Author: Caroline Wells
Could it be smart to keep a disease present in our population? This is a question faced by the scientific world; it is relatively easy to accomplish such a large feat (the removal of an entire disease) with the guidance of modern gene-editing technology, yet every day millions continue to suffer. This leads to the question: why haven’t we utilized this technology, and at what cost does using it come with?
CRISPR is an acronym seen in the news regularly, likely because its real name is a mouthful: Clustered Regularly Interspaced Short Palindromic Repeats. CRISPR was first discovered in 1987 in E. Coli bacteria, but its main use and potential to be applied to other organisms as a means of genome editing, wasn’t discovered until 2012. Without going into too much detail, CRISPR is an adaptive immune and defense system in bacteria. When infected, viral DNA enters the bacterium and is placed into the bacterial DNA and replicated into RNA, which then attaches to the protein Cas-9, essentially “snipping” out the areas in the viral DNA. Scientists discovered ways of “turning off” or “turning on” genes at this site, or altering them - adding new genetic material or removing others. This has opened a new world of genetic engineering and altering- genetic mutations meaning diseases such as sickle cell anemia can be fixed, and organisms (including humans) can be altered, from increasing bone strength to changing one’s eye color. The genome can also be altered to become resistant to terrible diseases such as HIV; in fact, this has already occurred.
In 2018, scientist He Jiankui helped to create the first gene-edited twins, bypassing the ethical regulations set for using such a technology. By altering the germline of the embryo, his intention was to create HIV- resistant human beings, modifying CCR5, a gene responsible for the encoding of a specific receptor protein in white blood cells used by HIV to infect. However, the job was poorly done and without ample preexisting knowledge about the technology and its impacts on patients: both short and long-term.
There are many concerns with this altering. First, because he chose to alter an embryo, which divides quickly, not all of the cells ended up having the mutation, essentially rendering the “experiment” useless, as the trait cannot be carried out due to its absence in many of the cells. Aside from this, there are effects on other targets of the genome that are affected by the altering of certain genes. For example, altering the genome to eliminate a genetic disease such as sickle-cell anemia can lead to greater susceptibility to malaria. In this case, the altering of the CCR5 gene (like that used in Jiankui’s study)s led to increased susceptibility to genital herpes in mice. Despite these risks in the use of CRISPR in this particular study, his decision to edit the germline trumps all in the riskiest action. Why? Because the germline (sperm and egg cells) not only affects all cells in an organism, but future generations as well, differing from the somatic cell altering which only affects the individual organism and is not passed onto future generations.
Graphic by Judy Blomquist/Harvard Staff
This presents many consequences; by essentially altering the genome of future generations, members with this mutation grow as the generations reproduce, and in the far future, it is unknown what the environment will look like. The environment is always changing, and if the genome of multiple future generations is permanently altered, the organisms could not have much fit and adaptation to these environmental changes. For example, if a new pandemic arose in the future and the genome of future generations was altered to “eliminate” HIV, the altering of genes concerning the immune system could make the population more susceptible to a different dangerous disease and wipe out a large number of human beings.
So, is it smart to remove a disease from a population? Maybe, but evolution and other ethical regulations say otherwise. Although some scientists believe gene editing in humans will be a stark reality in the near future, Jiankui’s jump to genetically altering twins only a few years after CRISPR’s discovery as a means for genetic modification presented many risks of CRISPR’s usage in humans that must be resolved before work on this level can be continued.