by Anisha Rajaselvam

source: Alexander Popov

In what seemed like a dystopian turn of events, in 2018, a Chinese biophysicist revealed to the world that he had secretly altered the genomes of human embryos. The birth of these “edited” children marked a major turning point for both the scientific world of genetic technology and its legal implications. Years later, the scientific community is still trying to analyze the outcome of this experiment, and ensure that necessary regulations are in place to avoid the future use of techniques with implications that are still not fully understood. 

The crime

In 2016, He Jiankui designed a project with the ultimate goal of delivering a human baby that had undergone necessary genetic modifications as an embryo to have lifetime immunity against HIV. The ex-researcher, then working from Southern University of Science and Technology in Shenzhen, recruited eight couples, each made of an HIV-positive father and HIV-negative mother. They agreed to He’s project after being denied access to existing assisted-reproductive technologies by other institutions. It was later found that fraudulent  paperwork and  blood test results were used by He to sidestep laws against assisted reproductive technologies for individuals with HIV. After collecting samples, creating viable embryos, performing genetic editing, and implanting the embryos, He achieved his final goal in November of 2018, and one woman gave birth to nonidentical twins. Later that month, his research was discovered and exposed to the public by the press. At a gene-editing summit in Hong Kong, He presented his work and faced immediate outrage. He was investigated by China’s National Health Commission, censured by Guangdong’s health ministry, and fired by his university. The World Health Organization assembled a specialist committee in 2019, putting forth recommendations for laws against human germline editing. Shortly after, the third of He’s edited implanted embryos was born. As a result of all his violations, He was sentenced to three years in prison. Now, in 2022, his release is imminent.

He defended everything he did in the name of medical advancement, arguing protection against HIV justified his work. However, even if immunity was attained, the experiments were still ethically and legally inexcusable, as argued by his prosecutors. He did not follow proper informed-consent procedures with participants, neglected the undetermined  possible long-term health dangers of changing the embryo genome, and unilaterally decided that his project’s potential outweighed every existing ethical regulation against germline editing. 

It gets worse

 During his time in prison, researchers have been assessing the scientific validity of He’s ideas.  Publications conclude the changes to the genome performed by He are not guaranteed to provide the intended immunity. He’s plan was to mimic a mutation seen in some northern Europeans that protects them against HIV infection. A set of nucleotide deletions in CCR5, a gene encoding a protein that facilitates HIV infection of some human immune cells, is responsible for the observed protection. But He himself admitted that his manipulations had induced novel mutations never yet observed in humans. This means that both the efficiency of protection against HIV and the overall safety of carrying those mutations cannot be confirmed. Further research revealed that He was too quick in assuming that inhibiting CCR5 protein function alone would be enough to stop HIV infection. Another receptor protein that appears in some white blood cells is now considered to be even more crucial in the infection process. So while the most common HIV strain may rely on CCR5 to infect cells, other strains will not be inhibited by mutating CCR5. Ultimately, not only did He commit fraud to evade numerous ethical barriers to his experiments, but he also failed in his primary scientific objective of creating fully HIV-immune humans. His chosen intervention is not optimal, and the effects of the actual mutations he created by using CRISPR remain unknown.

The capabilities of CRISPR-Cas 9

Adapted from a mechanism used by bacteria to eliminate foreign DNA, CRISPR-Cas9 allows us to selectively remove and replace parts of the genome. Paired with RNA, the Cas9 nuclease can cleave specific sections of a DNA double helix, and insert a chosen sequence during double strand repair. This incredible power to manipulate genomes has widespread implications in a variety of fields. In agriculture, it is now possible to increase crop yield, create tolerance to harsh conditions, and enhance desired nutritional properties. In medicine, it offers possible interventions to address the progression of genetic disorders, to prevent the spread of viruses, and to treat a number of illnesses. However, CRISPR’s potential has also generated unprecedented ethical discourse in the scientific community. The novelty of gene editing technologies means discussions are still ongoing and regulations look different in different countries. And yet, all concerned parties agree that the editing of human germlines should not be allowed (which brings us back to He). 

The current landscape of human genetic editing and embryo selection

To contextualize He’s project, we should consider what practices are currently acceptable. Assisted reproductive technologies (ARTs) are available to those who struggle with infertility, and this has been extended to individuals whom’s future children could be born with serious genetic diseases. Genetics is heavily involved in fertility, and as a consequence, many ARTs rely on genetic technology. Preimplantation genetic diagnosis (PGD) analyzes 3-day-old in vitro embryos of couples who carry alleles for serious genetic disorders, and therefore allows for the selection of unaffected embryos. PGD is generally accepted when it comes to avoiding serious future medical issues for the child, but it also could have the potential to be used for unethical forms of selection. Preimplantation genetic screening (PGS) is used in in vitro fertilization for infertile couples to enable them to select embryos without numerical chromosomal abnormalities and avoid associated failed pregnancies. However, there are no currently accepted practices that actually manipulate the genomes of human embryos. This is what made He’s project so controversial.

The scientific community reacts

He was not operating in isolation. A number of international scientists were aware of He’s project and chose not to come forward. Regardless of whether or not they encouraged him to conduct his unethical experiments, their silence at the time is still being scrutinized. 

Generally, the global scientific community condemned He’s work. It catalyzed necessary discussion on tightening ethical regulations for experiments involving new genetic technologies. However, there are some subtleties to consider when looking at the responses of researchers in related fields. Acknowledging the ethical disaster that is He’s work without inciting backlash against medical genetic technologies as a whole is a delicate process. Widespread disdain for gene editing could affect long term funding and regulatory approval. 

What happened to the babies?

There is limited information available about the toddlers, and this is in the interest of protecting their privacy. Chinese bioethicists are requesting certain facilities  to monitor the health of the children; but still, there is a balance to strike between the need to protect their health while avoiding intrusive surveillance. To date, there are no concrete plans on how their health will be managed.

So… what now?

Determining the moral standard when it comes to new medical technologies has proven to be complicated. Maybe some consider He’s theory of using CRISPR to manufacture immunity to HIV acceptable, even though the end should not justify the means. The potential for genetic editing to minimize human suffering keeps it relevant. With applications ranging from simply treating symptoms  to what is essentially a eugenic nightmare, we have entered this strange limbo where research and regulation are happening side-by-side. While, more conventionally, strict ethical paperwork should come before experimentation, genetic technology is in an era where precedents inspire regulation. As exciting as it is to witness the scientific power of mankind, it is terrifying to think He’s project is just one of many possible experimental violations of the moral code that incites necessary restriction.

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