After receiving his Ph.D., Wallace Carothers stayed at the University of Illinois for two years as an instructor in organic chemistry. In 1926 Carothers moved to Harvard University. In 1927, DuPont decided to fund fundamental, pure research: research not deliberately aimed at the development of a money-making product. Carothers traveled to Wilmington, Delaware, to discuss the possibility of being in charge of organic chemistry at the new DuPont laboratory for fundamental research. The decision to leave academia was difficult for Wallace Carothers. At first he refused DuPont’s offer of employment, explaining that “I suffer from neurotic spells of diminished capacity which might constitute a much more serious handicap there than here.” In spite of this admission, a DuPont executive, Hamilton Bradshaw, traveled to Harvard and convinced Carothers to change his mind. His salary was $500 a month as compared with only $267 at Harvard ($3200 per year). Later in a letter to Wilko Machetanz, his Tarkio roommate, Carothers expanded on his feelings of depression: “I find myself, even now, accepting incalculable benefits proffered out of sheer magnanimity and good will and failing to make even such trivial return as circumstances permit and human feeling and decency demand, out of obtuseness or fear or selfishness or mere indifference and complete lack of feeling.”

Wallace Carothers began working at the DuPont Experimental Station on February 6, 1928. The synthesis of a polymer with a molecular weight of more than 4,200, the mass achieved by Dr. Emil Fischer, was his primary goal. By the summer of 1928, Carothers boasted a small staff of Ph.D. chemists and two consultants: Dr. Roger Adams, his thesis advisor, and Dr. Carl Marvel, his instructor of organic chemistry at the University of Illinois. The laboratory where these top scientists worked became known as “Purity Hall”. It was discouraging that by the middle of 1929, “Purity Hall” had not produced a polymer with a weight of much over 4,000. In January 1930, Dr. Elmer K. Bolton became assistant chemical director in the chemical department, and thus, Carothers’ immediate boss. Bolton wanted practical results in 1930, and his wish was fulfilled. Bolton asked Carothers to examine the chemistry of an acetylene polymer with the goal of creating synthetic rubber. In April 1930 one of Carothers’ staff, Dr. Arnold M. Collins, isolated chloroprene, a liquid which polymerized to produce a solid material that resembled rubber. This product was the first synthetic rubber and is known today as Neoprene.

In the same year, Dr. Julian Hill, another member of the Carothers team, began work again on attempting to produce a polyester with a molecular weight of above 4,000. His efforts were soon met with great success when he produced a synthetic polymer with a molecular weight of about 12,000. The high molecular weight allowed the melted polymer to be stretched out into strings of fiber. Thus was created the first synthetic silk, described by the chemists as a superpolyester. Polyesters and polyamides are examples of condensation polymers formed by step-growth polymerization. Carothers worked out the theory of step-growth polymerization and derived the Carothers equation which relates the average degree of polymerization to the fractional conversion (or yield) of monomer into polymer. This equation shows that for a high molecular weight, a very high fractional conversion is needed (for step-growth polymers only). Hill also produced a synthetic fiber that was elastic and strong by combining glycols and diacids and heating under reduced pressure, using a molecular still to remove the last traces of water produced in the condensation reaction. Unfortunately, the fiber produced could not be commercialized because it reverted to a sticky mass when placed in hot water. Wallace Carothers dropped his research on polymers for several years.

In 1931, Wallace Carothers moved into a house in Wilmington, which became known as Whiskey Acres, with three other DuPont scientists. He was no recluse, but his depressive moods often prevented him from enjoying all the activities in which his roommates took part. In a letter to a close friend, Frances Spencer, he said, “There doesn’t seem to be much to report concerning my experiences outside of chemistry. I’m living out in the country now with three other bachelors, and they being socially inclined have all gone out in tall hats and white ties, while I after my ancient custom sit sullenly at home.” At about this time, Carothers showed Julian Hill that he kept a capsule of cyanide attached to his watch chain. Carothers hated the public speaking that was necessary to maintain his high profile. In a letter to Frances Spencer in January 1932, he related, “I did go up to New Haven during the holidays and made a speech at the organic symposium. It was pretty well received but the prospect of having to make it ruined the preceding weeks and it was necessary to resort to considerable amounts of alcohol to quiet my nerves for the occasion. … My nervousness, moroseness and vacillation get worse as time goes on, and the frequent resort to drinking doesn’t bring about any permanent improvement. 1932 looks pretty black to me just now.”

In 1932, the agreement under which Wallace Carothers was hired was modified by Dr. Bolton. “Purity Hall” would now focus on “effecting a closer relationship between the ultimate objectives of our work and the interests of the company.” This meant that funds were shifted from pure research to practical research. Carothers did not see himself as a skilled commercial researcher. He proposed that fundamental work be limited to two or three proposals, which would be consistent with DuPont’s interests. In 1934, Wallace Carothers turned his attention to fibers again. Now the team substituted diamines for glycols to produce a type of polymer called a polyamide. These substances were much more stable than the polyesters formed by using the glycols. The ability of polyamides to form crystalline domains through hydrogen bonding gives them increased mechanical properties. Therefore, they might produce a synthetic silk that would be practical for everyday use. His research resulted in the invention of a number of new polyamides. The lab work for this project was conducted by Dr. W. R. Peterson and Dr. Donald Coffman. In 1935 Dr. Gerard Berchet was assigned to this polyamide research. It was during this productive period of research, in the summer of 1934, prior to the eventual invention of nylon, that Carothers disappeared. He did not come into work, and no one knew where he was. He was found in a small psychiatric clinic, Pinel Clinic, near the famous Phipps Clinic associated with Johns Hopkins Hospital in Baltimore. Apparently, he had become so depressed that he drove to Baltimore to consult a psychiatrist, who put him in the clinic.

Shortly after his release from the clinic, Wallace Carothers returned to DuPont. Bolton instructed Carothers to work on polyamides. Carother’s work in linear super-polymers began as an unrestricted foray into the unknown, with no practical objective in mind. But the research was in a new field in chemistry and Du Pont believed that any new chemical breakthrough would likely be of value to the company. In the course of research Carothers obtained some super-polymers that became viscous solids at high temperatures, and the observation was made that filaments could be made from this material if a rod were dipped in the molten polymer and withdrawn. At this discovery the focus of the project shifted to these filaments and `Nylon` was the result. On February 28, 1935, Gerard Berchet, under the direction of Carothers, produced a half-ounce of polymer from hexamethylenediamine and adipic acid, creating polyamide 6-6, the substance that would come to be known as Nylon. It was difficult to work with because of its high melting point, but Bolton chose this polyamide as the one to develop commercially. He selected Dr. George Graves to work with Carothers on the project. Eventually Graves supplanted Carothers as the leader of the polyamide project. In addition, dozens of chemists and engineers worked on refining polyamide 6-6 into a viable commercial product. On April 28, 1937, Wallace Carothers went to the Experimental Station to work. He committed suicide in a hotel room in Philadelphia the next day by taking cyanide dissolved in lemon juice, knowing that the ingestion of cyanide in an acidic solution would greatly intensify the speed and effect of the poison. No note was found.