Each summer, as they have for almost a century, hundreds of students and summer investigators descend on Woods Hole and the MBL. For the past several summers, included in the hordes of cell biologists, physiologists, neurobiologists, and several other kinds of "ists", has been, of all things, a pediatrician. No, he hasn't been coming to treat the aches and pains of the other researchers' offspring--he comes to the MBL to do reasearch on the causes of birth defects--in sea urchins. Dr. William Speck is Chairman and Director of the Department of Pediatrics of Case Western Reserve University and Rainbow Babies and Childrens Hospital, institutions with which he has been affiliated since 1977. Dr. Speck, who claims to be the only pediatrician in the MBL Corporation, studies the effects of drugs and environmental pollutants on developing embryos. "The problems we see in the pediatric patients have changed," he explains. "Instead of infectious diseases, fifty to sixty percent of our patients now have some sort of congenital disorder." Dr. Speck is particularly interested in the effects of anticonvulsant drugs commonly prescribed for the management of epileptic seizures Dr. Speck has chosen the purple sea urchin, Arbacia punctulata as his research organism. Arbacia has several characteristics that make it an especially good choice: It is a common denizen of Woods Hole waters, it is easy to maintain in the lab and the female urchin can produce as many as half a million eggs during spawning season, which lasts throughout the summer. Fertilization and embryonic development are external and rapid. With sea urchin eggs, Dr. Speck can produce thousands of embryos and obtain results in 24 hours. Traditional research subjects such as mice and rats are expensive to maintain and provide much slower results. Among its other virtues, the sea urchin has been long and widely used as a study organism. Its development has been extremely well documented and described by generations of MBL embryologists; thus, when a particular effect is observed in an Arbacia embryo, the researcher immediately has very good clues as to the mechanism causing that effect. Dr. Specks research with Arbacia has shown that some drugs that cause birth defects in humans also cause developmental abnormalities in sea urchin embryos. For example, phenytoin (Dilantin), a commonly-prescribed anticonvulsant, causes a very specific set of abnormalities in babies born to mothers who have used the drug during pregnancy; the same drug causes specific abnormal cleavages in the developing Arbacia embryo. Valproic acid, another anticonvulsant, causes spina bifida in human infants and exogastrulation in Arbacia embryos.

Dr. Speck has also studied the effect of ethanol on Arbacia as a model for fetal alcohol syndrome in humans. Thus, the evidence is accumulating that substances that are teratogenic (i. e. substances that cause abnormal fetuses) in humans also cause developmental defects in the sea urchin. While there have been many false positives (altered pH, salinity, and abnormal light levels also are teratogenic in Arbacia), Dr. Speck has discovered no false negatives (i.e. drugs that are safe for sea urchin embryos and harmful to human fetuses) -- results that suggest Arbacia could used for quick, safe, and inexpensive initial tests for teratogenic effects of new drugs. Additional research is now proceeding in two directions. First, Dr. Speck is pursuing his initial interest in.the teratogenicity of anticonvulsant drugs. He has been testing a number of phenytoin derivatives to determine whether the anticonvulsive effect can be dissassociated from the teratogenic effect. Dr. Speck has found that one such derivative, discovered in Europe and proven therapeutically effective in tests there, causes no problems in Arbacia embryos. The next step will be to begin testing on mammalian embryos. Dr. Speck is also looking at possible synergistic effects of drugs -- for example, the commonly prescribed combination of phenobarbitol and phenytoin. Phenobarbitol has no teratogenic effect and appears to cause no potentiation of the phenytoin. Dr. Speck hopes that this line of research will lead to the development of additional non-harmful anticonvulsants, as well as other non-harmful drugs. Secondly, Dr. speck is trying to determine, on a molecular level, just what causes the teratogenesis. In the case of phenytoin, the data suggest a direct interaction between the drug and sea urchin DNA or RNA--rather than the presence of a reactive intermediate--is responsible for the developmental toxicity. It is possible that the drug interacts with embryonic MRNA via hydrogen bond formation and thus impairs the synthesis of critical proteins. Dr. Speck very much enjoys his summers of research in Woods Hole, and not only because he considers it a nicer place to be in the summer than Cleveland. He also finds his research with Arbacia medically valuable, and he believes laboratory research should be an important part of any physician's practice--so much so that he always brings a few medical students with him from Case Western ."The major breakthroughs in medicine don't occur at the bedside,". Speck explains. "They occur in the laboratory, and most are made by non-physicians. Learning this gives young physicians a sense of humility and perspective." It also, we might add, gives a few lucky ones a chance to participate in some valuable research with the MBL's resident pediatrician.