Professor Axel Ullrich is a pioneering German cancer researcher in molecular biology. He was the first person to isolate and clone the insulin gene. His discovery revolutionized medicine and made a significant contribution towards the production of human insulin in bacterial cells. This procedure is a well-established principle in how we make many protein-derived medications today.
Professor Ullrich was born on October 19, 1943 in Lauban, Silesia, which today belongs to Poland, but from 1871 to 1945 was part of Germany. His father served in the German Army in World War II. When Lauban was attacked and almost destroyed by the Allies in 1945, Ullrich’s mother took him and his brother to Dresden to keep them safe. After World War II, his father was imprisoned by the British in Northern Germany and his mother went to her hometown in what was then Czechoslovakia with her two sons. When his father was released, the family moved to Rastatt, a small town on the Germany-France border, where Ullrich grew up.
Ullrich studied Biochemistry at the University of Tübingen in Germany and earned a PhD in Molecular Genetics from the University of Heidelberg in 1975. That same year, he took up a postdoctoral fellowship at the University of California's Department of Biochemistry and Biophysics in San Francisco. There, he worked with a technique that allows genes to be moved from one organism to another.
Genes are small pieces of DNA that contain instructions for making proteins, such as insulin. Inside each cell, genes that are turned on are copied into a molecule called messenger RNA (mRNA), which looks like DNA, but has only one strand instead of two. This mRNA carries information that then gets translated into proteins.
To clone the insulin gene, one needs to first isolate the mRNA from human insulin-producing cells. Second, this mRNA is converted back into a DNA molecule, which is called complementary DNA (cDNA). This cDNA only contains information on how to make insulin, rather than all the genes in an organism. It is inserted into another cell so that its new host now has the information to make insulin protein.
Ullrich began his work trying to clone rat insulin. To get enough material, he harvested the pancreases from 200 different rats. In 1976 he isolated the rat insulin mRNA, converted it into cDNA and inserted it into E. coli bacteria to produce the insulin protein. That was the first time E. coli was used to produce a mammalian protein and a tremendous accomplishment.
In 1978 he left the University of California and joined the world’s first biotech lab, Genentech, in California. There, he continued his research. The challenge with cloning human insulin is getting enough material. Healthy pancreatic cells only produce a very small amount of mRNA for insulin. He would not have enough human pancreases to work with. Serendipitously, Ullrich was visiting the Diabetes Research Institute in Munich one day when a surgeon mentioned that he had a female patient who needed a tumour removed from her pancreas. This kind of tumour – an insulinoma – results from insulin-producing beta cells in the pancreas growing uncontrollably causing cancer. The surgeon removed the tumour and gave it to Ullrich. With this new abundant source of insulin-producing cells, Ullrich created the first E. coli able to produce human insulin. His research at Genentech led to the development of the first drug through gene-based technology, Humulin (Human Insulin for the treatment of diabetes, approved in 1984).
Ullrich worked at Genentech as a Senior Scientist until 1988. Afterwards, he returned to Germany to become the Director of the Research Department of Molecular Biology at the Max Planck Institute (MPI). He continued working on cancer and developed the first-ever specific anti-cancer drug, Herceptin (approved in 1998), designed to block the growth of cancerous cells for breast cancer. In November 2016 he resigned from his position at MPI to become an emeritus scientific member of the Institute.
Since 2004, Ullrich has also been the Program Director of the Singapore Oncogenome (SOG) Project at the Institute of Medical Biology (IMB), one of the research institutes at the Agency for Science, Technology and Research (A*Star), in Singapore, but he still lives and works in Germany. He has been involved in more than 100 patents worldwide, has founded five biotech companies and has earned some of the world's highest honours for his groundbreaking work.
— Written by Ana de Faria