GUESSING IN BIOLOGY Acceptance of the Special Award By J•ZROME GROSS, M.D.* MY SENSE of pleasure and of surprise were equally great on learning of this award you have given me. It is a very satisfying feeling to know that the work one is doing in a highly specialized and seemingly narrow area has evoked interest in totally unexpected quarters. I have also noted that a distinguished company of investigators has received this award, and I am honored to be listed among them. it is clear that the intellectual and scientific interests of your Society extend well beyond the confines of cosmetology. When a man is given the privilege of speaking for fifteen minutes to an intelligent captive audience on a subject of his own choosing, the re- sponsibility is considerable and the opportunity challenging. The easy way out is to discuss one's own work. Instead, I will take a risk and pose as a crystal ballgazer, focusing on a selected area. The word is out that the near future will witness explosive advances in biology comparable with those in nuclear physics. This may well be true. The rapid advances in analytical techniques, both physical and chemical, which can be applied directly to biological systems have produced giant strides in our knowledge of the structure and function of the substances controlling heredity, in the detailed pathways of synthesis for both small and large biologically important molecules, and in our understanding of the structure and interactions between large molecules such as enzymes and tissue proteins, which are at the root of physiological function. Our new knowledge of the intimate structure of cells and tissues down to the molec- ular level is permitting us to make direct correlations between controlled test tube experiments and the related chemical reactions within the cells. The great advances in our knowledge of the chemistry of bacteria are providing considerable insight into the mechanisms which regulate syn- thesis and growth. In my opinion, these advances are themselves the tools to be used in making possible the next biological giant step. My own crystal ball, along with that of others, projects an image of developmental biology, the field of study which examines the changes in structure and function * Massachusetts General Hospital, Boston 14, Mass. 421

422 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS of an organism from its birth to its death. This field of study not only encompasses embryologic development but also senescence. I have a strong feeling that the processes which operate in aging may be more clearly manifest in early development but have been obscured by our highly prejudiced modes of thinking. If we can but understand how an organism changes its form and function with time we should learn more of the nature of congenital malformations, of the crippling deformities of chronic disease, the mechanism of healing and regeneration and perhaps the true nature of aging processes. The vast descriptive knowledge accumulated during the past hundred years concerning the embryonic development of a variety of animals, plus the wealth of data obtained from more recent experimental embry- ology, provide the important biologic problems to be worked by the modern tools of molecular genetics, physical chemistry, metabolic chemistry, tissue fine structure analysis, and other rapidly advancing disciplines. Among the many exciting embryological problems hanging like near ripe plums I would like to discuss three very briefly. It was observed more than forty years ago that if the several tissue layers of a variety of organs, such as epidermis and dermis of the skin, were cleanly separated and allowed to grow independently in tissue culture they underwent dedif- ferentiation to a rather nondescript appearing cell layer. However, if the two cell types were placed in contact with each other they would revert back to their original form and function, and the whole culture would then resemble the organization of the original complex organ. This was shown most dramatically in glandular tissue where the separated duct glands in culture grow out as a thin flat layer of cells. Upon adding back the connective tissue they immediately grow into a series of tubes and lobules nearly identical with the original glandular organ. It has been demon- strated by the interposition of a barrier such as a fine pored filter between the epithelial and connective tissue cells that some as yet unknown chemical substances pass from the connective tissue to the duct cells and induce them to differentiate. This type of experiment has been performed in innumerable ways. Whole young developing embryos have been com- pletely taken apart, the cells dissociated from each other by chemical means to form a suspension and the scrambled cells piperted into a culture medium. In the most incredible way these cells unscrambled themselves to reproduce a well-organized developing embryo. The experiment has been carried even further. The well-developed kidney of a hatched chick has been dissociated into suspensions of its individual cells and samples of these cell suspensions cultivated upon the membranes of an embryo chick. Within days these cells reassociated themselves into the highly specific organization recognizable as a chick kidney. The mechanism whereby this type of remarkable cell sorting and spontaneous reconstruc-