- Pick a possibly unique position in a strand of DNA
- Cut and remove a sub-sequence of DNA
- Ligate a new sub-sequence of DNA into the same position
A very biased view of Joshua Lederberg, is that Joshua Ledererg is a founder of genetic engineering. In fact it has been claimed that "In 1952, working with Norton Zinder on the salmonella bacterium, [Joshua] Lederberg discovered that bacteria have a second method [aside from sexual recombination] for exchange of genes, called transduction. This takes place when viruses that infect bacteria transfer genetic material from one bacterium to another." (Obituary in "The Telegraph", published April 1, 2011).
Thus the discovery of transduction presaged what was to come. However, Norton Zinder's discovery of transduction most likely would not have taken place until after Esther M. Zimmer Lederberg discovered bacteriophage lambda. (See the reference to Transduction by A. D. Hershey, under Special Topics.) This discovery was followed by the research and paper "Transduction in Escherichia coli K-12", by Morse, M. L., Lederberg, E. M., Lederberg, J., Genetics, 1956, 41:142-156.
Exactly what does "genetic engineering" really mean? Genetic
engineering is based upon the idea that a specific sub-sequence
of DNA can be "cut" or excised from DNA, then possibly a new
sub-sequence of DNA replace the excised sequence by ligating
the cut DNA back into one piece. Thus, the steps required to
accomplish genetic engineering:
Werner Arber, Dan Nathans and Hamilton Smith were awarded the 1978 Nobel prize for Physiology or Medicine for their roles in the discovery of restriction enzymes. However, as already noted on this site, it was Daisy Roulland-Dussoix who actually discovered restriction endonucleases (blunt or sticky ends). (For a discussion of gender discrimination in the sciences, which affected both Dr. Roulland-Dussoix and Esther M. Zimmer Lederberg, see Special Topics.)
It may one day be possible to pick a unique position in a long strand of DNA and cut and remove a sub-sequence of DNA; restriction endonucleases make this a possibility. However, at the current time, restriction endonucleases that can uniquely specify a position within a long DNA strand, are not yet known. Research to engineer artificial restriction endonucleases with a capability to specify position in long strands of DNA, is in its infancy.
Once it was possible to genetically engineer new forms of transgenic life, it became obvious that new dangers confronted the world. It would be possible that genetically-engineered life could escape from the research lab and present dangers such as new diseases. Thus in 1975, a conference was held at Asilomar, Pacific Grove, California to examine the ethics and safety of transgenic life, and to set guidelines and to impose a voluntary moratorium on experiments which involved the transfer of genes from one species to another. The guidelines included such ideas as negative pressure gradient laboratories to prevent the escape of transgenic life. Another idea was to modify the DNA of transgenic life to require specific amino acids rarely encountered in the natural environment to exist. Escape of such transgenic life would likely result in the death of these forms of transgenic life, as the amino acid requirement could not be satisfied.
Herbert Boyer and Stanley Cohen opened the door to genetic
engineering and laid the foundations for gene therapy and
the biotechnology industry. For these outstanding achievements,
the two collaborators received the Lemelson-MIT Prize in 1996.
Their work enabled virus to be used as a vector to infect the DNA
of many cells at once with the same sequence of bases, thus
producing clones. The key discovery in Stan Cohen's lab was
that viral DNA could more easily pass through the prokaryotic
cell membrane if CaCl2 was
used.
Other major areas of research in genetic engineering include the research done by people such as Eric Kool of Stanford University. DNA is typically composed of the four bases: A, T, C and G. Dr. Kool constructed a stable novel form of DNA containing modified forms (derivatives) of A, T, C and G, as well as other bases X, to create an artificial DNA in which C' is held together by Watson-Crick bonds to G or G'. G' may be Watson-Crick-bonded to C or C', etc., with A, A', T, T'. In one experiment, X is Watson-Crick-bonded to itself (is self-complimentary). Research is also being done with artificial tRNA (transfer RNA) and artificial amino acids (amino acids not normally found in polypeptide chains).
Genetic engineering currently excludes major research programs in epigenetics, as well as research into the exact method whereby polypeptides can feed back and affect DNA (for example, "zinc fingers" and artificial "zinc fingers"), but these are aspects of genetic engineering research that are on the near horizon.
The research being done to create artificial restriction endonucleases, artificial DNA, cloning and even the discovery of restriction endonucleases, as well as conferences such as the 1975 Asilomar conference, all took place after Joshua Lederberg ceased doing bench research; in fact, he took no part, and has never been mentioned as having taken part, in any of this research.