Axel Ulrich clones the rat insulin gene

Shortly before Ulrich began cloning the rat insulin gene, a new vector called pBR322 had been developed by Herbert Boyer’s UCSF lab.  The vector, known as a plasmid, was named for its inventors, Francisco Bolivar and Raymond Rodriguez.  pBR322 offered many advantages compared to other vectors. According to the rules of the day, new vectors had to be approved by a committee.  Ulrich heard that pBR322 had been approved, so he used it for his cloning project.

Unfortunately, Ullrich didn’t understand the NIH vector certification process.  While, pBR322 had been approved by a scientific panel, it was waiting for certification by the official NIH panel, which took the scientific panel’s advice into consideration along with other factors.  So, pBR322 was not yet certified, although it was approved (and certified soon after).  The microbiologists who designed the vectors all thought that pBR322 was safer than any of the approved alternatives.[Ulrich oral history ]

Nevertheless, the scientific community had gone through a serious debate and decided that these voluntary restriction on recombinant DNA research was necessary to maintain the public’s trust.  Ulrich had to destroy his clones. He collected all the test tubes that held the clones, and dumped acid into each one.  He had about half of the RNA left, and had to start over.

Fortunately, repeating an experiment is often much easier than performing it the first time.  Ulrich quickly repeated the process using an alternative vector, pMB9 (named for Mary Betlach), and published his results in the journal Science.

Now that Ulrich had cloned the rat preproinsulin gene, he was ready to tackle the human insulin gene.  The primary challenge was to get enough starting material.  For his rat experiment he had started with several dozen rat pancreases, but how could he obtain enough material from humans?