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Gene Editing to Make Better Human Beings?

By David Prentice, PhD | September 14, 2017

by David Prentice, PhD

“I mean, if we could make better human beings by knowing how to add genes, why shouldn’t we do it?”
—Nobel Laureate James Watson, 1998

“Soon it will be a sin for parents to have a child that carries the heavy burden of genetic disease. We are entering a world where we have to consider the quality of our children.”
— Embryologist Robert Edwards, 1999

Gene editing (the current term of art for genetic engineering or genome manipulation) has potential for great benefit but also for great evil. In the medical realm, great advances are possible, treating individuals with genetic diseases, intractable cancers and previously incurable diseases, as well as designing new drugs. But this dual-use technology also could be used to design children, weaponize biological agents or even alter or dehumanize our concept of humanity. As with many cutting-edge biological technologies, much depends on the targets, attitudes and motivations of the innovators.

Genetic engineering is a hot research topic again, due primarily to the development of more accurate enzyme systems, including CRISPR-Cas, that can target the cutting and splicing of DNA with a precision not seen previously. Though still not 100 percent accurate, these new tools have fueled attempts to cut and paste specific gene sequences at targeted sites within the genome. Trials have already begun to modify the genes of people affected with genetic diseases or to treat cancer patients using genetically-altered immune cells. These gene editing projects are worthwhile pursuits, not least because they target alleviating the conditions of existing individuals.

However, there have also been ethically troubling attempts to alter the genomes of human embryos. This “germline” gene editing is aimed at creating new individuals with altered DNA, with the modified genome able to be passed on to future generations, along with unknown consequences for the gene-manipulated individual and future generations. Over the last two years, Chinese researchers have published three reports on their use of gene editing tools on human embryos. Now a U.S. researcher has reported a gene editing experiment on normal human embryos, including statements on his desire to gestate and birth some of these gene-edited children. Perhaps unsurprising, this researcher (Shoukhrat Mitalipov, PhD) is also the one who created cloned human embryos, created three-parent human embryos using cloning techniques and advocated for gestation and birth of three-parent embryos.

In this recent gene editing experiment on human embryos, the researchers were attempting to create embryos with correction of a mutation that causes hypertrophic cardiomyopathy. Their results, they claim, show their technique is safe and effective for genetic engineering of embryos. They injected the gene editing enzyme and template (the nucleic acid sequence used to produce “corrected” DNA sequence) into an egg along with a sperm, so that the germline gene editing occurred as the new embryo was conceived. In a series of experiments varying when the enzyme was injected, the scientists created 142 human embryos; all were subsequently destroyed. The results reported by the team were almost too good to be true and certainly much less than safe and effective. The mutation reportedly was corrected in 72 percent of gene-edited embryos, with no off-target snipping of DNA (sometimes the enzyme clips or mutates other spots in the DNA because it is not 100 percent accurate.) However, the numbers only indicate no off-target cutting for the sites checked by the team, which was not exhaustive and likely missed some unintended mutations. The researchers also reported that their injected template was not used for correcting the DNA; they suggest this may be due to a novel mechanism in early embryos, but it also suggests problems in the experimental design and interpretation. The data also suggest that in some cases the mutation was not corrected, but rather a large section of DNA deleted.

Other researchers have since published a paper online that calls into question the conclusions of the Mitalipov gene editing paper, noting the mechanism is biologically improbable and alternative explanations are likely. But whether the gene editing results are invalid in this experiment, there is a continued push by some scientists to do human embryo experiments. Korean scientists recently urged their government to relax restrictions on human embryo experiments, while scientists in the U.K. and Sweden have been approved to begin gene editing experiments on human embryos. Dr. Mitalipov himself encouraged others to do gene editing experiments on human embryos, and he has stated his hope that U.S. lawmakers would loosen restrictions currently in place that prohibit funding of such experiments as well as clinical trials placing gene-edited embryos in the womb.

There is still time to slow this headlong rush to perfect the quality of our children and make “better” human beings, time to change the trajectory of the science away from human embryos to the human patients who need the medical advances. In the movie Gattaca, the main character struggles to overcome the stigma of not being genetically designed and enhanced (a “valid” birth), as well as overcome the genetic caste system that gene editing of human embryos would create. Scientists who want to be the first to successfully modify human embryos should not be the only voices in the debate. Patients and their advocates should also be heard, especially on the question of whether we should engineer our children.

Related Resources

CMDA Ethics Statement on Three Parent Human Embryos

Techno-Babies: Some Assembly Required? by David Prentice, PhD

Outside the Womb by Scott B. Rae and D. Joy Riley, MD

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