HARVARD MEDICAL SCHOOL 
DEPARTMENT OF PATHOLOGY 
IB IMATTUCK STRICT 
BOSTON, MASSACHUSETTS OtllS 
BARUJ BENACERRAF, M.O. 
FABYAN FROFISSOR OF COMPARATIVE PATHOLOGY 
CHAIRMAN OF THE DEPARTMENT OF PATHOLOGY 
March 29, 1979 
tel. XTXXySXKOC 
732-1971 
Dr. Wallace P. Rowe, Chief 
Laboratory of Viral Diseases 
National Institute of Allergy and Infectious Diseases 
National Institutes of Health 
Bethesda, Maryland 20205 
Dear Wally: 
As you requested, I have carefully read the paper by Jonathan King, Recombinant 
DNA and Autoimmune Disease, as well as the copy of the letter addressed to Dr. 
William Gartland by ray colleague, Jon Beckwith. 
It is my opinion that the concern expressed, both in the article and the letter, 
is grossly exaggerated and based upon the occurrence of hypothetical events. 
Before I deal specifically with the issues, I would like to inform you that I 
have talked with both Drs. Unanue and Fields, who are among the authorities named 
by Dr. Beckwith as supporting his conclusions. Both Drs. Unanue and Field eApressed 
to n*e that they only have had a casual conversation with Dr. Beckwith of a general 
nature and that in no way this authorizes Dr. Beckwith to use their names and 
authority in the support of his views. I feel certain that the same is probably 
true for Drs. Baltimore, Benjamin and Schur but I have not been able to get in touch 
with them as yet. As to Dr. Dessein, he can hardly De considered an authority on 
immunological diseases, as his total experience in the field amounts to a year and a 
half of fellowship in my laboratory, which he spent primarily studying the control 
of IGE responses. I felt it would be useful for you to have this information as to 
Dr. Beckwith's sources. 
With respect now to the concerns expressed by Drs. King and Beckwith whereby 
potential autoimmune diseases of great severity could result from recombinant DNA 
techniques to construct strains which would produce hybrid proteins with 
hormonal activity, I again state that in my opinion the concerns are very much 
exaggerated. It is indeed possible to produce antibodies against autologous com- 
ponents, proteins or others, as a consequence ot appropriate forms of immunization. - 
Some of these techniques inVoh/e the use ot (1) bacterial adjuvants (2) immunization 
with foreign cross-reactive proteins (3) immunization with modified autologous 
proteins. These models have all been substantiated in the lab and the antibody re- 
sponses result from the activation of host T cells specific for the modified or 
! new determinants introduced. However, such responses are not easy to obtain even 
under experimental conditions and are not believed to be the mechanism of most 
' severe immunological diseases such as disseminated lupus or human acute glomerulo- 
| nephritis. In the case of lupus, it is increasingly believed that the disease results 
from an immunological imbalance in the T cell regulation of B cell response either 
through the unresponsiveness of B cells to the suppressive activity of suppressor 
i T cells or to genetic defects in the T cell regulatory mechanisms. As to acute 
.glomerulonephritis, the majority of cases are caused by the trapping of immune complexes 
in the glomeruli. 
[ 243 ] 
