1975: Development of Hybridoma Technology for Monoclonal Antibodies (1975)

The immune system generates an enormous diversity of antibodies, each secreted by a different B cell
clone and binding a different epitope. Before 1975, obtaining large amounts of a single, precisely
defined antibody was impossible: polyclonal antisera from immunised animals contained hundreds of
different antibodies with variable specificity and lot-to-lot variability that made them unsuitable
for diagnostic or therapeutic use.

César Milstein and Georges Köhler at the MRC Laboratory of Molecular Biology in Cambridge solved
this problem by fusing antibody-secreting B cells from immunised mice with immortal myeloma cells.
The resulting hybrid cells—hybridomas—combined the B cell's ability to produce a specific antibody
with the myeloma's indefinite proliferative capacity. A hybridoma clone derived from a single B cell
would produce unlimited quantities of a genetically homogeneous, highly specific antibody:
the monoclonal antibody (mAb).

Their 1975 Nature paper is among the most cited papers in biomedical science. Milstein and Köhler,
working with Jerne (who contributed theoretical foundations of clonal selection), were awarded
the 1984 Nobel Prize in Physiology or Medicine.

The commercial significance was enormous. Monoclonal antibodies enabled precise diagnostic assays
(pregnancy tests, HIV tests, troponin assays) and, after further engineering to reduce murine
immunogenicity—chimeric antibodies (1984), humanised antibodies (1986), and fully human antibodies
(1994 via phage display or transgenic mice)—became the largest class of biopharmaceuticals. By
2023, over 100 therapeutic mAbs had been FDA-approved, treating cancers, autoimmune diseases,
and infectious diseases. The global mAb market exceeds $200 billion annually.