Our understanding of biology rests first and foremost on evolutionary theory, the merger of Charles Darwin’s Theory of Natural Selection with Gregor Mendel’s Laws of Inheritance in the second half of the 19th century.  Together Darwin and Mendel taught us that living things carry genetic information and that this information determines biological traits. But what is the material that carries this genetic information?  As we will come to, the great Austrian physicist Erwin Schrödinger in his highly influential lectures (1943) and book (1944), What is Life?, drew the attention of physicists and biologists to this question. Schrödinger argued, correctly, that the hereditary substance in chromosomes must be as “an aperiodic solid with a regular array of repeating units in which the units are not the same.” But like many others, Schrödinger believed that the genetic material had to be protein; only protein with its diverse chemical features could serve as a storehouse for this code. Ironically, at the same time, Oswald Avery and his co-investigators at the Rockefeller Institute were making the startling discovery that the genetic material was not protein, but rather DNA. Surely, this discovery, which was slow to gain wide acceptance (with credit going to Avery belatedly and inadequately), must rank as one of greatest discoveries in biology, if not the greatest, of the 20th century.

The ensuing field of molecular biology was triggered by another major advance: the impactful discovery by Salvador Luria and Max Delbrűck that bacteria are subject to Darwin’s Theory of Natural Selection and acquire mutations spontaneously, meaning that they could serve as a highly accessible model system to investigate the nature of heredity. Thus, three transformative advances, one conceptual (by Schrödinger) and two experimental (by Avery and co-workers and by Luria and Delbrűck), that occurred at almost the same time (1943-1944) ushered in a new era in the biological sciences. Together with the subsequent elucidation of the structure of DNA, its mode of replication, and how it encodes information, the stage was set for transforming our understanding of how living things work at the level of molecules.  

Interestingly, the name “molecular biology” predates 1943 by five years. As we shall see, the Rockefeller Foundation and the Rockefeller Institute (later University) played critical roles in the early history of the field. The Foundation’s Director for the National Sciences, Warren Weaver, coined the term in the opening to his report on the natural sciences in 1938: "Among the studies to which the Foundation is giving support is a series in a relatively new field, which may be called molecular biology, in which delicate modern techniques are being used to investigate ever more minute details of certain life processes." Weaver was prescient, and we owe him our gratitude! Nonetheless, here we assign 1943 as the true birthdate for the field he so named.

A distinctive feature of how we tell the history of molecular biology in this volume is that we will delve into both the experiments and the stories of the scientists who carried them out.  Thus, in what follows we examine and discuss figures, tables, and text from classic publications and consider broad aspects of the scientists and the era in which they made their transformative discoveries.  

Viewed from the lens of contemporary social norms, the telling of these stories poses two special challenges.  First, and conspicuously, relatively few of the pioneers of molecular biology were women and even for those few women pioneers their contributions were often under recognized. We will highlight who these women were and cases in which their seminal contributions did not get fully appreciated. Fortunately, and as in other realms of society, many women have risen to prominence in molecular biology in recent decades and have received much acclaim. Sadly, this is not the case for underrepresented minorities, which remain underrepresented in the sciences.

The second challenge has to do with human nature.  A scientist may excel in one domain but fall short in others. Just because a scientist has won a Nobel Prize for his or her scientific contributions does not mean that his or her opinions and judgements in other domains are necessarily to be trusted.   We will consider some painful examples of this.  Even more distressing, just because a person is a brilliant scientist doesn’t mean that he or she adheres to a high moral standard outside the realm of their scientific activities. As we shall see, people are complex.  They can have good sides and bad sides and their behavior can change over time.  

With these challenges in mind, this volume traces the history of molecular biology from 1943 through the subsequent four decades, culminating with the transformative technological advances of DNA cloning, DNA sequencing and the Polymerase Chain Reaction.  This triumvirate, together with the discoveries that preceded it, have, in turn, led to a never-ending stream of breathtaking insights into how living things work and to innumerable medical, industrial, and agricultural advances. 

I am indebted to my hero Matthew Meselson who mentored me, often over lunch at the Law School, on the birth of molecular biology in which he played a pioneering role.  I am also grateful to the students and teaching fellows in my course on the History of Molecular Biology for their invaluable feedback as I developed my lectures upon which this eBook is based. 

Finally, the title, The River Divides into Thousands of Branches, is a quote from Matthew Meselson as explained in the Epilogue.