STEM CELLS, KNOCK OUT GENES, AND THE NOBEL PRIZE FOR MEDICINE IN 2007
The 2007 Nobel Prize in Medicine was awarded to Mario Capecchi (University of Utah), Martin Evans (University of Cardiff), and Oliver Smithies (University of North Carolina) for their work in using molecular techniques to create genetically engineered mice. Specifically, some 25 years ago they found a way to isolate a specific gene, alter it so it would not function, attach it to a another gene as an identification tag, insert the altered tagged gene into an embryonic stem cell of a mouse, and replace the normal gene in that cell. The resulting mice grown from that embryonic cell were eventually inbred to produce the tagged knocked out gene in every cell of those new tagged mice. The technique is known among geneticists as targeted knock out genes. Through this technique the three scientists and their colleagues around the world have created over five thousand strains of genetically engineered mice.
Why is this significant? For basic science it enables scientists to study the function of each of the 15,000 genes in a mouse sperm or egg. For medical science it allows scientists to identify diseases or other changes in the knock out strains that are comparable to human diseases. So far about 500 human diseases that have some genetic connection are found in mice. This is no surprise because humans and mice, both being mammals, share about 90 percent of their genes in common. The mice genes include those associated with cancer, heart diseases, neurological disorders, diabetes, and hypertension among the more familiar disorders of humans as well as rare types of single gene defects like cystic fibrosis. It is easier to do research on mice to find the way disease causing mutations work and how to treat such diseased mice than it is to do so directly on humans. For one thing, you can mate mice to yield important genetic information but you can’t manipulate human reproduction to get the same information unless your values are that of a Nazi medical scientist in a concentration camp. We don’t sacrifice prisoners, psychotics, or enemies in such experiments because we have some higher good in mind. We treat adult subjects as human beings, not guineas pigs. Trying out new cancer destroying agents is now much easier because of the existence of targeted knock out mice. Testing for new prescription drugs is also easier because of their work. One interesting but not surprising finding is that about 15 percent of mouse genes cannot be isolated as genetically engineered strains because they are lethal to embryonic development and abort. Lethal genes in animals have long been known (since 1912; they were first found in fruit flies). Those will likely turn out to be genes that form organs vital to life or genes that are essential for individual cells to survive or divide. The award of the Nobel Prize will give added weight to those scientists and physicians hoping to apply the findings of mouse stem cell research to human stem cell research.