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Mulling The Genetic Horizon: “Designer Genes”

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Should there be limits on using genetic techniques to make healthier—or perhaps one day, even enhanced—humans? This was the Big Idea on the table Thursday night at Designer Genes: Fashioning Our Biological Future, a program of the 2014 World Science Festival.

Genetic engineering was one of the first major scientific breakthroughs to be subject to meaningful public scrutiny, said panelist Sheldon Krimsky, a Tufts University bioethicist. In 1976, when scientists were first attempting to perfect the art of recombinant DNA techniques—inserting new genes into bacteria—Cambridge, Massachusetts mayor Alfred Vellucci attempted to ban the practice, which would have greatly inconvenienced the scientists of Harvard University and MIT. But scientists themselves were also hesitant to proceed with genetic techniques unchecked.

“It was first time in the history of science where scientists started out by saying to themselves, we should be careful before we start engaging in this research, figure out what risks are,” Krimsky said. “It hadn’t happened with chemistry or with nuclear power; here was an attempt to say what the future might be.

Panelist and Harvard geneticist George Church, who was a student at the time of the Cambridge genetics hearings, said he thought that both sides were overreacting: the scientists feared the government would attempt to control their research, while many citizens feared a new monstrous germ would escape from some laboratory. But, Church said, that climate of uncertainty and fear did lay the groundwork for the safety standards that genetics and biology labs practice to this day.

“We’re not designing anything,” Grifo said. “We’re trying to help people have healthy babies.”

Nita Farahany, a Duke University law professor and member of President Barack Obama’s Presidential Commission for the Study of Bioethical Issues, pointed out that every kind of new technology goes through an intense period of scrutiny.

“It doesn’t matter if it’s genetic engineering; it doesn’t matter if it’s a newer form of enhancement that’s better than caffeine,” Farahany said. “Whatever it is, people are worried about it because they don’t understand how it’s going to affect the population, and future generations. And even though most things we do affect future generations, [this concern] just happens to be particularly pronounced [with respect to] genetics for most people.”

New genetic techniques on the horizon are already garnering some sensational headlines. Paula Amato, a reproductive endocrinologist at Oregon Health and Science University, has been perfecting the art of a technique known as spindle transfer. This method is a type of genetically-engineered fertility therapy designed to help women who carry the genes for rare mitochondrial diseases. Unlike the 46 chromosomes in the nucleus of a cell, which are inherited from both parents, mitochondrial DNA is passed down solely through the mother. By taking the nuclear chromosomes from the mother’s egg cell and implanting them in a donor egg with healthy mitochondria, ideally the child should escape inheriting the disease. It also means that the child carries DNA from three “genetic parents,” a notion that has provoked some consternation.

Jamie Grifo, director of NYU’s fertility center, has been in Amato’s shoes before (right down to the screaming “Three Parent Baby!” headlines), and saw less than happy results. In the 1990s, he was essentially trying the same thing as Amato, putting nuclear DNA from one woman into the denucleated cell of another. In Grifo’s case, he was trying to develop more effective fertility treatments for older women, who typically have a harder time with IVF.

But when word of Grifo’s methods got out, he says, the negative media attention prompted an irate phone call from an assistant U.S. surgeon general, and letters from the U.S. Food and Drug Administration to his institutional review board. Grifo stopped working on the project, but gave the technology away to a lab in China. Further complications arose there: after receiving the treatment, a patient became pregnant with triplets (later reduced to twins), but miscarried. Even though the babies were physically normal, another round of negative media attention effectively killed the use of the method in China.

“It’s been dead in the water ever since,” Grifo said.

Grifo, with perhaps some understandably palpable frustration, said he dislikes the entire media framing around this type of genetic work—including the “Designer Genes” title of the Festival panel.

“We’re not designing anything,” he said. “We’re trying to help people have healthy babies. This gets presented in a way that is so un-empathetic to the patient.”

Farahany pointed out that the dark history of eugenics in America makes it difficult for geneticists to escape that shadow. The idea of weeding out undesirable traits, such as “criminality,” epilepsy, and “imbecility” was intensely popular in the early 20th century, and up to 30 U.S. states eventually adopted laws promoting involuntary sterilization. In fact, the U.S. Supreme Court case that allowed for the practice, Buck v. Bell, has never actually been overturned.

The new practice of genetically conscious reproduction, however, is a far cry from the government dictating who can and cannot reproduce: “This is private parents making private choices,” Farahany said. Plus, she doesn’t expect that allowing people to select for certain traits like eye or hair color (still out of our league thus far) will result in homogeneity. “Many parents just want children who look like themselves,” she said.

Krimsky pointed out that even spindle transfer is not the whole solution to mitochondrial disease. “Most mitochondrial disease is the result of mutations in the nucleus and the mitochondria,” he said. “Even if you get rid of the bad mitochondrial genes, you still have to deal with the nucleogenes that may be at fault as well.”

Krimsky also said he thinks there’s too little data from animal studies on techniques like Amato’s to begin the practice in humans.

“We cannot [truly] guarantee the safety of anything,” Grifo pointed out.

As for fears that genetic engineering would allow scientists to completely blank out certain personality traits? Not that possible, says Farihany: “You can’t just eliminate a gene; it’s a complex set of interactions, and just one of many different factors that go into personality.”

Grifo added that of his patients who want to select the gender of their babies, they’re usually looking to balance out the gender ratio in their families. Still, moderator Emily Senay noted, that might not be the case in some countries where girl children aren’t as desired.

Controversies, however, have a way of fading into acceptance. Church noted that IVF, once considered just as controversial as spindle transfer is today, was banned before British researchers succeeded in using it to produce Louise Brown, the first “test tube baby” (actually a Petri dish baby).

“The technology is coming down in price and up in quality, and we’re getting used to it,” Church said.

An audience member asked if the genetic engineering would exacerbate class differences, given that currently only the wealthy can afford these kinds of treatments. Church said that one important aspect of his job was to keep bringing the cost of the technology down. Just as cell phones were once solely playthings of the rich, and now common in Third World countries, and just as the cost of sequencing the genome has plummeted 3-million-fold in just over a decade, the price divide does not have to be fixed forever, he said.

Amato, meanwhile, is still awaiting word from the FDA on her application to move spindle transfer into human trials.

“I have patients lined up out the doorway, waiting,” she said.

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