A Paragraph in Slow Motion: Three-Person IVF in The New York Times
On June 27, the New York Times Magazine’s cover story was “The Brave New World of Three-Parent IVF” by Kim Tingley, a feature article on the new technique it calls “mitochondrial replacement therapy.”1 That technique would combine the nuclear DNA of two people with the mitochondrial DNA of a third, creating an embryo with three immediate genetic parents, in an attempt to avoid one kind of inherited mitochondrial disease. Human trials are currently proposed.
Because this procedure would cross the line into inheritable genetic modification—a bright line that forty-four countries have agreed, as a matter of policy, not to cross—I was curious to see how the Times would report on the procedure. Human biotechnologies are rocketing ahead under the radar; for many readers, the article will be an influential introduction to the issues. Since the article was presented as a feature, and not an opinion piece, the writer had an obligation to present the issues in a balanced way.
Unfortunately, Tingley’s reporting is strongly tilted in favor of the procedure: for her, it’s clear that fears of a brave new world are overblown, and potential benefits underrated.
Structurally, this bias is evident throughout. The article is anchored by a profile of the likable and apparently idealistic scientist Dieter Egli, an advocate of the procedure; we see him reflecting humanely, practicing science competently, listening carefully to opponents. In a truly balanced article, someone who disagreed with Egli would also be profiled, but no one opposing the technique is given remotely equal narrative weight.
Also profiled are families who benefited from cytoplasmic transfer, a precursor to the technique; the families are shown in color photographs, their heartfelt gratitude is recorded, and the health (and intelligence) of their children is emphasized. No such treatment is given to those who question the procedure. Their views are often represented by fearful anonymous comments; when people are quoted on the record, they are represented in brief snippets. Often, their objections are subsequently answered, giving those in favor of the procedure the last word. Significantly, strong arguments against the procedure are omitted.
Tingley’s rhetoric is broadly familiar from writing that advocates the adoption of new technologies. Therefore, “The Brave New World of Three-Person IVF” offers a case study of the way pro-technology assumptions have been absorbed into mainstream media. To show the pervasiveness of these ideas, I’ll dissect a single, pivotal paragraph, examining it point by point: in slow motion, as it were.
What often gets lost in the loaded language of the debate over three-parent babies is the fact that ordinary human reproduction is, by definition, genetic modification. The risks involved are unpredictable and potentially tragic; the subject of the experiment is a future person who cannot consent. We constantly try to control this process, to “design” our children, starting with our choice of sexual partner. During pregnancy, we try to “enhance” them by taking folic acid, not smoking, avoiding stress; once they’re born, we continue the process with vaccines and nutritious food, education, clean air and drinking water. Some of these pre- and postnatal environmental factors, we now know, change their biology in heritable ways. Is mitochondrial replacement, because it takes place in a petri dish, any more unnatural or morally repugnant than this? Would the answer change if the technique turns out to cure age-related infertility in addition to preventing disease?
Now, in slow motion:
What often gets lost in the loaded language of the debate over three-parent babies…
The paragraph’s opening move is familiar: to decry the quality of debate (“loaded language”), and to position the writer as rational. By implication, Tingley will offer language that is non-loaded and clear.
…is the fact that ordinary human reproduction is, by definition, genetic modification.
Words that conjure the rational—fact, definition—are opposed to “loaded language.” But to say “reproduction” is identical to “genetic modification” is neither factual nor definitive. It is an analogy: an argumentative chimera, engineered by the writer.
Here we see a second tactic common in discussions of new technology: the Analogy to the Familiar. In that tactic, a new, controversial thing is defanged by comparison to an old, familiar thing. (Clones are just twins, high-tech gene splicing is no different from ordinary plant breeding, and engineering kids for higher intelligence is just like sending them to private school.) The advantages of this tactic are obvious. If the new thing and the old thing are effectively identical, then the new thing shouldn’t be scary: it’s already here. In this case, it is no big deal to embark upon genetic modification, because we’ve already been doing it all along.
But the analogy between ordinary human reproduction and genetic modification is tenuous. In Ordinary Human Reproduction, we combine genes, but do not modify them deliberately. More relevant to the article, they are combined from two (2) people, not three (3). “Modification,” then, in the sense the writer uses it, is a red herring; at issue is “engineering.” Three-person IVF involves engineering, and “ordinary human reproduction” does not.
Having established a shaky foundation, the writer now begins to build:
The risks involved are unpredictable and potentially tragic; the subject of the experiment is a future person who cannot consent.2
Here Tingley notes two strong objections to human biotechnologies—they’re risky, and they entail human experimentation—while embedding them in dismissal. By the terms of her analogy, we’re already taking these risks, already ignoring consent; by implication, moving to genetic modification is not that big a deal. However, to make that argument stick, she enacts a subtle but important shift in terminology: “modification” becomes “experiment,” as if the two were synonymous. This shift makes for troubling ambiguities.
First, a “modification” is not necessarily an “experiment”; a knockout mouse, for example, is an example of a modification, but it’s not experimental. Second, Tingley’s point depends on two very different senses of “experiment.” There’s the colloquial sense—“an act with an unknown result”—and the stricter, scientific sense of “a controlled trial, with restricted variables, undertaken to test a hypothesis.” The first applies to Ordinary Human Reproduction; the second applies to clinical trials of three-person IVF.
To maintain her argument, Tingley focuses on the result: things can go “wrong” in ordinary reproduction, just as they can go wrong in engineering. But at issue is not only the result, but the process. Ordinary human reproduction works most of the time because it is evolved to work: one can say, after eons of evolution, that the safety studies have been completed. Our bodies know how to do this—though we know a great deal more, in the 21st century, about how to help them along.3
But a very different body of knowledge is needed to engineer the process. Our knowledge of the cell is incomplete and changing fast. If mtDNA and nuclear DNA are more intricately linked than we now suspect, then the experiment’s descendants, instead of being healthy, could pay the price for what we don’t know. To even find out in a truly scientific way would involve experimenting on human beings—and if we really want to know, we’d need to have a large sample size, and track the resulting humans through more than one generation. (Effects could potentially appear in later generations, which means that we’d not only be experimenting on the children who didn’t consent, but on their children as well.) For the procedure to be successful, we would have to assume both flawless technical execution and sufficient knowledge of the cell’s workings, neither of which can be realistically assumed.
It’s worth stepping back here to point out a couple of things. First, the number of women who would be candidates for this procedure is very small. Second, the procedure, even if it works reliably, is meant to deliver a related child, free of one very serious inherited disease.
These are absolutely worthy goals. The thing is, candidates for three-person IVF already have another option for having a related child free of mitochondrial disease: preimplantation genetic diagnosis, in which embryos are examined for mitochondrial defects, selected for health, then implanted. This procedure is significantly less experimental, and since a third donor is not involved, the resulting child would be related to his or her parents in a conventional, uncomplicated way—presumably, what is desired in the first place.
That procedure is not absolutely certain to succeed either, and as advocates of three-person IVF have noted, there are some women who will not be able to benefit. On the other hand, PGD detects other forms of mitochondrial disease which originate in the nucleus, and which account for 85% of all inherited mitochondrial disease.
Compared side-by-side with an idealized version of 3-person IVF—in which everything works, and we don’t care about crossing the line of inheritable modification—PGD does not work as well. It's probably soundest to say that it is an alternative route that isn't perfect, but that doesn't carry the safety risks of 3-person IVF. In addition, it doesn’t cross the germline, and it doesn’t necessarily involve human experimentation. As is the case in a world of imperfect medicine, when you look at the details, there are no absolutely clear choices.
Writing is always a matter of what you include, and what you exclude. From a rhetorical perspective, Tingley’s exclusion of the PGD point is troubling. Though that point is prominent in a letter with multiple signatories sent to the FDA panel, Tingley ignores it. (She returns to that collection of letters twice, but only focuses on the anonymous comments, framing them in terms of ignorance and fear.) Even more troubling, the PGD alternative was discussed extensively at the panel’s hearings, which are the centerpiece of her article.
But to include the PGD alternative would disrupt a central theme of Tingley’s article: that opponents of three-person IVF are fearful, or generally “anti-technology.” To argue for PGD as an alternative suggests a reasonable balance between risk and benefit, and a principled objection to crossing the germline.
At this point in the paragraph, Tingley is no longer just talking about “three-parent babies,” but about inheritable genetic engineering in general. That subtext now rises to the surface:
We constantly try to control this process, to “design” our children, starting with our choice of sexual partner.
Note the marked shift: while continuing the new-is-old, Tingley changes emphasis from “three parent babies” to “design.”4
Let’s set aside any number of inappropriate jokes and simply stipulate that choosing a sexual partner does not necessarily entail “designing” a child. Choosing a sexual partner may have many meanings, none of them necessarily related to reproduction.
In any event, “designing” implies selecting attributes in a fine-grained way. To assume that procreation necessarily involves design ignores the many ideas about parenting that actual people hold. One can, for example, believe that parenting is a matter of accepting, more than designing, and that trust in each others’ values, and in the ability to work things out, will always trump “design.” In fact, the child may be welcomed precisely because she is not designed, because she is her own person, a gift.
One may also feel that the qualities of each individual are of less importance than the qualities of the connections between individuals—in a family, in a community—and that if those fail, the best-designed attributes cannot succeed.
But I digress.
During pregnancy, we try to “enhance” them by taking folic acid, not smoking, avoiding stress;
One reason I wanted to work through this paragraph slowly is to show the rapid changes, the way the rhetorical ground shifts under the reader’s feet:
The shift from reproduction to enhancement takes exactly three sentences. One hopes that in real life, the slope will be less slippery.
“Enhance” is a vague word, but in discussions of genetic modification, it usually refers to enhancement of ability: either the mild stuff, like improvement of memory, or the sci-fi stuff, like the ability to breathe underwater. In these discussions, the enhancements are targeted (designed): they are specific measures, not general practices taken to ensure healthy development.
Given that context, the use of the word “enhance” in connection with smoking cessation or stress avoidance—even with quotation marks—is strained at best. These practices are sensible precautions, not examples of “enhancement.” “Enhancement” means improving on what is already there; “not smoking” and “avoiding stress” are ways of not actively harming the developing embryo. Taking folic acid is closer to the mark, but this, too, is meant to avoid impairing an existing process of development—which is categorically different from direct alteration of the DNA or mtDNA, a process which precedes development.
…once they’re born, we continue the process with vaccines and nutritious food, education, clean air and drinking water.
None of these things are controversial. Know why? Because they don’t make people with three parents, because they’re cheap, because they’re great for all people no matter their abilities, because they’re proven and non-experimental and generally tend towards a healthier and more equitable society overall and don’t set precedents which make disturbing things more possible.
Tingley’s article is about three-person IVF, not genetic enhancement. But since she’s gone there, let’s follow.
There are two possible problems with targeted genetic enhancement. The first is that it won’t work; the second is that it will. If it doesn’t work, you’ve at best spent a lot of money to no effect (except for the opportunity costs of, say, allocating that money toward research on treatments for mitochondrial disease), and at worst produced someone who suffers as a result of the experiment. If it does work, you’ve created a new kind of person: that fact alone disrupts the evolved commonality of the species.
There are two further problems, if enhancement does work. The first is that only a few people will be able to afford the technology: if so, we may be divided into “Genrich” and “Naturals,” to use Lee Silver’s terms. The second is that many people will be able to afford it, which, in Bill McKibben’s scenario, leads to an arms race of upgrades.
Again, I digress. The point is that eating leafy, dark green vegetables is different from re-engineering human embryos. Even the Cookie Monster can tell you that. However, if a person engineered to have three parents ever comes to term, I hope he eats lots of spinach—which, as Popeye taught us, is the natural way to human enhancement—and that his cupboards abound in gluten-free options to regular food, should that still be considered important, in the future.
Some of these pre- and postnatal environmental factors, we now know, change their biology in heritable ways.
The writer doesn’t specify what she means, but it’s safe to say that nutrition, clean water, and vaccines do not “change…biology in heritable ways” in the same way that engineering the genome does.
Important side note: If precision matters in the procedure, it matters in the language with which we discuss it.
Is mitochondrial replacement, because it takes place in a petri dish, any more unnatural or morally repugnant than this?
In the beginning of the paragraph, the writer pointed us towards what was “lost” in “the loaded language of the debate.” The paragraph concludes with two rhetorical questions that are nothing if not loaded. Let’s look at the first.
First, Tingley is asking a rhetorical question—typically a tool of persuasion, not information—as it’s clear from context that she doesn’t think “this” is unnatural or repugnant at all. But given the rapid shifts of her sentences so far, the pronoun “this” is hard to trace back to a definite concept: it seems to refer to reproduction-which-is-really-modification-which-is-really-experiment-which-involves-design-and-is-heritable. On reflection, I’m not sure what Tingley really means, though on first read the sentence goes down smoothly.
More significant, for me, is the implied view of those who oppose the procedure: that they find it “unnatural” or “morally repugnant.” Because this is a significant theme for those who advocate the new procedure, I want to spend a bit of time here to show how this theme pervades the article—often joined to the common theme that those who oppose the procedure are fearful or ignorant.
In the months leading up to the meeting, the F.D.A. received several hundred emails from members of the public objecting to the idea of three-parent embryos on grounds that included: ‘It’s bizarre’; ‘You are walking in Hitler’s footsteps if you allow this’; and ‘We will have a world of mad scientists.’
As the scientists who were pressing for mitochondrial replacement kept pointing out, these fears were somewhat unfounded.
This pattern—fear, and refutation—occurs elsewhere. In her account of the Asilomar conference of 1975, for example, in which scientists discussed splicing genes, Tingley describes the public reaction in terms of fear; then quotes a bioethicist who elaborates on this theme; then offers a conclusion: “In the end, the researchers did splice DNA; this has lead to many benefits, but not, as feared, a cancer-causing superbug.” Clear message: the fear was unwarranted.
Tingley also quotes Representative Jeff Fortenberry on the issue, with a clear contrast between his alarmist tone, and a sober response from the FDA:
At the end of March, at an F.D.A. budget hearing, Representative Jeff Fortenberry of Nebraska objected to the “three-parent embryos” meeting: “One quote from a professor of neurobiology is this,” he said. “‘The creation of three-parent embryos is not an innocuous medical treatment. It is a macabre form of eugenic human cloning in which a human being with a medical condition is killed and his or her parts are used to create a new human being with an improved biological state.’ Clearly there are consequences here, frankly, and these scenarios scare people, and I would be very worried if it didn’t scare people.”
Without correcting his scientific interpretation, the F.D.A.’s commissioner, Margaret Hamburg, said the agency was open to partnering with other agencies to host discussions of the ethics involved.
When she discusses the public-comment emails, Tingley’s condescension is evident:
In the United States, it seemed as if the most vocal members of the public felt disturbed by the technique without necessarily being able to articulate why: Of the nearly 250 emails the F.D.A. received before its February meeting, most objecting to ‘three-parent babies,’ more than half of them were form letters.
Among advocates of new biotechnologies, and of three-person IVF in particular, it’s a common tactic to say that opponents are afraid of the “unnatural”; closely allied is the charge that opponents don’t understand the science. In a recent article in The Lancet, for example, Phillip Ball cites the philosopher Russell Blackford, arguing that “appeals against violating nature” come from those who are “searching for ways to rationalize a psychological aversion.” At Slate, in an article favoring three-person IVF, Jessica Grose quotes a doctor approvingly. “Every time we get a little closer to genetic tinkering to promote health — that’s exciting and scary,” Dr. Alan Copperman, director of the division of reproductive endocrinology and infertility at Mount Sinai Medical Center in New York, told the New York Times. “People are afraid it will turn into a dystopian brave new world.” In The Guardian, Polly Toynbee writes of the decision contemplated in Britain: “Stuffed with the religious and rabble-rousers who stir up fears of Frankenstein babies, many in both houses will make noisy speeches, ignoring the science.” These writers strongly favor the procedure in question. Tingley’s frame, and her rhetorical approach, is similar to, if not identical to, theirs.
But this frame seriously misrepresents the opposition. While it’s true that many people find the practice “repugnant,” it is also true that serious, well-founded, and articulate objections exist. Jessica Cussins, writing for this blog, has summarized, and linked to, published scientific papers which raise questions about the clinic-readiness of the procedure in question. In particular, she cites
a paper in Science:
Reinhardt et al. explain why disruptions to the interaction between the nucleus and mitochondria could be problematic.
Energy production critically hinges on extensive cross-talk between genes dispersed across the nucleus and the mitochondria. Because phenotypes with less-than-ideal cross-talk are disfavored by natural selection, coordinated mitochondrial-nuclear interactions become highly specific over evolutionary time. If MR disrupts such specific, highly coordinated mito-nuclear allelic interactions, adverse health outcomes might occur.
They also problematize the notion that nuclear DNA is unaffected by this procedure.
Studies on model organisms, ranging from mice to fruit flies, indicate that MR can profoundly change the expression profiles of nuclear genes and affect a range of important traits such as individual development, cognitive behavior, and key health parameters. These studies also suggest that males of reproductive age are particularly sensitive to MR-induced effects.
The authors point out an important limitation to the only primate study carried out thus far, noting that the macaques born following MR need to be studied through to sexual maturity (they are only three years old currently) since, “the results from mice and invertebrates suggest that many deleterious effects of MR would not be revealed until adulthood.”
There are some issues—the effectiveness of vaccines, for instance, or the causes of climate change—on which scientific consensus is virtually unanimous. This is not the case for three-person IVF. It’s not at all a matter of Scientists Versus Fearful Rabble. It’s some scientists for, some against.
Since Tingley is clearly familiar with scientific objections to the procedure—though she gives them neither the space, nor the favorable tone, that characterizes her coverage of the other side—it’s all the more troublesome that, after (briefly) noting concerns about safety, human experimentation, and social justice, she implies that the worry is about the petri dish.
Would the answer change if the technique turns out to cure age-related infertility in addition to preventing disease?
Here’s a thought experiment for detecting bias in reporting: ask yourself if you can imagine a rhetorical question fitting seamlessly into an op-ed on one side of the debate. By that standard, Tingley’s rhetorical question clearly favors the procedure she’s reporting on: it has the tone of a challenge, and implicitly touts the benefit of the procedure. (It’s impossible to imagine this question being raised in opposition to the procedure.)
There’s so much to disentangle here. First, Tingley’s question reinforces the false assumption that opposition to three-person IVF is mainly based on fear. Second, the question assumes that the procedure does, in fact, prevent disease; we don’t know if that’s true. But third, and most significantly, Tingley’s question assumes that “age-related infertility” is in fact something to “cure.” This brings us to key questions which reach beyond the frame of Tingley’s article.
The first: What are the boundaries of health? Tingley’s description of “age-related infertility” as something to “cure” is at best controversial, and at worst an example of pathologizing a normal process. In a paragraph full of little shifts—from “modification” to “experiment,” from three-person IVF to enhancement—it’s this last one that disturbs me most. Those of us concerned about the unintended consequences of new technologies are frequently tut-tutted by those who claim “designer babies” could never happen. But if they do happen, it will be, in part, because we do not think carefully about what counts as disease, and what counts as part of being human.
The second question is closely related to the first. Advocates of new human biotechnologies tend to define disease broadly: in a market economy, there’s a motive to pathologize conditions that don’t currently count as disease.5 This tactic is, of course, endemic to pharmaceutical advertising: Carl Elliott has argued that the real effort in said advertising is to “sell the disease.” To do so—as has been done, for example, with ADHD, or erectile dysfunction—is to expand or even create the market. So, second question: Assuming the technology is adopted—and becomes a for-profit product—what effects can we anticipate in a globalized market?
That question leads to a suite of others. How will market pressures affect the science that supports the procedure, the language with which we speak about it, and the way the procedure is done? Given the very few women who would be candidates for this procedure, would there not be an incentive to expand it beyond disease, or to treat normal features of humanity—like, for example, not being able to get pregnant at age 60—as “curable”? Where will we get the many eggs needed, if this technique is scaled up—and how will we avoid either commodifying women’s bodies by paying for eggs, or having egg donors bear the risks of retrieval? And given the real concerns (expressed by scientists, not fearmongers) that something can go wrong, who will be responsible if someone does? How can we avoid yet one more scenario in which we privatize the gains, and socialize the costs?
We should remember that those scenarios—from leaking reactors to economic crashes—tend to begin with a toxic mix of optimism and complex human engineering, and are supported with a rhetoric of expertise. (Credit default swaps, or nuclear reactors, are too complicated to understand. Don’t worry, we’ve got it under control!) But an embryo is more complex than a nuclear reactor or an economy, and is less well understood. The idea that we would just be replacing the cell’s batteries belies a more sober and scientifically realistic perspective: that we would be intervening in an incompletely understood system, and passing the costs on to descendants with no say in the matter.
Those of us who oppose this particular technology, but who support the sensible use of other technologies for human health, need to reclaim both science and common sense. And we need to read carefully—both to see how our views are represented, and to see the messages that herald tomorrow’s developments. Not all “progress” moves us forward.
George Estreich received his M.F.A. in poetry from Cornell University. His first book, a collection of poems entitled Textbook Illustrations of the Human Body, won the Gorsline Prize from Cloudbank Books. His memoir about raising a daughter with Down syndrome, The Shape of the Eye, was published in SMU Press’ Medical Humanities Series. Praised by Abraham Verghese as “a poignant, beautifully written, and intensely moving memoir,” The Shape of the Eye was awarded the 2012 Oregon Book Award in Creative Nonfiction. Estreich lives in Oregon with his family.
Previously on Biopolitical Times:
- Anatomy of a Webpage: Marketing Fetal Gene Tests and Sequenom’s MaterniT21
- Anatomy of a Webpage, Part 2: Preconception Services
- Anatomy of a Webpage, Part 3: Selling “Peace of Mind”
(1) The technique has many names: three-parent IVF, three-person IVF, mitochondrial transfer, maternal spindle transfer. The differences are not insignificant. Strictly speaking, it is the nucleus, not the mitochondria, which is transferred. I use the phrase “three-person IVF,” which avoids the multiple meaning of “parents.”
(2) In The Guardian, in an article that aggressively supports three-person IVF, John Harris makes an essentially identical point. He writes that “’normal’ sexual reproduction [is] a very dangerous activity indeed and one often described as a ‘genetic lottery’. Human reproduction involves genes being recklessly combined, sometimes literally, but always figuratively in the dark, with unforeseeable consequences for the resulting children and generations.” Like Tingley, Harris moves easily to a rationale for enhancement: “Let's celebrate the advent of a new and life-enhancing therapy and the impressive science that enables this generation, and future ones, to correct the mistakes inherent in so-called normal sexual reproduction.”
“Skepticism that these highly intrusive manipulations, bringing together fragments of damaged cells and embryos, could generate a healthy individual, arises from the implausibility that such concoctions have ever been encountered in the course of animal evolution. Cells have evolved sophisticated ways of repairing aberrant conditions such as DNA or protein damage, but these have been common hazards for all organisms throughout the history of life. Sometimes programmed death — cell or embryo "suicide" — is the way out of untenable foul-ups, but this escape route may be thwarted in PNT and MST.
The described techniques also evade protective measures against "heteroplasmy," the mixture of mitochondrial genomes that occasionally results from the persistence of the sperm mitochondrion after fertilization. Ancestral animals that lacked such suppressive mechanisms did not contribute significantly to present-day populations, and recent evidence indicates that heteroplasmy has deleterious effects even when both types of mitochondria are healthy (which is not the case in the replacement protocols). Any humans that came to term and to maturity as products of these procedures would represent uncontrolled laboratory experiments.”
(4) Elsewhere in the article, Tingley is at pains to point out that “mitochondrial transfer” does not entail design. Profiling a family that used a similar procedure, Tingley writes, “as far as anyone knows, mitochondrial DNA (mtDNA) governs only basic cellular functions; Ott understood that her and her husband’s nuclear DNA would determine their child’s characteristics — height, eye color, intelligence and so on.” She also writes, “[a]s the scientists who were pressing for mitochondrial replacement kept pointing out, these fears [of playing God] were somewhat unfounded. It cannot allow people to design babies to their specifications — in fact, it comes with most of the same risks and uncertainties that attend old-fashioned reproduction.”
There’s a central inconsistency here: In one place, Tingley seeks to draw a sharp line between mitochondrial DNA and the “real” stuff of nuclear DNA; in another, she blurs that very line, moving quickly from three-parent IVF to “design.” Between the two approaches, the only consistent thread is the bias in favor of the procedure. (The offhand statement that “nuclear DNA would determine…intelligence” [italics mine] is, at the very best, questionable.)
(5) Tingley emphasizes the possible extent of mitochondrial disease: “About 1 in 4,000 children and adults is diagnosed with mitochondrial disease, but because symptoms are so varied, doctors think many more cases are misdiagnosed; one recent study suggests that 1 in 200 people is born with a mutation that could make him or her sick.”