Past, Current and Future Presidents gathered at the 31st Annual Meeting in Boca Raton. Pictured are (left to right): I-ront row - Bob Staples (83-84), Millie Christian (88-89), Daphne Trasler (72-73), Clarke Fraser (62-62), Carole Kimmel (90-91), Bob Brent (67-68), Meredith Runner (66-67); second row - Ernie Zimmerman (89-go), Rich Miller (9192), John Sever (76-77), Marshall Johnson (74-75), Tom Shepard (68-69), Lew Holmes (85-86); third row - Bill Scott (81-82), Andy Hendrickx (86-87), Al Beaudoin (78-79), Dave Kochhar (82-83), Cas Grabowski (87-88), Dick Hoar (79-80), Chet Swinyard (80-81), and Mason Barr (92-93).
Teratology Society Presidents photographed at the 31st Annual Meeting of the Society Boca Raton Club, Boca Raton, Florida, June 25, 1991
TERATOLOGY 45:587-588 (1992)
Letters
Comments on “Reply to ‘Comments on “Moebius Syndrome: Animal Model-Human Correlations and Evidence for a Brainstem Vascular Etiology” ’ ” To the Editor: Lipson et al., (‘91) in defending their pa- West German paediatricians in Dusseldorf per on the Moebius syndrome (Lipson et al., on November 18, 1961, ’89) emphasize the importance of careful documentation of events of pregnancy in Lenz stated that he had definitely been able to clarifying the etiology of Moebius syntrace the intake of this specific drug during drome. Few would disagree that careful early pregnancy to fourteen of the twenty-one cases of grave deformity of the extremities. In clinical records are an invaluable resource three cases it was very likely that intake of in research into any birth defects. t h i s drug had occurred, and in one case Dr Of equal importance is the correct use of Lenz had obtained information from the hospireferences, for the average reader does not tal that another mild sedative, Doriden (Gluhave the opportunity to check statements tethimide) had been consumed. However, an accepted by an authoritative journal such as inspection of the original hospital records Teratology.Lipson et al. cite only one refershowed that in this case also Contergan, and ence in their letter, to pages 95-103 of not Doriden, had been prescribed to the Sjostrom and Nilsson’s “Thalidomide and woman. In the remaining three cases no clue was yet available to a possible consumption of the Power of the Drug Companies” (‘69). the suspected drug. (In fact, at a later date, This book is now out of print, which further Contergan intake could also be virtually hampers the researcher who wishes to check proved in these three cases.) Dr Lenz’s original the reference made to the circumstances of material had to be considered as strong cirLenz’s discovery of the link between thalicumstantial evidence for a causal relationship domide and phocomelia. Lipson et al. have between Contergan and phocomelia. misquoted the book in two details. Lenz did not, in the first instance, take note of “a mother who had peripheral neu- This account of Lenz’s study illustrates the ropathy and was convinced thalidomide was importance of establishing accurate detail the cause of her child’s deformities.” Nor is in each case, questioning the mothers on there any statement that “all but one had several occasions, and searching the clinical taken thalidomide during the pregnancy.” notes for confirmation of a confident verbal Sjijstrom and Nilsson’s statement (p. 98) statement. Such attention to detail is the hallmark of a good scientist. He deserves to quotes Lenz as follows: be quoted correctly by those who come after ”We had not found any drug in our case records him. As far as the coincidence of sensory neuup to that time which was common to all cases,” Dr Lenz said. The whole investigation ropathy in a mother and deformity in her could have ended at that point. “Then, one day baby was concerned, Lenz found this to be a mother of a deformed child told me that she exceedingly rare. He did not find such a cohad taken Contergan (thalidomide) during incidence in his initial series, and it ocpregnancy. We started to question the other curred in less than ten instances in his subwomen again and it soon became apparent sequent reviews of many hundreds of that, indeed, most of them had taken this drug. Checking of receipts and medical records gave families during compensation claims (personal communication). This is a fascinating additional support.” illustration of the known hypersensitivity of They also go on to say that, a t a meeting of embryonic cells compared with their adult Q 1992 WILEY-LISS. INC.
588
LETTERS TO THE EDITOR
counterparts. Neurons, in general, are the most sensitive of all cells to adverse environmental changes such as anoxia. The sensory neurons of adults are highly sensitive to thalidomide. Prior to its use as an antiemetic in pregnancy, thalidomide was marketed as a general sedative and it generated an epidemic of adult cases with profound, relatively intractable sensory peripheral neuropathy (Fullerton and Kremer, ’61). Sales strategy switched t o the pregnancy market. It is not surprising that thalidomide should have induced an embryonic form of sensory neuropathy expressed as congenital malformations, by its putative action on neural crest cells, the embryonic precursors of sensory and autonomic neurons (McCredie,’74). The high incidence of congenital malformations contrasts with the low incidence of maternal sensory neuropathy, and this discrepancy is a measure of the relative sensitivity of the embryonic neural crest to the presence of sensory neurotoxins in the environment.
LITERATURE CITED Fullerton, P.M., and M. Kremer (1961) Neuropathy after intake of thalidomide (Distaval). Br. Med. J. 2: 855-858. Lenz, W. (1980) Personal communication. Lipson, A.H., W.S. Webster, P.D.C. Brown-Woodman, and R.A. Osborn (1989) Moebius syndrome: Animal model-Human correlations and evidence for a brainstem vascular etiology. Teratology, 40:339-350. Lipson, A.H., W.S. Webster, P.D.C. Brown-Woodman, and R.A. Osborn (1991)Reply to “Comments on ‘Moebius syndrome: Animal model-Human correlations and evidence for a brainstem vascular etiology.”’ Teratology, 43557. McCredie, J. (1974) Embryonic neuropathy. A hypothesis of neural crest injury as the pathogenesis of congenital malformations. Med. J. Aust. 1:159-163. Sjostrom, H., and R. Nilsson (1972) Thalidomide and the Power of the Drug Companies. Penguin Special, Penguin Books, London.
JANET MCCREDIE,MD Royal Prince Alfred Hospital Sydney, NSW Australia
Teratology Society Presidents photographed at the 31st Annual Meeting of the Society Boca Raton Club, Boca Raton, Florida, June 25, 1991
TERATOLOGY 45:587-588 (1992)
Letters
Comments on “Reply to ‘Comments on “Moebius Syndrome: Animal Model-Human Correlations and Evidence for a Brainstem Vascular Etiology” ’ ” To the Editor: Lipson et al., (‘91) in defending their pa- West German paediatricians in Dusseldorf per on the Moebius syndrome (Lipson et al., on November 18, 1961, ’89) emphasize the importance of careful documentation of events of pregnancy in Lenz stated that he had definitely been able to clarifying the etiology of Moebius syntrace the intake of this specific drug during drome. Few would disagree that careful early pregnancy to fourteen of the twenty-one cases of grave deformity of the extremities. In clinical records are an invaluable resource three cases it was very likely that intake of in research into any birth defects. t h i s drug had occurred, and in one case Dr Of equal importance is the correct use of Lenz had obtained information from the hospireferences, for the average reader does not tal that another mild sedative, Doriden (Gluhave the opportunity to check statements tethimide) had been consumed. However, an accepted by an authoritative journal such as inspection of the original hospital records Teratology.Lipson et al. cite only one refershowed that in this case also Contergan, and ence in their letter, to pages 95-103 of not Doriden, had been prescribed to the Sjostrom and Nilsson’s “Thalidomide and woman. In the remaining three cases no clue was yet available to a possible consumption of the Power of the Drug Companies” (‘69). the suspected drug. (In fact, at a later date, This book is now out of print, which further Contergan intake could also be virtually hampers the researcher who wishes to check proved in these three cases.) Dr Lenz’s original the reference made to the circumstances of material had to be considered as strong cirLenz’s discovery of the link between thalicumstantial evidence for a causal relationship domide and phocomelia. Lipson et al. have between Contergan and phocomelia. misquoted the book in two details. Lenz did not, in the first instance, take note of “a mother who had peripheral neu- This account of Lenz’s study illustrates the ropathy and was convinced thalidomide was importance of establishing accurate detail the cause of her child’s deformities.” Nor is in each case, questioning the mothers on there any statement that “all but one had several occasions, and searching the clinical taken thalidomide during the pregnancy.” notes for confirmation of a confident verbal Sjijstrom and Nilsson’s statement (p. 98) statement. Such attention to detail is the hallmark of a good scientist. He deserves to quotes Lenz as follows: be quoted correctly by those who come after ”We had not found any drug in our case records him. As far as the coincidence of sensory neuup to that time which was common to all cases,” Dr Lenz said. The whole investigation ropathy in a mother and deformity in her could have ended at that point. “Then, one day baby was concerned, Lenz found this to be a mother of a deformed child told me that she exceedingly rare. He did not find such a cohad taken Contergan (thalidomide) during incidence in his initial series, and it ocpregnancy. We started to question the other curred in less than ten instances in his subwomen again and it soon became apparent sequent reviews of many hundreds of that, indeed, most of them had taken this drug. Checking of receipts and medical records gave families during compensation claims (personal communication). This is a fascinating additional support.” illustration of the known hypersensitivity of They also go on to say that, a t a meeting of embryonic cells compared with their adult Q 1992 WILEY-LISS. INC.
588
LETTERS TO THE EDITOR
counterparts. Neurons, in general, are the most sensitive of all cells to adverse environmental changes such as anoxia. The sensory neurons of adults are highly sensitive to thalidomide. Prior to its use as an antiemetic in pregnancy, thalidomide was marketed as a general sedative and it generated an epidemic of adult cases with profound, relatively intractable sensory peripheral neuropathy (Fullerton and Kremer, ’61). Sales strategy switched t o the pregnancy market. It is not surprising that thalidomide should have induced an embryonic form of sensory neuropathy expressed as congenital malformations, by its putative action on neural crest cells, the embryonic precursors of sensory and autonomic neurons (McCredie,’74). The high incidence of congenital malformations contrasts with the low incidence of maternal sensory neuropathy, and this discrepancy is a measure of the relative sensitivity of the embryonic neural crest to the presence of sensory neurotoxins in the environment.
LITERATURE CITED Fullerton, P.M., and M. Kremer (1961) Neuropathy after intake of thalidomide (Distaval). Br. Med. J. 2: 855-858. Lenz, W. (1980) Personal communication. Lipson, A.H., W.S. Webster, P.D.C. Brown-Woodman, and R.A. Osborn (1989) Moebius syndrome: Animal model-Human correlations and evidence for a brainstem vascular etiology. Teratology, 40:339-350. Lipson, A.H., W.S. Webster, P.D.C. Brown-Woodman, and R.A. Osborn (1991)Reply to “Comments on ‘Moebius syndrome: Animal model-Human correlations and evidence for a brainstem vascular etiology.”’ Teratology, 43557. McCredie, J. (1974) Embryonic neuropathy. A hypothesis of neural crest injury as the pathogenesis of congenital malformations. Med. J. Aust. 1:159-163. Sjostrom, H., and R. Nilsson (1972) Thalidomide and the Power of the Drug Companies. Penguin Special, Penguin Books, London.
JANET MCCREDIE,MD Royal Prince Alfred Hospital Sydney, NSW Australia
