In 1984, Anfinsen wrote to a colleague, "I find myself in the position of becoming what might be called a professional petition and letter signer." Yet long before he was awarded the 1972 Nobel Prize in Chemistry, he was deeply involved in a variety of political causes that were inspired both by his scientific commitment and by his social conscience. Even in the 1950s, Anfinsen saw direct connections between the often apolitical world of the laboratory and the public sphere. Some scientists--particularly those who worked for government institutions like the NIH--thought of themselves as "public citizens" who were directly responsible for the social repercussions of their work, especially in the era of the civil rights movement and the Vietnam War. Anfinsen was involved, for example, in the organizational work leading to the 1963 treaty banning nuclear testing. He also demonstrated against the Vietnam War, and participated in a vigil held on the NIH campus in Bethesda after the passing of the Gulf of Tonkin resolution in 1964.

The social climate of the late 1960s and early 1970s encouraged scientists like Anfinsen to lobby for political reform, although he said in 1972 that he did not support "the Berkeley type of violent display." In May 1969, for example, Anfinsen and Marshall Nirenberg, a 1968 Nobel Laureate and NIH colleague, protested the Brazilian government's purging of its renowned scientists Isaias Raw, Alberto Carvalho da Silva, and Helio Lourenco de Oliveira. In January 1973, just a month after he was awarded the Nobel Prize, Anfinsen and other scientists--including 1970 Nobel Laureate Julius Axelrod --implored Richard Nixon to support greater scientific exchange between the U.S. and U.S.S.R. In June 1973, Anfinsen formed an alliance of NIH scientists, including Axelrod and Nirenberg, who circulated a petition to protest Nixon's Conquest of Cancer Agency. Over 3,000 biomedical scientists who signed the petition felt that the agency funneled money away from basic scientific research projects that, in the long run, actually contributed to cancer research. Ten years later, in June 1983, Anfinsen, Axelrod, Nirenberg, and 1976 Nobel Laureate D. Carleton Gajdusek publicly criticized the Reagan administration's severe budget cuts to biomedical research programs at the NIH.

In 1981, Anfinsen became chairperson of the National Academy of Sciences' Committee for Human Rights, a position he held until 1989. Anfinsen's committee work was not merely administrative. Like Julius Axelrod, he spent many hours of his own personal time writing letters to the leaders of Brazil, Mexico, Turkey, and the U.S.S.R., whose governments repressed and, in many cases, imprisoned scientific researchers considered politically or intellectually dangerous. In 1981, Anfinsen and other Committee members traveled to Argentina on a rescue mission to liberate twelve scientists who faced domestic coercion by the country's military government and its controversial president, Jorge Rafael Videla. "At that point in my life I had stopped smoking for ten years," Anfinsen wrote of the rescue mission a few years later. "[B]ut two weeks in Buenos Aires got me back on the weed as an antidote to nervewracking interviews with relatives and State officials at all hours of the day and night."

In the early 1980s, Anfinsen was a thoughtful critic of the potential misuses of biotechnology and genetic engineering at a time when many of his colleagues were swept up by their promise. In 1983, for example, he observed that "Surprisingly little effort or money are spent on using the new biotechnology in areas of food production and population control. We tend to forget that the number of sick people in the world is really rather small when compared with the number of relatively healthy people who go to bed hungry every night." In 1988, Anfinsen was among a core group of scientists who criticized the newly proposed Human Genome Project through circulated petitions and international workshops. "It is well-known," Anfinsen asserted in 1990, "that about 95% of the genetic material in the human genome is basically 'filler' and a total sequencing of the genome would involve a great deal of wasted time and effort."

Still, Anfinsen was not entirely pessimistic. As his research with interferon and thermophilic bacteria indicated, he believed that humanity could derive great benefits from biotechnology, but only with the right safeguards. In October 1983, he was invited to speak at the 19th annual Nobel Conference held at Gustavus Adolphus College in St. Peter, Minnesota. In a speech he made at the conference, he declared, "I sincerely believe that we can maintain adequate surveillance of the application of bioengineering to human beings so long as the human hunger for power and material gain does not become overwhelming." In combining biomedical research with political commitment to human rights and social justice, Anfinsen personified the public scientist in an age of rapid scientific advancement and social change.