And why does this process sometimes malfunction, leading to birth defects, cancers and other diseases?

Thanks in large part to the pioneering work of Stanford University's Roger D. Kornberg, scientists now are beginning to understand the process of copying DNA into RNA, called transcription. This knowledge ultimately will allow scientists to apply more effectively the results of the human genome project to better understand disease.

Today in Houston, TX, The Welch Foundation announced that Dr. Kornberg will receive its 2001 Welch Award, a $300,000 prize given for lifetime achievements in basic chemical research, in recognition of these contributions.

Dr. Kornberg, professor of structural biology at the Stanford University School of Medicine, discovered the nucleosome -- the basic unit from which all chromosomes are made -- and established its role in gene regulation.

He also discovered a giant complex of 20 proteins known as the "Mediator," which regulates the transcription process.

Most recently, he determined the atomic structure of RNA Polymerase II -- the complex enzyme that catalyzes the transcription process and is considered one of the most important proteins in biology. In doing so, he and his team captured the image of the substance in the act of transcribing DNA.

"These discoveries set the stage for further research that will bring remarkable new insights into the processes at work within the cells of humans and other organisms, leading to a better understanding not only of genetics but also of the progression of diseases," says Richard J. V. Johnson, chairman of the board, The Welch Foundation. "The achievements of Dr. Kornberg exemplify the guiding principle of The Welch Foundation and the spirit of the Welch Award: basic research in chemistry that contributes to the betterment of humankind."

"Dr. Kornberg has made vital discoveries that are now part of every basic biology textbook," says Norman Hackerman, chairman of the Welch Scientific Advisory Board. "His combination of biochemistry and structural biology, together with his ground-breaking work in the development of the new analytical techniques needed to achieve his goals, shows remarkable creativity, perseverance and enthusiasm for the scientific process.

"His recent determination of the structure of RNA Polymerase II in the act of 'reading' DNA will serve as the critical underpinning of further research."

Dr. Kornberg, studying structural biology as a graduate chemistry student at Stanford in the late 1960s, became interested in applying the techniques of nuclear magnetic resonance and electron paramagnetic resonance to the structure of cell membranes.

As a postdoctoral fellow at Cambridge University in the early 1970s, he sought to apply X-ray diffraction and a novel variant of the electron diffraction technique -- developed by Aaron Klug -- to the structure of chromatin, the material from which chromosomes are made. This work led to his discovery of the nucleosome.

After returning to Stanford in the late 1970s, Dr. Kornberg began studying the transcription process by working to identify all the proteins involved. In the process of this work, he discovered the existence of the 20-protein Mediator complex in human cells and later developed a technique that combined electron diffraction with the use of lipid sheets. This breakthrough eventually enabled him to determine the atomic structure of RNA Polymerase II.

"Once I began trying to identify the molecules responsible for copying the genetic message of DNA into RNA in complex organisms, I realized a method was needed to enable the analysis of such large molecular structures as they became available," says Dr. Kornberg. "Eventually my team discovered nearly all of the 60 proteins responsible for the expression of genetic information in higher life forms. The next challenge was to determine how transcription works. For this, it was necessary to determine the structure of RNA Polymerase II."

Combining the techniques of structural biology, genetics and analytical chemistry, Dr. Kornberg solved this complex substance's atomic structure in December 1999. An article detailing this discovery was published in the April 28, 2000, issue of Science.

The next step in Dr. Kornberg's research will be to determine the structures of the almost 50 additional proteins that act in concert to regulate the transcription process.

"All the necessary techniques are now in place to complete this work, so it should proceed much more easily than the previous structural studies, which required the development of new analysis methods," he says.

Born in 1947, Dr. Kornberg earned a bachelor's degree in chemistry from Harvard University and a doctorate in chemistry from Stanford University. Following postdoctoral work in Cambridge, England, he returned to the U.S. as an assistant professor of biological chemistry at Harvard Medical School.

He moved to Stanford in 1978 as a professor of structural biology. He served as chairman of the Department of Structural Biology from 1984 until 1992.

He has received many honors, including the Eli Lilly Award (1981), the Passano Award (1982), the Ciba-Drew Award (1990), the Harvey Prize (1997) and the Gairdner International Award (2000, shared with R. Roeder). He is a member of the National Academy of Sciences, the Japanese Biochemical Society (honorary) and the American Academy of Arts and Sciences.

The Houston-based Welch Foundation is one of the oldest and largest sources of private funding for basic research in chemistry. Since its founding in 1954, it has provided more than $441 million in support for science.

In addition to the Welch Award, first given in 1972, the Foundation hosts an annual chemical research conference; provides individual research grants; provides grants to chemistry departments at small and medium-sized educational institutions in Texas; underwrites 39 academic chairs in chemistry; organizes a visiting lecture series of prominent chemists; supports a summer scholar program in the chemical laboratory for high school students and helps fund a biennial conference for chemistry and science teachers at the high school and junior high levels.

The Foundation also bestows the Norman Hackerman Award in Chemical Research, a $100,000 prize that recognizes the work of young researchers in Texas.

24-May-2001