NINTH SPECIAL AWARD 423 tion of an organ can occur remains shrouded in mystery at this time. How- ever, on the molecular level we are learning rapidly the mechanism whereby populations of large molecules seek each other out in the test tube and under the influence of known physical chemical forces associate in the form of a fabric characteristic of the native tissue. The possible future implica- tions of these experiments are clear and exciting. They should give us important insight into the forces and factors responsible for growth, form, specialized development, and the aberrations in the processes. It has been well known for several hundred years that certain vertebrates can regenerate lost limbs. In 1768 the complete regeneration of the amputated limbs of the salamander was described in detail, and since that time libraries have been filled with published efforts to determine why the amphibian can regenerate a limb with a five-fingered hand composed of bones, joints, tendons, ligaments, muscles, nerve and skin, whereas mam- mals cannot. In the last few years there has been a new burst of activity in this field of study and new optimism with regard to the possibility of eventually learning how to regenerate functional structures in mammals. A third area of considerable interest has to do with the manner in which an animal remodels his tissues during growth and development. It is clear that the structural changes in organs such as bone and skin during embryonic growth, maturation and senescence involve a continuous process of new synthesis of structural elements, their deposition in a highly organized fashion and their removal, all synchronized in time and space in such a way as to provide continuous changing shape without loss of function. In order to study this process most efficiently, one hunts up and down the animal kingdom for the best subject to use. Perhaps the most dramatic example of remodeling is to be found in the transformation of the lowly polywog into a frog under the influence of the thyroid gland. The bullfrog tadpole over a period of two years grows to an average length of six to eight inches, of which the long muscular tail accounts for two- thirds his length. During spontaneous metamorphosis induced by the outpouring of endogenous thyroid hormone, or by artificial induction through the addition of the hormone to the aquarium water, the entire tail may be resorbed within two weeks, the four legs will erupt almost overnight and grow at a fantastic rate, the gills will be completely resorbed and replaced by lungs, the mouth change in shape from a small round hole to a broad gaping slit and the eyes move from the sides to the top of the head. The entire coloration of the animal skin will change. During the time when the skin is being rapidly resorbed in the tail it is being thickened over the body with increased collagen formation in the dermis and the rapid growth of large mucus glands in the epidermis. Thus, skin in two different regions of the animal will behave entirely differently to the stim- ulus of a single hormone. We selected the metamorphosing frog tadpole

424 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS for study because it represents a highly exaggerated example of the same type of changes which take place during the embryonic growth and matura- tion processes in human beings. Here in the tadpole we can study the detailed chemical and morphologic processes under highly controlled experimental conditions. By restricting ourselves to one universally distributed tissue component, namely collagen, which is involved in all remodeling processes in higher animals, we hope to find those principles which are followed in the remodeling of all the other structural elements. Once we understand the basic principles involved in any animal system and develop the necessary tools for studing these processes, we hope that we can in a much more effective and direct manner examine the analogous processes in the mammal. We are painfully aware of the limitations of reason and may easily be led by nature down the well-known garden path. However, in any investigative work, it is well worth shooting for the stars with the hope that you also know how to keep at least a toenail on the ground. Again, my many thanks to you for this handsome award.