Alfred Russel Wallace (1823-1913) and Charles Darwin (1809-1882) are honored as the founders of modern evolutionary biology. Accordingly, much attention has focused on their relationship, from their independent development of the principle of natural selection to the receipt by Darwin of Wallace’s essay from Ternate in the spring of 1858, and the subsequent reading of the Wallace and Darwin papers at the Linnean Society on 1 July 1858.
In the events of 1858 Wallace and Darwin are typically seen as central players, with Darwin’s friends Charles Lyell (1797-1875) and Joseph Dalton Hooker (1817-1911) playing supporting roles. This narrative has resulted in an under-appreciation of a more central role for Charles Lyell as both Wallace’s inspiration and foil.
The extensive anti-transmutation arguments in Lyell’s landmark Principles of Geology were taken as the definitive statement on the subject. Wallace, in his quest to solve the mystery of species origins, engaged with Lyell’s arguments in his private field notebooks in a way that is concordant with his engagement with Lyell in the 1855 and 1858 papers.
I show that Lyell was the object of Wallace’s Sarawak Law and Ternate papers through a consideration of the circumstances that led Wallace to send his Ternate paper to Darwin, together with an analysis of the material that Wallace drew upon from the Principles. In this view Darwin was, ironically, intended for a supporting role in mediating Wallace’s attempted dialog with Lyell.
Drug discovery and delivery in the 21st century
Drug discovery in the late 20th century has increasingly focused on the definition and characterization of the macromolecular substrates that serve as targets for drug design. The advent of genomics and the molecular biology revolution has permitted both the definition of new targets and the characterization of the genetic basis of disease states.
The introduction of powerful new technologies should greatly accelerate the pace of new drug discovery. Although genomics, both human and nonhuman, should in principle increase the number of potential drug targets and provide a greater understanding of cellular events contributing to the pathology of disease this has yet to occur in practice, primarily because of the underlying complexity of cellular signaling processes.
The emerging discipline of systems biology is attempting to bring both order and understanding to these signaling processes. Genomics has, however, impacted on drug discovery in ways that are important beyond a mere increase in potential drug target numbers. Genomics has provided the tools of contemporary drug discovery, the pharmacogenomic pathways to personalized medicine, and has greatly influenced the nature of synthetic organic chemistry, a discipline that is still the cornerstone of contemporary drug discovery.
In the future, genomics and the tools of molecular biology will have a corresponding impact on drug delivery processes and mechanisms through introduction of drug delivery machines capable of both synthesis and activation by disease-specific signals.
Such machines will be based on a synthetic genome, using an expanded genetic code, and designed for specific drug synthesis and delivery and activation by a pathological signal. This essay is based upon a lecture of the same title presented at the Faculty of Medicine, Kuwait University during a visit in the spring of 2005.
It is intended, as was the lecture, to be a broad, descriptive and speculative overview rather than a comprehensive and detailed review.