The hybridoma technique was developed by whom?
- (a)Louis Pasteur
- (b)George Kohler and César Milstein
- (c)Edward Jenner
- (d)Burnet
Correct — B, George Kohler and César Milstein.
The keyed answer is George Kohler and César Milstein.
In 1975, at the MRC Laboratory of Molecular Biology in Cambridge, Georges Köhler and César Milstein fused an antibody-producing mouse B lymphocyte with a myeloma (cancer) cell. The hybrid, called a hybridoma, kept the B cell's antibody specificity and the myeloma's ability to divide indefinitely.
That fusion is the whole point of the technique. A single hybridoma clone secretes one antibody of predefined specificity, in unlimited quantity: a monoclonal antibody. The 1984 Nobel Prize in Physiology or Medicine went to Köhler and Milstein for this discovery, shared with Niels Jerne.
The idea to carry away: hybridoma = B-cell specificity + myeloma immortality. The other three names on the paper are tied to vaccination and immune theory, and to earlier decades.
- (a)Louis Pasteur — Pasteur is the right answer to questions on the germ theory of disease, pasteurisation and the rabies vaccine, which he first gave to a human patient in 1885. He also produced attenuated vaccines against chicken cholera and anthrax.
His vaccine work of the 1880s predates even the discovery of antibodies (antitoxins), which Behring and Kitasato reported in 1890. Cell fusion in culture belongs to a different century.
- (c)Edward Jenner — Jenner is the right answer to smallpox vaccination with cowpox (1796), when he inoculated the boy James Phipps with material from a cowpox lesion. The word vaccine comes from vacca, Latin for cow, in tribute to that experiment.
His method protects a whole person with a live agent. The hybridoma is a cultured cell line that secretes a defined antibody, a different thing altogether.
- (d)Burnet — Frank Macfarlane Burnet is the right answer to the clonal selection theory of antibody formation (1957), which explains how one lymphocyte clone makes one antibody. He shared the 1960 Nobel Prize in Physiology or Medicine with Peter Medawar for acquired immunological tolerance.
His theory describes what B cells do naturally. The hybridoma technique that exploits that fact came from Köhler and Milstein eighteen years later.
A hybridoma is an immortalised antibody factory. An animal, usually a mouse, is immunised with an antigen; spleen B cells are harvested and fused with myeloma cells using a fusing agent such as polyethylene glycol. The mixture is grown in HAT medium (hypoxanthine, aminopterin, thymidine).
In HAT medium, unfused myeloma cells die because they lack the enzyme HGPRT, and unfused B cells die out on their own after a few days. Surviving hybrids are screened for the wanted antibody, and a single positive cell is cloned.
Because every cell in that clone descends from one B cell, the antibody it secretes is chemically identical from molecule to molecule: a monoclonal antibody.
Monoclonal antibodies turned immunology into a manufacturing science. One clone gives one antibody indefinitely, so the reagent is reproducible batch after batch, unlike polyclonal antiserum, which varies from animal to animal.
They are used in diagnostics (home pregnancy tests detect hCG with monoclonal antibodies; blood-group typing), in research, and in therapy, where drug names ending in -mab such as rituximab and trastuzumab mark the class. Later work humanised mouse antibodies to reduce immune reactions in patients.
- Georges Köhler and César Milstein reported the hybridoma method in 1975 at the MRC Laboratory of Molecular Biology, Cambridge.
- A hybridoma fuses an antibody-producing B lymphocyte with a myeloma cell, combining antibody specificity with indefinite growth.
- Hybrid cells are selected in HAT medium (hypoxanthine, aminopterin, thymidine), in which unfused HGPRT-deficient myeloma cells die.
- Köhler and Milstein shared the 1984 Nobel Prize in Physiology or Medicine with Niels Jerne.
- Monoclonal antibodies from hybridomas underpin diagnostics such as home pregnancy tests and therapeutic drugs whose names end in -mab.
- Edward Jenner introduced smallpox vaccination using cowpox in 1796.
- Louis Pasteur developed the rabies vaccine, first used on a human patient in 1885.
- Frank Macfarlane Burnet proposed the clonal selection theory of antibody formation in 1957 and shared the 1960 Nobel Prize with Peter Medawar.
Köhler and Milstein are the pair tied to cell fusion in culture; the other three belong to vaccination and immune theory.
- Treating the four options as famous names in immunology and choosing the most familiar one; the stem asks about a specific laboratory technique from 1975, which rules out figures from the 1700s and 1800s on date alone.
- Reading 'hybridoma' as a vaccine topic because three of the four options are vaccine-linked names; a hybridoma is a cultured cell line that secretes antibody, which is a different thing from a vaccine.
- Attaching Burnet to the technique because his clonal selection theory is about one clone making one antibody; the theory is from 1957 and the technique from 1975, by different people.
- Answering 'antibodies' where a question asks for the product of hybridoma technology; the distinctive product is monoclonal antibodies, as the UPSC 2000 twin of this question tested.
The hybridoma can be asked as a who-developed recall item like this one, as a what-does-it-produce item (monoclonal antibodies, as UPSC asked in 2000), or as a match-the-pairs list of immunologists and contributions where Jenner, Pasteur, Burnet and Köhler-Milstein sit side by side.
A related shape asks for the Nobel year or the co-laureate (Niels Jerne, 1984), or names the selection medium (HAT) and asks what it selects for.
UPSC_2000_GS1_Q1222000Same technique, different recall handle. The UPSC item asks what hybridoma technology produces (monoclonal antibodies, set against the looser option 'antibodies'); this UKPSC item asks who developed it. Together they cover the product and the discoverers of one fact.
- practice — not a real PYQ
In hybridoma technology, a hybridoma is formed by the fusion of which two types of cells?
- (a)An antibody-producing B lymphocyte and a myeloma cell
- (b)A T lymphocyte and a macrophage
- (c)A red blood cell and a plasma cell
- (d)Two myeloma cells from different mice
Answera — the B lymphocyte supplies the antibody specificity and the myeloma cell supplies indefinite division; that pairing is the definition of a hybridoma.(b) names two cells that do not secrete antibody; (c) includes a red blood cell, which plays no part in the technique; (d) fuses two immortal cells and leaves out the B cell that carries the antigen specificity.
- practice — not a real PYQ
Who shared the 1984 Nobel Prize in Physiology or Medicine with Georges Köhler and César Milstein?
- (a)Niels Jerne
- (b)Peter Medawar
- (c)Frank Macfarlane Burnet
- (d)Emil von Behring
Answera — Niels Jerne was the third 1984 laureate, cited for theories on the specificity and control of the immune system.Medawar (b) and Burnet (c) shared the 1960 prize for acquired immunological tolerance, and Behring (d) received the first Physiology or Medicine prize in 1901 for serum therapy.
- practice — not a real PYQ
Which one of the following pairs is correctly matched?
- (a)Edward Jenner — rabies vaccine
- (b)Louis Pasteur — smallpox vaccination using cowpox
- (c)Frank Macfarlane Burnet — clonal selection theory
- (d)César Milstein — germ theory of disease
Answerc — Burnet proposed the clonal selection theory of antibody formation in 1957.The rabies vaccine (a) belongs to Pasteur, cowpox vaccination (b) to Jenner, and germ theory (d) to Pasteur; Milstein's name belongs with the hybridoma and monoclonal antibodies.
- practice — not a real PYQ
HAT medium is used in hybridoma technology because it:
- (a)selects fused hybrid cells by killing unfused myeloma cells
- (b)induces the B lymphocyte and the myeloma cell to fuse
- (c)stimulates the hybridoma to secrete more antibody
- (d)removes the antigen from the culture
Answera — aminopterin in HAT medium blocks the main route of nucleotide synthesis, so cells must use the salvage pathway, which needs the enzyme HGPRT that the myeloma partner lacks; unfused myeloma cells die, unfused B cells die out naturally, and hybrids survive.Fusion (b) is done by an agent such as polyethylene glycol; the medium is a selection step, so (c) and (d) describe functions it does not perform.