The Original Gene Targeting Equipment

The original gene targeting equipment used by Nobel laureate Mario Capecchi in his early research at the University of Utah.

In 1970s & 80s, Dr. Mario Capecchi, Professor of Biology at the U of U, had the revolutionary idea to use gene targeting as a means to create genetically modified mammals to understand the function of individual genes and develop gene-based therapies. He envisioned leveraging homologous recombination – a natural process in which genetic information is exchanged between strands of DNA with similar sequences- to target specific genes for replacement with DNA modified in the laboratory. To do so required answering two critical questions:

1)   Do mammalian cells possess the molecular machinery to perform homologous recombination?
2)   What experimental conditions are necessary to drive homologous recombination at a frequency high enough to be of practical value?

To answer these questions, Dr. Capecchi with the help of his colleague, Dr. Larry Okun, pieced together an apparatus from standard laboratory equipment, scavenged from colleagues in the Biology Department. An early prototype even included a wooden popsicle stick as a critical component, which was eventually replaced by a custom-crafted metal part. The equipment displayed in the case below allowed Mario to inject DNA directly into the nucleus of an individual cell and to follow the fate of the injected DNA as the cell continued to grow and multiply.

The results of the experiments conducted with this apparatus convinced Mario and the world that it would be possible to modify genes at will in mammals. These observations underpinned subsequent experiments in the Capecchi laboratory that led to the generation of the first genetically modified mice, resulting in the Nobel Prize in Physiology or Medicine awarded in 2007 to Drs Mario Capecchi, Oliver Smithies and Martin Evans. Dr. Capecchi’s pioneering work was conducted here on the University of Utah campus in the South Biology Building in the Department of Biology.