Riding the Germline: The Unforeseen Effects of Genetically Modified Humans

In 1990, Herman the Bull was born in Leiden, the Netherlands. He was the first transgenic bovine, having been micro-injected with human embryonic cells with the gene coding for lactoferrin. This allowed the bull’s female offspring to produce the human milk protein in its own milk, which could then be extracted. Since then, a large variety of genetically modified animals have been produced in laboratories all over the world— from colorful fish, to glowing rats, to translucent frogs. On a more practical level, goats have been modified to produce drugs in their milk, pigs have been given a gene that makes them more efficiently digest phosphorus, and a cow was given a gene allowing it to produce human breast milk.

In many of these cases, human genes were injected into animals— but what if someone did the opposite? In October 2018, Lulu and Nana were born in secrecy at China’s Southern University of Science and Technology, the first genetically modified human beings Using Cas9, a protein developed from CRISPR (1), Dr. He Jiankui had targeted the CCR5 gene of two zygotes in an attempt to inflict the CCR5 Δ32 mutation (2), which is believed to confer innate immunity to HIV. At the time, human genetic modification of this type was illegal in the United States due to risks associated with passing on modified genes to children, but its legality was unclear in China (3).

Nonetheless, following the announcement of this achievement in November of that year, widespread controversy ensued, both about the experiment itself and the secrecy surrounding it. One biochemist, Jennifer Doudna, said she was “horrified and stunned” by the process, and the Chinese Academy of Medical Sciences denounced the research, stating that it was “opposed to any clinical operation of human embryo genome editing for reproductive purposes” . In December of 2019, Dr. He Jiankui was sentenced to three years in prison for “illegal medical practices,” the official document stating “he had defied government bans and conducted the research in pursuit of personal fame and gain”.

When discussing the ethics of He Jiankui’s actions, criticism largely surrounded three major topics: the experiment’s/plan’s secrecy and violation of norms, its danger to the children, and on the very concept of embryonic genetic engineering itself. 

Jiankui’s choice to keep the experiment a secret, even failing to mention his genetic modification of human embryos to his ethics committee, was greatly criticized (7).  Further criticism centered around his use of a germ-line editing technique that would affect any future offspring of the children. Such germ-line editing is considered to be something that is only done to “treat a serious disease for which there are no other options— if it is to be done at all”. To cover this up from an ethics board is a serious offence.

Though the secrecy surrounding the experiment is a major ethical issue, it is also a largely procedural concern that could have theoretically been solved with greater transparency and care. Those criticisms revolving the potential danger to the children, as well as human engineering itself, deal with more fundamental ethical concerns.

The Cas9/CRISPR technology used by He Jiankui is still in its relative infancy and prone to mistakes. CRISPR often “inadvertently alters genes other than the one being targeted,” and can lead to a form of “chimeric mosaicism” whereby only some cells contain the desired gene. Many believe that the technology is too underdeveloped to be used on human embryos in such an aggressive manner. Further ethical complications were introduced when it was revealed that the children may have unintentionally had their brains altered by the experiment, possibly improving their memory, as well as other unintended effects (8).

Alongside these concerns about the experiment’s design, there are additional concerns about human genetic modification as a whole. The specific form of human engineering used by He Jiankui, human germline modification, is illegal in more than 40 countries including the United States. Moreover, there is a growing international movement towards a total moratorium on this type of research (10). Most of these concerns are based on fears surrounding unintentional side effects being inherited by the children of the original patient (10). Similar outcries have also arisen against so-called “designer babies”

Many bioethicists are concerned that modification of the human germline for medical purposes will inevitably lead to similar modification for cosmetic purposes and, perhaps, even to improve human attributes such as intelligence and strength (11). The societal implications of a caste of genetically modified humans, mostly born to those with the means to obtain such genetic modification, can be hard to fathom, but seem largely negative. 

The ethical concerns around “designer babies” are numerous. However, much of the concern around He Jiankui’s research was not based solely on the fact that he was modifying the human germline, but rather that his reckless approach would “have a chilling effect on support for legitimate and valuable gene-editing research”. Indeed, prior to Jiankui’s experiment, many medical research institutions had given qualified support of the idea of human germline modification, albeit with “stringent oversight”. One bioethicist, Mrs. Charo, notes that even f we have an absolute prohibition [on genetic engineering] in the United States with this technology advancing, it’s not like it won’t happen” anyway. Some bioethicists, like Dr. Kincaid, have come out fully in support of germline engineering, considering it the “logical continuation of the way we’ve long approached parenting”.

He Jiankui’s experiment was extremely irresponsible and unethical by most standards, both national and international. His secrecy is difficult to defend, as was his choice to ignore the great potential dangers of using such a young technology on children — especially considering it could affect their future potential offspring. At the same time, this experiment forces medical authorities to deal with the fact that the ability to genetically modify the human germline, however crudely, is here. We will increasingly have to face the question: Can we afford to keep this technology illegal?

Edited by: Amaan Qazi
Illustrated by: Shubhanjali Minhas

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