These concepts were extended to systemic disease in 1981, when Ian A. Clark, from the Australian National University, in collaboration with Elizabeth Carswell in Old's group, working with pre-sequencing era data, reasoned that excessive production of TNF causes malaria disease and endotoxin poisoning.
Estes conceptos foron ampliados a doenzas sistémicas en 1981, cando Ian A. Clark, da Universidade Nacional de Australia, en colaboración con Elizabeth Carswell no grupo do Dr. Old, traballando con datos anteriores á era da secuenciación, razoaron que a produción excesiva de TNF causa malaria e envelenamento por endotoxinas.