According to Christopher Lipinksi and Andrew Hopkins, fellows with Pfizer Global Research and Development, in vivo research has an advantage in that: Whether the aim is to discover drugs or to gain knowledge of biological systems, the nature and properties of a chemical tool cannot be considered independently of the system it is to be tested in. Compounds that bind to isolated recombinant proteins are one thing; chemical tools that can perturb cell function another; and pharmacological agents that can be tolerated by a live organism and perturb its systems are yet another. If it were simple to ascertain the properties required to develop a lead discovered in vitro to one that is active in vivo, drug discovery would be as reliable as drug manufacturing.
In the past, the guinea pig was such a commonly used in vivo experimental subject that they became part of idiomatic English: "to be a guinea pig for someone/something". However, they have largely been replaced by smaller, cheaper, and faster breeding rats and mice.