DANIEL NATHANS
University of Delaware B.S. 1950
1978 Nobel Laureate in Physiology or Medicine
"Dr. Daniel Nathans graduated with distinction with a B.S. degree in Chemistry from the University of Delaware in 1950. Nathans, a Wilmington native, was a professor at The Johns Hopkins University School of Medicine and chair of its Microbiology Department when he received the Nobel Prize in Physiology or Medicine in 1978. The Prize was awarded “for the discovery of restriction enzymes and their application to problems of molecular genetics.” Nathans is known as one of the founders of molecular biology and modern genetics. His research laid the groundwork for the mapping of the human genome."
Daniel Nathans, a Delaware native, was born in Wilmington on October 30, 1928, the last of nine children born
to Russian Jewish immigrants. He attended public schools and, like most of his brothers and sisters before him, went
to the University of Delaware. Being from a family of limited means meant living at home and commuting to campus by hitchhiking. As a student he enjoyed the study of chemistry, philosophy, and literature. In his senior year, he was president of the Student Affiliates chapter of the American Chemical Society, and vice-president of the Philosophy Club. He graduated in 1950 with a Bachelor of Science degree in Chemistry. In 1979 when he received an honorary doctorate from the University, Nathans reflected on his undergraduate career and gave particular praise to his chemistry professors Quaesita Drake and Elizabeth Dyer.
Following college, Nathans went to Washington University Medical School in St. Louis, Missouri, with the intent of returning to Wilmington and practicing medicine. While a medical student, he spent a summer working on vitamin C in the laboratory of Oliver Lowry where he discovered a love of basic research and the chemical aspects of biology. After receiving his M.D. in 1954, he did a one-year internship at Columbia Presbyterian Hospital in New York City, which was followed by two years as Clinical Associate at the National Cancer Institute, part of the National Institutes of Health in Bethesda, Maryland, where he did research on cancer and attended cancer patients. He then returned to Columbia Presbyterian Hospital in 1957 for a two-year residency. In 1959, he joined Fritz Lipmann’s laboratory at the Rockefeller University in New York City as a research associate. Lipmann, a Nobel Prize recipient, encouraged Nathans to pursue
his interests in protein synthesis. Using RNA from a virus, Nathans and a collaborator were the first to show that
RNA could direct the synthesis of specific proteins. His years at the Rockefeller Institute helped him realize that he preferred to continue basic medical research rather than practice clinical medicine.
In 1962, Nathans moved to a faculty position in the Microbiology Department at The Johns Hopkins University School
of Medicine in Baltimore, Maryland, where he did his Nobel prize-winning work. He served as department chair (1972-1982) and was interim president of The Johns Hopkins University in 1995-1996. In addition to being an outstanding researcher, he was recognized also as a gifted administrator who was wise, thoughtful, and fair. In 1993, he received the National Medal of Science. Nathans remained at Johns Hopkins until his death on November 16, 1999.
“Throughout my schooling
there was an abundance of opportunity and encouragement. Several of my teachers were remarkable individuals who had a lasting influence on me.”
Significance of Nathans’ Work: From a chemical perspective, DNA is an endlessly monotonous polymer of four quite similar monomeric units (nucleotides) arranged in a seemingly random order. Yet biologically the order of these units is critical because it encodes the information necessary for all organisms to live and reproduce. Segments of the DNA polymer encode genes in which a single change (mutation) in a sequence of millions can cause death or cancer. Each gene has a unique nucleotide sequence. In 1953 when Watson and Crick discovered the basic structure of DNA, the prospect of determining the actual sequence of even short segments of DNA seemed hopelessly complex.
Nathans did not set out to solve this intractable problem. He had decided to study tumor viruses and in 1969 took a sabbatical leave from his position on the faculty of The Johns Hopkins University School of Medicine to learn how to culture and study simian virus 40 at a laboratory in Israel. SV40, a tumor virus that causes cancer in monkeys, provided a useful model for studying how a virus can cause cancer. Furthermore, it was a “simple” virus. Its entire DNA circular genome was “only” about 5000 nucleotide pairs and encoded only a few genes. (In contrast, the human genome is approximately 3,300,000,000 nucleotides pairs and contains on the order of 25,000 genes.)
Hamilton Smith, a colleague from Johns Hopkins, sent Nathans a letter describing an interesting enzyme he had
discovered that seemed to break DNA at specific places, and Smith wondered if Nathans might find it useful. It turned
out that this enzyme functioned like a pair of molecular scissors that would cut DNA at very specific places determined
by short sequences of nucleotides. Thus, when Nathans returned to Johns Hopkins, he and his colleagues treated SV40 DNA with this enzyme. The SV40 DNA was broken reproducibly into 11 different pieces that could be isolated and studied separately. Furthermore, the enzyme studied by Smith was just one of a large family of “restriction enzymes”, each recognizing a different short DNA nucleotide sequence. With these new tools, it was possible to arrange the 11 pieces and many others in order and create a detailed genetic map of the SV40 DNA with the location and function of specific genes, the first genetic map of a DNA molecule. This approach was soon adopted by others and combined with methods for sequencing DNA fragments.
“What is unique about universities is their educational role. Our primary responsibility as faculty members is to help young people become fuller human beings and contributing members of society.” (Dan Nathans speaking at dedication of Lammot duPont Laboratory in October 1993)
Now, determining the nucleotide sequence of genes is routine and highly automated to the
point that the entire human genome is known. It is fair to say that the techniques developed by Daniel Nathans and associates to explore the structure of DNA marked a monumental breakthrough. For that, Nathans is considered one of the founders of molecular biology.
He shared the 1978 Nobel Prize in Physiology or Medicine with his colleague Hamilton Smith at Johns Hopkins and Werner Arber of Switzerland- “for the discovery of restriction enzymes and their application to problems of molecular genetics.” Nathans’ discovery exemplifies how a solution to a specific problem turns out to transform a whole field of science.
RICHARD F. HECK
Professor of Chemistry & Biochemistry
2010 Nobel Laureate in Chemistry “For Palladium-Catalyzed Cross Couplings”
"Here in Brown Laboratory, Professor Richard F. Heck discovered the palladium- catalyzed cross coupling of aryl halides and olefins. Named for its inventor, The Heck Reaction transformed modern organic chemistry, changing how carbon–carbon bonds are made. By advancing pharmaceutical, materials, chemical, and biotechnology industries, the Heck reaction has impacts throughout our lives. Heck’s achievements ushered in a revolution of palladium-catalyzed reactions that were recognized by the 2010 Nobel Prize in Chemistry."
Professor Richard F. Heck was born in Springfield, Massachusetts, in1931. Heck developed an early passion for chemistry inspired by gardening with his father. He completed both his B.S. (1952) and his Ph.D. (1954) degrees in chemistry at University of California at Los Angeles, working with Professor Saul Winstein.
After postdoctoral stays at the ETH in Zurich, Switzerland with Vladimir Prelog and at UCLA, he took a position with Hercules Company in Wilmington, Delaware, in 1957. His remarkably productive research career at Hercules led to his move to the University of Delaware’s Department of Chemistry in 1971. At the University of Delaware, Heck led a highly productive research program and taught graduate and undergraduate courses in the lecture hall before you. During his career he made several landmark contributions to transition metal-mediated catalysis that transformed modern organic chemistry. He retired from the University of Delaware in 1989.
The Heck Reaction: The Heck Reaction is the palladium-catalyzed coupling of an aryl halide and an olefin. The origins of the Heck Reaction began with Heck's investigations of the coupling of arylmercury, aryllead, and aryltin compounds with olefins using palladium catalysts in the late 1960’s. Remarkably, this work was published in a series of seven back-to-back articles in the Journal of the American Chemical Society in which Heck was the sole author. In the early 1970's Mizoroki and Heck independently reported the use of the less toxic aryl halides as the coupling partner in the reaction. Now recognized as the Heck Reaction, this most widely used cross-coupling reaction was performed by Heck and coworkers here in Brown Laboratory. During his remarkable career, Heck continued to improve the transformation, expanding its scope and utility into a powerful tool for organic synthesis. Today, the Heck Reaction stands as one of the widely used methods for carbon-carbon bond formation in organic chemistry.
The Launch of a Revolution: The Heck Reaction was the first of a new class of palladium-catalyzed carbon-carbon bond-forming reactions that stitch together organic precursors under remarkably mild conditions. The reaction has remarkable functional group tolerance and can be used to assemble complex organic molecules under a new reaction manifold. The Heck Reaction formed the foundation for all palladium-catalyzed cross-coupling reactions that followed. Following Heck’s discovery, researchers have found ways to expand Heck’s cross-coupling chemistry to include the coupling of aryl halides with boronic acid derivatives (Suzuki-Miyaura coupling), organotin reagents (Stille coupling), organomagnesium compounds (Kumada-Corriu coupling), silanes (Hiyama), and organozincs (Negishi coupling).Together with the Heck Reaction, these palladium-catalyzed coupling reactions represent a mainstay of modern chemistry.
Other Firsts by Heck: Heck’s interest in organometallic chemistry began while at the Hercules Company where he was the first to work out the mechanism of the catalytic hydroformylation reaction and was the first to fully characterize a pi-allyl metal complex. Heck’s contributions are not limited to the activation of halides by the oxidative addition of Pd(0). Heck was also the first to demonstrate the palladium-mediated coupling of an alkyne with an aryl halide. Sonogashira later described a modification of the Heck Alkynylation that could improve yields with the addition of a Cu(I) salt. This reaction was critical to the synthesis of fluorescently-labeled nucleotides, used in the sequencing of
the human genome. Heck demonstrated that vinyl boronates were effective coupling partners in palladium-catalyzed cross-coupling reactions. This chemistry was a precursor to the Stille and the Suzuki coupling reactions.
Ahead of His Time: Interest in Heck’s discovery grew slowly at first. At the time of the Heck Reaction’s discovery, transition metal chemistry was not part of mainstream practice or education of organic chemists. Today thousands of research papers are published each year that have their origins in Heck’s pioneering discoveries, and the Heck Reaction is an essential part of the organic chemistry curriculum.
The Heck Lectureship: In 2004 the Department of Chemistry and Biochemistry at the University of Delaware established an annual lectureship named in Heck’s honor to recognize other leaders in the field of organometallic chemistry. Several Heck Lecturers have received the Nobel Prize themselves. Professor Heck delivered the first Heck lecture to a standing-room-only crowd in Brown Auditorium. Following the Heck Lectureship, Heck received other recognitions and awards for the science he conducted almost three decades earlier. These included the 2005 Wallace H. Carothers Award bestowed by the Delaware Section of the American Chemical Society for creative applications of chemistry that have had a substantial commercial impact and the 2006 Herbert C. Brown Award for Creative Research in Synthetic Methods from the American Chemical Society.
The 2010 Nobel Prize: Heck was honored alongside fellow researchers Akira Suzuki of Hokkaido University in Sapporo, Japan, and Ei-Ichi Negishi of Purdue University, “for palladium-catalyzed cross couplings in organic synthesis.” The Nobel committee stated that Heck developed “more efficient ways of linking carbon atoms together to build the complex molecules that are improving our everyday lives.” After receiving his award in Stockholm, Heck and his co-laureate Ei-Ichi Negishi, the 2011 Heck Lecturer, returned to a hero’s welcome at the University of Delaware to attend a daylong symposium celebrating Heck’s achievements.
Heck’s discoveries laid the foundation
for all modern cross-coupling reactions. These reactions have revolutionized organic chemistry and are used to make new organic materials, agrochemicals, pharmaceuticals, and enabling technologies that impact our daily lives in innumerable ways.
