In 1943 Kamen was assigned to Manhattan Project work at Oak Ridge, Tennessee, where he worked briefly before returning to Berkeley. He was fired from Berkeley in 1945 after being accused of leaking nuclear weapons secrets to Russia, and for a time was unable to obtain an academic position, until being hired by Arthur Holly Compton to run the cyclotron program in the medical school of Washington University at St. Louis. Kamen taught the faculty how to use radioactive tracer materials in research, and his own interests gradually shifted into biochemistry.
By bombarding matter with particles in the cyclotron, radioactive isotopes such as carbon-14, were generated. Using carbon-14, the order of events in biochemical reactions could be elucidated, showing the precursors of a particular biochemical product, revealing the network of reactions that constitute life. Kamen is credited with confirming that all of the oxygen released in photosynthesis comes from water, not carbon dioxide. He also studied the role of molybdenum in biological nitrogen fixation, the biochemistry of cytochromes and their in photosynthesis and metabolism, the role of iron in the activity of porphyrin compounds in plants and animals, and calcium exchange in cancerous tumors.
Kamen was a target and victim of American anti-communist fervor in the 1940s and 1950s. He described his experiences during this era in his autobiography, Radiant Science, Dark Politics. He first aroused suspicion while working at Oak Ridge. A cyclotron operator prepared radioactive sodium for an experiment, and Kamen was surprised that the resulting sodium had a purple glow, indicating it was much more intensely radioactive than could be produced in a cyclotron. Kamen recognized immediately that the sodium must have been irradiated in a nuclear reactor elsewhere in the facility. Because of wartime secrecy, he had not been aware of the reactor's existence. He excitedly told his colleagues about his discovery. Shortly thereafter, an investigation was launched to find out who had leaked the information to Kamen.
After returning to Berkeley, Kamen met two Russian officials at a party given by his friend, the violinist Isaac Stern, whom he sometimes accompanied as a viola player in social evenings of chamber music. The Russians were Grigory Kheifets and Grigory Kasparov, posted as undercover KGB officers in the Soviet Union's San Francisco consulate. One of them asked Kamen for assistance in getting experimental radiation treatment for a colleague with leukemia. Kamen made inquiries, and in appreciation the official invited him for dinner at a local restaurant. In the aftermath of the Oak Ridge incident, Kamen was under continuing surveillance by FBI agents who observed the July 1, 1944 dinner, where Kamen was alleged to have discussed atomic research with Kheifets. Kamen lost his Berkeley position shortly afterwards.
The House Committee on Un-American Activities summoned Kamen to testify in 1948. A Congressional investigation established that Kheifets had received classified information from Kamen concerning uranium stockpiles . Subsequently the State Department refused to issue him a passport. In 1951 the Chicago Tribune named him as a suspected spy. Kamen attempted suicide. After a 10-year effort to establish his innocence and prove that he had been blacklisted as a security risk, he won a libel suit against the Tribune in 1955 and was able once again to obtain a passport.