The Midwife Toad and Alma Mahler: Epigenetics or a Matter of Deception?
2010; Wiley; Volume: 24; Issue: 8 Linguagem: Inglês
10.1096/fj.10-0801ufm
ISSN1530-6860
Autores Tópico(s)Science, Research, and Medicine
ResumoThe FASEB JournalVolume 24, Issue 8 p. 2591-2595 EditorialFree Access The Midwife Toad and Alma Mahler: Epigenetics or a Matter of Deception? Gerald Weissmann, Gerald Weissmann Editor-in-ChiefSearch for more papers by this author Gerald Weissmann, Gerald Weissmann Editor-in-ChiefSearch for more papers by this author First published: 01 August 2010 https://doi.org/10.1096/fj.10-0801ufmCitations: 1AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Alma Mahler Gropius Werfel (1879–1964), Getty Images. The principal matter of importance in this is an artificial coloring, probably with India ink, through which the black coloring of the skin in the region carrying the stripes is said to have been faked. Therefore it would be a matter of deception that presumably will be laid to me only. Who besides myself had any interest in perpetrating such falsifications can only be very dimly suspected. … I hope that I shall gather together enough courage and strength to put an end of my wrecked life to-morrow. Paul Kammerer Science, 1926 (1) Rather than committing fraud, it seems that Kammerer had the misfortune of stumbling upon non-Mendelian inheritance at a time in which Mendelian genetics itself was just becoming well accepted. A. O. Vargas, "Did Paul Kammerer Discover Epigenetic Inheritance?" 2009 (2) I kept records, very exact records. That, too, irritated Kammerer. Somewhat less accurate records with positive results would have pleased him more. Alma Mahler-Werfel Mein Leben [My Life] 1960 (3) Paul Kammerer (1880–1926), from J. R. Whittaker (Aug. 1985) Paul Kammerer and the suspect siphons. MBL Science. THE ORIGIN OF THE SPECIOUS When a scientist commits suicide a few weeks after a paper in Nature shows that he faked a critical experiment, we might assume the case closed. However, if the scientist is the Viennese biologist Paul Kammerer (1880–1926) and if the case is the notorious "Case of the Midwife Toad," then the docket remains open. Kammerer's wacky campaign to prove the heritability of acquired characteristics is as topical today as on September 23, 1926, when he shot himself on an Austrian hill. Not one of his controversial "discoveries" has ever been duplicated, his notion that musical talent is heritable remains on the shelf, and his contention that the Prohibition laws in America would induce a genetically superior race of teetotalers is too absurd to consider (4–6). However, his star has risen once again, thanks to a bold claim that he is the father of epigenetics (7) and a new look at his place in the history of image manipulation (4). Kammerer's claim in 1909 that male midwife toads pass on acquired nuptial pads to the fourth generation of their progeny has made him a hero to armchair generals in the nature/nurture wars (8). His career was first resurrected by a great writer, Arthur Koestler, who pleaded Kammerer's innocence in "The Case of The Midwife Toad" (9). Reviewing that book, Stephen Jay Gould thought that Kammerer's tale of the toad was probably alright; he cut Kammerer slack for his progressive politics and his "penetrating intelligence" (10). That was 1972, and the case became moot for a generation as DNA became RNA, etc., etc. Suddenly, last October, A. O. Vargas of Santiago, Chile, re-reinterpreted the midwife toads in the light of modern epigenetics and paternal imprinting. Based on his analysis of "parent-of-origin" data buried in Kammerer's toad papers, Vargas argued that Kammerer was "the actual discoverer of epigenetic inheritance" (2, 7). Editorial fanfares in the Journal of Experimental Zoology and Science praised Vargas for unearthing what "may have been the first demonstration of a recently recognized [sic] phenomenon: epigenetics" (11, 12). Shucks, and I thought Waddington charted the epigenetic landscape, Shirley Tilghman got imprinting right, and Jean-Pierre Changeux planted the flag for epigenesis in synaptic affinity (13–15). ALMA TELL US … Well, epigenetics may be looking for a father, but I'm persuaded that Kammerer's short, frantic career was based on error and—his word in the suicide note—deception. Indeed, error and deception pop up in his science, his personal life, and his public statements. It's rare for a scientist to commit suicide after his work has been refuted. It's rarer still for the suicide note to be published in Science (1). However, it's completely unheard of for folks in the same lab to snitch on their colleague in print. Franz Megusar, who was Kammerer's co-worker in Vienna's Biologischen Versuchsanstalt (the Experimental Biology Station of Vienna, also called the Vivarium), included these comments in the annual Proceedings of the Conference of German Scientists in 1913: The processes that Kammerer reports I could not confirm, neither in his experiments nor in my own even though I have been monitoring his imprecisely executed experiments constantly for nearly ten years … Kammerer's representations contain crude untruths and falsifications of the actual circumstances. (16) Megusar was not the only close observer of Kammerer's sharp practice at the Vivarium. There was Alma Mahler, the femme fatale of 20th century Vienna modernism. Married, successively, to Gustav Mahler (the symphonies), Walter Gropius (the Bauhaus), and Franz Werfel ("The Song of Bernadette"), her close intimates included Gustav Klimt and Oskar Kokoschka (the painters), and Gerhart Hauptmann (the playwright), as well as a legion of others (17). She was celebrated on both sides of the Atlantic, winding up in a ditty of Tom Lehrer's: Her lovers were many and varied,From the day she began her—beguine.There were three famous ones whom she married,And God knows how many between.Alma, tell us!All modern women are jealous.Which of your magical wandsGot you Gustav and Walter and Franz? (18) One of those "many between" was Paul Kammerer, known to the gratin of Vienna as a womanizer, a "wizard of lizards," an amateur musician and friend of Gustav's. Although Alma later confessed that the biologist was not up to his artistic competitors—"he was the clown of my whole circle"—they had a brief fling. He had more of a fling than she: in one of his passionate letters, Kammerer threatened Alma that he would shoot himself over Gustav Mahler's grave if she did not marry him. She didn't; Walter was groping about. She was soon on to the next but not before warning Kammerer's current wife (he had begun his own beguine) to "get that pistol out of the house" (17). Yet, for 2 years, 1911–1912, between Gustav and Walter, Alma assisted Kammerer at the Vivarium. She helped Kammerer with spotted salamanders, the skin patterns of which were alleged to be heritably affected by the color of sand on which they were reared. Her autobiography describes the reptile work and its later refutation by E. G. Boulenger of the London Zoo. It corroborates Megusar's description of Kammerer as a mendacious observer: He wanted positive results in his research so much that he would unconsciously depart from the truth. This trait explains to me his later problems when English researchers showed that "on further examination, his [salamander] experiments proved invalid." On that occasion the mimicry of salamanders was the subject. These experiments, with which I helped, were rushed into print and not accurately documented. (3) The salamander experiments that Alma had witnessed established Kammerer as the father of photographic image manipulation (19, 20). Kammerer explained to his protesting editor that he had inked in colored spots on photos of experimental salamanders, as "The glare from the skin gave the impression of spots where none were present and the spots that were present were washed out in the glare" (21). The passage is worthy of Danny Kaye in "The Court Jester": "The pellet with the poison's in the vessel with the pestle, the chalice from the palace has the brew that is true," but image manipulation is serious business these days. Although there is general agreement over what may legitimately be "image-enhanced" in biological images (22), matters of deception pop up all too often. Picassos of Photo Shop and Raphaels of the Raster map have been involved in a flock of "Retractions" or "Editorial Expression of Concern" in recent pages of Science, Proceedings of the National Academy of Sciences USA, and the FASEB Journal (23–27). The mischief has been followed by extensive self-flagellation and almost universal calls for forensic examination of each pre-publication image. Using such programs to detect artful dodgers, our colleagues at the Journal of Cell Biology report that an astounding 25% of the articles accepted for publication contain at least one image that violates the journal's guidelines (28). What hath Kammerer wrought? A male midwife toad, Alytes obstetricians, Getty Images. BLACK PADS AND SPURIOUS SIPHONS Our Viennese friend was finally undone, not by image manipulation but by India ink. Kammerer, it seems, had mastered another art form: the manipulation of actual specimens. We know now that his unrepeatable salamander data were the result of fraud or foolishness but so was the midwife toad. Kammerer admitted in his suicide note that he had found his preserved salamanders "blackened," ditto the pads of the midwife toad (12)! Kammerer had claimed that land-dwelling, male midwife toads, which carry their partner's fertilized eggs on their own back (see image above), would not only acquire nuptial pads when arid conditions forced them into water but also that these black, horny protrusions could be passed on to male progeny to the F6 generation. The inheritance of that acquired characteristic would permit land-dwelling toads to take on the phenotype of their water-dwelling cousins. (Male frogs and toads that live in ponds develop nuptial pads with which to clasp their slippery partners while mating.) G. K. Noble, a herpetologist from the American Museum of Natural History, went to Vienna to examine Kammerer's last pickled specimen with "inherited" nuptial pads and discovered that India ink had been used to create the illusion of the blackened stucture (29). Noble's 1926 article in Nature, which detailed "this matter of deception," led to that shot in the head. Ciona intestinalis, J. R. Whittaker, Op. cit. Kammerer's last words about the matter pointed to another origin of the specious: "Who besides myself had any interest in perpetrating such falsifications can only be very dimly suspected" (1). Thomas Hunt Morgan of Columbia wrote to his friend G. K. Noble shortly after Kammerer's suicide note appeared in Science: Kammerer has done one more dirty trick in trying to put the fraud over on to one of his assistants. Remember that this is not the first time. either, that he has been caught and all responsible people will, I think, draw the same conclusion. (30) It was certainly not the first time that he had been caught. Kammerer claimed that the critical experiment, which "prove the inheritance of acquired characteristics," was the heritability of hyper-regenerating siphons in the tunicate, Ciona intestinalis (31). Kammerer purported to show that when the two siphon ends (see photo above) of this protochordate were amputated, the new siphon tubes became longer upon regeneration than the original tubes and that the complete elongation was inherited by the next generation. The whole experiment supposedly involved two sequential siphon regenerations, after which, a regeneration of a lower section of the body, containing the gonads, was caused to occur before the animals were crossed for the next generation (32). Three refutations of these claims have been published. In 1923, Harold Munro Fox of Cambridge wrote in Nature that "I have repeated the amputation experiments and find that the regenerated siphons do not grow beyond the normal length" (33). In 1930, a Russian scientist, Julius Wermel, published 26 pages of data about Ciona regeneration and concluded: no elongation, no heredity (34). The most damning refutation was that of J. R. Whittaker, a former director of the Marine Biological Laboratory (MBL) at Woods Hole, who spent two summers following up Arthur Koestler's charge that someone, somewhere try to repeat the Ciona work (35). Whittaker had followed Kammerer's directions to the letter and concluded: Ciona siphons did not, of course, regenerate longer after their surgical removal. But most telling was the gonadal regeneration part of Kammerer's supposed experiment. This involved a completely lethal operation from which animals could not recover … I was left with no remaining doubt that the Ciona results were also an invention of Paul Kammerer's high-strung imagination. (32) A HIGH-STRUNG IMAGINATION The conclusion Whittaker drew in 1985 could apply to Kammerer's entire output. Kammerer had presented evidence for his neo-Lamarckian notions about the inheritance of acquired characteristics to two audiences. To persuade biologists, he had performed all of those experiments—refuted or not—and published scores of technical papers and seven full-length books. For the wider public of his day, his lecture-demonstrations, books, and pamphlets attracted broad attention. To the crowds who came to listen in Europe and America, he must have sounded like E. O. Wilson on one day and Deepak Chopra on the other. In 1912, he'd written a short work assuring the world that musical talent was heritable; he dedicated the volume to Alma and her daughter (5). Jacques Loeb, writing from the MBL, commented on the notion: Kammerer … claims that an interest in music on the part of parents produces offspring with musical talent. In such claims much depends upon the subjective interpretation of the observer. The writer is not aware that there is at present on record a single adequate proof of the heredity of an acquired character. (36) However, lack of adequate proof didn't bother Kammerer. On a visit to America, he gave a series of lecture demonstrations, collected as The Inheritance of Acquired Characteristics (1924) (37). Scrutinized today, it's a collection of Ripley-derived Believe-It-or-Nots. The volume features his drawing of a Japanese dancing mouse with a "mutilated" tail and two of her young progeny also "born with mutilated tails," an observation on the heritability of acquired characteristics that might have surprised readers whose forefathers had long practiced the art of circumcision. He also hit the press with this headline in the The New York Times. (6): BIOLOGIST TO TELL HOW SPECIES ALTERDR KAMMERER, "DARWINS SUCCESSOR"ARRIVES FROM VIENNA FOR LECTURES A scientist who did not hesitate to explain to his editor that he was forced to manipulate spots on photos of salamanders had no trouble assuring the Times that "The next generation of Americans will be born without any desire for liquor if the prohibition law is continued and strictly enforced" (6). He also assured those packed audiences at his lectures that Germany and Austria were far ahead of the United States in their effort to improve the race by cultivating physical fitness and eugenical breeding in accord with his personal notion of Korperkultur und Rasse (Bodily Fitness and Race Culture) (38). I'm afraid that Kammerer's story remains pertinent today, when our journals print retractions of articles that have sported manipulated images, duplicated data, and fabricated authorship. 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