This month, headlines have been filled with speculation about the social and ethical implications of “three-parent” children—that is, children born containing DNA from two mothers and one father through a set of in vitro fertilization procedures known as mitochondrial manipulation technologies. These technologies have been sought out to combat a host of inherited disorders affecting the mitochondria—small, energy-producing structures inside our cells. Disorders of the mitochondria are most likely to strike children, attacking the parts of the body that need energy most, such as the brain, muscles, heart, and liver. These diseases tend to be fatal before adulthood and impact 1 out of every 1,000 children in the United States alone. People like Sharon Bernardi, a British mother who has lost seven children to mitochondrial disease, says, “I have babies in three different cemeteries. … Without a heartbeat I would have gone for [MMT] … I hope people take it seriously and it’s approved.”
But not everyone is singing the praises of MMT. According to a 2014 New York Times Magazine feature, at an open-door meeting of the FDA in February 2014, Marcy Darnovsky of the Center for Genetics and Society said, “These manipulations are not meant to treat people who are sick and suffering. … What we’re talking about is radical experiments on future children and future generations.” The Times’ Kim Tingley writes that Darnovky was followed by several others voicing concerns, including Enola Aird, of Mothers for a Human Future, who referenced the 1997 dystopian science-fiction film Gattaca and warned that “Allowing the creation of children with genetic material from three or more parents would open the door to the alteration of the human species and the creation of different biological ‘Gattaca’-like classes of human beings and the dissolution of our common humanity.”
Since then, the door has opened ever so slightly for MMT in the United States. On Feb. 3, the National Academy of Sciences, Engineering, and Medicine released a report—in response to a request from the Food and Drug Administration—that makes several recommendations intended to encourage that people proceed cautiously with this controversial technique. The NAS recommendations include initially limiting gestation to male embryos; ensuring only centers with demonstrated expertise in and skill with MMT be allowed to conduct initial investigations; and long-term monitoring of children born through MMT to evaluate potential social and psychological effects.
Those who are urging caution here worry that the changes created by MMT would be passed onto future generations, raising concerns about eugenics and possible violation of international treaties against germline modification. Germline modification refers to a genetic modification such that the alterations are intentionally passed onto future generations through reproduction. Mitochondrial DNA is only passed on from the mother, however, and not the father, unlike nuclear DNA that is combined and passed on from both parents. Their arguments also rest in part on the novelty of the thing. For instance, in Science magazine, bioethicist Jeffrey Kahn of the Berman Institute of Bioethics at Johns Hopkins University, who chaired the panel, was quoted as saying, “This is the first time it will happen in humans. We don’t know how it will work.”
But this is not entirely accurate. Right now, alive and breathing, are somewhere between 30 and 50 living human beings who were born using techniques that could have given them DNA from three parents, two mothers and one father, through early MMT used nearly 20 years ago. Looking back at that history can help us understand the debate underway now.
In 1997, clinical embryologist Jacques Cohen, while at the Institute for Reproductive Medicine and Science, Saint Barnabas Medical Center in Livingston, New Jersey, successfully completed the first implantation of an embryo conceived through cytoplasmic transfer. Cytoplasmic transfer, which Cohen created, was developed to revitalize the mitochondrial portion of an egg cell in women experiencing infertility due to their age, by using the same portion of a much younger woman’s egg cell. The actual procedure involves removing material from one a donor egg, containing mitochondria, and implanting it into the egg cell that is to be fertilized. Once this is completed, the new egg cell, containing nuclear DNA from the mother, as well as mitochondrial DNA from the donor, is fertilized with sperm cells from the father.
As of April 2001, Cohen reported in the Human Reproduction Update that there had been 16 successful births including 10 singles, a set of twins, and one quadruplet birth using this technique in his laboratory. According to this report, there was also a twin birth at the Eastern Virginia Medical School using a variation of the technique. In Israel, six more births were recorded using a technique identical to Cohen’s original protocol, while five successful births were recorded using another modification of the technique at the Lee Women’s Hospital Infertility Clinic in Taichung, Taiwan. According to the report, some of the resulting embryos were shown to have DNA from all three donors; however, there were no protocols in place to follow up with each of the children conceived to verify which ones did or did not have DNA from all three donors.
More MMT-lite babies must have been born, too—because in the summer of 2001, the FDA announced that 23 children had been born using the technique, three U.S. clinics had published papers on it, and five additional clinics were advertising the procedure online. In response, it sent letters of notification advising practitioners of the FDA’s jurisdiction over cytoplasmic transfer.
Next, from May 9 to 10, 2002, the FDA held a Biological Response Modifiers Advisory Committee Meeting on the topic of Ooplasm (Cytoplasmic) Transfer to Treat Infertility. The BRMAC meeting found that researchers could not prevent two possible risks to the offspring at that time: 1) inadvertent transfer of chromosomes, chromosome fragments, or other cellular constituents, and 2) enhanced survival of abnormal embryos, increasing the likelihood of children born with significant birth defects. Due to these risks, further human trials in the United States were suspended.
The United Kingdom began its own investigation into MMT in April 2011 with a report from the Human Fertilisation and Embryology Authority. The report jump-started a debate in the U.K., culminating in February 2015, when both the House of Commons and the House of Lords passed a measure allowing the use of MMT in the United Kingdom.
Soon after the United Kingdom began to publicly show interest in MMT, the United States took up the topic again. The FDA held a briefing in February 2014, to reconsider the 2002 decision in light of new scientific evidence. Interestingly, issues of ethics and social policy were explicitly not considered, although they were acknowledged. The briefing concluded with a general feeling that more results indicating the technique was without unintended consequences would be required before moving to human trials.
But of course there have already been human trials, albeit limited ones, that can help us answer some of the questions surrounding the technique. Take that first FDA concern—that it could result in inadvertent transfer of chromosomes, chromosome fragments. While we call these kids “three-parent babies,” it’s not actually clear whether the mitochondrial donor’s DNA will end up in the child. At least two of the children born using MMT techniques, Alana Saarinen of Michigan, and Emma Ott of Pennsylvania, now 15 and 18 years old respectively, are known through several media stories done both in the United States and in the United Kingdom. While Emma Ott has been tested and found not to have traces of the third donor, Alana has not been tested. Without knowing for certain the third-donor status of Alana’s DNA, if she were to have a child, she could be the first to pass along a germline modification, created in a lab by human beings, to her offspring. The first generation of children produced through MMT is already here, entering adulthood after nearly two decades of existence. Admittedly, the numbers are small. But the line has already been crossed, and thus far designer babies and dystopian futures don’t seem inevitable.
Bioethicists are correct to emphasize that we are unsure about the long-term effects of MMT, but it’s not accurate to say that trials have never been done. And given the strong emotional response some people have to three-parent children, it is important to—with their permission—turn to those already born using these techniques. They can be a resource to, at least, examine questions about the social and psychological implications of MMT.
The 30 to 50 children who might have three parents’ DNA can’t settle all of the debates: Perhaps most importantly, we don’t yet know the impact of this science on future natural-born generations. We don’t have those answers yet, but as those 30-50 people born in the late ’90s and early ’00s grow up and have children of their own, we will soon have some data points.
This article is part of Future Tense, a collaboration among Arizona State University, New America, and Slate. Future Tense explores the ways emerging technologies affect society, policy, and culture. To read more, follow us on Twitter and sign up for our weekly newsletter.
