- 2 - 
2. All the recombinants anyone here proposes to insert into 
strain LT2 could be made in vivo . The only difference is the labor 
(which could be immense) involved in finding the right ones. The 
in vitro methods make certain experiments (such as sequencing the 
Ames tester mutations) practically feasible. 
3. Failure to permit reasonable and non-hazardous experiments 
which are within the spirit and the letter of the Guidelines is 
demoralizing in the extreme to a productive community of scientists 
whose contributions include some of the most useful techniques and 
results of molecular genetics. We do not believe that the current 
predicament is the result of reasoned intention to prevent absolutely 
Salmonella experiments; we think that the situation is the result 
of a simple oversight since the Advisory Committee could not think 
of every possibility. Since the guidelines are supposed to regulate, 
but not to forbid reasonable work, we cannot understand why our 
field should be singled out for an absolute prohibition; after 
all no one has actually suggested Salmonella to Salmonella recombi- 
nants constitute a hazard. 
In conclusion, we hope that you can consider our position and 
that you will allow us to proceed, under the same rules that apply 
to everyone else, with our experiments. 
Sincerely yours 
' ) ' /? 
David Botstein 
Associate Professor of Genetics 
Massachusetts Institute of Technology 
John Roth 
Professor of Biology 
University of Utah 
Enclosures 
[Appendix A — 128] 
