History of Genetic Engineering

Let’s review the history of genetic engineering. A scientist named Werner Arber studied bacterial viruses. Bacterial viruses are also called bacteriophages, they eat bacteria. Arber was born in 1929. As a graduate student at the University of Geneva in the 1950’s, he studied with a physics professor who converted from doing pure physics to biophysics. This was the 1950’s, the DNA structure and the double helix had just been announced, and genes were the rage in science. Even physicists were catching the biology bug.

Arber’s PhD thesis was on the phenomenon of bacteriophages restriction. This is a phenomenon in which a specific type of bacterial virus can only infect a specific genetic strain of bacteria. The virus, with its body and DNA, lands on the outside of the bacterial cell, injects its DNA into the cell, and this DNA takes over the cell. Half an hour, that cell, which was converted into a virus factory, is dead.

Arber was specifically interested in the fact that only certain host cells seem to work for a particular virus. Other bacteria didn’t. Arber’s professor must have been really impressed with him, because their hire him in 1960 as a junior professor. In 1962, he and his graduate student Daisy Dussoix found that bacteria seemed to evade infection by viruses by chopping up the invading virus DNA into fragments. So, the virus DNA gets in, and all of the sudden gets chopped up in fragments.

Arber proposed the hypothesis to explain this phenomenon: virus restriction. First, host bacteria make an enzyme that recognizes a specific DNA sequence on viral DNA. Second, the bacteria have an enzyme that modifies its own DNA to make it resistant. This is what stops the restriction enzyme from chopping up the bacteria’s own DNA.

Arber’s hypothesis was soon confirmed in the 1960’s. In the US, at John Hopkins University, Hamilton Smith and his team isolated and described the chopping enzyme from bacteria. Because it only cuts DNA at certain sequences, they call it a restriction enzyme. The second point of Arber’s hypothesis was also confirmed. Arber himself characterized this system that modifies the bacterial DNA. Arber was doing only basic research, but his discovery was essential in the history of genetic engineering.

How is this discovery relevant in the history of genetic engineering? Scientists soon described other restriction enzymes that would cut DNA at other DNA sequence sites. Each of them was highly specific for a certain site. Earlier in the 20th century it was recognized that if you take a protein out of a cell, the protein would fold in the same it does inside the cell. The cell is mostly water, so if you take a protein and put it in water, it would fold the same way. This means that you can study and use proteins outside of the cell. This includes restriction enzymes.

First Success in the History of Genetic Engineering

Two scientists, Stanley Cohen at Stanford and Herbert Boyer at the University of
California San Francisco, saw the method of cutting DNA and mapping it in a test tube, and wanted to follow it up. Their idea was to take a DNA sequence, cut it, and put it back together again. At Stanford University, another scientist discovered that there is an enzyme that would put cut DNA’s together. Cohen and Boyer tried the experiment using chromosomes from E. coli (bacteria).

They had two different strains of bacteria. One bacterium had resistance to antibiotic A. Another bacterial strain had resistance to antibiotic B. They isolated chromosomes from both of these, put them in the test tube, and just how they planned, they cut the chromosomes open with the restriction enzymes, and glued the two chromosomes together. They took another bacterium that doesn’t have any resistance to antibiotics, and they put this new chromosome into it. Low and behold, this bacterium was now resistance in some cases to both A and B antibiotics.

It was 1973. These scientists had taken two chromosomes, cut them open, put them back together, and showed that they were functional in a cell. They had created genetically functional recombinant DNA. It was a revolutionary discovery. It meant that genes from any sources in nature could be taken out of the cell and swapped and spliced beside one another. We were no longer limited in genetics by normal processes like fertilization. This could be considered the real beginning of the history of genetic engineering.

Soon, within a couple of months, they had taken human genes in a test tube, spliced and put them into bacterial chromosomes. The bacteria did not turn into humans, it was a single gene that makes RNA. This could never happen in nature.
Arber and Smith both won Nobel prizes. The two California universities patented the method of making recombinant DNA and reaped millions of dollars in royalties. Boyer soon cofounded Genentech, the first genetic engineering company.

The revolution of genetic engineering had begun.

Return from History of Genetic Engineering to Genetic Engineering Main Page