Scripps Qinic and Research Foundation 
(0666 North Toney Pines Road 
La lolla California 92037 (714) 455 9100 
FRANK J. DIXON. M.D 
Senior Vice President 
Director. Research Institute of Scripps Clinic 
April 2, 1979 
Wallace P. Rowe, M.D. 
Chief, Laboratory of Viral Diseases 
National Institute of Allergy and 
Infectious Diseases 
National Institutes of Health 
Bethesda, Maryland 20205 
Dear Wally: 
I am happy to respond to your request for an evaluation of the questions raised by Drs. King 
and Beckwith concerning the possibility of autoimmune diseases as complications of the 
research program in recombinant DNA. The concerns of these individuals are obviously 
well intentioned, but suffer somewhat from a lack of familiarity with the field of auto- 
immune disease. 
Let me comment first on the article by Jonathan King in the Journal of Infectious Diseases 
137:663, 1978. The initial point raised here about the dangers of having in the gut antigens 
cross-reactive with normal human protein would seem to me to be a matter of no great concern. 
The meat eaters in our society are regularly exposed to all manner of mammalian proteins 
including milk which cross-reacts extensively with their counterparts in the human body. 
Such exposures are usually without any demonstrable immunologic response and on the occasion 
when a response occurs there is little or no evidence that it leads to significant pathologic 
sequelae. Such cross-reactive antigens are, of course, present in the gut along with all 
manner of enteric bacilli capable of providing an adjuvant effect to the cross-reacting anti- 
genic exposure. The second point in this paper, namely that microbial infections such as 
streptococcal pharyngitis lead to pathogenic autoimmune responses is quite contrary to the 
best immunopathological evidence available. It is quite true that streptococcal infection 
may lead to glomerulonephritis but there is no substantial evidence that this glomerulonephritis 
is the result of an autoimmune response. The same reference quoted by Dr. King (The Kidney 
) Vol . 2, 1976, pp. 838, Wilson and Dixon), to suggest an autoimmune response as a result of 
’ streptococcal infection really indicates the opposite. Poststreptococcal glomerulonephritis is 
an immune complex disease apparently involving streptococcal antigens, but certainly lacking 
any demonstrable autoantibodies against glomerular antigens. Also, streptococcal infection is 
rarely if ever involved in those cases where autoantibodies against glomerular basement membrane 
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