A New Form of Stem-Cell Engineering Raises Ethical Questions

As biological research races forward, ethical quandaries are piling up. In a report published Tuesday in the journal eLife, researchers at Harvard Medical School said it was time to ponder a startling new prospect: synthetic embryos.

In recent years, scientists have moved beyond in vitro fertilization. They are starting to assemble stem cells that can organize themselves into embryolike structures.

Soon, experts predict, they will learn how to engineer these cells into new kinds of tissues and organs. Eventually, they may take on features of a mature human being.

In the report, John D. Aach and his colleagues explored the ethics of creating what they call “synthetic human entities with embryolike features” — Sheefs, for short. For now, the most advanced Sheefs are very simple assemblies of cells.

But in the future, they may develop into far more complex forms, the researchers said, such as a beating human heart connected to a rudimentary brain, all created from stem cells. Such a Sheef might reveal important clues about how nerves control heartbeats. Scientists might be able to use other Sheefs to test out drugs for diseases such as cancer or diabetes.

Whatever else, it is sure to unnerve most of us.

Established guidelines for human embryo research are useless for deciding which Sheefs will be acceptable and which not, Dr. Aach argued. Before scientists get too deeply into making Sheefs, some rules must be put in place.

Dr. Aach and his colleagues urged that certain features be kept off limits: Scientists, for example, should never create a Sheef that feels pain.

“We’re going to have to get a lot of input from a lot of quarters,” Dr. Aach said in an interview. “The problems are just too big.”

Scientists began grappling with the ethics of lab-raised embryos more than four decades ago.

In 1970, the physiologist Robert G. Edwards and his colleagues at the University of Cambridge announced they had been able to fertilize human eggs with sperm and keep them alive for two days in a petri dish. During that time, the embryos each divided into 16 cells.

Dr. Edwards won the Nobel Prize in 2010 for his research, which opened the door to in vitro fertilization. The discovery also made it possible to study the earliest moments of human development.

Governments around the world began deliberating over how long research laboratories and fertility clinics should be allowed to let these embryos grow. In 1979, a federal advisory board recommended that the cutoff should be 14 days.

The so-called 14-day rule came to be embraced not just by scientists in the United States but in other countries as well. One attraction of the guideline was that it was easy to follow.

At 14 days, a human embryo develops its first clear feature: a ridge of cells, called the primitive streak, which marks the body’s central axis. It is where the spine will later develop.

There are even more important changes happening at the same time, although they are harder to see. The embryonic cells develop into three types, called germ layers. Each of those germ layers goes on to produce all the body’s tissues and organs.

Adherence to the 14-day rule led to tremendous advances. In 1998, scientists isolated stem cells from early embryos and eventually figured out how to develop them into just about any tissue in the body, from heart muscle to nerves.

In 2007, scientists figured out how to reprogram adult cells into embryolike stem cells, a discovery that one day may lead to personalized treatments for degenerative diseases.

For decades, scientists did not break the 14-day rule — but only because they did not know how. Scientists could keep human embryos alive for just over a week, without freezing them.

But last year, two teams of scientists determined how to grow human embryos for 13 days. Those advances hinted that it might be possible to allow scientists to tack on a few days more, by changing the 14-day rule to, say, a 20-day rule.

But Dr. Aach and his colleagues argued that rules based on the time since fertilization were useless for embryos that were not formed by fertilization.

A hint of the future arrived in a study published this month by researchers at the University of Cambridge. They built microscopic scaffolding into which they injected a mixture of two types of embryonic stem cells from mice.

This triggered communication by the cells, and they organized themselves into the arrangement found in an early mouse embryo.

While these artificial embryos developed from embryonic stem cells, it may soon become possible to build them from reprogrammed adult human cells. No fertilization or ordinary embryonic development would be required to build a mouse Sheef.

“We need to address this now, while there’s still time,” Dr. Aach said.

Sophia Roosth, a Harvard historian of science who was not involved in the new paper, said she did not think ethicists would have to start from scratch to find rules for these strange new Sheefs. She was optimistic that experts could draw on the many regulations in place for other kinds of research — including cloning, human tissue studies, and even studies on animals.

“I don’t think the baby has to be thrown out with the bathwater,” she said.

Henry T. Greely of Stanford University was less optimistic. While it is important to have a discussion about Sheefs, he said, it may be hard to reach an agreement on limits as enforceable as the 14-day rule.

“Whether you could come to some consensus is really doubtful,” he said.

Even if ethicists do manage to agree on certain limits, Paul S. Knoepfler, a stem cell biologist at the University of California, Davis, wondered how easy it would be for scientists to know if they had crossed them.

Spotting a primitive streak is easy. Determining whether a collection of neurons connected to other tissues in a dish can feel pain is not.

“It gets pretty tricky out there,” Dr. Knoepfler said. “They’ve opened the door to a lot of tough questions.”