Q&A: Gene Editing Ethics

By Stephen Shoemaker, December 7, 2018
Assistant professor Te-Wen Lo discusses the scientific and social implications of world’s first genetically modified humans.

In late November, the scientific community was shocked when a Chinese scientist announced that the first genetically modified babies had been born. The female twins were the result of an experiment conducted by He Jiankui of the Southern University of Science and Technology in China, who used CRISPR/Cas9 gene-editing technology to tweak very specific areas on the genome of the embryos that would develop into the twins.

His intent was to provide the twins with HIV immunity, as their father is infected with the virus. His work was confirmed during the Second International Summit on Human Genome Editing, which was organized to address exactly the sorts of ethical questions posed by the possibilities of tweaking human DNA. He drew widespread criticism from those in attendance and around the globe.

Te-Wen Lo, assistant professor of biology in Ithaca College’s School of Humanities and Sciences, uses CRISPR extensively in her research. She discussed some of the implications of this bombshell announcement with two of her students and lab workers, seniors Emily Siniscalco and Carolina Gaudenzi.

IC NEWS: This news is likely many people’s first introduction to CRISPR. What is important for people to know about how thousands of scientists around the world — including you here at Ithaca College — are utilizing this technology?

SINISCALCO: One thing that's important is that our lab specifically works with C. elegans, which is a type of roundworm maybe a millimeter long. That’s very different from [working on] something like a human, which is much more complex. Genome editing in worms doesn't have social implications the way it does in humans. No worm baby is going to be subjected to a media circus like these two twins likely will. So that's one reason why it's not so ethically ambiguous.

LO: We're just trying to understand basic biological functions which could potentially be applied to higher order organisms [including humans] later. But as far as the work that's going on in my lab, it's basic biology; which is I think the large portion of what scientists who are using CRISPR/CAs9 are doing; I think most people are using it as a tool to create specific mutations to study how different genes or proteins will behave in different circumstances.

GAUDENZI: If this is the first [introduction] of the general public to CRISPR, it is possible the general public will start thinking that this is the only way CRISPR can help humans. As Te-Wen was saying, a lot of scientists use CRISPR in lower-level organisms; that research could ultimately apply to humans, as well. So modifying embryos is not the only benefit that can come to humans from CRISPR.

At the same time, this has such huge social implications, and [raises] such big ethical questions. If the public is given these questions, in relation to CRISPR, as part of their first introduction, they might think that CRISPR can only bring bad things or very complicated questions. 

SINISCALCO: It's not always this dramatic. Also, I think it's important to note that the scientific community has been doing genome editing since before CRISPR was introduced. Now that CRISPR is one of the most accurate ways of editing genomes, it's starting to become applicable to human embryos. Before, the techniques weren't accurate enough to provide enough certainty that a viable embryo would actually be produced. Now we're getting into the realm where we can actually edit the human genome as opposed to just editing lower level organisms. [With lower level organisms], if we only get a certain subset of the population that has a successful mutation and doesn't have off-target effects, we're successful; with humans, you can't count on that.

IC NEWS: If the goal of much of the research in which CRISPR is utilized is to ultimately help address human genetic conditions or diseases, does He’s work mark a point-of-no-return?

Three women stand shoulder-to-shoulder in a laboratory.

From left to right: Assistant Professor Te-Wen Lo, Carolina Gaudenzi ’19, and Emily Siniscalco ’19.

GAUDENZI: Well it's definitely a line you can't erase, because it happened and now there are two humans who are living — and who will hopefully continue on living.

SINISCALCO: I think it all depends on how these kids grow up. If all of this goes super well and the concerns people have aren't fulfilled, and the benefits outweigh the drawbacks, then I think this kind of work will probably be more likely to continue in the future. But [it may not] if something catastrophic happens, like it did in the 90s in the case with Jesse Gelsinger. He enrolled in a gene therapy study, and there were some dubious ethical things behind it that only came out after the fact — issues of consent, conflicts of interest, improper procedure. He died as a result of this study, and gene therapy in this country was brought to a halt, and it really hasn't been started back up again. So if something like that happens with this, it will be a similar situation: we'd either see the genie shut back in the bottle for a really long time, or the genie is now out. 

IC NEWS: Is the genie the technology, or the questionable/unethical use of the technology?

SINISCALCO: I would say this particular application of the technology. I don't necessarily think that if this goes poorly our use of CRISPR would be more regulated; I think it would just be using CRISPR in human embryos and in embryos carried to term. We might see regulations in other parts of the world that have previously been less stringent get more stringent.

LO: I'm actually just super fascinated now in how we're going to proceed. Partly because I feel like I'm constantly surprised by human behavior. I think one of the reasons why they put a pause, in this country, on not editing embryos for the use of pregnancy is because we haven't had enough time to think about what we do with the children once they’re born in addition to what might be the long-term effects. How do we proceed? At what point are we satisfied this is a good thing, or what are the criteria for “worth it” or “not worth it?” We need to work all that out.

But now, we have to build the bicycle while we're riding it, because these humans exist. There needs to be some discussion, otherwise crisis can ensue. What's going to be really difficult is: At what point are you convinced that it's fine? When they're 2? When they're 10? When they live to 84?

SINISCALCO: I think with the Jesse Gelsinger thing, there was a lot of drama in a really short period of time. He was administered the gene therapy and then within a week he had passed away. But [these babies] have already been carried to term and born, so I think something would have to happen soon for the same sort of catastrophic effect to occur. 

LO: The problem is, now we have these two humans. How do we behave? What is reasonable to expect? That is what we, as a scientific community, need to figure out.

SINISCALCO: Which would be a lot easier to implement if the regulations had been in place before He went and decided on his own to do this thing.

Genome editing in worms doesn't have social implications the way it does in humans. No worm baby is going to be subjected to a media circus like these two twins likely will.

Emily Siniscalco ’19

IC NEWS: You used the analogy of building the bike as it is being ridden. Could it happen any other way, though, without someone going rogue, doing the thing, and setting off a new phase?

LO: As a scientist, I think CRISPR is super cool and has a lot of potential. So I also feel like if the damage is done, we should at least take advantage [of this opportunity]. I would like to know at the very least, every five years or so, are these twins [alright]? Not a ton of information, and definitely not invasive, but are they okay? I think that would satisfy a lot of people's anxieties and curiosities enough. I hope that society is respectful enough of their privacy. And I also hope their parents behave appropriately.

SINISCALCO: On top of that, there was some concern in the question-and-answer panel that He did; apparently the two twins have different genotypes for the CCR5 gene which he attempted to edit. Using CRISPR, he was able to give one HIV immunity, but not the other. Someone [in the Q&A] expressed a concern whether these children would be treated differently either by their parents or society because the world knows what their genotype is for this now.

GAUDENZI: For me, the focus was not ‘Oh, they managed to do this,’ but ‘Why did they choose this?’ Yes, I understand HIV is [a leading] cause of death in the world, but at the same time I thought ‘But why are you editing this, and what is it going to prove if you don't take the next step?’

SINISCALCO: There are genetic diseases that you could then prove the absence of in a baby because of the mutation. That's a step forward. This is just him saying that he can edit a gene. If you wanted to move the world forward and cure a disease, this is not the gene to choose.

IC NEWS: Did this announcement trigger any new reflection on these issues for you personally, and if so, how does that influence your day-to-day work in the lab?

LO: For me, I've already decided the type of research I want to do. It affects my day-to-day in that we have these interesting conversations, which I think are important to have and I appreciate. As far as my research goes, I don't think it affects me any which way. My lab does not and never will use CRISPR for gene therapy. For us, it is a fantastic genetic tool.

Now, for these two, who are just at the beginning of their careers, and are literally in the process of applying to graduate school — which means next year they have to think about what their theses are going to be — it's more timely and will potentially have more of an effect on changing their trajectory or day-to-day lives in the future.

GAUDENZI: For me, it definitely settled me on the things I don't want to do as a scientist. This is not the kind of storm I would want to be in the middle of. And not even the storm in terms of media; I know — now, because I never thought about this — it opened my mind to pondering the consequences of what my research is, both positive and negative. At the same time, it's teaching me what I don't want to do. What is crossing the line, for me? Which might not be [the case] for every researcher. But for me, this is going too far. At least now, because we're not ready in terms of societal norms and laws.

SINISCALCO: I actually do want to go into translational research: things that have biomedical and direct applications. And I am really interested in human disease. So I've already been thinking about this a little bit. Hearing this really just reiterates how much in the future I will need to think about what I'm doing and the impact it can have, and not just do it because I think science is awesome, but keeping in mind that the end goal is helping people, not just doing things for the sake of doing things.

I think a different mindset can be applied to basic research — it's so cool that we get to use our knowledge, skills and tools to learn more about the world. But if you're trying to put something out in the world that can’t be put back in or taken back, then you really need to be deliberate and careful. And I have to focus on making myself a deliberate and careful person so I can do this effectively.

This interview was edited for length and clarity.