(Image via usatoday.com)
Staff Writer: Maya Arruda
Email: marruda7@umassd.edu
When I was a kid, I loved comic book-level evil scientists. Lex Luther’s lethal machines made to triumph over his alien rival Superman were iconic. Mesogog from Power Rangers flipping a switch to make creatures with wacky DNA experiments and random tech was awesome.
Dr. Hojo from Final Fantasy VII has to be the best evil scientist. His unrivaled cruelty with human genetic experiments had disastrous consequences for the entire planet. His most plot-important and revolting experiments occurred on Sephiroth, his son, where he mutated his fetal DNA inside his mother’s womb.
Dr. Hojo thought he could experiment on a human fetus without consequences. Then, the results of his actions brutally killed him and millions of innocent people. It was a simple enough lesson: don’t do unethical human experimentation.
This is why I was confused when my high school biology teacher started going off on some guy who did the exact same thing as Dr. Hojo in real life.
Introducing Dr. Jiankui He, a Chinese biophysicist focusing on gene editing using CRISPR/Cas9. In 2018, Dr. He decided to tackle one of the most prevalent human health problems in the world: HIV.
Human Immunodeficiency Virus (HIV) is a particularly nasty retrovirus. It infiltrates T Helper cells, macrophages, and dendritic cells depending on the strain (some strains can only target some cell types while others can infect all of them). These cells are, ironically, all part of the human immune system.
Virus-infected cells digest viral proteins with a proteasome (which sounds like some sort of Roman arena), then present the digested fragments to neighboring cells on a protein called MHC-1. Natural Killer Cells and Cytotoxic T cells can recognize the viral sequence and essentially make the infected cell kill itself via apoptosis.
By infiltrating immune cells, HIV functionally uses the immune system to destroy the immune system. What’s worse is that HIV is a retrovirus, so it can remain latent inside T cell lines as they reproduce before activating again without the cytotoxic immune cells realizing the threat is still there.
Over time, the immune system gets so worn down that it can’t fight against other pathogens anymore. At that point, it’s called AIDS, a death sentence.
HIV can only do all this damage because it targets receptors on the host cell surface: a receptor called CD4 and its coreceptor, CXCR4 and/or CCR5, depending on the cell type.
Consequently, Dr. He decided that he was going to stop the spread of HIV by preventing binding to the CD4 coreceptors, specifically CCR5. He and his associates, Zhang Renli and Qin Jinzhou, used CRISPR/Cas9 gene editing to modify the protein structure of the immune cell receptors to prevent HIV infiltration.
Two families where either one or both parents were infected with HIV were chosen for this clinical trial.
Dr. He proudly presented his magnum opus in November 2018 at the International Summit of Human Genome Editing in Hong Kong to the horrified disgust and shock of the scientific community.
It’s important to note that no research paper on this experiment is available online. Dr. He’s work was not published, so it’s impossible to tell if he used mouse models before escalating to human clinical trials (the standard medical practice) or if the families had given fully informed consent. Both the prior mouse study and informed consent in human trials are vital for the integrity of standard medical treatment trials.
There is, however, a short series of videos on Dr. He’s YouTube channel explaining his research.
Additional criticism for Dr. He’s work stems from him trying a CCR5 mutation, which has essential functions in brain development and the immune system. It is unknown how the mutation Dr. He caused would impact the children’s brains.
In 2019, Dr. He, Dr. Zhang, and Dr. Qin were all tried in court in Shenzhen for illegal medical practices. These practices were breaking government bans on human genome editing and forging ethical review documents to dupe medical doctors into planting modified embryos into two women.
All three pleaded guilty in court. The project leader, Dr. He, was fined 3 million yuan (USD 429,000) and sentenced to prison. Qin and Zhang received lesser fines and shorter sentences.
Considering it’s been way over three years, Dr. He is now free as a bird, and with his newfound freedom, he returned to do what he loved best: editing human genes.
For obvious reasons, Dr. He’s new lab in Beijing, called the Jiankui He lab, is now working on finding a treatment for Duchenne Muscular Dystrophy (DMD) using CRISPR/Cas9 gene editing.
Unlike HIV, DMD is a genetic disease rather than a viral infection, and DMD is the result of a mutation in one gene: dystrophin. Any therapy would be wholly targeted at people already with the disease and would merely return the gene to its standard, wild-type form with a known function.
Subsequently, I think Dr. He’s research avenue is more feasible and more appropriate. It’s a disease with a clear, single-gene cause that is fatal.
Genuinely, I hope Dr. He succeeds with his therapy to help DMD patients and their families and to make this therapy accessible to all people. I certainly think this is also a better avenue of research for his interests.
In a plethora of mad scientist media, morality is pretty black and white. Experimentation, even if it’s for a good cause, always ends badly in those stories, and ill-intentioned experimentation even more so.
However, research like Dr. Hojo’s and Dr. He’s can be beneficial in eradicating genetic diseases if used responsibly and carefully — emphasis on responsibly and carefully.