Imagine if antibodies were standardized with respect to their sequences, their concentrations, and their buffers. Antibodies would inspire confidence, not doubt. And we could stop wasting huge sums on “bad” antibodies. Worldwide, the losses mount to $800 million each year, roughly half the spending on protein-binding reagents. In the United States, the corresponding figure is $350 million.
Noting that antibodies are the only widely used reagents in biological research that are not defined at the sequence level—unlike genes, oligos, plasmids, recombinant proteins, etc.—a pair of scientists has issued a proposal that could fundamentally alter how antibodies are used.
“We call for an international collaboration and funding initiative to define all binding reagents according to the sequences that encode them,” the scientists wrote. “Crucially, researchers should use recombinant antibodies or binding reagents.”
The call for standardized antibodies was prepared by Andrew Bradbury, Ph.D., a researcher and group leader at Los Alamos National Laboratory, and Andreas Plückthun, Ph.D., a professor and head of the Biochemistry Department at the University of Zurich. These scientists, together with more than 100 co-signatories from around the world, outlined the equivalent of an antibody “bar code” system February 4 in Nature, in an article entitled, “Reproducibility: Standardize antibodies used in research.”
The quality of all antibodies produced varies enormously according to the manufacturer, and most antibodies are rarely validated and between-batch differences are common, the article noted. Another problem, the article continued, is the quality of the documentation accompanying the batches. Such documentation—which may, for instance, indicate the concentration of antibody—is enormously variable. Often it doesn’t even correspond to the batch being supplied. It may even be entirely absent.
“To stem the enormous waste in materials, researcher time, and money caused by their lack of validation and characterization, antibodies must be defined by their sequences, and in the main, produced de novo under standardized conditions,” the writers point out. “De novo” production in this case would refer to the process of generating antibodies or other binding reagents from scratch using methods that do not involve animal immunization, rather than cloning antibodies from cells derived from immunization.
“What we are proposing is to move over to an in vitro method of generating antibodies that will not require the use of animals at all, and importantly, will directly lead to molecules with known sequences,” Dr. Bradbury said.
The scores of researchers signing the letter are united in their desire for a more structured, accurate antibody identification system, although Dr. Bradbury, Dr. Plückthun, and their cohorts recognize that significant costs will be associated with the effort.
“The National Institutes of Health and European Union were very proactive in starting pilot programs to address part of this issue, and given the long-term investment required, we wanted to encourage them to continue,” Dr. Bradbury pointed out. “Given advances in the generation of specific binding reagents by in vitro methods, and the recent discussions on reproducibility in science, we thought it was about time this issue was addressed.”
To make uniform reagents in the laboratory for all 20,000 human gene products, the authors estimate that using current technology, an investment of roughly a billion dollars would be required. “This is less than the money wasted worldwide on bad reagents in under two years,” Dr. Bradbury indicated, and it would be recovered in time through the production of better research results. However, the total amount required would be expected to be far less if appropriate investments in technology development were made.