AS RESEARCHERS INCH CLOSER TO CREATING A ‘SYNTHETIC’ EMBRYO, THE SCIENCE IS RAISING STICKY ETHICAL QUESTIONS — INCLUDING WHETHER THESE THREE-DIMENSIONAL BALLS OF CELLS CAN FEEL PLEASURE OR PAIN.

Complicated ethics surround the science

Could miniaturized human brains growing in a petri dish, or lab-grown “synthetic” embryos that look and behave remarkably — some might say creepily — like the real thing, have the capacity to experience pleasure, or pain? Rapid advances are allowing scientists to goad balls of stem cells into organizing themselves into organoids — from structures mimicking mini eyes, guts, livers and brains to, so far in mice at least (and researchers want to do the same with human cells), an early embryo. The goal is to create models of early organ and human development to study diseases, screen new drugs and ultimately produce new tissues and organs for transplant. But as organoids grow more sophisticated, the science is raising sticky ethical questions, including whether these three-dimensional balls of cells could develop morally worrying features. How close to the real things should scientists be making them, and could the burgeoning field lead to the first complete human embryo created from stem cells, and not eggs and sperm? With brain organoids, “the closer the proxy gets to a functioning human brain, the more ethically problematic it becomes,” 17 leading scientists, ethicists and philosophers write in last week’s issue of the journal Nature. So far brain organoids are minuscule, the largest to date only about four millimetres in diameter and containing just two to three million cells, the group writes. An adult brain, by comparison, measures roughly 1,350 cubic centimetres and is made up of 86 billion neurons alone. Given those constraints, “the possibility of organoids becoming conscious to some degree, or of acquiring other higher-order properties, such as the ability to feel distress, seems highly remote,” the Nature authors wrote. “But organoids are becoming increasingly complex.” In fact, one of them detected neural activity in an organoid after shining a light on the region where cells of the retina had formed with cells of the brain — illustrating that “an external stimulus can result in an organoid response.” Last week, scientists at California’s Salk Institute announced they had transplanted human brain organoids into the brains of lab rodents — for the first time giving organoids a crucial blood supply. Without vasculature, organoids can only divide and develop so far. The grafted human brain tissue settled into the mice brains, sprouting new neurons that fired in synchronized patterns. But researchers are also working on more complex and organized assemblies known as SHEEFS — synthetic human entities with embryo-like features. Instead of one organ, SHEEFs could combine several, leading to novel and unnatural combinations, like a SHEEF with a human-like form and a beating heart, but no brain. SHEEFs are still very early in development. But whether they deserve the same protection around their use as authentic embryos is already being debated.

In a recent paper, a panel of ethical, scientific, policy and legal experts seeking reforms to Canada’s Assisted Human Reproduction Act (AHRA) say current prohibitions banning the creation of embryos for research purposes shouldn’t extend to synthetic forms not requiring human eggs “and likely incapable of developing into a human being.” Among other recommendations, the panel says SHEEFs should be “explicitly excluded” from prohibitions under Canada’s Assisted Human Reproduction Act, and that an oversight committee determine any limits on their creation or use. Their paper, published in the journal Healthcare Policy, is one of a series produced by a workshop funded principally by the Stem Cell Network.

“Health Canada should issue public guidance regarding how the AHRA applies to SHEEFs to avoid an unnecessary chill on promising avenues of research while ensuring scientists are not risking criminal liability for work in currently ambiguous areas,” the authors report. “The law clearly when it was made in 2004 did not contemplate anything like this,” said Ubaka Ogbogu, a health law professor at the University of Alberta and the paper’s first author. SHEEFs also wouldn’t meet the definition of “embryo,” as defined by Canada’s assisted human reproduction act, “if they are not independently capable of forming a human being,” Health Canada told the Post. “As a result, and based on the current state of science, the AHRA would not apply to research involving these entities.”

In paper published last year in eLife, Aach and colleagues argue that instead of tying research on SHEEFs to the 14-day rule — a prohibition limiting research to the period before the appearance of the “primitive streak,” a band of cells that mark the beginnings of a central nervous system — scientists should instead come up with a catalogue of features signifying “moral status.” The problem is deciding exactly which features might qualify and how, exactly, to test for them.