For pioneering studies on eukaryotic RNA polymerases and the general transcriptional machinery, which opened gene expression in animal cells to biochemical analysis.
The 2003 Albert Lasker Award for Basic Medical Research honors a scientist who pioneered studies of the process by which nucleated cells copy DNA into RNA. This reaction — transcription — manufactures the template for protein production and thus determines which genetic information is retrieved, or expressed, at a particular time. As a result, it dictates a cell’s biochemical capabilities and underlies all physiological processes. Through his work on transcription, Robert Roeder opened up the study of gene expression in animal cells to biochemical analysis. This accomplishment triggered an explosion in the field that has generated enormous insight into the mechanisms by which multicellular organisms decode the genome.
All of an animal’s body cells carry the same genetic blueprint. Yet cells in different tissues perform radically different jobs because each contains proteins tailored to specific functions. Red blood cells, for example, funnel their resources into making hemoglobin, which carries oxygen from the lungs to the tissues, whereas pancreatic cells churn out insulin so the body can absorb glucose properly. In the mid-1960s, when Roeder began his graduate work, scientists knew that bacteria turned genes on and off in response to signals from the environment. They inferred that eukaryotes — organisms such as humans that encase their DNA in a cellular compartment called a nucleus — would similarly regulate protein production, but no one knew how. The machinery that transcribes DNA into RNA would lead to the answer, Roeder reasoned. He aimed to get his hands on the essential components of the reaction and, eventually, to reconstruct the process from its constituent parts. He hoped that the ability to faithfully reproduce eukaryotic transcription in a test tube would allow him and others to study exactly how the cell chooses which genes to express — and the molecular details by which that process occurs.
Award presentation by Joseph Goldstein
Every field of science has one big problem that defies solution. In mathematics, the great unsolved problem is the Reimann hypothesis, which attempts to describe the irregular distribution of prime numbers. In physics, the Holy Grail is The Final Theory, which is supposed to explain all the known forces of nature with a single mathematical equation. In chemistry, the grand challenge is to enhance the reactivity of the carbon-hydrogen bond so that the Earth’s vast quantities of hydrocarbons can be converted into cheap chemicals and drugs.
Biology may not have the exalted status of its three sister sciences, but its big unsolved problem may be the most challenging of all, and for sure it will be the most fun to solve. How does a single cell, the fertilized egg, give rise to a complex organism, a human being, which is made up of 250 types of cells, all having the same genetic instructions, yet each performing a different function? Red blood cells, for example, manufacture hemoglobin; pancreatic beta cells produce insulin; skin cells make keratin.
Acceptance remarks by Robert Roeder
Acceptance remarks, 2003 Lasker Awards Ceremony
It is with utmost gratitude to the Lasker Foundation, and its distinguished jury, that I humbly accept this most prestigious award. Having devoted over 35 years of my life to an understanding of a fundamental problem in gene control — and with a sustained belief in its ultimate relevance to broad areas of physiology — it is remarkably satisfying to have this view substantiated by an organization that plays such a pivotal role in promoting public awareness of the nature and importance of biomedical research.
This singular award is all the more meaningful because it comes at a time when there have been so many exciting developments not only in the transcription field, but in other important areas as well. What the award reemphasizes to me is the value and reward of picking an important new problem, even if risky, and pursuing it with confidence, diligence and rigor. My own success, of course, has benefited from many remarkable (and carefully chosen) individuals and institutions.
Interview with Robert Roeder