Scientific research is only as good as the tools used to carry out the experiments.
So with one of the most common scientific tools reportedly working consistently only 49 percent of the time, many scientists are concerned.
The tool? Custom-built antibodies.
Like the antibodies produced naturally by the immune system in response to an invader such as a bacterium or virus, customized antibodies bind to specific molecular targets.
By measuring how well antibodies bind, scientists can determine whether a protein is present in a cell or tissue sample — or how protein levels change in response to certain tests.
This helps scientists understand how diseases develop as well as find new ways to treat or diagnose them.
But only if antibodies work as advertised.
“Antibodies need to be tested to ensure they are detecting the correct protein of interest and only that protein,” Deborah Berry, Ph.D., a research assistant professor and co-director of the Histopathology and Tissue Shared Resource at Georgetown University, told Healthline.
This “validation” can be done by the company that makes the antibody, by the researcher, or by a specialized laboratory like Berry’s.
How are antibodies flawed?
Flawed antibodies come in many forms.
An antibody may bind to proteins other than the intended target. Or to no protein at all.
Experimental conditions — like the solutions used — can also affect how well an antibody works.
Even the same type of antibody made in separate batches — or from different companies — can give different results.
“As such, a ‘result’ with one antibody may be very different from a ‘result’ with another antibody, even when performed with the same samples under the same conditions,” said Berry.
Flawed antibodies can also create major headaches for scientists.
In one case, highlighted in the journal Nature, researchers from Mount Sinai Hospital in Toronto, Canada, used an antibody from a commercial protein detection kit to create a test for pancreatic cancer.
They eventually realized that the antibody didn’t bind to their target protein. Instead, it stuck to another cancer protein.
The result? Two years of hard work, thousands of patient samples, and $500,000 down the drain.
One of the researchers told Nature that in a rush to move their research along, they had failed to make sure the antibody worked as promised.
Scoring system for antibodies
So if checking the quality of antibodies is so important to the integrity of scientific research, who should be making sure it happens?
“In terms of validating, it is really up to both the producer/seller, and the end user, i.e. the individual researcher,” Leonard Freedman, Ph.D., president of the nonprofit Global Biological Standards Institute (GBSI), told Healthline in an email.
But it’s no big secret among the scientific community that some companies sell “crappy” antibodies.
Which is why many scientists are pushing for better performing commercial antibodies.
“Companies need to be held to higher standards to ensure poor quality antibodies do not make their way onto the market,” said Berry.
At a meeting last week in Asilomar, California, hosted by GBSI, more than 100 biomedical experts offered a possible solution to inferior antibodies — create a scoring system that tells scientists how reliable a company’s antibodies are.
The scientists at the meeting — along with industry and government representatives — agreed on a strategy to create guidelines for validating research antibodies. These standards would shape the ratings system.
Currently, no standardized and widely accepted guidelines for antibody validation exist.
The attendees of the Asilomar meeting hope that better validation of antibodies will save research time and dollars.
It will also improve reproducibility in research — the ability of scientists to get the same results when they run an experiment again.
Better training for scientists
Also coming out of the meeting is a roadmap for how antibody companies would be certified and how scientists can be better trained to use antibodies.
A survey last year by GBSI concluded that more than half of researchers were not trained on the importance of antibody validation.
Younger scientists were even more likely to disregard this key step.
So far, the antibody scoring system remains on the drawing board, but pressure from the right corners could help move it forward.
“In terms of implementation or compliance of the standards, the funders, journals, and even the host institutions should play critical roles,” said Freedman.
Berry said this might mean requiring “the scientist to demonstrate — either through distributing company documentation or in-lab testing — that the antibody used in the experiment appropriately detects the protein of interest.”
And validating and scoring the millions of antibodies sold by dozens of companies would not be easy — or cheap.
“It is expensive to take every antibody through full validation, and the company would need to convey that cost to the customer,” said Berry. “The cost of validation raises the cost of the antibodies and reduces a company's ability to compete for customers.”