On this page
Bacteria divide in two, so for a long time biologists assumed every bacterium in a culture was a genetic copy of its parent. NCERT's Class 11 chapter on biological classification now says bacteria also reproduce "by a sort of sexual reproduction by adopting a primitive type of DNA transfer from one bacterium to the other". That sentence rests on an experiment by a graduate student. This post explains it, works through the numbers from his Nobel lecture, and ends with what you can learn from how he worked.
Who was Joshua Lederberg?
His Nobel Prize facts page records that he was born on 23 May 1925 in Montclair, New Jersey, and died on 2 February 2008 in New York. He received half of the 1958 Nobel Prize in Physiology or Medicine "for his discoveries concerning genetic recombination and the organization of the genetic material of bacteria".
His Nobel autobiography says he studied at Columbia, then went to Yale in 1946 to work with Edward Tatum, and earned his PhD in 1948. A 1997 addendum notes that he received the Nobel Prize at the age of 33. He went on to lead genetics at Wisconsin and Stanford and later served as president of the Rockefeller University.
What did the 1946 experiment show?
The facts page summarises it: "Joshua Lederberg and Edward Tatum demonstrated in 1946 that bacteria's genes can also change in a way similar to that of sexual reproduction". Their short report, Gene Recombination in Escherichia Coli, appeared in Nature in October 1946.
His Nobel lecture explains the design. He used auxotrophic mutants, strains that cannot make certain nutrients and must be given them. Two such strains, each lacking different abilities, were grown together. Some cells appeared that were prototrophic, able to grow on minimal food with nothing added. Neither parent could do that, so the new cells must have combined genes from both. At first, he said, "only one recombinant appeared per million parental bacteria", so the selective method, which lets only the recombinants grow, was essential.
Later work, he explained, showed that bacteria join by a conjugation bridge through which part or all of a male genome passes into a female cell.
Worked example: Lederberg's dilution arithmetic
Lederberg's lecture includes a calculation showing how to isolate rare drug-resistant mutants without ever exposing them to the drug. Follow it step by step.
A culture has 10⁹ bacteria per ml. Plating on streptomycin shows one per million is resistant, so 10⁹ × 10⁻⁶ = 10³ resistant bacteria per ml.
Dilute in plain broth to samples of 10⁵ bacteria each. The expected number of resistant bacteria per sample is 10⁵ × 10⁻⁶ = 0.1.
Bacteria cannot be split by diluting, so about nine samples in ten contain none, and about one in ten contains one.
After growth, the sample that had one resistant cell now has a resistant share of 1 in 10⁵ instead of 1 in 10⁶: a tenfold enrichment. Repeat the process and the resistant line becomes pure.
The lecture adds that replica plating, "transposing a pattern of surface growth from plate to plate with a sheet of velvet", does the same job more conveniently. Joshua and Esther Lederberg described that method in the Journal of Bacteriology in 1952. The point of both methods is that the resistant mutants were already there before the drug arrived.
What else did Lederberg find?
The facts page notes that Lederberg also proved transduction, in which DNA is carried from one bacterium to another by bacteriophages. That work, with Norton Zinder, appeared as Genetic Exchange in Salmonella (1952). Gene transfer between bacteria later became a basis of genetic engineering; our post on the principles of biotechnology covers plasmids and cloning vectors for NEET.
Common mistakes students make here
Calling conjugation reproduction. It transfers genes; it does not make a new cell by itself. NCERT says "a sort of sexual reproduction" for a reason.
Confusing the three routes. Conjugation is cell-to-cell contact, transduction uses a phage, and transformation is uptake of free DNA, as in Griffith's experiment in your molecular basis of inheritance chapter.
Thinking drugs cause resistance. Lederberg's indirect selection showed resistant mutants arise on their own and are then selected.
If those three routes keep blurring together, the Fermi Concept Library has every concept in biology with its own lesson and its place in the map, so you can see how they connect.
What can a student learn from Lederberg's way of working?
Lederberg designed experiments so that the rare event he was looking for would be the only thing that could grow. Instead of searching a million cells by hand, he let the conditions do the searching. Do the same with revision: design a test that only the correct understanding can pass, such as explaining a process without notes.
Today, write one line each defining conjugation, transduction and transformation, and name the experiment that showed each.



