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Working with Francisco Varela has alwaysbeen extremely rewarding: his intelligence,excitement, humor, gentleness, but alsosolidity in the principles and the arguments,were all there. Perhaps most inspiring washis clarity in identifying the goal, often theessence of the problem at hand, and thepath to a solution. And certainly exemplaryin a scientist were his openness, his abilityto change his opinion, to adapt his frame ofmind to new ideas and evidence, if theywere appealing and good enough.I first discovered Francisco’s interests inimmunology some time in 1977 or so, whenNiels K. Jerne, the Director of the BaselInstitute for Immunology, gave me a pre-print of an article by Nelson Vaz andFrancisco on ‘Self and non-sense,’ a playon words to remind immunologists, oftenconcerned with the conventional ‘self-nonself discrimination’ question, of theircontradictions. This paper considered ‘theimmune system as a closed network ofinteractions,’ such that “whatever fallsoutside this domain … is simplynonsensical” (emphasis mine). Whileappreciating their provocative views, andjoining in their opinion that the currentimmunological theory was in a great needof shaping up, I did not agree (and I still donot agree today, despite many discussionswith Nelson Vaz) that their central claimwas right. I continue to think that a‘decision-making behavior’ naturally

biological research

A walk with Francisco Varela from first- to second-generation networks: In search of the structure, dynamics and metadynamics of an organism-centered immune system