Ethical Considerations in Gene Therapy

While targeted genomic changes in mice and yeast cells have been around since the 70s and 80s, the ability to edit specific genes easily, efficiently, and precisely has been a major goal in genetic research for decades. Recent advancements in gene editing technologies, such as CRISPR-Cas9, have revolutionized how scientists approach genomic modification.

Ethical considerations of gene therapy have always been at the forefront of scientists’ and ethicists’ minds—however, this all became front page news in November 2018, when Dr. He Jiankui, a Chinese researcher, made an unprecedented announcement: he had successfully altered the genes of twin girls using CRISPR-Cas9, a powerful gene-editing tool. The specific gene-targeted, CCR5, is involved in the HIV infection pathway, and Dr. He claimed that this modification would render the twins immune to the virus. 

The backlash from the scientific community was immediate. “We don’t know exactly what the consequences could be on the two girls from that experiment. The fact that he decided to use HIV was also concerning because we have therapies for that, so most people do not die from HIV anymore,” shares Dorothée Caminiti, director of the bioethics program with the Markkula Center for Applied Ethics at Santa Clara University. 

Another concern was the apparent lack of transparency and oversight in Dr. Jiankui’s work. It was discovered that he had fabricated ethical review documents and misled the scientific community and the medical professionals involved in the procedure.

Gene therapy can hold a lot of promise in treating diseases, but scientists must tread lightly: “There is a lot of excitement around gene therapy, and rightfully so. We are developing treatments that can ease suffering and make lives better. But there are also many risks involved,” shares Caminiti. “Tools like CRISPR-Cas9are really amazing. I’m not against the tool itself. But I’m against the potential issues that can be derived from the tool.”

Keep reading to learn more about the ethical considerations in gene therapy, including the concerns related to the two types of gene editing, current regulations, and what the future may hold for gene therapy.

There are two primary ways to edit genes, and one carries more ethical concerns than the other: “There is somatic and germline gene editing and from an ethical standpoint, those two are very different,” says Caminiti. 

Somatic gene editing refers to the modification of genes in non-reproductive cells. It involves making changes to specific cells within an individual’s body, such as lung or skin cells, to treat a particular disease or condition. Somatic gene editing affects only the treated patient and is not passed onto future generations. This approach aims to address genetic disorders or diseases in a targeted manner, offering potential treatments or cures for various conditions.

On the other hand, germline gene editing involves modifying genes in reproductive cells, such as sperm, eggs, or embryos. These genetic modifications would be heritable, meaning they could be passed on to future generations. Germline editing raises broader ethical concerns due to the potential for long-term and far-reaching effects on the human gene pool. This is the kind of editing Dr. Jiankui used when he altered the twin’s DNA.

The distinction between somatic and germline gene editing is crucial in understanding the ethical, legal, and societal implications of these technologies. At the surface level, there are fewer ethical concerns with somatic gene editing than with germline: “There are some safety concerns with somatic editing, but when you do somatic gene therapy, you only impact the individual,” explains Caminiti. “The question comes down to what is the risk and benefit to an individual? Also, you also have to ask what is the price. At some point, there will be life-saving therapies, and there will be people who can afford it, and the people who cannot.” 

Germline gene editing, on the other hand, is very controversial: “My main concern is the fact that we are impacting lives of people who don’t exist yet as well as future generations. Germline gene editing is passed through future generations to your children, your grandchildren, and so forth. This kind of decision has a huge impact and should not be taken as lightly,” urges Caminiti. 

When you modify one gene, it has the potential to impact other genes and there is very little understanding of what the long-term genetic consequences will be. “Using germline gene editing, you could prevent a disease like Huntington’s from future generations in your lineage. So it makes sense. But again, once you do the germline gene editing, you might modify other genes involuntarily, and those modifications might have huge consequences that are still unknown,” warns Caminiti. “Once those edits are done, it will be too late to come back and say, ‘Oh, sorry, I didn’t mean to modify this or that gene.’” 

Currently, there are options to select out embryos with specific genes for genetic diseases such as Huntington, cystic fibrosis, or osteogenesis imperfecta, which is far less invasive or controversial as germline gene editing. 

Beyond the long-term or short-term consequences, germline editing poses ethical concerns around choice and autonomy: “Who gets to decide actually what is okay and what is not? Is it the autonomy of the parents, or should the government and society regulate treatments based on therapeutic goals? Also, what does that mean for other kinds of goals, such as enhancements? Do parents have a moral obligation to use that technology to offer their children the best life? Where should you put the limit?” asks Caminiti. 

At this point, these questions and ethical concerns are still largely hypothetical. “It’s really hard to say definitely one way or another because it’s not available yet. In the future, when it will become available, what are we going to decide, and how are we going to handle it?” she adds.

Somatic gene therapy has been regulated in the United States by the Food and Drug Administration since 1993. In addition to regulations, there are also extensive guideline documents to encourage best practices that align with national and international ethics. 

Germline gene editing, on the other hand, is heavily regulated worldwide. A 2020 study published in the CRISPR Journal found, “96 out of 106 surveyed [countries] have policy documents—legislation, regulations, guidelines, codes, and international treaties—relevant to the use of genome editing to modify early-stage human embryos, gametes, or their precursor cells. Most of these 96 countries do not have policies that specifically address the use of genetically modified in vitro embryos in laboratory research (germline genome editing); of those that do, 23 prohibit this research and 11 explicitly permit it.” 

“We are relying on governments, guidelines, and laws to protect. We’re also relying on the integrity of the scientists to do the right thing. That’s the reason why this doctor went to jail. He did something wrong and against the law, but also because he was a rogue scientist in a way,” says Caminiti. “The US government doesn’t permit the use of federal money to study germline gene therapy because they want to prevent scientists from working on it. But of course some people are working on it privately.”  

“We have to rely on the ethics of the scientists to not go too far for the sake of technology, fame, or power,” she cautions. 

Gene therapy holds significant promise. There are several successful therapies on the market already, including Luxturna, which helps treat vision loss due to Leber congenital amaurosis (LCA); chimeric antigen receptor (CAR) T cell therapy that works by programming a patient’s immune cells to recognize and target cells with cancerous mutations; and CTX001, a CRISPR-Cas9-based therapy, to treat sickle cell anemia. 

Germline gene therapy is still a ways off. “With further research and guidelines and laws that make sure that we prevent harm, I wouldn’t be surprised to see germline editing in 10 or 20 years,” says Caminiti. 

However, Caminiti believes some essential things are needed as this type of therapy moves forward: “I would love to see more transparency around these technological advances. We are always very excited because we see a huge evolution and the positive impact , but we rarely think about the risks. It’s only when someone is badly impacted that we discuss it. There is a kind of opacity around the risks. We balance the excitement and the reality,” she says.