What Does ‘Cure’ Really Mean?

Editor's note: A shorter version of this article appeared on our website last year.

The terms “gene therapy” and “cure” go together. Physicians often suggest or outright promise patients that the high-tech treatment will be curative. People with untreatable diseases often pin their hopes on it. A title/abstract search of PubMed, the National Library of Medicine’s database of research articles worldwide, returns more than 1,800 hits containing both terms. But what does “cure” mean?

Lieke Baas, M.Sc., M.A.

“I noticed that while everybody talks about a cure, nobody defines it,” says Lieke Baas, M.Sc., M.A., and a Ph.D. candidate in biomedical ethics at University Medical Center Utrecht, Utrecht University, in the Netherlands.

Baas is first author of a research paper with three coauthors, all in the Netherlands, who work in bioethics, philosophy and hematology. Their study delves into the meaning of the term “cure” in gene therapy.

You might think it’s obvious. You would be wrong. As the researchers explain in their analysis, published online Aug. 22, 2024, in Medicine, Health Care and Philosophy, cure means different things to different people. So, should the word “cure” be banished from gene therapy?

In the context of doctor-patient conversations, the researchers recommend that it should be banished, although they identify two other circumstances where the use of “cure” may be appropriate.

Here’s how they got there: The research team started by examining the concept of a cure in several fields — oncology, psychiatry, care for people infected with the hepatitis C virus and care for individuals who are deaf — in which the term is contested and therefore frequently discussed.

Oncologists, for example, who are often unsure about the risk of relapse, have moved on to the term “remission” or statistical measures, like 5-year survival rates, instead of “cure.” People with cancer histories decades ago adopted the term “cancer survivor” to avoid being called patients while simultaneously drawing attention to the care required after active treatment as well as the health effects and emotional toll of a cancer diagnosis on family, friends and caregivers.

Gene therapy works by altering or substituting a gene to treat or eliminate a disease that in most cases is caused by a single faulty gene. Scientists in a lab typically bioengineer a working gene to replace or change the faulty one, then use a viral vector to deliver it to targeted cells. (For hemophilia, they add a recombinant gene to liver cells.) Most gene therapies target diseases, often debilitating or fatal, for which there is no treatment.

The Dutch researchers examined how their definitions of cure could be applied to hemophilia, a congenital bleeding disorder that can be fatal without treatment. Unlike many other gene therapy targets, however, several good treatment options offering full life expectancy were available — at least in resource-rich countries — before the first gene therapy was approved approximately two years ago. The FDA approved Hemgenix (etranacogene dezaparvovec), a gene therapy for hemophilia B, in November 2022, and the European Medicines Agency, which covers the Netherlands, granted its approval three months later. The FDA approved Roctavian (valoctocogene roxaparvovec), a gene therapy for hemophilia A, in June 2023.

As a result, undergoing astronomically expensive gene therapy for hemophilia is likely to become “a personal choice in the palette of treatment choices,” Baas and her coauthors write — and a good test of the three definitions they developed (see box).

In their model, all three interpretations worked with hemophilia, to a greater or lesser extent.

The “normalization of the body” definition could apply to the most stringent clinical definition of curative treatment for hemophilia: a complete end to bleeding five years after treatment and no further treatment of any kind, for any reason, ever. Yet achieving a normal body may not be appreciated by disabled people.

Using “cure” to refer to “obtaining a normal life” also fits — if you ignore previously lost education, career opportunities and financial consequences that cannot be returned to normal.

And while “cure as a change in identity” might work for some, the researchers cite qualitative accounts in the literature of people living with hemophilia who reject gene therapy because they don’t want to lose their identity as a person with hemophilia because, for example, other family members may have the disorder.

Now that the research team had developed and tested their definitions for how “cure” is understood, at least in the theoretical world of gene therapy for hemophilia — and found them usable but also flawed — the authors returned to their original, practical question: Should “cure” continue to be used with gene therapy? Once again, Baas and her colleagues have three answers.

In “interactions between people with hemophilia and health care providers,” they write, “it might be desirable to refrain from using the term cure and instead opt for merely using specific end points and effects on quality of life when discussing potential benefits of a treatment or trial.”

In the context of deciding how to allocate the enormous resources required for gene therapy, the authors write, “cure” can be appropriate but “it is important to be explicit about what is meant and in what ways a product with a potential to cure differs from other treatment options,” noting that gene therapy’s curative potential may justify its high price.

Their third answer involves use of the word “cure” in trial protocols and research proposals to fund new gene therapy trials. Including cure as an outcome measure requires very specific “normalization of the body” type of end points, they write, adding that typically secondary quality of life end points — including what the paper defines as “obtaining a normal life” and “change in identity” — perhaps should be considered as primary end points.

Asked if there was anything in the study that surprised her, Baas responded more generally that she hadn’t fully believed it would be possible to specifically define the different interpretations of cure. She’d been expecting “to find some things,” she said, “but it was really nice that it actually worked out.”

3 ideas about what 'cure' means

Dutch researchers developed three nuanced formulations of what “cure” can mean for patients.

1. Cure as normalization of the body. Regenerative medicine, for example, promises to replace or regenerate human cells, tissues or organs, thereby restoring normal function. For gene therapy patients, this likely is the most common understanding of cure, Baas says. But the idea that a body can be returned to normal has been criticized by people with disabilities, who say it does not value their lives and bodies.

2. Cure as obtaining a normal life. Cure in this case is understood to mean an end to illness and its effects as well as restoration of a prior state of health and well-being. Cure is seen as an end point. Critics of this “cure as an end point” formulation say that it overlooks patients’ ongoing experiences, needs and suffering following treatment. And they note that a normal life isn’t just about medicine. It also involves laws, policies and social structures, such as access to insurance coverage.

3. Cure as a change in identity. This interpretation focuses on how both the experience of illness and the transition to health can become integrated into a person’s narrative identity. For example, people with hepatitis C, many of whom around the world inject drugs or are incarcerated, value outcomes other than a sustained virological response, such as how being cured lightens the social stigma they have long endured. Here, again, disability advocates raise objections. Some people who are deaf, for example, see deafness as part of who they are and the community to which they belong, making the notion of a cure for deafness undesirable.