Yesterday, it was announced that a Chinese scientist claimed that he has created the world's first genetically-edited babies. The scientist, He Jiankui, stated that he altered the twins' genes before implanting them in the mother to make them resistant to Human Immunodeficiency Virus (HIV). He reported that he recruited couples where the male was infected with HIV, and used in-vitro fertilization to create embryos and used CRISPR-Cas9 to disable the CCR5 gene that creates the proteins that HIV needs to enter the cells (source). However, he didn't publish his work anywhere and didn't provide evidence to show that his attempt was successful.
HIV works by attacking CD4 cells, which are a type of T cell. The virus binds to receptors on the surface of the cell and its RNA enters the cell. From there, reverse transcriptase converts the HIV RNA into HIV DNA. That DNA inserts into the nucleus and replicates. The cell is able to create and push out HIV proteins and RNA (it is noninfectious at this point), a protease cleaves the protein chains, and then the chains can combine to form infectious HIV (source). HIV is able to evade the immune system because the proteins on the surface of the cells are constantly mutating and changing shape, and this is what antibodies latch onto (source).
Globally, ~37 million people have HIV, and 1% of people aged 15-49 live with HIV (source). People with HIV initially experience flu-like symptoms, such as fevers, muscle aches, and swollen lymph nodes. If left untreated by anti-retroviral therapy (ART), it can progress to Acquired Immunodeficiency Syndrome (AIDS). People with AIDS often have an immune system that is so destroyed by the virus that they frequently get opportunistic infections and infection-related cancers, which is why HIV/AIDS is so dangerous, especially since HIV does not have a cure (source).
Conceptually, it makes sense that CRISPR-Cas9 could be used to solve this problem. The CRISPR mechanism was discovered in E. coli, which uses it as an immune response to defend against viral infection by cutting up viral DNA and storing it so that it can recognize it if it appears again (source). It’s been described as a “ninja-assassin-meets-DNA-editing-tool” because CRISPR turns the immune response process that the bacteria utilize as a defense mechanism into a repair mechanism (source). A cell is transfected with DNA matching the gene of interest, the Cas9 cuts the matching DNA sequence in the host cell, resulting in the host cell beginning the process of DNA repair, effectively correcting the targeted gene sequence (source).
While this might sound like a good thing, many people were outraged by it. There is a possibility that there was an off-target cleavage, and the effects of that might not arise for several years (source). From an ethical standpoint, many people think that this could lead to a slippery slope of people creating "designer babies" (source).
Is it the right thing to do to attempt to eradicate HIV via genome editing, especially given that now people being actively treated for HIV have a near-normal life expectancy (source)? What do you think?
P.S. The first source I used to describe CRISPR is one of the coolest podcasts ever (Radiolab). I highly recommend giving it a listen!
This was a very interesting post elucidating one of the most pressing issues in science today! I definitely think that as a scientific community, we are not at a point in time or knowledge where we can even begin to perform direct genome edits. There are a lot of epigenetic factors that we still don't understand. Changing a gene can drastically change the way it interacts with other genes and the environment, which can result in unintended consequences. I also think that this experiment raises further ethical questions about patient autonomy.
ReplyDeleteI also came across this article today before reading your post and agree that it is very risky for Dr. Jiankui to perform these genome edits. What raised my concern, and that I read from another article of this matter, was the children’s privacy. They were born into this world without knowing the intention that they would soon be under surveillance of curious scientists and health professionals until they turn 18 years old. Their genetic information will likely be shared with other scientists for analysis in confirming that prevention of HIV was intended (Pappas, 2018). However, having their lives under surveillance and all their genetic information available to identify them by name may not be what these children would want. More harm could possibly be placed on them through this process than having the slight risk of contracting HIV that can be prevented through lifestyle care.
ReplyDeletePappas, S. (2018, November 28). Why the Gene-Edited Babies Will Never Have Genetic Privacy. Retrieved December 2, 2018, from https://www.livescience.com/64182-gene-edited-babies-genetic-privacy.html
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ReplyDeleteOne concern is that changing one gene and replacing it with another could have unforeseen and harmful consequences somewhere else in the genome. These consequences are known as “off-target” effects, the unintended modifications were rare but not unheard of in CRISPR experiments done in mice (Hay et al., 2017). When it comes to humans an intended mutation that is beneficial or even lifesaving could turn out to have serious, or even permanent negative effects somewhere else. The second concern might be that CRISPR editing of the human genome will work all too well leading to parents seeking to have designer babies, offspring whose genomes have been edited so that they will be more athletic or more attractive or more intelligent. The ethical concerns there range from the obvious, the values of the baby’s autonomy, beneficence, non0-malfeseance and justice, to the subtler ethical concerns, it could enhance class differences between those with access to the technology and those without. Because knowing the society that we are in today, those who are rich and influential would most likely want their offspring to be well rounded in order for them to have a better life than their lower-class counterparts.
ReplyDeleteHay, E. A., Khalaf, A. R., Marini, P., Brown, A., Heath, K., Sheppard, D., & MacKenzie, A. (2017). An analysis of possible off target effects following CAS9/CRISPR targeted deletions of neuropeptide gene enhancers from the mouse genome. Neuropeptides, 64, 101–107. https://doi-org.dml.regis.edu/10.1016/j.npep.2016.11.003