Genetic Screening Gene Therapy Cloned Humans and Targeted Evolution

Let's return briefly to the real world. It is now practical, on a very limited scale, to check the genetic makeup of a fetus by methods such as amniocentesis and decide whether to continue or end the pregnancy on the basis of whether or not the child is likely to suffer from some debilitating condition such as chromosomal abnormality or a genetic disease. This type of genetic prescreening also is being done on embryos grown in vitro. For example, a colleague and his wife are both carriers for a mutation (i.e., are m/+) causing Marfan's syndrome, which is a connective tissue disorder causing various problems including elongated bones. Marfan's syndrome has been in the headlines recently as it has been shown using modern forensic techniques that it afflicted Abraham Lincoln. The couple used in vitro techniques to fertilize eight eggs. The resulting embryos were grown for a period in the laboratory and a single cell from each embryo was removed and tested for the defective Marfan gene. It was determined that three of the eight embryos were free of the mutation (i.e., were +/ +). These three eggs were then transplanted into the mother, and the result was a successful pregnancy. The other eggs were discarded. The age of eugenics is already here.

With help from the human genome project, it will soon become practical to screen for all known genetic diseases, which currently total more than 5000. There are obvious ethical and social issues that come with this technical advance, because it will also be trivial to pre-screen embryos for a wide variety of genetically determined characteristics other than defects associated with disease. Thus, it will also be possible to evaluate traits such as sex; height; strength; eye, hair, and skin color; the tendency to gain weight; predisposition to alcoholism; intelligence; resistance to particular diseases; etc., prior to embryo implantation. One concern regarding the use of genetic prescreening, should this practice become widespread, is that important sources of "good" genetic variability might be closely linked to the "bad" genes being so carefully rejected. If there were a systematic attempt to eliminate these bad genes from the human population by genetic pre-screening, the neighboring favorable traits might be lost before we knew they even existed. Because it seems highly unlikely that it would be technically or politically possible to cleanse our "dirty" DNA in such a total fashion, this scenario may not be a significant worry in the short term; however, it should be borne in mind that even limited selection against a bad gene might also result in loss of a "good" one. This picture is becoming frighteningly similar to that painted by Aldous Huxley in Brave New World, only in Huxley's work of fiction the technology required to create different strains of human beings had not yet been invented.

As described above, it also is now possible to change defective genes in cells taken from an individual afflicted with a genetic disease such as p-thalassemia, correct the genetic defect, and reintroduce these repaired cells into the affected person. In this way, the disease could be cured for the lifetime of that person. It is hard to imagine any compassionate person arguing against the merits of doing this—society at large would not be at risk and people faced with a debilitating disease could be cured. Similarly, gene therapy could be used to cure cancer, treat diabetes, and possibly halt the course of various autoimmune diseases such as multiple sclerosis or lupus erythematosus. A variety of start-up biotech companies have such laudable goals as their major focus.

In Chapter 1, we discussed Gurdon's famous frog cloning experiment (i.e., making genetically identical copies of an individual) and the

Regarding this last and most coveted of traits, studies in a variety of animals indicate that aging is a genetically controlled process. Many scientists who study aging do not think it unreasonable to increase human life expectancy to 150-200 years.

recent popularized application of this method to clone a sheep named Dolly. Successful cloning of other animals has also been reported. It is very likely that cloning any mammal, including humans, will soon become technically trivial. Currently, it is routine to make specific changes in a gene in embryonic mouse cells, inject these altered cells into a mouse blastula-stage embryo, and generate living and fertile mice carrying this modified form of the gene in place of the normal gene. Recently, a human embryonic cell line equivalent to that used to generate mutant transgenic mice has been established. There you have it. We now possess the tools to change our genetic makeup and not only correct defective disease-causing cells afflicting our bodies, but also transmit these changes to our children. In addition, if we want to have a bunch of talented individuals such as Einstein and Mozart, we could make thousands or millions of copies of this great being. Is this science fiction? Not really, only modest technical advances will be necessary for making this possible within the next few years. We are building some pretty powerful tools. The question is, will we make good or bad uses of them? This is a good time to open a dialogue between scientists, politicians, and lay people about the ethical implications of human engineering. Whether we like it or not, future generations will judge us by how we handle our new-found abilities.

For a fantasy finale, let's take a trip 500-1000 years into the future along the lines of First and Last Men by Olaf Stapeldon. Within the next century it becomes possible to change genes, introduce them into eggs, and create children with any desired genetic trait. Of course, this technology first becomes available to the wealthiest members of society because in its early days, this technology is quite pricey. The rich are happy to pay the price, however, so that their kids will be disease-free and blessed with high intelligence, physical strength, coordination, beauty, and of course, longevity.

The resulting supertots eventually go to the best schools, as the privileged classes always have, and then become the leaders of their day. They have the distinction, however, of being the first generation of the ruling class to be truly genetically superior to those they govern, a fact which gives them a secure grasp on power felt previously only by the great rulers of history.

These superhumans are not satisfied for long. They want more—to be smarter, to see and sense new things, and to go where nobody has gone before. They develop microchips that can interface with the human nervous system.

These neurochips store massive amounts of data—whole encyclopedias of information are available at an instant. As this increased memory capacity necessitates much enlarged cortical regions of the brain to handle the enormous flow of new information, appropriate targeted changes are made to genes controlling development of the cortical regions of the brain to enlarge these areas. Over the next few generations, these bionic creatures become truly superhuman. They can think orders of magnitude faster than anyone alive today, create forms of music we could not comprehend, and become immortal. Old or malfunctioning chips are replaced with more powerful designs, and aging biological tissues are similarly replaced with more efficient and durable tissue lines. They redesign themselves and then yet another generation of more sophisticated creatures. Natural selection is definitely over. These brave new Homo electricus are now in full control of their destiny. When they peer back through the fog of time at the dim-witted creatures, the last of the biologically derived forms of humans, who made the first genetic changes in humans, these omnipotent beings ask themselves, how could such pathetic animals have been our ancestors? What happens next is a blur as this species vanishes in a flash deep into the future, perhaps to join similar creatures from distant worlds. The funny thing is, when they finally meet the first alien form of life, it looks just like them. I guess that there really aren't that many ways to skin a cat. Too weird? Maybe, and then again, maybe not.

This final fantasy scenario is just that—my stab at a little science fiction. On the more serious side, however, many, if not all, of the technical advances featured in this wild story are likely to become reality. It is difficult to believe that future generations will never take part in their own redesign. Using the analogy of weapons of war, it is worth noting that there has never been a significant weapon that has not been used at least once in combat. Is it conceivable that we will never tamper with our genetic material? If someday we or our descendants choose such an auto-evolutionary path, the big question is how this could be accomplished in a fair and ethical fashion. Maybe the answer is that it cannot be done ethically, and that if it does happen, it will be the work of villains—at least according to us. What should we do now? Should we even bother thinking about these still abstract issues? Should we plant our feet firmly and forbid any kind of human engineering, and let the next generation worry about the problem? Should we go full speed forward and meet our destiny, uncertain and possibly horrifying as it may be? I do not pretend to have answers to any of these troubling questions. Although I believe that it is impossible to stop the progress of science, I also think this is a good time for us to step back a moment and ask ourselves, What are we doing and where do we want to go? We have landed on the naked shores of the brave new world, and we need a plan for the future we wish to create.

A primitive form of this bionic technology exists today to aid people who have been blinded as adults to see— at least to distinguish light and dark. Similarly, cochlear implant technologies are being developed which are hoped to restore hearing to the deaf.

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