Human genetic engineering

Human genetic engineering is the alteration of an individual's genotype with the aim of choosing the phenotype of a newborn or changing the existing phenotype of a child or adult.

It holds the promise of curing genetic diseases like cystic fibrosis, and increasing the immunity of people to viruses. It is speculated that genetic engineering could be used to change physical appearance, metabolism, and even improve mental faculties like memory and intelligence, although for now these uses seem to be of lower priority to researchers and are therefore limited to science fiction.

History

Gene therapy trials on humans began in 2004 on patients with Severe Combined Immunodeficiency (SCID). In 2000, the first gene therapy "success" resulted in SCID patients with a functional immune system. These trials were stopped when it was discovered that two of ten patients in one trial had developed leukemia resulting from the insertion of the gene-carrying retrovirus near an oncogene. In 2007, four of the ten patients had developed leukemia. Work is now focusing on correcting the gene without triggering an oncogene.

Trial treatments of SCID have been gene therapy's only success; since 1999, gene therapy has restored the immune systems of at least 17 children with two forms (ADA-SCID and X-SCID) of the disorder.

Human genetic engineering is already being used on a small scale to allow infertile women with genetic defects in their mitochondria to have children. Healthy human eggs from a second mother are used. The child produced this way has genetic information from two mothers and one father. The changes made are germline changes and will likely be passed down from generation to generation, and, thus, are a permanent change to the human genome.

Other forms of human genetic engineering are still theoretical. Recombinant DNA research is usually performed to study gene expression and various human diseases. Some drastic demonstrations of gene modification have been made with mice and other animals^{[citation needed]}. In some instances changes are usually brought about by removing genetic material from one organism and transferring them into another species.

Applications

Genetic Engineering can be broken down into two applications: somatic genetic engineering and germline genetic engineering. Both processes involve changing the genes on a living cell through the use of a vector carrying the gene of interest. The vector integrates the new gene into the cell’s genetic material.

Somatic Cell Therapy

As the name suggests, somatic cell therapy alters the genome of somatic cells. This process targets specific organs and tissues in a person. The aim of this technique is to correct a mutation or provide a new function in human cells. If successful, somatic cell therapy has the potential to treat genetic disorders with few therapeutic options. This process does not affect the genetics of gametic cells within the same body. Any genetic modifications are restricted to a patient individually and cannot be passed on to their offspring.

Several somatic cell gene transfer experiments are currently in clinical trials with varied success. Over 600 clinical trials utilizing somatic cell therapy are underway in the United States. Most of these trials focus on treating severe genetic disorders, including immunodeficiencies, haemophilia, thalassaemia, and cystic fibrosis. These disorders are good candidates for somatic cell therapy because they are caused by single gene defects. While somatic cell therapy is promising for treatment, a complete correction of a genetic disorder or the replacement of multiple genes in somatic cells is not yet possible. Only a few of the many clinical tries are in the advanced stages. The only case of a genetic disorder being cured by somatic cell therapy occurred in 1990 with the successful treatment of ADA-SCID, a severe immunodeficiency disorder.

Germline Cell Therapy

Germline cell therapy alters the genome of germinal cells. Specifically, it targets eggs, sperm, and very early embryos. Genetic changes made to germline cells affect every cell in the resulting individual’s body and can also be passed on to their offspring. The practice of germline cell therapy is currently banned in several countries, but has not been banned in the US.

Theoretically, germline cell therapy could treat or cure individuals who are predisposed to certain genetic disorders before birth. This process has not been attempted on larger animals or humans, but has been applied to some plants and small animals. Several problems have arose with this method, including only partial or multiple insertions of the desired gene, inaccurate placing of the desired gene in to the genome, and interference with other critical genes in the genome. While most defects are detectable in embryos, it is likely that some would be overlooked. Animal studies have shown that gene transformations involving the early embryo can be more effective than somatic cell transformations. However, attempts of germline cell transfer on human embryos will not be attempted unless the inefficient transformation that occurs during germline cell therapy is overcome.

Current Studies

Disease	Method	Current status
SCID-X1	MMLV vector	completed, ongoing
Leukemia	HIV vector	"Wild success" (on a small population)
HIV	ZFN cleavage	Ongoing

Rules and Regulations

The ethical and legal issues about human genetic engineering span internationally. Many countries do not have clear laws regarding genetic modification. Rather, their policies on this controversial issue tend to fall in the realm of general guidelines about human involved biomedical research. Universal restrictions and documents have been made by international organizations to set a general standard on the issue of involving humans directly in research.

One key regulation comes from the World Medical Association Declaration of Helsinki (Ethical Principles for Medical Research Involving Human Subjects) last amended by at the World Medical Association’s General Assembly in 2008. This document focuses on the principles physicians and researchers must consider when involving humans as the research subject. Additionally, the Statement on Gene Therapy Research initiated by the Human Genome Organization in 2001 also provides a legal baseline for all countries. HUGO’s document reiterates the organization’s common principles researchers must follow when conducting human genetic research including the recognition of human freedom and adherence to human rights, and the statement also declares recommendations for somatic gene therapy including a call for researchers and governments to attend to public concerns about the pros, cons and ethical concerns about the research.

United States

No federal legislation specifically lays out protocol and restrictions about either germline or somatic human genetic engineering. Instead, this subject is governed by overlapping regulations from local and federal agencies. Included agencies, from the Department of Health and Human Services, are the Food and Drug Administration and the Recombinant DNA Advisory Committee of the National Institutes of Health. Additionally, researchers who wish to receive federal funds when conducting research about an investigational new drug application, which is commonly the case for somatic human genetic engineering, are required to obey international and federal guidelines dealing with the protection of human test subjects.

The National Institutes of Health (NIH) mainly serves as the gene therapy regulator for federal funded research institutions and projects. Privately funded human genetic research can only be recommended to voluntarily follow their regulations. NIH exists primarily to provide funding for lab research that develops or enhances devices utilized in human genetic engineering and to evaluate the ethics and quality of science present in current research labs. An important aspect of the NIH is its maintenance of a mandatory registry of human genetic engineering research protocols from all federally funded projects. An advisory committee to the NIH published a set of guidelines on the manipulation of genes. The document for the NIH guidelines discusses safety considerations for the lab as well as for any human patient test subject. A wide range of various experimental types which involve any type of gene transfer or alteration are discussed. Several sections specifically pertain to human genetic engineering including Section III-C-1. This section states the review process researches must undergo and the aspects that are considered when attempting to be approved to begin clinical research involving human genetic transfer into a patient. This document is an important tool required for scientists to follow in order to further scientific progress in the field of somatic cell therapy.

The Federal Food and Drug Agency (FDA) asserts jurisdiction in the field of human genetic engineering by mainly ensuring the quality and safety of gene therapy products and supervising how these products are implicated clinically. The main documentation from the FDA comes from its Federal Food, Drug and Cosmetic Act. The FDA declares that alteration of the human genome with hopes to be utilized in therapy falls under the same regulation requirements as any other biological drug. As can be viewed in the Federal Register of 1993, the FDA says that it has full legal right to regulate human gene therapy because it involves the manipulation of genetic material with intent for medical treatment and prevention in humans. This classifies the products of human genetic engineering to be regarded as general biological drugs. What this means for researchers is that, before any clinical trials or research on somatic gene therapy begin, they must apply, be reviewed and approved by the FDA and the Institutional Review Board.

Controversy

Ethics

Within the very recent history of life humans have been able to gain such an understanding of evolution that it is now possible for intentional modification of the human genome. Due to the numerous successful genetic modifications of laboratory animals, it will only be a short time until human beings are able to change their physical, cognitive, and emotional capacities by modifying their genes. Humans will be able to control their own biological and evolutionary development; however, the extent of this control is unknown. Understanding how evolution works is enabling to humans to modify the course of their own evolution. Unfortunately, the potential for new technologies and genetic modifications brings along many ethical and moral concerns. Some of these concerns include the belief that every fetus has an inherent right to remain genetically unmodified, the belief that parents hold the rights to modify their unborn offspring, and the belief that every child has the right to be born free from preventable diseases.

The ability to alter the course of human development ranks among the most significant changes in modern science to date. The sex and eye color of a child can be planned in advance. A test for the presence or absence of certain genes can be performed, and if the results indicate an embryo that will not reach “normalcy”, that embryo can be aborted. The potential for curing diseases and enhancing human capabilities is immense. Stems cells that are capable of becoming almost any cell in the body can be obtained and cloned. The question that must be asked is: Even if we can do such things, should we do such things? What benefits could these technologies have for the human population?

Molecular Biologist Lee M. Silver has posited that unlike Aldous Huxley’s Brave New World, where a totalitarian government employs eugenics to control the genetic makeup within society, the use of gene therapy to design children will be spread through what he calls “free market eugenics” (Silver 315). Wealthy families will opt to design their child with genetic advantages because other families are doing so. Silver believes this use of germline gene therapy will mean wealthy families pass down enhanced traits to their children, potentially disadvantaging poorer families that cannot afford the technology. (Silver 313)

Pros

Perhaps one of the most beneficial aspects of genetic engineering is genetic testing. By identifying which genes cause specific diseases, it has become much easier to make a diagnosis for many genetic conditions. This testing supplies the ability to test pre-symptomatic individuals, at-risk individuals, and carriers to determine whether they will develop a specific condition. This testing is particularly useful to people who are intending on reproducing, and want to ensure they will not pass their genetic condition to their offspring. Current advances include preimplantation genetic diagnosis, which allows for embryos to be created in vitro, and only those embryos that are not affected by a specific genetic disorder will be implanted in the woman’s uterus.

Another hugely beneficial aspect of genetic engineering is the potential to cure numerous genetic diseases. The majority of genetic disorders are cause by single point mutations in the DNA. By somatic cell therapy, these diseases can be easily cured. Additionally, the implementation of germline cell therapy can not only cure many other genetic diseases, but can also prevent the passing of the disease to the next generation.

The last major benefit of genetic engineering is the potential advantages of human enhancements. Humans value intelligence, beauty, strength, endurance, and certain personality characteristics and behavioral tendencies. If these traits were found to be due to a genetic component, humans could be improved to obtain those traits. Many people try to improve themselves already through diet, exercise, education, cosmetics, and plastic surgery. Humans try to do these things for themselves and parents try to provide these things for their children. Exercising to improve strength, dexterity, and fitness is a worthwhile goal. Pursuing education to increase mental capabilities is considered a praiseworthy act. Accomplishing these goals through genetics could be more efficient and completely worthwhile.

Cons

While the use of genetic therapy on human beings is good in theory, transformation techniques have not yet been perfected. Problems occurring during the transformation of new genes could cause multiple or incomplete insertions or insertions into the wrong locations. Until the transformation process is perfected, mistakes during this phase have the potential to cause more harm than good.

If genetic engineering were to be applied to humans, the idea that individuals who have undergone a gene altering procedure may be superior or inferior to those who have not altered their genome. Genetic manipulations may one day be able to not only affect disease resistance, but could also affect appearance, intelligence, and personality. Even though DNA is only one aspect of development, those who have undergone some form of genetic engineering may be enhanced to have qualities that are desired by the species. Optimization of human traits by genetic modifications may be considered a form of eugenics, and could lead to social issues between humans that have been “engineered” and humans that have not.

Another problem that presents itself with the possibility of genetically modifying humans is gene doping. Gene doping is defined by the World Anti-Doping Agency as "the non-therapeutic use of cells, genes, genetic elements, or of the modulation of gene expression, having the capacity to improve athletic performance". Genetic enhancements could improve athletic performance by increasing muscle growth, blood production, endurance, oxygen dispersal or pain perception. Unlike other doping methods, like steroids, there is no way to detect genetic modifications. This process has already been implemented in animal models. “Marathon Mice” and “Schwarzenegger Mice” have already been created through this technique, leading to mice with increased muscle mass and stamina. This procedure has no yet been perfected in large animal models, making it very risky for athletes to use these methods.

Conventional vs. Genetic Neglect

The conventional idea of a parent neglecting their child is the lack of providing the essentials needed for survival and basic happiness. A parent who possesses the ability to provide adequate care for their child but fails to do so is considered guilty of “conventional neglect”.

With the new medical and genetic technologies available today, parents are able to detect early in a pregnancy if their child will be born with a genetic disease. If a genetic technology exists to prevent the child from being born with this disease, is the parent responsible for obtaining this treatment for their unborn child? If the parent has the resources available to utilize this new genetic technology but does not, are they guilty of “genetic neglect”? The result of the parent not receiving treatment would be their child having to grow up with a genetic disorder, unable to live the same lifestyle as a “healthy” child.

How does this genetic neglect equate to the accepted idea of conventional neglect? Would the parent be held responsible for their child’s genetic disease, knowing they could have prevented it? A parent is help responsible for failing to provide the essentials for their child to live a happy life. So, why would they not be held responsible for failing to utilize a technology that would lead to a happy, disease free life for their child? These questions need to be considered when moving forward with the research and application of genetic engineering technologies. If a certain technology is developed to cure a genetic disease before birth, would it then become the moral obligation of the parent to receive this treatment? Would there be some kind of punishment for those parents who did not receive the treatment? All of these questions need to be at the forefront of everyone’s minds when forging ahead with genetic engineering.

See also

• Bioethics
• Genetic Engineering
• Transhumanism