After 2 years as a technician at the MRC Radiobiological Research Unit, Harwell he became an undergraduate at Christ Church, University of Oxford where he graduated with a first-class honours degree in Biochemistry in 1963.

David Smith co-founded the International Brain Research Organization's journal Neuroscience[10] and he served as Chief Editor from 1976 to 2001.

Squibb & Sons Inc., which led to the donation of £20 million to the University of Oxford for a new building for the Department of Pharmacology and funding for research into brain diseases.

[12] In 1988 Smith co-founded the Oxford Project to Investigate Memory and Ageing (OPTIMA[13]), a longitudinal clinico-pathological study on more than 1,000 people to identify modifiable risk factors contributing to dementia, which continued until 2015.

[14] In 1998, OPTIMA discovered that elevated homocysteine and low levels of B vitamins are important risk factors for the development of Alzheimer's and vascular dementia.

[16] The results showed that the accelerated rate of brain atrophy in elderly with mild cognitive impairment can be significantly reduced in over half of cases through treatment with homocysteine-lowering B vitamins in subjects with a good omega-3 fatty acids status.

In 1981 he and his wife organised the first visit of the Berlin Philharmonic Orchestra to Oxford for a concert with Herbert von Karajan in the Sheldonian Theatre, broadcast by the BBC.