Designing Humanity: Regulations on Gene Editing

Illustration by Dili Chen

Illustration by Dili Chen

When doctors diagnosed her with one of the most aggressive forms of acute lymphoblastic leukaemia, Layla Richards was only 14 weeks old. After rounds of chemotherapy, followed by a full bone marrow transplant, Layla showed no signs of improvement – her only remaining option was palliative end-of-life care. Then, a one-milliliter infusion of white blood cells genetically engineered to target her cancer cells forced Layla’s cancer into remission within four weeks. Two years later, Layla remains healthy and cancer-free.
Layla’s story reads like a miracle, and perhaps it is. Human trials in gene therapy for certain forms of cancers have been around for years, but what was unique about Layla’s case is that the experimental treatment she received had only previously been tested in mice. Even Dr. Waseem Qasim , whose lab developed the genetically modified cells that Layla received, cautioned against extrapolating Layla’s results onto all children with similar conditions. In a sense, Layla was the human subject in a study with a sample size of one.
Dr. Qasim’s experimental treatment was possible, in part because of the unique and structured British regulatory system on genetic engineering. In 2016, the UK – also a pioneer in in vitro fertilization (IVF) technologies – legalized genetic modification in early human embryos and its Human Fertilization and Embryology Authority (HFEA) permitted the use of donated mitochondrial DNA under few specific conditions, which means that babies may be born with DNA from three parents.
Around the same time in the US, the National Institutes of Health (NIH) reminded the public of its stance against gene editing in human embryos, and Congress withdrew funding from the Food and Drug Administration (FDA) for research involving the use of embryos. So, is the UK acting unethically by deliberately putting the lives of its people at risk? Or are regulations in the US unreasonably restrictive?
Surprisingly, regulations on gene editing technologies are in some senses stricter in the UK than in the US. The HFEA is sponsored by the British Department of Health and is the UK’s independent board regulating human embryo research and IVF treatment. It is also the world’s first independent legislative body of its kind and gathers experts from various fields. Its members include geneticists, bioethicists, former civil servants, and business professionals. Early in 2015, the British government had already legalized mitochondrial DNA transfers, but the power to regulate and permit clinical trials on the technology still rests with the HFEA.
“Research and clinical applications of IVF are generally unregulated by the federal government. We don’t have a standardized process or a special committee to look at [human gene editing], not in a way that the UK does,” says Professor Rebecca Dresser of Washington University School of Law . Professor Dresser is also a former member of the President’s Council on Bioethics and the NIH Recombinant DNA Advisory Board.
To begin with, mitochondrial DNA represents only a small portion of the human genome, so many do not even consider mitochondrial replacement therapy (MRT) to be genetic engineering. The majority of human traits and human diseases depend on variations in nuclear DNA. Germline genetic engineering of nuclear DNA (that is, the editing of DNA in the nucleus of sperm and eggs) is more controversial, and to date has only been performed in animal models.
Layla’s case is an example of somatic cell gene modification (more commonly known as “gene therapy”) where the genetic modifications are not passed down to children. Although no clinical applications of gene therapy are currently approved by the FDA, it is less controversial than other gene modifications in the US, and regulations do not differ significantly compared to the UK.
On the other hand, germline gene modifications may be performed in fertilized eggs, embryos, or somatic cells induced to become germline cells. The potential may be in preventing certain heart diseases and in treating inherited diseases like sickle cell anaemia, Huntington’s disease, and cystic fibrosis. Germline gene modifications are passed down to offspring – this is the main danger cited by critics. Any effects of germline gene editing should be considered permanent.
Currently, the biggest obstacle to furthering research and regulation of genetic engineering is our tremendous lack of knowledge on its safety and efficacy. Aside from various off-target effects that occur when the wrong gene is edited, germline gene modification could cause unforeseen problems for future generations. Some concerns brought up at the 2015 International Summit on Human Gene Editing were the polygenic nature of many traits, human tolerance to genetic mutations, multiple functions of any single gene, unclear interactions of genes with different environments, and the lifespan of edited genes. Genes affect our bodies in complex ways and there is still a lot we don’t know about how they behave in humans.
In order to devise appropriate regulations for germline genetic engineering, benefits need to be weighed against the costs of this technology, though we know almost nothing about potential consequences.
“Maybe in five years we’ll have proper regulations in place, but it really depends on the data from research. There’s still a lot to clear up about the risks of genetic engineering,” says Professor Dresser. “It’s a very complicated human research endeavour that requires very long follow-ups. And there’s still a lot of uncertainty, so I think we’re right to be more careful.”
However, many scientists and bioethicists argue that the recent Congressional ban on germline gene editing is a premature act and will lead to the US losing out on the development of a revolutionary and potentially life-saving area of biomedical research. Furthermore, an official government ban could actually be counterproductive, by forcing the technology to develop through private clinics or other unregulated routes that puts human subjects at unreasonably high risks.
“I don’t think the US is more restrictive in regulating gene editing. The regulatory system [in general] is about scientific evidence. It prevents resources from being wasted on treatments that don’t work. And drug companies certainly don’t want to invest resources into treatments where data is lacking or dubious,” says Professor Dresser.
Most would agree that scientific claims and technologies supported with questionable data should not receive significant attention or be developed further. However, legitimate scientific discoveries are not always accepted by the scientific community or the public. Ultimately, the challenge is finding a balance between promoting scientific innovation and stifling scientific progress with regulations.
The main goal of the 2015 International Summit is to develop a set of “soft laws” (or voluntary guidelines) for scientists which take into account that the sociocultural and political settings of different countries. “This is not government regulation. This is the scientific community coming up with their own set of guidelines,” says Professor Dresser.
At the summit, Dr. Thomas Reiss of the Fraunhofer Institute for Systems and Innovation Research argued that all members of a society must share mutual responsibility for the development and effects of scientific innovation. He called this “responsibilization”, a key step in the regulation of science. Scientific technologies affect all members of a society; thus the public must engage in discussions of its regulation and direction. Likewise, Professor Charis Thompson of University of California at Berkeley called for more broadly based discussions on gene editing that involve input from a diverse range of expertise and social aspects. Essentially, everyone has a stake in this issue.
Since the US has no equivalent of the HFEA and lawmakers are not scientists, getting the green light on germline gene editing may largely depend on how it aligns with our moral principles. In a survey of 100 WashU students, 72% agreed and 5% disagreed (23% undecided) that it is morally acceptable to use germline gene editing in healthy human individuals to prevent serious genetic diseases. 86% agreed and only 1% disagreed (13% undecided) that it is morally acceptable to use germline gene editing to treat serious genetic diseases. The top two concerns regarding germline gene editing technologies were unintended biological consequences (52.53%) and the reinforcing of existing social inequalities (31.31%).
There’s no question about having regulations on scientific research. The challenge is deciding how much we want to restrict our research endeavors. Just because the technology is currently banned by the US Congress does not mean that it won’t be practiced. Regulations differ from country to country, and even within the US, many private clinics are not regulated by the FDA. Recent developments in CRISPR-Cas9 have also had profound impacts on how we look at gene editing and its future directions. But, as with all new discoveries and technologies, these claims should be taken with a grain of salt.
“Remember the embryonic stem cells? And how [they were] supposed to make people walk again? Progress is incremental. Those embryonic stem cells were not a miracle and this probably isn’t either,” says Professor Dresser.
Like it or not, gene editing will become a part of our future reality, so we might as well start the conversation and be prepared for it.


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