CMDA's The Point

Treating Patients or Creating New Patients with Technology

November 8, 2018
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by David Prentice, PhD

Emerging technologies offer opportunities for development of useful therapeutic interventions, but they can also offer temptations to rush ahead with risky, scientifically unproven and ethically questionable applications. The old question that looms large on the frontiers of medicine again needs to be asked: “Not can we do it, but should we do it?” Failure to fully consider the ethics of a particular technique can endanger patients, as well as erode public faith in science and lead to questions about the motivations of healthcare professionals. In most cases, alternatives exist or are under development that can deliver the same or even a better end, if only we will open our eyes to possibilities and not blindly rush ahead.

A case in point is the proposal to create “three-parent babies” or, as some have termed it, “mitochondrial replacement therapy.” The problem to be addressed is treating individuals who bear mitochondrial genetic diseases, many of which are life threatening. Passed solely through the maternal line via the egg, high percentages of mitochondrial DNA mutations can have a lethal outcome for babies who inherit the mutations. Even low percentages of mutated mitochondria per cell can cause significant physiological problems.

Sadly, rather than focus on therapeutic interventions for those with the mitochondrial genetic diseases, scientists proposed using cloning technology to combine non-mutated mitochondria from one egg donor with nuclear DNA from another woman, to create new embryos who would supposedly not carry the genetic mutations. The phrase “mitochondrial replacement therapy” is highly deceptive, since it is not mitochondria that are transferred, nor is it therapy. Rather, this is nuclear transfer, a.k.a. human cloning technology, using micromanipulation of nuclei and of oocytes. (Diagrams and discussion of these cloning, i.e., “nuclear transfer,” techniques can be found at the Charlotte Lozier Institute website.)

And no existing individual is treated. The manipulations are non-therapeutic, creating new genetically engineered individuals with altered genetic composition, that it is hoped will not inherit the mitochondrial mutations. Compassion for individuals suffering from mitochondrial disease is replaced with a focus on the design of their replacements—new, genetically-correct individuals.

Moreover, alternatives existed even when the U.S. Food and Drug Administration (FDA) in 2014 and the Institute on Medicine in 2015 heard testimony. These alternatives focus on those with mitochondrial mutations, with the potential to ameliorate their conditions.

Nonetheless, the desire to wield high-tech power and manipulate human life led the Institute on Medicine to ignore ethics and propose moving ahead with embryo-destructive research. The FDA was precluded from acting on this unethical proposal by a Congressional appropriations rider, but one fertility doctor ignored the legal prohibitions and created several three-parent embryos, doing the embryo transfer in Mexico to avoid U.S. law. Tests on the little boy who was subsequently born showed the technique reduced but did not eliminate all mitochondrial mutations, with DNA mutations retained in the nuclear transfer procedure. It’s unknown whether these levels of mutation may present physiological problems, although other research suggests that retention of mitochondrial mutations may be unavoidable with this technique, endangering the health of any babies created in this manner. And the levels of mutation might increase through the boy’s life, even to the point that there could be significant health problems. These events were reviewed in a previous blog on The Point.

The FDA has repeated its notice that creation of three-parent babies is prohibited within the U.S. Still, some continue—despite the scientific, safety and ethical arguments against the technique—to agitate for carte blanch to manufacture genetically modified babies, including wild assertions that Congress is preventing people from having healthy babies.

But what about those who have the mitochondrial mutations? Though still ignored and pushed aside by the advocates for genetically manufactured babies, patients’ voices must be heard. Research is showing new hope for authentic therapeutic interventions. Two recent papers show the ability in animal models to correct the mitochondrial mutations. Both use gene-editing technology, but target the mutated mitochondria in cells rather than germline alterations of embryos. These technological uses actually stand to benefit patients. As one of the researchers noted, “It’s a hopeful moment for these diseases.” When there is a pause to truly consider ethics, ethical and beneficial alternatives emerge.

David Prentice, PhD

About David Prentice, PhD

CMDA Member and Vice President & Research Director for Charlotte Lozier Institute

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