In early 1942, Merck & Co. began producing penicillin with the intention of making it available for soldiers in the field. Up to that point, the company was able to produce only tiny amounts of the drug, making it a truly precious commodity. They needed a way to mass produce penicillin.

While chemists and biologists worked frantically to devise a better production method, Pauling began to consider a completely different approach to the problem. What if smaller quantities of penicillin were needed to treat a patient? One of the biggest issues with conventional gelatin-based plasma substitutes was that they typically left the bloodstream at a rapid rate, requiring multiple injections. Pauling and Campbell's process for treating gelatin in the oxypolygelatin program had caused molecular chains to form and required more time to cycle out of the blood. Pauling theorized that, by pairing a penicillin molecule with a protein molecule, the substance would remain in the bloodstream for a longer period of time, greatly increasing its effectiveness.

Pauling first began presenting his and Campbell's idea for penicillin in the fall of 1943, and correspondence from the OSRD and CMR demonstrated some official interest in their suggestion. After conducting more experiments with Oxypolygelatin, Pauling had enough evidence to move forward. In May 1944, he sent a proposal and contract request to the CMR. The proposal was accepted and in September he received 1,000,000 units of the drug for experimentation. By 1944, the Northern Research Lab in Illinois had developed a method for producing penicillin from a corn byproduct. Penicillin had gone from being a novelty drug to a major medical landmark and, in light of this advance, Pauling was receiving official attention. A.N. Richards, the chairman of the CMR, seemed particularly interested in the work, noting in one letter that his request for additional information was "simply a suggestion which emerges from my interest and curiosity."

Unfortunately, all of the enthusiasm that Richards, Pauling, and Campbell could muster wasn't enough to make the project succeed. At the time of the experiments, the molecular structure of penicillin was still classified, forcing Pauling to make guesses as to the way the molecule could combine with gelatin. What should have been a well-planned series of experiments instead became a game of guess-and-check.

By late December 1944, Pauling was ready to submit his first report and the results were not promising. Pauling and Campbell had treated the penicillin samples with urea, alkaline chemicals, and high temperatures - each a denaturing agent meant to break down the penicillin and reform it with the gelatin. On the contrary, these treatments appeared to cause the penicillin to deactivate. Instead of causing the penicillin to bond with the gelatin, the denaturing agents were destroying it.

Pauling and Campbell provided Richards with a one-page report accompanied by a two-sentence cover letter. The investigation was going nowhere and there were other projects to be looked after. What the researchers didn't say was that Howard Florey and his team at the University of Oxford had discovered a method to mass produce penicillin and were in the process of creating a large cache for military use. The need for augmented penicillin was gone.

After the informal report given to Richards, no other mention of the penicillin project appears in the Pauling Papers. It seems that the project was quietly discontinued without so much as the traditional report to the CMR.