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Discovery Series: Hybridomas
A while ago, we started a series of posts with the aim of commenting on some of the most impacting scientific discoveries ever made. Our first post was about antibiotics. Today, we are going to write about the hybridoma technology. As a company that offers over 11,000 products, a majority of which are based on this technology, it is a subject that is very near and dear to us.

So, what is a hybridoma? A hybridoma is an immortalized B cell that produces a unique immunoglobulin. It results from the fusion of a naturally antibody secreting B cell, and a B cell myeloma that does not produce any immunoglobulin. The resulting hybrid cell has the capacity for antibody production of the natural B cell, and the capacity for growing and proliferating indefinitely in culture of a myeloma cell (which is basically a cancer cell). The fused cell can be further selected and cloned based on it’s ability to produce an antibody that recognizes a particular antigen.

Other famous hybrids...
https://www.familyholiday.net/the-great-egyptian-sphinx-of-giza
And how were hybridomas developed? The main idea is credited to César Milstein and Georges J. F. Köhler. Dr. Milstein, an Argentinian biochemist, was at the time investigating immunoglobulins at the Medical Research Council Laboratory of Molecular Biology, Cambridge, UK. Dr. Köhler was a German postdoctoral fellow at Milstein‘s laboratory. In 1975, they published a paper that remains one of the most influential papers of the 20th century: "Continuous Cultures of Fused Cells Secreting Antibody of Predefined Specificity, Nature, 1975. 256 (5517): 495-97".

Photo showing Milstein (left) and Köhler (right), during a trip to Kenya in 1979.
Photo by Celia Milstein, MRC Laboratory of Molecular Biology (https://www.whatisbiotechnology.org/exhibitions/milstein/monoclonals)
Interestingly, shortly after the publication of the article, several scientists, and even Milstein’s group, were having problems replicating the results, to the point that he wondered if retracting the paper was necessary. Luckily, they refined the methods and collaborated with other scientists, to overcome the difficulties in reproducibility, which were mostly a reflection of the lack of standardization at the time.

Milstein and Köhler, together with Niels K. Jerne, shared the Nobel Prize in Physiology or Medicine in 1984, for "theories concerning the specificity in development and control of the immune system and the discovery of the principle for production of monoclonal antibodies".
Since then, the hybridoma technology has been highly optimized. It is a very strong, reproducible technique, with countless applications. The availability of monoclonal antibodies, that can uniquely recognize a specific target with high affinity is truly an invaluable research, diagnostic and even therapeutic tool.

Sorry Neo, a good monoclonal antibody won't miss its target...
(The Matrix, Warner Bros. Pictures)
If you want to know more about how antibodies are made, the hybridoma technology, and the scientists that discovered it, please click these links:

How to Make an Antibody

What is Biotechnology? The Story of César Milstein and Monoclonal Antibodies

The Nobel Prize in Physiology or Medicine 1984

Feel free to leave us your comments: mtam@biolegend.com

Contributed by Miguel Tam, Ph.D.
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