SiS is proud to feature the winners of the "2009 Integrated Graduate Program in the Life Sciences (IGP) Science and Society Class Distinction Award." Written as part of a course on science and society, these papers were chosen by IGP faculty to be published on SiS. This month, we present the following piece by PhD student Laura Hix.
In Aldous Huxley’s futuristic novel Brave New World (1932), human beings are selectively bred to be genetically perfect. Based on their genes, they are sorted into a caste system that defines their social hierarchy. While capturing the scientifically misguided notions of the early 20th century eugenics movement, the novel also foreshadowed developments in reproductive technology that are now coming to fruition. The consequences of these reproductive advancements and their impact on the evolution of our society are only beginning to be explored.
The term eugenics is derived from the Greek word “eu,” meaning good or well, and “genos,” meaning offspring. Conventional eugenics, or intentional selective breeding for improved genetic traits, has been performed on crops and livestock for thousands of years. The term eugenics as it pertains to humans was first coined by Sir Francis Galton in 1883. Eugenics gained popularity throughout the late 19th and early 20th centuries, as some scientists incorrectly believed that many human behaviors, like alcoholism or social dependency, were solely the product of genes, independent of environmental influences. However, as other scientists began to refute these ideas experimentally, the movement abruptly fell out of favor when its ideas were co-opted by the Nazis during World War II to justify genocide.
Recent advances in genetics and reproductive technology have opened the door to a new form of eugenics, termed “modern eugenics,” or “human genetic engineering,” that is focused on repairing faulty genes associated with disease or other health conditions. Human genetic engineering is the science of manipulating an individual’s genetic makeup, or genotype, with the intention of altering his or her observable traits, or phenotype. Human genetic engineering can be divided into two categories—negative engineering, referring to the correction of genetic disorders and deficiencies; and positive engineering, referring to the enhancement of an individual’s genetic make-up.
Negative genetic engineering involves modifying or removing genes to prevent or treat genetic disease. Genetic engineering of non-reproductive, or somatic, cells in order to correct genetic deficiencies is known as gene therapy, or somatic cell gene transfer (SCGT). Gene therapy harnesses the powerful technology of recombinant DNA to correct disease genes in a patient’s cells, which are then reintroduced back into the patient to replace the diseased cells.
However, in order for all of the diseased cells to be replaced, self-renewing stem cells, or specialized cells that continuously divide to replenish all the cells within a specific cell type, are required. For example, bone marrow contains cells that continuously regenerate to replenish all the white and red blood cells of the body, known as hematopoietic stem cells. Unfortunately, not all cell types in the body, like nerve cells, have this ability to self-renew. Researchers hope to utilize embryonic stems cells, which have the potential to become any cell type in the body, to someday overcome this hurdle. Learn more about the potential of stem cells.
While the potential of gene therapy is exciting, clinical trials are in the early stages and many challenges remain. Delivering the corrected genes to their destination remains one of the greatest challenges. Many studies use certain kinds of viruses to transport the new genetic information. This presents a number of problems, including a patient’s immune response to the virus. In 1999, clinical trial patient Jesse Gelsinger died of multiple organ failure, which doctors believe was a result of a severe immunological response to the virus carrying the corrected gene.
However, there have been notable successes. In 1990, four-year old Ashanthi DeSilva, a child with SCIDS (Severe Combined Immune Deficiency Syndrome), became the first patient to be successfully treated using gene therapy as part of a clinical trial at the National Institutes of Health. As of early 2007, she remained in good health and was attending college. Researchers are now working on several promising studies that use gene therapy to combat blindness, cancer and bone marrow syndromes.
Negative genetic engineering is currently being used to detect genetic disease either prior to or during pregnancy. Prenatal diagnosis, such as amniocentesis (sampling of the embryonic fluid), has been traditionally used to detect abnormalities in fetuses during the first trimester of pregnancy. Another option for parents undergoing in vitro fertilization (IVF) is preimplantation genetic diagnosis (PGD). During IVF, doctors test each embryo for genetic abnormalities, allowing parents to choose the healthiest embryos for implantation.
Both of these procedures have their own ethical implications. After a prenatal diagnosis, parents must make difficult decisions if their fetus is found to have a life-altering genetic disorder. Following PGD, embryos that were not selected for implantation are usually discarded. Even the ability to select embryos for implantation based on their genetic profile brings its own range of ethical questions— should embryos with medical conditions that can be effectively managed by medical intervention be discarded? What distinguishes a true genetic “disease” from other unwanted genetic characteristics? What about selecting for traits, like sex or even eye color?
The combination of reproductive and genetic technologies raises the possibility of someday genetically modifying embryos and even their future progeny. For example, gene therapy techniques could theoretically be performed on a newly-fertilized embryo’s DNA during IVF, prior to implantation. Corrections to DNA at this stage of development would not only affect all non-reproductive cells in the developing fetus, but also the gametes (sperm or eggs). Termed “inheritable genetic modification” (IGM), this would allow transmission of the corrected genes to all future progeny.
Genetic modification has great promise to treat, and perhaps someday even permanently cure genetic disease. However, genetic changes could also be made in order to improve an individual in ways that may or may not serve a medical purpose. Genetic modification with the intention of enhancing an individual or their progeny is known as “positive genetic engineering.” For example, the use of gene therapy techniques for the purpose of enhancement has given rise to the term “gene doping,” defined in 2008 by the World Anti-Doping Agency (WADA) as the “nontherapeutic use of cells, genes, genetic elements, or modulation of gene expression having the capacity to enhance performance.”
While actual cases of gene doping have yet to be documented scientifically, several recent animal studies have raised the possibility that use in humans is not far behind, if not already illicitly occurring. In 2002, researchers reported that inserting the insulin-like growth factor 1 (IGF-1) gene into the muscle cells of mice led to enlarged muscles and the creation of so-called “Schwarzenegger Mice.” Another group reported that injecting mice with the gene for the fat-burning protein PPAR-δ enabled them to run twice as fast.
The intense pressure on professional athletes to perform has already led to the illicit use of steroids, highlighted by recent scandals involving professional baseball players. Gene doping could potentially offer a novel way to enhance performance, and would likely require complete sequencing of the athlete’s genome to detect the change. This raises the question of whether non-therapeutic gene therapy will eventually be medically sanctioned and regulated, similar to other therapeutic gene therapy, and if so, where will the limits be drawn?
With the advent of revolutionary reproductive and genetic technologies, humans have begun to acquire the ability to directly, and perhaps permanently, shape our evolutionary destiny. There are many arguments that can be made in favor of the ability to permanently cure genetic disease in future progeny. Fewer arguments can be made in favor of permanently “improving” the genetic traits of future progeny, but a small yet influential group of scientists does advocate for them. In 1994, Sir Walter Bodmer, former president of the Europe-based Human Genome Organization famously proclaimed, “Would it really be so bad, if we added genes for height to small people, or for hair to the bald, or good eyesight to the myopic? Probably not.” But in response to whether we should add genes for intelligence or athleticism? “Just where we get off the slippery slope is therefore a matter for society to choose…we have plenty of time to debate the issues and resolve them.”
As scientists move closer to making the possibilities of human genetic engineering a reality, open debate on the subject becomes increasingly crucial. We must raise public awareness of emerging technologies and foster an open and honest dialogue between scientists and the public about their potential uses and ramifications. If we are to learn from past mistakes, we should all be actively engaged in how these technologies are deployed.