As biological research races forward, ethical quandaries are piling up. In a report published on March 21, in the journal eLife, researchers at Harvard Medical School, USA said it was time to ponder a startling new prospect: synthetic embryos. In recent years, scientists have moved beyond in vitro fertilisation. They are starting to assemble stem cells that can organise themselves into embryo-like structures. Soon, experts predict, they will learn how to engineer these cells into new kinds of tissues and organs.
In the report, John D Aach and his colleagues explored the ethics of creating what they call “synthetic human entities with embryo-like 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.
The 14-day rule
Established guidelines for human embryo research are useless for deciding which SHEEFS will be acceptable and which not, John argued. Before scientists get too deeply into making SHEEFS, some rules must be put in place. John 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,” John 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, physiologist Robert G Edwards and his colleagues at the University of Cambridge announced they had been able to fertilise 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. Robert won the Nobel Prize in 2010 for his research, which opened the door to in vitro fertilisation. 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 US 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.
In 2007, scientists figured out how to reprogramme adult cells into embryo-like stem cells, a discovery that one day may lead to personalised 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 John and his colleagues argued that rules based on the time since fertilisation were useless for embryos that were not formed by fertilisation. 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 organised themselves into the arrangement found in an early mouse embryo.
Drawing the line
While these artificial embryos developed from embryonic stem cells, it may soon become possible to build them from reprogrammed adult human cells. No fertilisation or ordinary embryonic development would be required to build a mouse SHEEF. “We need to address this now, while there’s still time,” John 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.
Even if ethicists do manage to agree on certain limits, Paul S Knoepfler, a stem cell biologist at the University of California, Davis, USA, 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,” Paul said. “They’ve opened the door to a lot of tough questions.”