(CN) – While incredible progress has been made in the field of genetic engineering for embryos over the past 25 years – discovering how to screen them for inherited diseases caused by genetic mutations – researchers revealed Thursday it will be a long time before would-be parents will be able to order designer babies.
Recent technological advances have made it possible for scientists to read an entire genome at an affordable price, allowing parents to learn about any gene mutation. This raises the inevitable question: Is it even ethical to engineer embryos to grow with desired traits?
“When you think about it, if you have the entire genome, you can calculate predictions for traits, not just diseases. This includes sex, eye color, any trait really,” said co-corresponding author Shai Carmi of the Hebrew University of Jerusalem.
Designing a baby, however, would involve screening for multiple genes that comprise a single trait, rather than the mutation of a single gene that causes genetic diseases. In a study published Thursday in the journal Cell, Carmi and his team looked at two traits caused by multiple genes – IQ and height – and learned the ability to select for traits like these is more complex and far off than most people realize.
“The ability to do genomic sequencing of embryos is much easier than it was even five years ago, and we know many more gene variants linked to certain traits,” says Carmi. “But selecting embryos for particular traits is very controversial except when it relates to a serious disease like cystic fibrosis. It raises many issues related to eugenics and unequal opportunities.”
Carmi’s team looked specifically and IQ and height for their thought experiment because both are considered an advantage in life. IQ has been the center of many debates over genetic engineering because it raises the issue of eugenics – improving the human race through controlled breeding – while height is not only objectively measurable, but much is known about the gene structure influencing this trait.
The team found that although a small boost is possible, current knowledge of the genetics for these traits is not yet enough to generate substantial increases of the desired traits in an IVF embryo selection scenario.
To conduct the study, Carmi’s team ran computer simulations using genomic sequences from real people. By pairing some couples here and some artificially paired people there, they could model genomic profiles of hypothetical embryos that would result from pairs of those people.
They assumed that in each simulation, the couples would have 10 embryos to choose from. They then predicted the IQ or adult height for each of the offspring based on the gene variants present in the genomes of the simulated embryos and assumed the embryo with the top score would be chosen.
The researchers found that if successful, the gains would be relatively small: IQ reaching 3 points above average and height just over an inch above average.
“There is much about these traits that is unpredictable,” Carmi says. “If someone selected an embryo that was predicted to have an IQ that was two points higher than the average, this is no guarantee it would actually result in that increase. There is a lot of variability that is not accounted for in the known gene variants.”
Carmi adds that there are several limitations that would make it difficult to accurately select an embryo for desired traits.
One issue is that the simulations accounted for 10 embryos per couple, but in reality most couples have far fewer viable embryos through in vitro fertilization. For example, with five embryos the gain would be reduced to 2.5 IQ points and less than an inch in height.
Interestingly, when they based the simulation on 50 or 100 embryos, they found that the benefit per embryo decreased as the number of embryos increased, indicating diminishing returns even with large numbers of hypothetical embryos to choose from.
“If parents have the money and patience, they can do multiple rounds of IVF and they can generate more embryos, but keep in mind it is very expensive and very difficult for the mother,” Carmi says. “Five to 10 embryos will improve the gains, and the best embryo will have better predicted IQ, but if we double again the gains will be smaller and lead people to believe that gain is limited. Multiple IVF cycles will be very slow, and progress is going to come from more genetic study to achieve more accurate predictions.”
Additionally, what is known about the gene variants related to traits like height and IQ – and health-related traits like blood pressure and cholesterol – mainly applies to people of European descent and is not very applicable to people from other places of the world. And future scenarios involving the improvement of other traits will make embryo selection far more complicated – an embryo that scored highest for IQ could rank lowest in height, or vice versa.
The researchers used real-world data to confirm that predictions about traits made using what’s currently known about gene variants are not always accurate. They reported on an analysis of 28 families with up to 20 children who have grown to adulthood and found the offspring they would have selected for height based on gene variants did not always grow up to be the tallest adult.
“This paper provides for the first time ever empirical data about expected success for selecting embryos for traits currently and in the future,” Carmi says. “Gain is limited now, but we may need to revisit when we have a better understanding.”