The First Genetically Engineered Mouse Used to Fight Cancer

Now held in the Smithsonian Institution among millions of other historically significant objects and documents, the Oncomouse – known as the first transgenic mammal to be subject to a US patent – has played a key role in recent scientific history.

The mouse was first announced in 1984 by Philip Leder and Timothy Stewart from Harvard, as well as Paul Pattengale from the University of Southern California. It was the first time a living creature of its size and complexity was genetically engineered for the purpose of scientific study.

The Purpose of Oncomouse

The three scientists started working on the Oncomouse project in order to develop real, carefully controlled tumors they could study in a lab. The obtained animal model was a laboratory mouse genetically programmed to develop tumors after a certain amount of time, so that the researchers could closely observe their development and study cancer in a complex mammal, rather than a simple petri dish.

Stewart and Leder wanted to study cancer itself – specifically breast cancer, as it developed in mice – in a dynamic fashion that no other research method would allow at the time. Their research focused on MMTV (mouse mammary tumor virus), which is known as a triggering agent for breast cancer in mice, and went on to encompass anything from the tumors’ spread through living tissue, to possible treatments and the prediction of how tumors would develop in mice.

Their work in studying the Oncomouse has led to an entirely new branch of experimental science which started with the development of a patented bacterium in 1981, and culminated with the patent #4,736,866 for “Transgenic Non-Human Mammals” being awarded to Harvard in 1988.

Oncomouse: The Story, the Success and the Controversy

The Oncomouse is different from any other malignancy-prone mice bred or developed in the lab before the mid ‘80s, and it’s also the first to be patented. The scientists created it by isolating the DNA sequence from the MMTV virus and implanting it in embryos together with the cancer-promoting “myc” and “ras” oncogenes. The result led to a predisposition to predictable tumors being inherited easily from mother to pup.

Aside from the controversial animal rights debates started by the Humane Society of the United States that condemned the use of sentient animals in such a manner, there were legal and commercial controversies as well.

The patent was licensed by Harvard to DuPont, a chemical company that had supported Leder and Stewart and now wanted a return from the popularity that the Oncomouse had gained. The company set high prices for these new and unique lab mice and placed several restrictions regarding breeding programs and the academic use of the mice, while also requesting a share of any commercial success obtained by other researchers and companies through the animal specimens.

Although the scientific community didn’t take kindly to these restrictions, it was only in 1999 that Harold Varmus, head of the National Institutes of Health, helped reach an agreement that would waive any fees for the academic use of transgenic mice.

Philip Leder refers to the Oncomouse as a “model system” that brought more concrete evidence that cancer is a genetic disorder. This revolutionary breakthrough that started with a single mouse specimen continues to shed new light on possible treatments to fight the disease more effectively in the future, even as the original Oncomouse remains preserved by freeze-drying at the Smithsonian National Museum of American History since its acquisition in 1994.