Life Lines 60

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.

LIFE LINES 37

HOW SCIENCE WORKS: CONSTANT CHANGE IS THE RULE


The debate over stem cell research will soon disappear or shift to a more esoteric philosophic or theological level. Three scientific teams have learned how to shift normal differentiated adult skin cells of mice into embryonic stem cells that were capable of producing an embryonic mouse. In a few years this will likely happen in humans and persons with neurologically degenerative disease, pancreatic diabetes, spinal cord injury, damaged heart muscle, or other infirmities will have their own cells to generate the stem cells they need to insert into the defective organ. At present the trick is done using four genes introduced by viruses. But introducing viruses can lead to cancers so look forward to synthetic carriers of these genes that do not induce cancers. If we are lucky this will happen in five years or less because you can bet that dozens of laboratories will be racing to find ways to improve this new technique.

Very frequently in science, especially the life sciences, there is a huge outcry against new techniques as immoral (when anesthesia was first used for childbirths, male critics of this technique in the 1840s argued that women were supposed to endure pain as punishment for giving Adam the apple and disobeying God). Life sciences are vulnerable to such religious attacks because humans are living things and religion pays more attention to humans than the physical world. One could argue that this is legitimate practice because without those outcries wicked techniques would be used indefinitely. This is not likely because science and technology always change. Without religious protests cars, TVs and refrigerators have changed. We do not drive Model Ts, watch TV in black and white, or get a cold drink out of the ice box.

Here’s the rub. By converting a human skin cell into an embryonic cell, you have avoided using gametes for potential life. But you have created quite a few potential embryonic cells each of which (or clusters of which) could become a clonal twin of a person whose skin cell was donated. If the critics of stem cell research are motivated by the potential and not the source of stem cells, they should oppose all stem cells no matter how derived, because cells set back to a blastomere state (such as cells found a few divisions after fertilization) are still functionally like blastomeres. I suspect that this shift in attitude won’t happen because the donor will be the sick person, the recipient will be the same sick person, and the cures will convince most of humanity that they would rather be healthy than chronically ill or prematurely dead. Tens of thousands of infertile women around the world have conceived by in vitro fertilization and have voted by raising healthy children rather than remaining childless. Are these women to be told they were wicked because they used artificial means to bring about a reproduction using their own gametes (fertilization in a dish)? Should their physicians be condemned as immoral for providing children to the infertile?

If stem cells do successfully treat human diseases the incentives to invest more staff and funding for improved techniques will mushroom. This is good news for medical science and patients in need. I hope it will not disappoint, too much, those who favor mortification of the flesh and admire those who reject new allegedly immoral treatments in favor of being “chastened and hastened” through pain and dying for the greater glory of their unburdened souls.