Fundamental Discoveries of the Nature of Genes
Molecular Cloning had a tremendous impact on science, but Maniatis’ scientific discoveries are also being honored by the Koshland-Lasker Award.
As a young researcher first at Cold Spring Harbor and later Cal Tech, Maniatis wanted to understand how genes are switched on and off in the cell. All cells in the body possess the gene for hemoglobin, for example, so why is hemoglobin only produced in red blood cells?
Using the genetic engineering techniques developed in his lab, and propagated in Molecular Cloning, Maniatis was the first to isolate a human gene (human β-globin) and the first to use the cloned genes to identify mutations in a human gene that causes disease. β-globin is one part of the hemoglobin protein complex, and the mutations Maniatis identified cause an inherited blood disease called beta thalassemia.
Maniatis’ laboratory also made the first complete human “genomic” DNA library — a collection of DNA fragments containing every human gene – this made it possible to isolate any gene, study its regulation and produce the encoded protein. This was a major step forward in the identification of disease genes and in the understanding of disease mechanisms. And as he did with genetic engineering techniques, Maniatis freely shared this library with other researchers.
Other discoveries made by Maniatis and his students have uncovered important details in how information in genes is turned into proteins, including the mechanisms by which DNA is transcribed to produce RNA, and the process called RNA splicing.
Not content to see discoveries contained in the basic science community, Maniatis also helped launch one of the first biotech companies. In 1980, he co-founded Genetics Institute (eventually bought by Wyeth), which developed blood clotting factors, the blood stimulating protein erythropoietin used to treat anemia, and bone morphogenic proteins used in the treatment of severe fractures and other orthopedic indications. ProScript, which he co-founded in 1994, developed a cancer drug based on discoveries made in his lab and others. The drug, Velcade, is now the most effective treatment for multiple myeloma, and is the first in its class of so called “proteasome inhibitors” that are being tested in a wide range of cancers.
“The years I’ve been involved with biotech have exposed me to human biology and medicine in a way that would not have been possible otherwise,” Maniatis says. “I became a scientist because of the excitement of making discoveries, but to see the impact these discoveries have on the treatment of human disease is particularly gratifying.”