GENETIC ALLIANCE BY BY BLAINE ELIAS
“Genome-engineered humans are not with us yet. But this is no longer science fiction,” says Jennifer Doudna, speaking at a London TED Talk in September. Doudna, a biologist and science researcher at the University of California, Berkeley, addresses an international audience in order to discuss her latest discovery.“Genome-engineered animals and plants are happening right now,” Doudna continues. “And this puts in front of all of us a huge responsibility: to consider carefully both the unintended consequences as well as the intended impacts of a scientific breakthrough.” This scientific breakthrough is none other than the latest technological tool in gene editing: CRISPR Cas-9.
Before diving into a discussion about CRISPR Cas-9, it may be useful to see some basic definitions.
Genetic engineering refers to technology that is able to change the genes (structures in the body that contain a person’s DNA) in a living organism.
Gene editing, a type of genetic engineering, is when DNA is placed in or taken out of a living organism with the help of enzymes or molecules.
CRISPR Cas-9 (CRISPR is short for Clustered Regularly Interspaced Short Palindromic Repeats; Cas-9 is a protein in the body) is considered to be one of the fastest and most efficient ways to edit genes. The work of CRISPR Cas-9 can be organized in a few steps.
HOW CRISPR CAS-9 EDITS A HUMAN GENE
1. A sequence in a DNA strand changes because it was made that way or because it was later changed by the environment in which a person lives. Genetic editing can be used to replace that changed sequence with a new, unchanged sequence.
2. Scientists attach the Cas-9 protein onto a RNA sequence that looks identical to the changed DNA sequence in a cell.
3. Because the changed DNA sequence and the RNA sequence match, the RNA sequence guides the Cas-9 protein to the spot where the changed DNA sequence is located. [Imagine the RNA to be a tour guide, who is taking tourist, the Cas-9 protein, on a trip throughout different cities of cells]
4. The Cas-9 protein cuts the DNA strand at this spot of where the sequence changed, similarly to how a pair of scissors cuts a piece of paper. After this, the Cas-9 protein and the RNA leave.
5. Scientists usually insert a new DNA sequence where the Cas-9 protein cut the DNA strand.
6. At the end, a human gene is officially changed and edited! (see Fig. 1)
Researchers have investigated the potential for CRISPR Cas-9 to address a variety of topics. Among the many possibilities, CRISPR technology has been predicted to create engineered mosquitos that are resistant to the Malaria parasite or the Zika virus, produce more efficient pharmaceutical drugs, and make crops more resistant to different diseases in order to increase agricultural production. Beneath this predictive hubbub lies one of the greatest scientific debates of this generation: the ethics of gene editing humans and human embryos.
It is important to understand the different types of genetic editing that this technology could introduce. CRISPR Cas-9 can be used to edit two kinds of human cells: somatic and germ line cells.
A somatic cell is any cell in our body that is responsible for making bones, skin, and blood. This means that any change to a somatic cell does not pass down to a person’s children.
You can think of somatic mutations as non-communicable illnesses, or illnesses that aren’t contagious. These types of illnesses only affect those who have it, and don’t physically influence those who don’t.
In the scientific community and beyond, controversy tends to arise around discussions of genomic engineering on human germ line cells.
Germ line cells include the reproductive cells of the sperm and the egg, so children can inherit mutations of germ line cells.
For example, if a person has a BRCA1/2 gene germ line mutation, which increases a person’s likelihood of contracting breast and ovarian cancer, that person’s children (and their children’s children) will at least have one copy of this mutated gene. It may be useful to compare germ line mutations to contagious illnesses, which can be passed from person to person.
How will CRISPR Cas-9 address human genetic conditions in the future? There are several key ways in which CRISPR Cas-9 could impact the world of genetic conditions. CRISPR Cas-9 could be a simple way for researchers to provide somatic gene editing and therapy to clinical patients with single-gene conditions. According to the American Medical Association, somatic gene therapy is the only type of genetic editing that is allowed to be performed on humans and can be solely offered to participants in clinical trials. Though scientific institutions, such as the American Association for the Advancement of Science, have pronounced humans ethically unready and unsuitable to modify human germ line cells, some researchers believe it won’t be long before this practice is approved.
These questions highlight important issues, but what about the general question: is it ethical to edit the human genome? More specifically, is gene editing an ethical approach to treating and curing genetic conditions? Clinicians, researchers, and ordinary families each have differing viewpoints on CRISPR Cas-9 and what its progression might mean for our generation.
Though there are blurred lines in this debate, the general divide lies between supporters and opponents of gene editing. Individuals who support its advancements argue that genetic engineering could decrease the incidences of some dangerous diseases. Diseases such as Tay-Sachs disease and cystic fibrosis have significant genetic influences and could be treated or cured with CRISPR Cas-9 for both humans and their future offspring. Additionally, supporters state that this technology could increase the lifespan of humans by helping us evolve faster to respond to natural disasters such as global warming.
On the other hand, opponents dispute that genomic engineering counteracts natural human population dynamics. They reason that difficult genetic conditions like sickle-cell anemia are needed to prevent overpopulation. Opposition, especially skeptical parents of children with genetic conditions, wonder if gene editing would negatively influence their children’s originality or character. Deriving from Erika Check Hayden’s article in science journal, Nature, Hayden follows father, Ethan Weiss, who has a daughter with albinism. Weiss thinks that if he participated in prenatal genomic engineering, he would have regretted it. Hayden writes, “And he [Ethan Weiss] believes that if he had had the option to edit blindness out of Ruthie’s [Ethan Weiss’s daughter] genes before she was born, he and his wife would have jumped at the chance. But now he thinks that would have been a mistake: doing so might have erased some of the things that make Ruthie special — her determination, for instance.”
Larry Bram counteracts this by claiming that his daughter’s disability does not define her. Bram is the Senior Vice President for Innovation and Program Development at Easter Seals Serving DC | MD | VA; a nonprofit organization that focuses on providing medical and social services to people with special needs. He is also the father to a 22-year old woman born with polymicrogyria and agenesis of the corpus callosum. Though there may be genetic links found in the future, his daughter’s condition is neither genetic nor hereditary. This disease impairs her physical skills, complicating her ability to walk and causing her to be in chronic pain. In response to Weiss’s argument, Bram states, “My daughter has completely changed my life, as both a human being and professional. But you know what, if she had been born without disabilities, she would have changed my life in different, but equally profound, ways.”
Nevertheless, opponents argue that gene editing may have some unforeseeable consequences, which could lead to further medical complications for humans. The biggest argument from this side of the debate is the fear that genomic engineering provides families with an outlet to superficially “customize” their future offspring. The idea is that genetic engineering could be a tool not only used for prevention and treatment of genetic conditions, but also for the artificial enhancement of unborn infants. The same technology that could be used to remedy genetic disorders could also allow parents to provide their child with supposed “desirable” traits, like being tall.
With all this discussion, what do people with genetic disorders and their families have to say about the CRISPR tool? Where are their voices within this scientific debate? People affected by genetic diseases have been absent and unfortunately muted from the public discussion. According to Jackie Leach Scully, a professor of Social Ethics and Bioethics at Newcastle University, “When researchers focus on correcting genetic mutations, they may be overlooking the individuals’ personal experience of disability.” She, along with other advocates, have urged scientists and medical professionals involved in the CRISPR debate to provide people with disabilities with more of a say in how to approach genomic engineering utilizations. In accordance to Scully, Larry Bram desires for inclusion to be above and beyond. Bram contends that even voices within groups of people with special needs may become unheard. He states, “It is important to have an expansive vision of what it means to live with a disability. Who do you picture when someone says ‘disability’? Down syndrome, spinal cord injury, Asperger syndrome, profound cognitive/intellectual disabilities? It really changes the conversation. When including the community, you need to make sure you include lots of voices in the community.”
Patricia Lang is a Minnesota representative of Region 4 Midwest Genetics Collaborative (a coalition made up of seven states who strive to better health care access and genetic services) and the mother of a 19 year-old daughter, named Maddie, with metachromatic leukodystrophy. Metachromatic leukodystrophy is a genetic progressive condition (involves a mutation of the ARSA – a gene) that leads to an accumulation of fatty substances in areas of the central and peripheral nervous systems. Because of this accumulation, the casing around the axons (structures in the brain that send electric information to different parts of the body) becomes damaged, which leads to irregular muscle contractions and difficulties in walking, speaking and eating. According to Lang, “Maddie can no longer walk, talk or move herself from side to side in her bed. She cannot use her hands and must have 24-hour care. 100% of her feeding is through a feeding tube. She is intellectually on target and understands and communicates in several different ways.” When asked about the personal use of genomic engineering, Lang illustrated the struggle with picking a side in this debate. Lang explains, “There’s no answer that is right or wrong, that’s the one thing people need to know. I think it is what is right for you that you can live with, when it comes to genetic intervention.”
Patricia Lang believes that gene editing could have several positive effects, such as eradicating the heritability of ovarian cancer and providing people with more chances at living a healthy life. Noting the financial strains parents commonly encounter when tending to their children’s medical needs, Lang addresses how each case is different for each family. “Some families can’t handle what other families can. And it’s really difficult,” Lang says. “I just know too many families that live this life and it’s a hard life.”
When Larry Bram was asked if he would partake in fetal genomic engineering if he learned his child had a gene mutation for one of these conditions, Bram answers, “Yes, I would, absolutely.” Bram challenges opponents of CRISPR Cas-9, especially those who argue that a person’s disability is a part of their identity, and who claim that any change to eliminate a certain disease disrupts human diversity. Bram argues that advocates for such ideas of neurodiversity tend to ignore the many ways in which a particular disease can affect someone. He highlights autism as an example. Bram exhibits the differences in autism spectrum disorder and how some affected individuals may be more severely influenced by their diagnosis than others. Bram says, “Are we looking out for those who can’t speak for themselves? It is the profoundly disabled that, unfortunately, aren’t fully integrated into society. The impacts on their lives and the lives of their families are profound.” He continues, “And if we could ease or prevent that, of course we would want to prevent that. At the very least, it should be their family’s choice.”
Though both Bram and Lang recognize the benefits the CRISPR technology could provide, they are aware of how genomic engineering could be used for the wrong reasons. Bram understands that gene editing could be a scientific method that becomes abused. He commends Dr. Jennifer Doudna for acknowledging these risks and believes the use of gene editing should be limited to treating genetic disorders. On a similar note, Patricia Lang says, “If there’s an illness, like a catastrophic illness, I don’t have a problem with it [using genomic engineering].” Conversely, Lang considers that the way in which someone may use gene editing is not up for her to judge.
What does the future entail for CRISPR Cas-9? What does CRISPR Cas-9 entail for those with genetic diseases and for their families? How will we make sure this technology isn’t brought into the wrong hands and is properly utilized? There is still long ways to go in the progression of the CRISPR technology. But as we move along in this process, it is essential to keep everyone’s best interests in mind. If genomic engineering becomes accessible to ordinary clinics, let’s hope our future actions include everyone in the conversation.•
*The opinions of Larry Bram and Patricia Lang do not represent both of their employers’ official opinions and viewpoints on gene editing and/or CRISPR Cas-9. They personally held the opinions stated.
ABOUT THE AUTHOR:
Blaine Elias is a BioTrust intern at Genetic Alliance. BioTrust is about providing people with the proper tools to influence the health systems around them. She assists with work on PEER [Platform for Engaging Everyone Responsibly]; a registry that allows individuals to privately provide their health information to medical researchers, in order to better health care. Elias is a rising junior at Duke University in Durham, North Carolina. She is pursuing a double major in Public Policy Studies and Global Health, with a certificate in Information Science and Studies.
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