Hilde Mangold: Another Rosalind Franklin?

One of the most famous Nobel Prizes ever presented was given to three scientists, Watson, Crick and Wilkins, in 1962 for shedding light on the secondary structure of DNA. But it was also one of the most controversial. This is mainly due to these scientists using and ‘abusing’ the results obtained by their young colleague, Rosalind Franklin, who unfortunately had passed away by that time and could not longer receive the award. However, there is another case that took place several years before this that shares some similarities with Franklin. It took place with the German embryologist Hilde Mangold (October 20, 1896 – September 4, 1924) and the director of the laboratory where she worked on her thesis, Hans Spemann, who also received the Nobel Prize in Medicine in 1935. 

SCIENCE AND LIFE

Hilde Mangold worked on her doctoral thesis in Spemann’s laboratory starting in the early 1920s. There, following multiple tests and experiments with transplants of the dorsal lip of the blastopore (the hole that opens during the gastrula stage in animal development) in an amphibian embryo onto the ventral side of another embryo in the same stage, she confirmed that another amphibian started to grow in the transplant area, and a Siamese amphibian appeared in the whole embryo. In order to determine what was taking place, for the donor in the transplant she used embryos of a species of amphibians that was a different color than the recipient species. She observed that the new, additional amphibian that originated after the transplant had some parts that were the color of the donor species, and others the color of the recipient species. At the time, molecular techniques did not exist, such as DNA analysis to identify the nature of the tissue and organs that grew after the transplant, but she was able to clarify this.

In her thesis, Mangold clearly demonstrated for the first time that there were regions of animal embryos that seemed to serve as ‘organizers’ and inducers of organ and tissue development. With it, she gave rise to a new field of research that still exists today: experimental embryology. And in the first half of the 20th Century, this discovery was as important as the discovery of the secondary structure of DNA in the second half of the century. In fact, Spemann receiving the Nobel Prize in 1935 was primarily based on research that Mangold had carried out in her doctoral thesis. 

Mangold presented her doctoral dissertation in 1923 and published an article ⁽¹⁾ based on it in 1924 with Spemann listed as the first author and Mangold as the second author. (See below for more information.) But the young researcher died that same year in 1924 in an unfortunate household accident while preparing food for her baby. She therefore never lived to see the publication that was based on  her thesis, nor could she aspire to the Nobel Prize (Would they have considered her? See below.). She also did not live to see her son grow up, who later died in World War II. 

MACHISMO

After her doctoral dissertation, Mangold denied that Spemann actively participated in the research, also insisting that she should be listed as the first author of the publication. She also reported an environment of machismo in the laboratory, which was confirmed by other female researchers ⁽²⁾. For example, Spemann initially assigned her an abstruse research topic that led to nothing. Finally, when Spemann received the Nobel Prize in 1935, although he mentioned her, he tried to downplay her role. ⁽³⁾ In fact, there is an embryology principle that recognizes this discovery and is currently known as Spemann-Mangold, but due to his comments at the Nobel awards ceremony, it was initially attributed only to Spemann, something that unfortunately continues to occur in some cases.

Taken near the blastopore of a pigmented amphibian embryo, a graft is transplanted to a different place on a non-pigmented embryo. The transplant initiates secondary invagination and gastrulation, which eventually result in an entire secondary larva. The tissues that come from the graft are perfectly integrated anatomically with those of the host cells, as seen in the transparent view of the secondary region of the tail (bottom right). 

Furthermore, some embryologists maintain that Spemann did not take into account the experiments that another young American female scientist Ethel Browne (1885-1965) carried out in the early 20th Century on hydras and sea urchins, which proved the same thing that the Germans later demonstrated in amphibians.  Ethel  Browne sent this research to Spemann, who even highlighted the conclusions that were just like his, but he never mentioned them. On occasion, he has tried to justify this omission by saying that sea urchins and hydras are biologically very distant from amphibians, but it has recently been attributed to Brown being a woman, and very young ⁽⁴⁾.     

NAZISM 

It has been said that at some Nobel award ceremonies, Spemann pronounced the Nazi greeting, or something similar, shocking the other Nobel recipients that year, including the daughter of  Madame Curie and her husband. In Spemann’s case, the Nazis were preaching to the choir. In fact, before Hitler rose to power in 1933, he participated in a tribute that was held for the death of a student-soldier affiliated with the Nazis. Then, although he was not a member of the Nazi party, he did have ties to Nazi philosophers and published articles praising the great contributions of Nazis to science.  Finally, when he retired in 1937, he transferred his position as a professor and the ‘power’ of the Nobel Prize to one of his students: the widowed husband of Mangold, who was a convinced member of the Nazi party. 

Spemann’s diverse research – he also researched cloning – had enormous repercussions on a scientific level both in his country and in the rest of the world, hence the recognition with a Nobel Prize. But it also had repercussions on a philosophical level in Nazi Germany. In fact, they maintained, even Spemann himself, that the discovery of the organizing region of the embryo demonstrated the existence of a holistic vital force within living beings. It was one of the last attempts to defend vitalism.

And it even had repercussions on a political level in Germany because when the Nazis came to power in 1933, they took advantage of the prestige that came from Spemann’s Nobel Prize to make a ‘sui generis’ interpretation of the finding. They tried to popularize the idea that a force exists in nature, the organizing center, that plays a hierarchical and leadership role. A force that was even above hereditary factors. In this way, they ‘justified’ the need to also have a leader with omnipresent hierarchical authority.  

This concept fell apart because advances in biology demonstrated that when the ‘organizer’ of development is transplanted, no magical omnipresent vital force is transplanted. Only certain proteins and other development initiating and development inducing compounds are transplanted. But the research that has been conducted, and continues to take place, in this field on a molecular level is one of the most fruitful in biology.

CONCLUSION

What is reported here is a bit of a summary of the life and scientific legacy of Hilde Mangoldt. Like Rosalind Franklin, she had to fight against chauvinistic attitudes in her short life, especially from her research director, who, to make matters worse, had several ties to the Nazis. And after Mangold’s death – just like what Watson, especially, did to Franklin – he even tried to erase or blur her great contribution to science. 

This has been changing in recent years. For example, to recognize the importance of the work by the young scientist, in 2021 the research building at Freiburg University (Germany) where she and Spemann did their work was named after her, but they did not ‘remember’ the Nobel Prize.

Manuel Ruiz Rejón

BIBLIOGRAPHY

1. Spemann, H. and Mangold, H. 2001. Induction of embryonic primordia by implantation of organizers from a different species. 1923. Int. J. Dev. Biol.Classical Article. 45(1): 13-38.
2. Papaioannou, V.E. 2019. Salomé Gluecksohn-Welsch. Biographical Memoirs of  Fellows of the Royal Society, 67:153-171.
3. Spemann, H. Dec. 12. 1935. The Organizer-Effect in Embryonic Development. The Nobel Prize Lectures.
4. Lenhoff, H.M. 1991. Ethel Browne H.S. and the Discovery of the Organizer Phenomenon. Biol. Bull.
5. When searching for ‘Mangold H, CIBSS’ in Google several pages on her are found. The one entitled ‘Hilde Mangold: A pioneer in signalling [signaling] research’ is especially interesting.