How rDNA technology began

Recombinant DNA (rDNA) technology, also called genetic engineering, is the set of methods that change an organism's genome by working directly on its DNA. Its basic aim is gene cloning: take out a gene we want, multiply it, and get its product in large amounts.

It did not appear overnight. It grew out of biochemistry, genetics, cell biology, microbiology and molecular biology, through a chain of discoveries:

• 1944: Avery, MacLeod and McCarty showed that DNA is the genetic material.
• 1952: Lederberg discovered plasmids, small circles of DNA in bacteria. Bacteria were also seen to take up foreign DNA from their surroundings.
• 1953: Watson and Crick proposed the double helix. Over the next years, replication, transcription and translation were worked out.
• 1967: DNA ligase was discovered: the enzyme that joins two pieces of DNA, the 'glue'.
• Late 1960s and early 1970s: restriction enzymes were found: enzymes that cut DNA at specific places, the 'scissors'.

Then two scientists brought their skills together. Stanley Cohen knew how to put plasmids into E. coli and clone them; Herbert Boyer knew how to cut DNA with restriction enzymes, leaving identical ends. In 1973 they cut open a plasmid, inserted a gene from another species of bacterium, and closed it again. The result was the first recombinant plasmid, and the bacteria carrying it were the first genetically modified organisms.

Many milestones followed:

• 1972: Paul Berg made the first rDNA molecule.
• 1982: Humulin, human insulin made by bacteria, was approved.
• 1983: Kary Mullis invented PCR, a way to copy DNA in a test tube.
• 1984: Alec Jeffreys developed DNA fingerprinting.
• 1990-2003: the Human Genome Project read the whole human DNA.
• 1996: Dolly the sheep, the first cloned mammal.
• More recently: CRISPR-Cas9 gene editing, and mRNA vaccines.

In short, rDNA technology comes down to four actions: cut the DNA, join the gene to a carrier, put it into a host, and let the host multiply it.