We Don’t Need A (New) Ban Of Human Gene Therapy

We Don’t Need A (New) Ban Of Human Gene Therapy

Animal products used in or on humans have been an invaluable part of medical practice for almost a century. Examples include animal insulins to treat diabetes and pig heart valves transplanted into humans.

A related medical breakthrough was just published on Dec. 5 in the journal “Nature”: Genetically modified pig hearts transplanted into baboons can function long-term, a major step towards the clinical use of pig donor hearts in human patients.

But suppose bioethicists objected, on the grounds that such mixing of species crossed ethical boundaries. The result would be untold human misery and mortality.

That thought occurred to me last week when bioethicists and some scientists became completely unhinged over unverified claims from a Chinese scientist that he has used gene-editing techniques to modify human embryos.

Professor He Jiankui said that one experiment was performed to make them resistant to the HIV virus (the father is HIV-positive) and resulted in twin girls, and another has resulted in a “potential pregnancy.”

The sisters who underwent this “germline gene therapy” via modification of early-stage embryos before they were implanted into the mother’s uterus, are reportedly healthy. But the claims spurred a furor, with critics condemning the procedure as dangerous and irresponsible, and “rogue human experimentation.”

Let’s all take a few deep breaths and consider the broader context, including the regulatory landscape.

“Human gene therapy” has been one of the goals of biotechnology since the advent of molecular techniques for genetic modification in the 1970s. There are two distinct conceptual approaches, presenting different kinds of benefits, risks and controversies.

Somatic cell human gene therapy alters genes — either by the editing of genes or the insertion of new ones — in the cells of human subjects, in order to correct conditions present at birth or acquired later in life. (Somatic cells are any cells in the body except eggs or sperm, so modifications in them are not inheritable — that is, passed on to offspring.)

It can be performed outside the body of the patient, such as by obtaining the patient’s cells, modifying and then returning them, or by injecting a customized virus or some other substance that migrates to a site(s) in the body and modifies the function of a malfunctioning organ.

Somatic cell gene therapy resulted in the approval last year of three treatments for serious diseases – and holds promise for afflictions ranging from rare and fatal genetic diseases to Parkinson’s.

Up to several years ago, gene therapy had been of a type that affects only the patient being treated; it has not modified sperm or eggs cells or embryos in a way that would constitute “germline gene therapy” by creating an inheritable change and affecting future generations.

But in a proof-of-principle experiment to perform gene editing with a system called CRISPR, published in 2015, Chinese researchers reported an unsuccessful attempt to perform germline gene therapy on embryos that were nonviable and were going to be discarded in any case.

That led to a meeting in December 2015 of “interested stakeholders,” which concluded: “At present, the potential safety and efficacy issues arising from the use of this technology must be thoroughly investigated and understood before any attempts at human engineering are sanctioned, if ever, for clinical testing.”

If ever? Really?

The move toward a moratorium has gained momentum since then, and, a “summit” on gene editing of humans was held only last week in Hong Kong, just prior to the beginning of which the embryo gene-editing was announced. And denounced.

The scientists attending the conference said that such interventions are irresponsible because not enough is known yet about their risks. But Professor Paula Amato of the Oregon Health & Science University in Portland Oregon was less negative, saying that her group planned to use gene-editing techniques to try to correct defects that increase the risk for breast cancer and Huntington’s disease.

Like the other conferences on gene editing, the one in Hong Kong was heavily attended and influenced by bioethicists, whose discipline Harvard University’s Steven Pinker characterized (correctly, in my experience) as “fetishizing sweeping rubrics such as dignity, equity, social justice, sacredness, privacy, and consent at the expense of the health and lives of actual people.”

In the end, however, the Hong Kong conference’s final statement did not call for a global moratorium on similar studies, as some attendees had wanted; instead, it called for a “translational pathway” that might eventually bring the technology to patients in a responsible way.

Although the purported genetic manipulations by Professor He should not have been performed — because the goal could have been accomplished by other, proven, conventional means — a sweeping government-imposed moratorium on all germline gene therapy would be misguided and, as discussed below, unnecessary.

Even if it is premature to perform germline gene therapy now — Dr. He’s claims of success notwithstanding — we should recognize that medical technologies are seldom successful right out of the gate, but as they’re applied and refined, they improve, sometimes with astonishing rapidity.

When I was a medical student during the 1970s, for example, bone marrow transplants were being performed in only a few institutions and as a last resort, and the success rate was abysmal. But the discovery of potent immunosuppressants and other technical advances improved the success rate dramatically, and bone marrow transplants are now routine in many institutions.

As a result, some leukemias that were once a death sentence now have cure rates around 90 percent. There are many similar stories in medicine, including open-heart surgery, which was remarkably primitive in its earliest incarnation, but which is usually uneventful now.

The reality is that successful innovation requires continual learning and incremental improvements, and in medicine, it is in clinical settings that this process must occur.

Adherence to ethical principles in human experimentation is essential, and it would be unethical to modify normal embryos for purposes of “enhancement” — i.e., to create “designer babies,” but nobody is proposing to do that. In any case, no regulatory agency would ever sanction gene therapy in the absence of an unmet medical need.

What’s inhibiting progress, at least in the United States, is anachronistic regulations. The FDA is blocked by law from accepting applications for research involving gene editing of the human germline — meaning eggs, sperm and embryos.

The NIH, whose approval also would be needed, is similarly barred from even considering applications to conduct such experiments in humans. These rules date as far back as the 1970s when the technology was in its infancy. It’s easy to invoke hypothetical fears and to impose bans when actual lifesaving interventions are decades away.

Given that regulators could reject applications for any reason, those absolute regulatory prohibitions are shameful and unwise public policy.

Today, successful germline gene therapy interventions are within sight — and desperate patients deserve access to whatever cures this technology may be able to provide. The public thinks so, too. A survey last year found that nearly two-thirds of Americans support therapeutic gene editing — in somatic and germ-line cells alike.

Popular opinion is in tune with scientific reality. Legislators and regulators need to catch up.