At that point, his research team wanted to test the notion that the gene was actually involved in the development of cancer.
"We thought that the problem was that the fundamental control of that gene had been broken, or left behind, so that when it was brought into the new chromosome, it was brought in under the influence of a different control region," says Leder.
This different control region, he says, was found to be involved in the synthesis of antibodies.
The team cloned the normal gene and systematically removed what were thought to be the gene's regulatory sequences. In their place were inserted regulatory sequences borrowed from a virus which would induce irregularities in breast epithelial cells and would lead to breast cancer.
This gene was then injected into a mouse egg. After the altered gene was taken up by the nucleus of the egg, the egg was placed in the uterus of a 'sham' female mouse, one which had been mated top a sterile male.
Leder says the female would give birth to a litter of mice, some of whom will have taken up that gene.
"When that happens, we then ask whether or not the gene we produced will develop malignancy," he says.
Sure enough, after 300 days, Leder says, 50 percent of the mice had developed breast cancer.
Another important result, according to Leder, was that the tumor was only present in a certain part of the animal's breast.
"Since the tumor is the descendant of a single cell, only one cell, therefore, has changed enough to develop cancer," he says. This meant that some other cancer-causing event had taken place in that cell.
This led to the conclusion that the gene suspected as causal in Burkitt's lymphoma was necessary but not sufficient for cancer, Leder says. It was also concluded that the gene could cause cancer in other mammals, and in regions of the body other than the blood.
Current Uses of Technique
One of the issues that Leder's research team is currently trying to understand is how the immune system might provide protection against malignancy. One arm of this study is growth factors which affect the immune system, known as lymphokynes.
"One of these [lymphokynes] initializes a host response which causes the rejection of tumors. We are testing the notion that this might represent a natural host system to prevent development of malignancies," Leder says.
In other research, the group is studying problems of the development of the embryo.
"We created a mutation which affects development of limbs. This is a wonderful opportunity to understand what goes on when you shape a normal limb," says Leder.
By using the transgenic mouse, he says that the system of limb pattern development can be understood in animals ranging from the mouse to humans, since this system development is very well-preserved.