By Marcy Darnovsky, Elliot Hosman

from GeneWatch 30-1 | Jan-March 2017

As of this year, the creation of genetically engineered and enhanced future human beings is no longer a scientific hypothetical. It is a social justice challenge.

Human germline modification - that is, altering the genes of gametes or early-stage embryos in order to manipulate the traits of future children and generations - raises hugely consequential safety, social, and ethical concerns. The risks range from irreversible health harms to the introduction of a new era of eugenics, with exacerbated or new forms of social inequality, discrimination, and conflict. For these reasons, human germline modification has been widely considered off-limits, and is formally prohibited in more than 40 countries.

Over the past several years, the development of "gene editing" techniques has triggered renewed debate about human germline modification because they provide a relatively more accurate way to attempt to engineer traits by altering DNA in the nuclei of cells. During the same time period, a different set of biological engineering techniques has also become highly controversial. These "mitochondrial manipulation" (or "three-person IVF") techniques involve removing and recombining components of cells - more specifically, transferring the nucleus of one egg affected with mitochondrial mutations (or of an early-stage embryo created with it) into an unaffected, enucleated egg or embryo, in an effort to produce a reconstructed egg or embryo with non-mutated mitochondria.

Although mitochondrial manipulation techniques do not make targeted changes to DNA sequences, they do constitute a form of germline modification. Many scientists are deeply concerned about their safety for any resulting children, and dispute the adequacy of the limited evidence from animal models. After a hotly contested policy process, mitochondrial manipulation was approved in 2015 by Parliamentary vote in the UK (required in order to carve out an exception to the country's prohibition on human germline modification). It has not yet been attempted in clinics there. In the U.S., a policy process is under way.

Several fertility doctors have decided to simply ignore these scientific and policy deliberations. In late September and early October of this year, fertility clinics in Mexico[1] and in the Ukraine[2] announced human experiments with mitochondrial manipulation. A New York City-based doctor, who said he took his work to Mexico where "there are no rules," reported that a child born on April 6, conceived with this technology, appears healthy. Two women in the Ukraine are believed to be pregnant via mitochondrial manipulation, even though they are not affected by mitochondrial disease - the doctor there is using the technique to treat general infertility. There are rumors of additional pregnancies and/or births in China.

It is difficult to escape the conclusion that some fertility doctors are rushing to stake a claim to being the "first" to make a baby in a novel way. David King, PhD, director of the UK watchdog group Human Genetics Alert, issued a press statement condemning the news from Mexico, stating:

This is entrepreneurial reproductive technology at its most unethical and irresponsible. It is outrageous that [these fertility doctors] simply ignored the cautious approach of US regulators and went to Mexico, because they think they know better....These scientists have used an experimental technique that many scientists still think is unsafe, in order to create a world first. When are the world's governments going to stop rogue scientists crossing crucial ethical lines?

In contrast, much of the media coverage in the U.S. and the UK seemed to celebrate the creation of the world's first "three-parent baby." And unfortunately, similar hyperbolic and celebratory rhetoric has accompanied media accounts of gene editing. Since early 2015, an imminent "genetic revolution" of "editing humanity" has been featured on cover after cover of magazines and newspapers.[3]

With the door to high-risk embryo engineering techniques in fertility clinics now ajar, some are pointing to the UK's policy debate around mitochondrial manipulation techniques as a model for moving forward with germline editing using CRISPR and similar tools.[4] In fact, the controversy over "three-person IVF"[5] holds many lessons for the ongoing discussion of "germline gene editing"[6] - as a cautionary tale rather than an instruction manual.


Market-Drive Mission Creep

In the extended policy conversations about mitochondrial manipulation, researchers depicted it as a preventative medical technology for parents at risk of passing on serious mitochondrial disease to their children. On that basis, the techniques would be indicated for only a very small number of people, given that some 85% of mitochondrial disease involves mutations in nuclear DNA that these methods would not address.

However, if they were to be used for infertility, the potential uptake would be very large indeed. The almost immediate adoption of these risky embryo engineering procedures for a purpose never seriously considered in the risk assessments seems to demonstrate that market forces will drive fertility clinics to widen their customer demographic to the greatest extent possible.

In fact, the medical justification for germline techniques of any kind is dubious. People at risk of transmitting genetic diseases to their children have a number of alternatives. In every case, they could be guaranteed unaffected children by using third-party eggs or sperm. And in nearly every case (though not quite as reliably for mitochondrial DNA conditions), the embryo screening method known as pre-implantation genetic diagnosis or PGD would provide children who were unaffected by the condition in question and fully genetically related to both parents.


Dangerous Risk-Benefit Imbalance for Future Generations

Children born via embryo engineering methods - whether mitochondrial manipulations or germline editing - would face not just the high risk of biological complications, but also compromises to their privacy both in terms of media coverage, and medical display and tracking. Both procedures would involve a dangerous imbalance between medical and social risks to future children on the one hand, and the benefit to parents in pursuit of a genetic connection on the other.

Germline editing, with its potential ability to engineer specific traits, presents even greater dangers to children, familial relationships, and society. Children would risk being broadly defined by an engineered trait: Regardless of the germline intervention's actual biological impact or the value that the child placed on that trait in relation to their forming sense of self, it could deeply affect the way the child is treated. This could be particularly disconcerting for children who grow up and find their values differ significantly from their parents.


Reinforcing Inequalities and Introducing Novel Forms of Discrimination

We know that zip code is more important than genetic code when it comes to shaping health and longevity. But what if the affluent were given the ability to choose not only their zip codes but also their children's genetic codes? Today elite groups pour money and resources into making their neighborhoods upscale and exclusive. Tomorrow will they be working to define their progeny's costly modified genes as markers of prestige and privilege? We run the risk of programming slippery notions of desirable traits, conditions, and bodies into the biological makeup of future generations. A "biologization" of inequity could prove to be even more recalcitrant to change than existing social structures of power. Further, the social and commercial dynamics that would constitute the context for human reproductive germline modification could easily exacerbate global disparities and take structural inequality to a new (molecular) level.


Unenforceable Policy Distinctions

Some who advocate pursuing germline genome editing say they would support using it only to prevent serious disease, and not for other improvements. In practice, however, there is no clear distinction between medical and enhancement uses. Indeed, there is no objective way to draw clear lines among "difference," "disorder," and "disease."

The therapy/enhancement distinction is also untenable from a policy perspective. In many countries, including the United States, it would simply not be possible to restrict the purpose of an approved procedure. If the Food and Drug Administration were to approve germline interventions for serious disease, immediate off-label usage would be completely legal.

The only meaningful policy line is the one that has been consistently and repeatedly drawn up to now: a ban on genetic engineering for human reproduction using intentional germline modifications. Germline modifications are considered medically unnecessary human experimentation by the Council of Europe's Convention on Human Rights and Biomedicine, as well as by UNESCO, which called for a moratorium on such interventions in the 2015 update to the UN's Universal Declaration on the Human Genome and Human Rights.[7]


Undemocratic Strides toward a Brave New World?

At the conclusion of the December 2015 International Summit on Human Gene Editing, a statement issued by the organizing committee stated that "it would be irresponsible to proceed" with human germline editing for reproduction unless and until "there is broad societal consensus about the appropriateness of the proposed application."[8] Unfortunately, there have been few efforts to encourage public engagement on anything like the level that is clearly needed. Most of the meetings and consultation processes that have taken place are monopolized or dominated by scientific and technical experts, with selected individuals who are known supporters of a "full speed ahead" approach to new biotechnologies.

A wide range of publics are in fact being "edited out" of stakeholder meetings and policy debates, including advocates (for disability rights and justice; racial justice; environmental justice; public health; reproductive health rights and justice; and sex and gender minorities including intersex and transgender communities), artists, and scholars from the social sciences and humanities. These groups' values, traits, identities, and perceived "inferiorities" risk ending up on the cutting room floor.

In fact, public opinion studies show wide support for a "don't go there" approach to human germline modification. Opinion in the United States in particular has been consistent over recent decades.[9] Although polls on this issue are highly sensitive to framing bias, their results, along with data from focus groups, show a rich range of articulated concerns that belie techno-enthusiast efforts to dismiss public concern as stemming from religious ideologies or a lack of scientific understanding.


Preventing a New Era of High-Tech Eugenics

From a U.S. policy perspective, the needed steps are clear, if far from simple: establishing a federal ban on germline modifications for human reproduction, and joining in international agreements that put such human experimentation off-limits. In addition, we need a broad international dialogue about establishing scientific and medical norms that observe human rights and prevent practitioners from forum-shopping until they find a jurisdiction lax enough to proceed.

We also need to build a domestic dialogue that includes the range of unheard voices beyond the standard "stakeholder" models. Among the themes that need to be explored in these conversations: commercial and status incentives in biomedicine and biotechnology; the history of human experimentation in vulnerable populations for government, academic, and corporate research; the history of eugenics; and how social inequities warp the distribution of benefits and risks in research and development.

We can and should stand in the way of an era driven by eugenic upgrades and increased genetic surveillance. We can and should preserve for future generations the right of self-determination. We can and should promote democratic debates that shield publics from a cohort of elites bent on the individualistic technological transcendence of human "limits." We need not risk a never-ending repro-genetic upgrade cycle that threatens to split human society even more dramatically than our current tolerance for social inequality already allows.


Elliot Hosman, JD, Senior Program Associate at the Center for Genetics and Society, is an investigative writer on law and policy and a social justice advocate.

Marcy Darnovsky, PhD, Executive Director of the Center for Genetics and Society, speaks and writes widely on the politics of human biotechnology, focusing on their social justice and public interest implications.














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