Adventures with the Fabulous mAb, Part One

Monoclonal antibodies are all the rage in pharmaceuticals these days. They make up over one fourth of all the medicines approved by the FDA in 2024. They’re advertised everywhere, recognizable by their generic drug name ending in “mab”. (You’ll start seeing them once you look past the brand names given to medicines these days, which are heavy on the high-scoring Scrabble tiles.) The antibody has to be the smartest molecule out there, a superstar of medicine because it locks on to one target only. It’s so highly specialized that we can rely on it to do one single job and nothing else, thus driving down the incidence of side effects.

It was a long road getting to where we are today, and one of the most familiar intersections on that road is the at-home pregnancy test, a perfect example of antibody technology. Once upon a time, we discovered that a live animal test subject could reliably recognize the human pregnancy hormone, hCG. When injected into a rabbit, hCG would bring about predictable changes in the rabbit’s ovaries; these changes were used to diagnose pregnancy in the human that provided the urine sample. A fresh lab animal was consumed with every test, hence the expression, “The rabbit done died.” A later protocol consumed fewer animals that were smaller in size, required less handling, and were capable of rendering a more rapid diagnosis. Good news for rabbits, bad news for frogs.

Scientists, being scientists, kept looking for something even smaller and more efficient to perform the task. Frogs were on board with this idea. Antibodies were trained to recognize hCG and attached to a microscopic particulate material that could only appear to the naked eye if it were clumped together in a blob or dot. The first such material was sheep’s blood, but this rapidly advanced to tiny latex beads. (The frogs were elated.) This development resulted in a “dot” pregnancy test that was highly specific: it yielded almost no false positives, because the antibody could not recognize anything except hCG. Dye replaced beads and blood during the 80’s, and the first “stripe” test (the lateral flow assay) was made available in 1988. The stripe pregnancy test is now estimated to be the second most utilized assay in the world, making it a familiar example of lateral flow technology. That pregnancy test went on to have a massive batch of babies, including the also-familiar COVID test which was run approximately 3 billion times during the recent pandemic.

But what does that have to do with your pet? Antibody-based assays like the stripe test are now used for almost every condition you can think of. They’re used millions of times a day on human and animal samples. When your pet is tested in the clinic for some specific disease such as pancreatitis, leptospirosis, Lyme disease, heart failure, or parvo, that’s lateral flow (“stripe”) technology helping to save your companion’s life. It’s all based on the miracle of the monoclonal antibody, the smartest molecule in the world, the one that brought medicine out of the rabbit hutch and right to our fingertips.

Dr M.S. Regan