410 THE BIOLOGY OF HYDRA : 1961 



primitive hydra. We have made the most extensive investigations 

 in this respect with regeneration in planaria (5). It has been most 

 gratifying to find that many of the phenomena we have observed 

 in hydra regeneration have analogous responses in the planaria. 

 For example, exposure of a decapitated planaria to low concen- 

 trations of lipoic acid during the first part of the regenerative 

 process results in arrest of regeneration and the development of 

 an acephalic organism. These planaria appear to lead normal 

 lives except they do not respond to the presence of food— they 

 literally must be led to their piece of rat liver, but once they are 

 on it they feed normally. Cutting again in the non-regenerating 

 head area will initiate normal regeneration, a situation analogous 

 to that observed in hydra. 



Because planaria provide larger amounts of material with which 

 to work, we are using this organism for enzymatic studies. Because 

 the lipoic acid effect is so unique in regenerating hydra and 

 planaria (and in a number of other organisms undergoing de- 

 velopmental changes), we have concentrated our efforts on 

 determining the biochemical mechanisms which this compound 

 must alter to produce the unusual morphogenic effects. It was 

 found (a) that the presence of oxaloacetate (but not aspartate 

 or a-ketoglutarate ) during the exposure of regenerating systems 

 to lipoic acid prevented the latter from arresting regeneration and 

 (b) that lipoic acid inhibited certain enzymatic activities of plana- 

 ria homogenates and preparations from mammalian tissues. Fur- 

 ther investigation on enzymes related to oxalacetate metabolism 

 showed the DPN-dependent malic dehydrogenase to be unusually 

 sensitive to lipoic acid and to other related cyclic disulfides but 

 not to the reduced (dithiol) derivatives. On the basis of several 

 types of observations on a number of other enzymatic systems, 

 we have concluded that the mechanism of action of these cyclic 

 disulfides is unique for the DPN-malic dehydrogenases ( 6 ) . 



This was true not only in extracts prepared from planaria but 

 was shown to be the case in highly refined porcine preparations 

 obtained commercially. Subsequent tests with extracts of acetone 

 powders prepared from hydra showed that their malic dehydro- 

 genase activity was likewise inhibited by very dilute concentra- 

 tions of lipoic acid and its homologs. In both planaria and hydra 



