Hybridomas represent uossibly the biggest impact of B-cell biology and the technology to generate these immortal antibody-producing cell lines has reached the grand old age of 40 this year. In 1975 Georges Köhler and César Milstein at the MRC Laboratory of Molecular Biology in Cambridge, UK published a paper in Nature describing their success in fusing B cells with a myeloma cell line to produce a hybrid cell that continuously produced its specific antibody. Monoclonal antibody technology was born.
It is hard to overstate the effect that this achievement has had on both the fields of biology and medicine. Experimental biology has embraced these specific affinity reagents to identify, isolate and perturb nearly any molecule or cell of interest. They have shown their worth in the clinic as potent diagnostics and therapeutics. In recognition of the importance of hybridoma technology Köhler, Milstein and Niels Jerne were awarded the Nobel Prize in Physiology and Medicine in 1984.
Hybridomas exhibit the antibody producing qualities of B cells along with the rapid reproduction of cancer cells and have the ability to grow in tissue culture without the need for chain synthesis to produce the antibodies. This combination of B cell and cancer cell characteristics creates antibody factories of the hybridoma cell, allowing us to produce specific antibodies in excess.
Though antibodies are one of the most widely used biological research reagents a number of problems have been identified with their use over their long period of dominance in the affinity market.
The issues associated with antibodies include their the long lead times required for the development of a new antibody, their relatively poor intracellular expression and instability in the cytoplasm due to their internal disulphide bonds, their large size which limits their use in applications such as intracellular labelling, where the attachment of big antibody structures can cause aberrant trafficking of the target molecule, their cross-reactivity and more often that you could believe with commercially available antibodies an inability to detect their targets or any targets at all.
There is much talk within the life sciences community about the very real issues that stem from antibody use causing setbacks in research projects, wasting both time and money and on a number of occasions causing published papers to be retracted from journals. Although the community is now trying to broach these problems and has established antibody review websites, journal banks that contain antibodies validated in different applications and recommendations to end users to help with validation, thousands of antibodies already exist on the market that do not function. With lot-to-lot variation in an antibodies performance it seems the task of validating research antibodies for even basic function is getting out-of-hand.
Now that we have reached the 40th birthday of the hybridoma, built for churning out monoclonal antibodies, we can look back with awe at the achievements that this technology allowed.
So happy birthday to the hybridoma, fabulous technology which has taught us so much.