A Chinese scientist shocked the scientific community a couple of days ago with the announcement of having modified the very blueprint of life. If his claims are true, he tried to bestow two baby girls the ability to resist possible future infections with HIV. The outrage shows that humanity is not prepared to utilize the power of gene editing on embryos yet. We have no idea about the biological consequences, and we haven’t tackled the necessary legal and ethical issues.

Genes to become toys of the “Gods”?

Humanity has come a long way since Aldous Huxley pinned down how methods of genetic engineering, biological conditioning, and predestined genetic stratification lead to a society of “obedient, efficient and happy” citizens in his Brave New World. No wonder that most newsrooms go back to this dystopian masterpiece when breaking news about the latest advancements of genetic engineering erupt.

How could we meddle with matters of nature, God or the universe? In opening Pandora’s box (it is clear humanity is doing that), what horrors are we inviting upon us? Are we placing babies in the hands of future parents as toys in the arms of Gods? What happens if the more affluent layers of society edit their genes into long and healthy lives while the poorer groups stand in line for medication? Will gene technologies give a new direction to inequality? What if governments with authoritarian inclinations start using it for shaping society?

Before we dive into the ethical, legal and social issues around gene editing and the baby girls with edited DNAs, let’s start with the basics. Gene editing technologies bestow scientists the power to add, alter or remove parts of any creature’s DNA. Well, unicorns or dragons may be out of the question, but mosquitos’ or even Christmas trees’ tiniest building blocks may be the subject of such scientific meddling. While numerous approaches emerged to gene editing, one of the most well-known is CRISPR, the fastest, cheapest and most efficient method developed so far.

Gene editing
Source: www.allphysicianjobs.com

CRISPR-Cas9 and combatant bacteria

By CRISPR (pronounced crisper), the medical community means the CRISPR/Cas9 system. It is a bacterial-derived RNA-directed endonuclease that generates blunt ends. I know that’s kinda difficult to digest, so let me explain. The method works on the same principle how bacteria fight viruses. When a nasty measles virus invades bacteria, the latter captures snippets of DNA from the intruder and creates DNA segments known as CRISPR arrays. These function as “most wanted” posters as they allow bacteria to “remember” viruses when they attack the next time. If the measles comes again, the bacteria fight back by taking the appropriate CRISPR array to produce RNA segments and target the viruses’ DNA. The bacteria then use Cas9 (the word Cas comes from CRISPR Associated) or a similar enzyme to cut the DNA apart, which disables the virus.

The CRISPR-Cas9 system works similarly in the lab. Scientists produce a small piece of RNA binding to the Cas9 enzyme and a “guide” sequence that attaches to a specific part of the DNA. As in bacteria, the modified RNA is used to recognize the DNA sequence, and the Cas9 enzyme cuts the DNA at the targeted location. Once that’s done, researchers use the cell’s own DNA repair machinery to add or delete pieces of genetic material or to make changes to the DNA by replacing an existing segment with a customized DNA sequence. Easy-peasy, right?

gene editing
Source: www.emag.medicalexpo.com

Does CRISPR have potential?

Although the technology is being explored in research on a wide variety of diseases with promising preliminary results, gene editing is costly, risky and not examined in detail yet. The first conditions to be most likely corrected by the CRISPR-Cas9 system constitute “single gene” conditions, such as beta-thalassemia, cystic fibrosis, muscular dystrophy or sickle cell disease. As these disorders presuppose that either parent passed down one mutation in a single piece of DNA to the given patient, gene editing could be more targeted and the results more unambiguous. The FDA already approved in October 2018 the first clinical trial of a stem cell therapy for sickle cell disease using CRISPR.

While the method also holds promise for the treatment and prevention of more complex diseases, such as cancer, heart disease, mental illness, and HIV, humanity is light years from effective therapies. As Eric Topol, director and founder of the Scripps Research Translational Institute said with six billion letters in the genome that could be affected, the risk of unintended editing is considerable. We don’t know what happens when another DNA segment gets targeted instead of the originally planned. Moreover, in a study published in Nature Biotechnology in July 2018, British researchers found that CRISPR caused more damage to DNA than previously thought. If the scientists are right, gene editing could disrupt healthy genes when it is meant only to fix faulty ones.

gene editing
Source: www.geneticsandsociety.org

A quick fix to mutated genes?

On the other hand, research efforts are underway with regards to gene therapies for patients with inherited genetic diseases. For example, researchers in Oxford’s Nuffield Laboratory of Ophthalmology help restore eyesight to patients with genetic vision defects. One of the methods is to inject working genes into the back of the eye. Early December 2018, Scripps Research scientists have made a significant breakthrough by precisely cutting the DNA specter from the genome, which prevents blood vessel cell abnormalities related to life-threatening cardiovascular diseases, such as heart attacks, aneurysms or strokes.

When it comes to patients whose genetic composition is manipulated through technology, fixing, altering or removing parts of the DNA, it is clear that the intervention narrows down to that individual – not the future generation. That’s the main problem with gene editing in human embryos, and that’s one reason why the recent announcement of Chinese scientist, He Jiankui, a physicist on the faculty of Southern University of Science and Technology in Shenzhen outraged the scientific community.

So, here comes the more difficult question: do we allow intervening and changing human embryos’ genetic makeup? If so, to what end shall we do so? The Nuffield Council on Bioethics said in July 2018 that changing the DNA of a human embryo could be “morally permissible” if it was in the future child’s interests and did not add to the kinds of inequalities that already divide society. However, what does the interest of the future child entail? Do we talk about averting future health risks and inherited diseases or about enhancing the kid with better IQ, better eyesight and blue eyes? While the former could be considered as a logical and rational step from parents, the latter already belongs to the area of eugenics – the enhancement of humans by genetics – for an assumed better life or pure aesthetics.

gene editing
Source: www.biopharma-reporter.com

Embryo selection: Who should or shouldn’t be born?

There are already methods for genetically testing embryos and picking the one with immaculate genetic makeup to prevent diseases, for example, dystonia. Parents undergo in vitro fertilization (IVF) and have their embryos genetically tested while still in a laboratory dish. Using a technology called pre-implantation genetic testing, they could pick the embryos that didn’t inherit the given mutation and ensure that their future baby is healthy. However, parents have to pay at least $30,000, and the process also requires an unpleasant two-week process of ovarian stimulation and egg harvesting. Thus, it is unlikely that people will flock to try the technology at the moment, but advancements in egg harvesting and a drop in price could change that in the future.

And while the idea of selecting embryos based on their future health risks has strong grounds, how far are we from cherrypicking lives arbitrarily? What are the guarantees currently that humans won’t abuse gene editing – if the practice of picking the „right” embryos flourishes even without the latest technologies? Just think about China or India where the birth of a baby girl is a tragedy for the family, and in many cases, pregnant women rather abort their fetuses than giving birth to a female. That tradition causes massive distortions in both societies and has enormous negative consequences for generations to come. Why would communities treat gene editing any differently or more cautiously?

gene editing
Source: www.ted.com

Well-designed babies for future societies

The Chinese or Indian practice for preferring a gender is just as an arbitrary selection as picking hair or eye color. If gene editing were used on embryos to end up with more boys than girls – we would arrive at the territory of designer babies. When it comes to enhancing a capacity, such as intelligence, or picking traits that nature planned some other way, that’s when the issue of “baby design” is put on the table.

On an individual level, it might be a dangerous tool in the hands of helicopter parents with the aim to create the perfect child, while on a societal level, it might reproduce the notion of standardization and homogenization. Who doesn’t want a tall, strong, beautiful child with high IQ and empathy? Does that mean that in the future, we will have people as similar to each other as never before? Bioethicist Ronald Green of Dartmouth College in New Hampshire believes that “we’ll start seeing the use of gene editing and reproductive technologies for enhancement: blond hair and blue eyes, improved athletic abilities, enhanced reading skills or numeracy, and so on.” He added, though, that it’s further down the road: within the next 40-50 years. So, we still have time to strengthen our ability to love one another with all our imperfections and see how foibles outweigh any notion of ‘improving’ children through genetics.

gene editing
Source: www.geneticliteracyproject.org

Do we really need gene editing?

Besides the skyrocketing costs, the uncertainties around the consequences of the technology and the ethical concerns, some believe that in the case of human embryos, gene editing is overridden by other options. Mainly because the achievements of the technology can mostly be realized already in different ways, too. For example, in the recent case of the twin baby girls, Eric Topol explained that the genetic intervention against HIV was needless as studies have shown earlier that the given gene could be turned off in adults.

Also, some experts see embryo selection in the process of IVF as a viable alternative to gene editing. Bioethicist Henry Greely of Stanford University in California told The Guardian that in the future, embryos produced by IVF will be genetically screened and prospective parents will be able to choose which embryos to implant in the hope of achieving a pregnancy. He believes that embryo selection will become a more viable and appealing way in 20 years to ensure a healthy baby – especially with the advancement of harvesting or producing human eggs, or preimplantation genetic diagnosis (PGD) of IVF embryos.

designer babies
Source: https://babymaybeinfertility.wordpress.com

What does the law say?

Previous examples show that scientists and the public could more or less expect an experiment of similar scope to happen in China as the one carried out by He Jiankui. In 2015, other Chinese scientists already maddened the global scientific community with their reckless research leading to an international moratorium on the use of CRISPR in human embryos. While most countries have not yet legislated on genetic modification in human reproduction, but of those that have, all have banned it. James Clapper, US director of national intelligence even added gene editing to a list of threats posed by “weapons of mass destruction and proliferation” in 2016, explaining the move with the “relative ease of use” of the technology.

Ignoring the international moratorium and the broad scientific consensus that gene editing is not considered as safe and any genetic modifications – whether beneficial or unintentionally harmful – affect not only the child but their children and future generations, Chinese researchers proceeded to experiment twice more. And now again. Jennifer Doudna, professor of chemistry and molecular & cell biology at UC Berkeley and co-inventor of CRISPR-Cas9 genome editing technology announced that human germline editing should not proceed at the present time.

Although Chinese authorities have opened an “immediate investigation”, placed the scientist under house arrest and ordered those involved in the project to suspend their activities, that’s a one-time response, and the overall consensus of the international scientific community did not materialize in any regulation or serious oversight so far. “It’s ethically Swiss cheese, more holes than substance,” says Arthur Caplan, a bioethicist at New York University.

gene editing
Source: www.uk.businessinsider.com

The genetic haves and have-nots

If not regulated well-enough legally, gene editing could soon result in catastrophic consequences. Nevertheless, the letter of the law could not embody the ultimate solution for CRISPR. Gene editing already constitutes specific social barriers, which might further grow in the future. As these technologies are very costly, only the affluent social groups have access to them. Moreover, certain religious groups or ethnicities with belief systems about the sanctity of life might also decide against the use of such medical innovations. These disparities might create a future society where the differences in wealth could already flip over into a biological rift – deepening with every new generation.

Japanese writer, Kazuo Ishiguro warned that due to CRISPR and gene editing, a two-tiered society with elite citizens, genetically engineered to be smarter, healthier and to live longer, and an underclass of biologically run-of-the-mill humans could evolve.

To avoid this scenario, governments should intervene: not only with regulations but good policies. But then again, too many questions arise. When is it proper for governments to coerce people into, or prohibit them from particular choices, such as not selecting a human embryo due to a disability? How can one balance individual freedoms and social consequences? In a darker scenario: what if the government has its own interests in creating a society along certain lines drawn by genetic engineering? What if a central authority decides that an army of genetically modified soldiers is the best “tool” for border defense?

With going deeper and deeper into the rabbit hole, we end up with Aldous Huxley and the vision about “obedient, efficient and happy” citizens in a Brave New World. Again. Shouldn’t we step up our game to make sure we avoid this scenario becoming too familiar?