Nirenberg's lifetime of scientific achievement might easily obscure his significant contributions to society outside the laboratory. Even before he gained fame for winning the Nobel Prize, Nirenberg consistently recognized and advocated the special accountability of scientists to society. Addressing the future of scientific inquiry in a hand written note in 1966, Nirenberg invoked the words of eminent virologist Salvador Luria to explain that, "the impact of science on human affairs imposes on its practitioners an inescapable responsibility." He was able to utilize his well-earned status as a respected scientist to expand the scope of both his professional and social responsibilities. The broad recognition of his contributions to the fields of genetics and neurobiology allowed him to become a prized adviser across traditional disciplinary boundaries as well as an authoritative voice for the ethical and social responsibility of scientists.

As an advocate of social consciousness and the extraordinary responsibility of scientists, Nirenberg capitalized on his prominence to promote various social and political issues and often participated in public debates within the scientific community. Anticipating the ethical and moral implications of genetic research in a 1967 editorial in Science, he noted that the expansion of scientific knowledge could soon lead to man's "power to shape his own biological destiny. Such power can be used wisely or unwisely, for the betterment or detriment of mankind." Nirenberg further stated that, "When man becomes capable of instructing his own cells, he must refrain from doing so until he has sufficient wisdom to use this knowledge for the benefit of mankind." His comments generated numerous responses and ignited a public debate over the future of genetic research that moved beyond the pages of scientific journals. Joshua Lederberg, winner of the 1958 Nobel Prize in Physiology or Medicine, suggested that, "Nirenberg's language could generate public misunderstandings that might undercut the very research needed to reach sufficient wisdom." Later he added that Nirenberg's "cautions would generate a police and thought-control bureaucracy exactly contrary to his fundamental humanistic aims." Nirenberg's commentary similarly piqued the interest of scientists around the world; a letter from the head of the Department of Chemistry at Simon Fraser University demonstrates that his editorial inspired the Chemical Institute of Canada to hold a panel discussion at their 1968 annual meeting on the technical, economic, and political consequences of genetic research.

The core social and professional issues that comprised the debate over genetic research in the late 1960s continued to resonate with Nirenberg throughout his life. In February 1998, he signed a letter from the American Society for Cell Biology to President Bill Clinton and members of the U.S. Congress opposing human cloning, so long as the ban did not "deliberately or inadvertently interfere with biomedical research that is critical to the understanding and eventual prevention of human disease." Arguing that, "it would be tragic to waste this opportunity to pursue the work that could potentially alleviate human suffering," Nirenberg similarly supported a statement in favor of stem cell research written by eighty Nobel Laureates and given to President George W. Bush in 2001. Further symbolizing a consistent concern for the biomedical applications of scientific work, in April 2002, he joined forty American Nobel Laureates in support of therapeutic cloning.

Over his career, Nirenberg also utilized his stature as an eminent scientist to protest the political repression and detention of scientists around the world. In May 1969, he and Christian Anfinsen, the 1972 Nobel Laureate in Chemistry and an NIH colleague, protested the Brazilian government's purging of its renowned scientists Isaias Raw, Alberto Carvalho da Silva, and Helio Lourenco de Oliveira. In a letter to President Artur da Costa e Silva, the two scientists argued for the continuity between the scientific exchange of ideas and political freedom. They noted that the nation's actions would certainly result in "serious repercussions among scientists in the world community, whose sympathy and cooperation is essential to the continued technological development of Brazil." Coordinating with members of the Committee of Concerned Scientists in 1975, Nirenberg sent a letter to the President of the Soviet Union pleading for the release of Mikhail Shtern, a noted endocrinologist who was vilified then arrested shortly after he applied for permission to emigrate to Israel with his family. Nirenberg again joined with Anfinsen in asking Pope John Paul II to investigate the disappearance of several physicists in Argentina during the Pontiff's planned visit to that country in June 1982. Although these appeals for political freedom by scientists did not always have positive results, Nirenberg's correspondence reveals that they placed significant pressure on governments and perhaps saved the lives of many scientists and political activists.

Nirenberg regularly lent his support and name to strengthen various environmental and humanitarian causes or to speak out on fundamental political issues. Nirenberg was one of eighty Nobel Laureates who issued the "Manifesto Against Hunger" in 1981, calling for the worldwide end of starvation. The following year, Nirenberg was asked to support the "Declaration on Prevention of Nuclear War," presented to Pope John Paul II by an assembly of presidents of scientific academies and scientists from all over the world convened by the Pontifical Academy of Sciences. In 1986, Nirenberg joined a group of over 1600 scientists who signed an "Open Letter to Congress," which protested plans for the Strategic Defense Initiative (SDI). Arguing that the SDI represented a "significant escalation of the arms race," the letter countered claims by some supporters of SDI who said that the scientific community gave the program "virtually unanimous support." In 1997, along with 148 noted chemists and two Nobel Prize recipients, Nirenberg urged the U.S. Senate to ratify the Chemical Weapons Convention. Recently, he again demonstrated his concern over nuclear proliferation when he joined with other Nobel Laureates in writing to President Clinton in 2000 to oppose the development of an anti-ballistic missile program.

As an authoritative figure in science, many organizations and interest groups called on Nirenberg, as an authoritative scientific figure, to support various causes. His interest in these issues always stemmed from his sense of social responsibility as a scientist. He believed that decisions regarding scientific discovery and the expansion of knowledge "must eventually be made by society, and only an informed society can make such decisions wisely." Nirenberg's participation in numerous political, humanitarian, and social causes were rooted in his sense of "inescapable responsibility," and helped bring about that informed society.