or in Germany. I am even starting to learn some English (with Maria), even though the foreign and strange pronunciation does not come easily to my 66-year-old tongue. I dearly hope that you will write more often than before, and more extensively. In particular, please let me know soon the nature of the position you will obtain, whether it is a lectureship or a research position, salary, prospects, etc.

In conclusion, one more thing: If everything goes well for you abroad, as I dearly hope, do not forget your siblings who live in Germany! Especially not little Gisela and her mother, whom you may be called upon to protect and support.

I embrace you with all my heart,

Father”


Early June 1933
Because Krebs' laboratory equipment had been acquired with funds from the Emergency Association of the German Sciences and the Rockefeller Foundation, he obtains permission to export it. Because he is no longer allowed to enter his laboratory, his loyal co-workers pack his instruments, including two Warburg baths and 24 manometers, into 16 wooden crates and several suitcases and ship them to England.


June 19, 1933
In his autobiography, Hans Krebs wrote the following about this day:

"On June 19th, I said 'goodbye' to Henseleit and all of my co-workers at the university hospital. It was a very sad and deeply moving moment. Then I made my way alone to the Freiburg railway station to catch the 11 o'clock train."

Even when a German is being driven out of his homeland, he must properly give notice of his departure, including indicating his religion on the document. In this column, Krebs writes "non-denominational".


June 20, 1933
At 7:45, Hans Krebs arrives at Victoria Station in London. He is officially allowed to take 10 Marks with him; he smuggles 200 Marks between his books. His longtime friend Hermann Blaschko picks him up at the train station and they go to Blaschko's aunt, Helene Nauheim, with whom Krebs finds accommodation for the first few days.


June 22, 1933
Ban on the German Social Democratic Party


June 22, 1933
With linguistic help from Blaschko's aunt, Helene Nauheim, Krebs writes to Hopkins:

"Dear Sir Frederick Hopkins,

This is to tell you that I have arrived in England, since it became almost dangerous for me to stay in Freiburg any longer. ... I shall be very grateful if you could make it possible for me to see you at Cambridge this weekend."


June 24, 1933
Hans Krebs travels to Cambridge for Sunday tea with Sir Hopkins. Hopkins is only able to offer a Rockefeller stipend of 300 British pounds (a year!), an amount he considers to be too little for a scientist like Krebs. However, Krebs "did not hesitate for a moment".


June 28, 1933

Move to Cambridge. His first investment is a used bicycle for 3 pounds.


June 30, 1933
Röhm Putsch: In a combined action of the Armed Forces and the SS, SA leader Ernst Röhm and 200 high-level SA leaders are killed at the Stadelheim prison and at the Dachau concentration camp. In Berlin, Goering and Himmler use the opportunity to remove unpopular conservatives like General von Schleicher, Strasser, and others. The number of individuals murdered in Berlin is estimated at 100.


July 4, 1933
Forced self-dissolution of the Center Party


July 4, 1933
In his laboratory notebook, only the heading "Cambridge" indicates that Krebs had to leave his homeland. He is finally able to begin his work. The first entry in his laboratory notebook notes that he tared his weighing boats.


July 11, 1933

Hitler believes he has reached his goal and speaks of the "end of the National Revolution".


July 15, 1933

Heidegger signs the final dismissal of Hans Krebs. "The Minister of Education and Justice has ruled the following: according to the preliminary investigations, § 3 in the Law for the Restoration of the Professional Civil Service is applicable to Dr. H. A. Krebs. He is required to provide a statement within three days: You are herewith required to make your statement, should you even want to make one, in my office no later than 10:00 on July 20th."


July 23, 1933
Finally, the first real experiment in Cambridge: Investigation of the oxidative degradation of acetic acid in guinea pig livers. A new life begins for Hans Krebs.




References

[14] H. A. Krebs, W. A. Johnson, The role of citric acid in intermediate metabolism in animal tissues, Enzymologia 1937, 4, 148.

[15] H. Eitel, H. A. Krebs, et al., Hypophysenvorderlappen und Schilddrüse (in German), Klinische Wochenzeitschrift 1932, 12, 615.

[16] Dr. Birgit Ebbert, Bücherverbrennung 1933: Zur Erinnerung an ein fast vergessenes Ereignis (in German), www.buecherverbrennung.de. (accessed September 9, 2020)

[17] H. A. Krebs, Weitere Untersuchungen über den Abbau der Aminosäuren im Tierkörper (in German), Hoppe-Seyler’s Z. physiol. Chem. 1933, 218, 157.

[18] H. A. Krebs, Metabolism of amino-acids: The synthesis of glutamine from glutamic acid and ammonia, and the enzymic hydrolysis of glutamine in animal tissues, Biochem. J. 1935, 29, 1951.


The article has been published in German as:

and was translated by Caroll Pohl-Ferry.


Sir Hans Adolf Krebs (1900 – 1981) – Part 1

Discoverer of the citric acid and urea cycles forced to leave Nazi Germany in 1933


Sir Hans Adolf Krebs (1900 – 1981) – Part 3

The Nobel Prize in Physiology or Medicine in 1953 and Krebs' thoughts about life as a displaced person (will be published in January 2021)


See similar articles by Klaus Roth published on ChemistryViews.org

 

 

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