What It Is and How It’s Made? The Synthesis of Rabbit ATG (rATG)

Used in over 55% of transplant cases rATG is by far the most commonly used. When most people are asked to imagine how it is synthesized most would say by a process of mixing solutions, enzymes, and proteins in a lab. This induction agent, however, is actually one two such agents made by immunizing another species to our white blood cells. Serums from over 26,000 (2012) immunized rabbits are pooled to ensure batch to batch consistency, an incredible effort on the part of both rabbits and humans.

The first report of immunizing an animal of one species against the immune cells of another species (mouse lymphocytes) was by Russian zoologist Ilya Metchnikoff. His trial (in 1899) involved injecting cells taken from mouse lymph nodes into a guinea pig. This guinea pig was then given time to develop antibodies specific to the immune cells of the mouse. A serum (ATG) was crafted from the blood of the guinea pig and then reinjected into other healthy mice. Metchnikoff observed a drop in the T cell count of the mice, and thus made an incredible breakthrough in the new field of immunology (and would later win a nobel prize for his work).

Our process for synthesizing rATG nowadays is still very similar to Metchnikoff’s. The notable difference is that instead of mice we immunize the rabbits to our own T cells. Rabbits are mainly utilized because of their ability to reproduce very quickly. The downside, that much like a blood donation for humans, they can only give so much within a given time. It is for this reason that sometimes equine ATG is also used, with a horse being able to give much more per donation. rATG and hATG are functionally identical and so they are chosen based on current price and availability.

It’s incredible to think that in order to keep one person’s organ alive and functional within another we appropriated the immune system response of another species.