Why Dr. He Jiankui ended up in prison?
That morning, back in the summer of 2018, hiking to the very top of Victoria Peak, I stared down at Hong Kong downtown regretting not having breakfast, I was, however, oblivious of Lulu and Nana’s awaited birth. The Shenzhen hospital, where two months later the twins were born, a quick one hour drive from The Peak in Hong Kong.
In October 2018, Chinese twin girls were born in Shenzhen HarMoniCare Women and Children’s Hospital in China. Lulu and Nana are the world’s first genetically modified babies. A few weeks after their birth, Dr. He Jiankui, a researcher from Shenzhen University, announced in his YouTube video that two beautiful and healthy Chinese girls were born. Twins’ father Marc is human immunodeficiency virus (HIV) positive; mother Grace is HIV-negative. The embryos, as per the trial design, were genetically modified using clustered regularly interspaced short palindromic repeat tech, also known as CRISPR. Successful pregnancy was established by In vitro fertilization (IVF).
Two days before the International Summit of Human Genome Editing in Hong Kong, Dr. He Jiankui’s video was uploaded to YouTube. He announced another pregnancy was ongoing at that time.
At first, the media proclaimed the news as a dramatic scientific advance in preventing diseases. After all, the reputation of Dr. He Jiankui was impeccable — a young, highly educated, and gifted scientist was declared a founding father of gene editing in China. As more detailed information began to surface, the scientific and medical community reaction changed drastically. The community did not support using CRISPR to modify human reproductive cells. Dr. He Jiankui’s troubles have begun.
That year, Dr. He Jiankui had been invited to the International Summit of Human Genome Editing in Hong Kong. The invitation to the Summit was granted long before the viral video describing genetic editing used to establish the pregnancy appeared. It was decided to let him present at the Summit and explain himself to his peers. Dr. He addressed the audience to explain what exactly had happened.
Is genetic editing ethical?
Dr. He Jiankui announced to his peers the preliminary results of his clinical trial. According to him, the team applied genetic editing tool CRISPR to create genetically HIV-immune babies. He reiterated the results of his preclinical studies in animals. Motivated by success in animals, he proceeded to enroll seven couples to a first human clinical trial.
The fathers were HIV positive, and mothers were healthy. Seven couples had a strong desire to have babies immune to HIV. Dr. He Jiankui genetically edited human embryos to delete parts of the CCR5 gene (CCR5-delta32) and implanted altered embryos via IVF. He also explained that he received consent from trial participants and the hospital’s Ethics Committee approval. In his video, he emphasized that the babies are healthy. His team had already completed the Whole-Genome Sequencing (WGS) of babies’ DNA; only one unintended off-target modification of DNA in one of the newborn girls was detected as a result of editing.
Genetic alteration of human embryos
Was the inactivation of CCR5 in these infants justified or necessary? Not at all. HIV/AIDS is not a genetic disease, but the susceptibility to HIV infection in exposed individuals may vary depending on genetics. The role of CCR5-delta32 variability, for example, is highly suspected. However, CCR5-delta32 variability is not the only factor.
An HIV positive mother may introduce a perinatal HIV infection to her future child. After birth, the transmission of the virus from mother to child could theoretically occur through breast milk or saliva. However, the chance of a father transmitting the virus to an unborn baby is close to zero. If the father is treated with antiviral medications, as the trial participants were, the risk is null.
Couples who desire offsprings have alternative, simple and straightforward solutions to ensure that the future children are HIV-free. For example, HIV positive women treated to lower viral load have slim chances (0.4%) of transmitting the virus to the newborn. Seven couples who participated in Dr. He Jiankui’s pioneering trial consisted of HIV negative mothers. There is an easy way to ensure their future babies are born HIV free by giving antiviral therapy to prospect fathers.
Immunity to HIV virus
It seems Dr. He Jiankui's main goal was not the disease-free Lulu and Nana. Was he really trying to create humans genetically immune to contracting HIV infection after birth? How ethical is that?
CCR5-delta32 deletions are thought to be protective of HIV infection. A CCR5-delta32 mutation is a deletion of a particular part of the CCR5 gene, something that genetically occurs in healthy humans. It seems people with the deletion of CCR5-delta32 are born highly resistant to contracting HIV. Mutation CCR5-delta32 may block the entry of the virus into immune cells. The variation of mutated CCR5-delta32 is seen in up to 2 % of the general healthy population. These individuals may have resistance to other viral infections, especially when two copies of the CCR5-Δ32 mutation gene are present.
The polymorphism CCR5-Δ32 is rare and found in 10% of the European population almost exclusively. The theory was first proven by the so-called Berlin Patient, who was the first patient declared HIV free after undergoing allogeneic bone marrow transplantation for his leukemia. The donor that provided stem cells for the allogenic graft was intentionally chosen to have CCR5-delta32 deletion. Düsseldorf patient and six more patients followed since. HIV patients with a new immune system derived from people with two genetic copies of a rare genetic variant of CCR5-Δ32 have been reported to have undetectable HIV load.
What went wrong with the trial?
The consent that Dr. He Jiankui obtained from 14 trial’s participants was a 23-page document in English. The participants may have experienced difficulties fully understanding consent written in complicated medical terminology. The consent mentioned that “trial generated costs estimated to be around the equivalent of 40,000 USD to be paid by the research team”. Additionally, participants withdrawing the consent in the late stages of the trial were required to reimburse spendings immediately or pay an additional equivalent of a 15,000 USD fine. Some patients might have felt trapped. Dr. He Jiankui was conscious of the limitation and possible side effects of CRISPR editing, such as off-target editing. His team might have failed to explain the unmeasurable and unpredictable future consequences of the editing mistakes to prospective parents. The future implications of on-target CCR5 editing are not fully understood as well. Dr. He Jiankui somewhat randomly edited the CCR5 gene since one of the girls ended up having a heterozygote variant of the gene. Did patients know that HIV free babies can be born to an HIV positive father without taking the unnecessary risk of genetic editing?
Unfortunately, the hospital’s approval was also meaningless; this private hospital did not have proper registration for its Ethics Committee. Dr. He Jiankui failed to provide the future trail participants with the scientific results and reports of his preclinical animal studies. He raced to start the procedure before the participant’s consent was received.
The fears of modifying the human race genetically
CRISPR is a genuinely life-saving technology used to genetically modify the DNA of patients with serious diseases like cancer. In such medical treatment, CRISPR is employed to alter an individual patient’s DNA, not the reproductive cell lines of babies. Dr. He Jiankui’s team was the first to modify a germline (inheritable) DNA of a human embryo and initiate a pregnancy by IVF.
Despite Dr. He Jiankui’s recent troubles, medical genetic editing is now successfully applied to treat genetic blood disorders and blood cancers, and the editing is done to blood stem cells. Many patients have already been treated. The fears of permanently modifying the human race, in that case, are unsubstantiated. Scientists are evaluating the potential off-target effects of the treatment and refining the tool to develop more precise and safe techniques. Although in the context of cancer and the absence of alternative therapy options for particular individuals, the risk/benefit is justifiable. And that was not a case with Dr. He Jiankui's latest endeavor.
Our hopes that one day, CRISPR editing will be safely used to correct and cure genetic diseases and cancer. Dr. He Jiankui, however, will spend three years in a Chinese prison.