Dr. Jonas Salk commissioned Louis Kahn to design the Salk Institute of Biological Research near La Jolla, California. Salk believes that medical research should not be confined to science alone. In response to Salk's view, Kahn saw the possibility of uniting art and architecture with the functional aspect of the design. He agrees with Salk that someone with a mind in art, like himself, could contribute in creating a mental environment of scientific research. Kahn's pursue of this vision is apparent in his design process.

The earliest massing strategy was to place a linear group of vertical towers parallel to the face of the cliff (diagram 1a). In the second version, a year later, the towers were replaced by four rectilinear, two-storey blocks set perpendicular to the sea (diagram 1b). In this version, the four blocks of laboratories were made up of clear span spaces, made possible by five box girders running across each rectangle, with a 'V'-shaped folded plate system perpendicular to the girders, spanning between them. Later, Kahn simplified the configuration of the laboratories, from four rectangular blocks to two, upon Salk's request (diagram 1c).

In the process, Kahn kept he basic idea of the scheme, which was to place scientists' studies away from the laboratories in the central garden and to place auxiliary spaces in vertical towers on their external walls. However, he increased the number of floors to three, including the basement, and replaced the 'V'-shaped folded plates above each of the three floors with concrete Vierendeel beams.

Stringent seismic criteria related to construction in the San Diego area made it difficult for Kahn's structural engineer to convince local building officials, who wanted him to use steel frame, that concrete, Vierendeel truss system would have the required flexibility. They agreed only after a 400 page report of undoubtedly integrated deflection computations that shows how post-tensioned columns would provide the main resistance to lateral seismic forces. These columns absorb both dead and live load compression plus vertical post-tensioning forces. They were also designed to maintain zero tension if subjected to lateral movements by earthquake. The trusses are 9 ft deep, spaced 20 ft on center and have a clear span of 65 ft (diagram 2). He made use of the 9 ft high resultant space as service area, allowing pipe chases to be dropped to the 65x 245 ft floor below with more latitude than before. The vertical end of the trusses alternate with the columns to form the integral, vertical support of the building. The post-tensioned stress steel bars were coated with asphalt paint and inserted in metal conduit to prevent bonding with the concrete. Three of these bars are draped through the bottom chord of each of the 18 ft wide trusses, acting like elastic 'tendons' that will elongate if an earthquake should occur. In this way, the building has twice the amount of controlled ductility of a steel structure of comparable size. This structural system is as unique as Kahn's composition of positive (i.e. laboratory towers) and negative (i.e. courtyard) elements in this project.

Kahn consulted Luis Barragan about the design of the courtyard. Barragan told Kahn, 'Don't put one leaf nor plant, not one flower, not dirt. Absolutely nothing... a plaza... will unite the two buildings, and at the end you will see the line of the sea.' He also said that the courtyard would act as a facade that rises to the sky and unite the two buildings as if everything had been hollowed out. The simplicity of this idea supports Kahn's believe in 'timeless' architecture which was high above whim and fancy. Concrete was chosen as the material for the exterior facade of the towers, the Living and Meeting places, and slate was chosen for the courtyard to further emphasize the simplicity of the design.

In determining the mix to be used in the concrete, Kahn researched the components used in Roman pozzolana, in order to achieve a similar reddish hue. Pozzolana additive was put in the mixture to soften its appearance and to make a symbolic connection through time to the origins of this composite material. He paid close attention to the forms, which were made of 3/4-inch exterior plywood, filled and sanded, and finished with coats of polyurethane resin. Thus, they can be used as many as eight times before being repaired and refinished. Kahn also decided to accentuate the joints between the panels instead of hiding them by chamfering the edges to produce a V-shaped groove at these points along the wall surface. Solid corners and gasketed joints were used between sets of gauged forms to avoid bleeding and leakage. The conical holes left by the form ties were also not patched, so their spacing were carefully placed, and they were filled by a lead plug, hammered tightly to prevent corrosion of the steel ties.

Slate was chosen as the material for the courtyard because of its striking contrast with the concrete and its ability to convey the sombre dimension of an institution engaged in a constant struggle against life-threatening diseases. Later, the material was eliminated because of cost and replaced with travertine, which has similar symbolic connections. The travertine has not lasted as long as slate may have over time because of its relative softness, but has proven to be a perfect visual and tactile foil to the concrete walls. Teak was another material that was thought to be financially excessive at first, but Kahn decided to leave the material unvarnished and weather naturally to further reduce maintenance. Each decision in the design, such as mentioned above, has ensured longevity in an endeavor increasingly fraught with the risk of renovation or demolition.
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