27 December 1976 Dear Dr. Singer, Recent progress in molecular genetics and cellular biology has opened new avenues to the modification of the genetic properties of living organisms. The most relevant discoveries include the ability to fragment in controlled ways the macromolecules bearing genetic information, i.e. the nucleic acids, the organo-chemical synthesis of nucleic acids, the recombination of segments of nucleic acids derived from unrelated sources into biologically active structures, their transfer into selected host systems, the transplantation of nuclear material, the hybridization of somatic cells from phylogenetically distant species, etc. Scientific and medical experts realize that these discoveries and their developments can greatly contribute to a deeper understanding of the structure of the genetic material, of its normal functions and its pathological deviations. The recognition that the potential benefits, derivable from the practical applications of the resulting knowledge, are inextricably linked with potential risks, associated with the unpredictable outcome of some genetic manipulations, has led to a deep disagreement both among the scientists and the general public. It is within the constitutional responsibilities of the World Health Organization toward the health and welfare of mankind to take appropriate steps to contribute to the identification and minimization of the risks, so that fruitful experimentation can continue with stringent safeguards for people inside and outside the laboratories. Accordingly, the Advisory Committee on Medical Research of the World Health Organization has requested the Director General to collect information concerning the establishment of regulations and procedures for the proper control of this work so as to guide countries to formulate and harmonize their policies in the area of genetic manipulations. Dr. Maxine F. Singer Laboratory of Biochemistry National Cancer Institute Bldg. 37, Room 4A01 National Institutes of Health Bethesda, Md. 20014 USA