A cancer treatment with genetically engineered cells may change how we think about human modification.
By Michael White
(Photo: johnjobby/Flickr)
When Mary Shelley wrote Frankenstein 200 years ago, there was no such thing as genetic engineering, and nobody knew what a gene was. But Shelley’s sense that it is wrong, even monstrous, to tinker with the building blocks of life haunts genetic engineering today. This is especially true of human genetic engineering, which our popular culture often portrays as an obsession of mad scientists or a totalitarian tool of social control. We’ve inherited our views of human genetic engineering from a time when it was just an idea, not a reality. But now that the reality is here, it turns out that widespread human genetic engineering, at least in its initial form, won’t look as radical as we thought it would.
One sign that routine human genetic engineering has nearly arrived appeared earlier this month, when the Food and Drug Administration allowed French biotechnology company Cellectis to initiate United States clinical trials for a new cancer therapy. The therapy is based on so-called CAR-T cells (“chimeric antigen receptor T cells”), which are human immune cells genetically engineered to be cancer fighters. Various forms of CAR-T therapy have been in clinical trials for a few years now, and scientists first started trying to build the cells in the late 1980s. But what’s notable about the Cellectis CAR-T cells is that they are the first “off-the-shelf” version. That is, unlike other CAR-T therapies—which are custom products made by genetically engineering each patient’s own cells—Cellectis manufactures CAR-T cells from healthy donors. Human genetic engineering is about to become a commodity trade.
The report recommends that human genetic engineering should only be aimed at curing disease, and that “genome editing for enhancement should not be allowed at this time.”
What’s striking about CAR-T therapies—both the custom form and Cellectis off-the-shelf version—is that they are simultaneously a radical departure and an incremental step from existing medical techniques. In practice, CAR-T therapies involve a familiar procedure, the transfer of cells into a patient to treat an illness. The first successful human blood transfusion was performed in 1818 (coincidentally, the year Frankenstein was published), and the first bone marrow transplant to treat leukemia occurred in the 1950s. Seen from this angle, CAR-T therapy is just a new variation on an old theme.
But though CAR-T therapy may look familiar, it is unprecedented. The first CAR-T treatments for cancer may become generally available within the year, despite some recent setbacks. This means that, over the coming years, there will likely be hundreds of thousands, and eventually millions, of people treated with genetically engineered human cells. This is what the first widespread use of human genetic engineering is going to look like.
Scientists have long anticipated this development because the powerful genetic tools that we routinely use to control biology in a petri dish have such obvious medical potential. We shut genes on or off at will, add or subtract them, and even build synthetic genes with new functions. The advantage of genetic engineering for medicine is that, unlike chemical drugs, cells are functioning systems with the ability to sense signals, to make decisions, and to perform complex behaviors. Cellular signal-sensing and decision-making are key built-in features of the cells that make up our immune system; CAR-T technology harnesses those abilities to help the immune system train its tremendous firepower on cancer cells. Genetic engineering is essentially a form of biological reprogramming, and scientists talk about building CAR-T cells with AND, NOT, and OR circuits; feedback control systems; and kill switches. No drug will ever have those capabilities.
Reprogramming human biology like this may sound ethically suspect in the abstract, but when we’re talking about a life-saving therapy for someone’s child or grandparent, it’s hard not to be sympathetic. Human genetic engineering is thus making its entrance to society as a medical treatment that, on the surface, seems incremental, avoiding the drama and questionable ethics that we expected.
There is an upside and downside to this. The obvious benefits of something like CAR-T therapy make it easier to set aside any knee-jerk moral disgust with genetic engineering, and instead think clearly about ethical boundaries. But the risk is that we become too complacent about the ethics, especially as genetic engineering for health purposes comes to seem normal.
For this reason, it’s fortunate that the U.S. National Academy of Sciences has just released a report laying out ethical guidelines for human genetic engineering. Recognizing that human genetic engineering is no longer just a fantasy, the report lays out two key questions we should ask ourselves as we consider whether particular cases of human genetic engineering are justified.
Most importantly, we should ask: Is the genetic change limited to one person, or will it be passed on to future generations? Patients who receive CAR-T cells don’t transmit the genetic edits on to their children, and thus each patient can choose for herself whether to accept any risks posed by genetic engineering. But children who are born from genetically modified embryos will pass on those modifications, together with any associated health risks or social stigmas, to their descendants. The National Academy report therefore argues that we should set a much higher ethical bar for genetic edits to human embryos, only allowing them as a last resort to prevent certain inherited genetic diseases.
The second question to pose is: What is the purpose of the genetic edits — to cure disease or to simply enhance human abilities? The report recommends that human genetic engineering should only be aimed at curing disease, and that “genome editing for enhancement should not be allowed at this time.” That rules out genetic engineering to, say, make someone a better athlete. Why? The report provides two reasons: First, the technology still poses risks that aren’t outweighed by any benefits of enhancement. And second, the public doesn’t seem ready to go there yet. A society in which only the rich have access to genetic enhancements, or, conversely, where everyone is under tremendous social pressure to buy such enhancements, sounds as dystopic as science fiction.
But the question of what qualifies as “enhancement” is almost certainly going to be a sticking point, because there is a wide range of things you can do between curing cancer and producing super-athletes. What if a company sells a product like CAR-T cells that, rather than fighting cancer, prevents it instead? If you use genetic engineering to lower your cancer risk, is that enhancement? If it is, why should we reject it?
The National Academy report purposely leaves the answer to such questions unanswered, recognizing that there are “inevitable differences, rooted in national cultures, that will shape perspectives on whether and how to use these technologies.” Our national culture’s perspective has been shaped by 200 years of science fiction. But as human genetic engineering becomes real—taking the form of a life-saving cancer treatment—we will get used to it, and our perspective is likely to change.
