For the first time, scientists have edited the DNA in human embryos to make a fundamental discovery about the earliest days of human development.
By modifying a key gene in very early-stage embryos, the researchers demonstrated that a gene plays a crucial role in making sure embryos develop normally, the scientists say.
The finding might someday lead to new ways for doctors to help infertile couples have children, and could aid future efforts to use embryonic stem cells to treat incurable diseases, the researchers say.
The work also provides the first direct evidence that manipulating DNA in human embryos can yield insights into how a single cell becomes a complex human. That has been the major justification for allowing scientists to change human DNA in ways that could be passed down to future generations, a step that had long been considered off limits because of fears about safety and opening the door to "designer babies."
"This proof of principle lays out a framework for future investigations that could transform our understanding of human biology," the researchers write in reporting their findings in the journal Nature on Wednesday.
That statement was seconded by other scientists.
"It opens up a new area of research," says Dietrich Egli, a Columbia University biologist who studies stem cells and was not involved in the study. "Understanding early human embryonic development is of great importance, and gene-editing is a powerful tool to answer questions that will ultimately improve human health."
But the research is renewing a long, intense debate about whether it's ethical to make changes in the genes in eggs, sperm or very early embryos that would be passed down to succeeding generations. While using gene editing for basic research about human development may be useful, critics worry it could lead to attempts to create genetically modified babies.
"The concerns are that we would be opening the door to fertility clinics vying to offer gene-editing to make future children taller or stronger or whatever they wanted to market," says Marcy Darnovsky, who heads the Center for Genetics and Society, a genetics watchdog group. "That could put us into a situation where some children were perceived to be biologically superior to other children.
The new research was led by Kathy Niakan, a developmental biologist at the Francis Crick Institute in London. Niakan's team used a powerful gene-editing technique known as CRISPR to disable a gene that produces a protein known as OCT4. The procedure was performed in 41 embryos donated by women undergoing treatment for infertility.
In the study, more than 80 percent of the embryos with the disabled gene failed to develop into a blastocyst, a ball of 200 cells that is the stage when embryos are usually implanted into the womb during in vitro fertilization (IVF). Many cases of infertility occur because embryos fail to reach this stage.
"That tells us that OCT4 is really important for the development of a human blastocyst," Niakan told reporters during a briefing.
"By understanding the key genes that are involved in the development of the blastocyst, this can really inform our understanding of this important, critical window of human development," Niakan says.
The experiments also show that the gene is involved in forming the cells that eventually become the placenta, the organ that nourishes pregnancies, the researchers reported.
In addition, OCT4 helps embryonic stem cells specialize into various tissues, which could help scientists figure out how to turn stem cells into replacement cells, tissues and perhaps entire organs to treat diseases, Niakan says.
In an unexpected finding, the researchers discovered the gene functions differently in human embryos than in mouse embryos. That shows the need for experiments on human embryos and not just animal embryos, the scientists say.
"This is opening up the possibility of using a really powerful, precise genetics tool to understand gene function," Niakan says. "We would have never gained this insight had we not really studied the function of this gene in human embryos."
Jennifer Doudna, a biologist at the University of California, Berkeley, who led efforts to develop CRISPR, agrees.
"One of the most fundamental aspects of becoming human is, how do egg and sperm cells combine to form embryos that develop into a person?" Doudna says. "So understanding the genetic basis for that is, in my view, one of the fundamental aspects of developmental biology — or all of biology in a way."
In 2015, Chinese scientists sparked an uproar when they reported attempts to use CRISPR to edit human embryos. And in 2016, the British government approved editing of human embryos for research purposes.
In February, the U.S. National Academy of Sciences and the National Academy of Medicine concluded that editing DNA in humans could be permissible in certain circumstances. That has critics like Darnovsky worried.
"In a world already plagued by distressing levels of inequality, that seems like a very bad idea," Darnovsky says. "We don't want to add ideas that some people are biologically better and some people are biologically inferior to others. That is an idea that has led to horrific abuses throughout history."
But Niakan defends the work, saying she is only interested in making fundamental discoveries about basic human biology.
"As with any technology, as with any tool, it can be used for a variety of different purposes," Niakan says. "We're choosing to use it to uncover critical roles of genes in development that can increase our knowledge about how human embryos develop."
ARI SHAPIRO, HOST:
For the first time, scientists have altered the DNA in human embryos to make a fundamental discovery about early human development. Scientists say this proves that modifying genes and human embryos can reveal powerful insights into the earliest days of human life. NPR health correspondent Rob Stein explains.
ROB STEIN, BYLINE: Tinkering with genes in human embryos has long been considered off-limits because of fears it could mess up the human gene pool or lead to genetically modified human beings. But scientists like Kathy Niakan of the Francis Crick Institute in London have argued that they could make big discoveries about basic human biology.
KATHY NIAKAN: The purpose of this research is to uncover insights into the function and the role of key genes in this important, critical window of human development.
STEIN: When a single cell somehow begins the journey towards becoming a fully formed human being. So Niakan's team used a powerful new gene editing technique to inactivate a single gene in dozens of very early embryos.
NIAKAN: This research is really the first time that genome editing has been used to study the function of a gene or the role of a gene in human embryos.
STEIN: And the results of the experiment were dramatic. Most of the embryos that had their gene inactivated failed to develop normally. The gene's called OCT4.
NIAKAN: So that tells us that OCT4 is really important.
STEIN: Important because a lot of women can't get pregnant or have miscarriages because they can't make healthy embryos. So this provides clues to how doctors could someday help them.
NIAKAN: This is opening up the possibility of using genetics - a genetics tool - a really powerful, precise genetics tool to understand gene function and to unlock a lot of important aspects of our human biology.
STEIN: The researchers also discovered the gene plays an important role in helping form the placenta, the organ that nourishes pregnancies. And that's not all. The OCT4 gene looks like it's a key player in embryonic stem cells.
NIAKAN: Embryonic stem cells have tremendous potential because they can help us to understand and even potentially treat diseases in the future as varied as heart disease, Alzheimer's and diabetes.
STEIN: Because of all this, other scientists say this is a big deal.
DEITRICH EGLI: It's a landmark study.
STEIN: Dietrich Egli is a biologist at Columbia University.
EGLI: The human embryo as an experimental system is a new groundbreaking concept that so far very few have dared to walk into. And this is something that Kathy Niakan clearly has done here in a pioneering way.
STEIN: But the research is also setting off alarm bells for some. While basic research like this could be important, Marcy Darnovsky of the Center for Genetics and Society worries about other scientists trying to take this too far.
MARCY DARNOVSKY: The concerns are that we would be opening the door to fertility clinics vying to offer gene editing to make future children taller or stronger or whatever they wanted to market. That could put us into a situation where some children were perceived to be biologically superior to other children.
STEIN: For her part, Niakan just hopes to learn more secrets about the basic biology of human development. Rob Stein, NPR News. Transcript provided by NPR, Copyright NPR.