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A first look into early human embryonic development

In a major breakthrough in human embryology, researchers have breached the 7-day limit to studying human embryos outside the maternal womb. The improved techniques employed by them in nurturing the “blastocyte,” a small hollow ball of cells formed after fertilization of the egg by the sperm in the lab, allowed them to study the molecular and cellular development that occurs during the first 14 days after fertilization. Being able to clinically observe the blastocyte beyond seven days is important because this is the time when the blastocyte normally attaches itself to the mother’s womb in a process termed implantation. Over the next few days, the blastocyte undergoes a differentiation process into three basic cell layers (called gastrulation) from which the bodily structures of the embryo, and, eventually, the individual, are derived. Studying the blastocyte beyond seven days has been extremely challenging until these new techniques were developed by the Rockfeller University, researchers, who published their results in Nature recently.

A human embryo 12 days after fertilization in vitro, with different cell types marked by separate colors. Photo: AP/Rockfeller University

“This portion of human development was a complete black box,” says Ali Brivanlou an author of the paper.

The development of mouse blastocyte “lineage specification” as this process is called, was studied previously by co-author Magdalena Zernicka-Goetz and colleagues from University of Cambridge. The process is now well understood. It was earlier believed that these pathways are evolutionarily conserved, namely, that they would be replicated in the case of humans. But this belief has been shattered as the new observations show that both with respect to the time of onset of differentiation and the pathways taken, humans differ from mice! Thus, the major discovery is in figuring out that cell lineage specification is species specific.

Janet Rossand, writing in Nature, comments that there are limitations to this study as the cultured embryos are largely two-dimensional and are imperfect models of normal ones.

The methods, therefore, need to be refined to yield useful results.

The 14-day rule
There are also external limits to how researchers in this field may proceed. For instance, there is the 14-day rule disallowing research on human embryos beyond fourteen days after fertilization. This is a law in some countries including Canada, the U.K. and Spain and falls under the list of recommended scientific regulations in countries such as India, the U.S., Japan and China.

Though it sounds arbitrary, the fourteenth day is an important day in the development of the embryo because it is when the “primitive streak,” a faint band of cells marking the head-to-tail axis, is formed. The primitive streak is the first indication that the embryo has developed a biological identity, because, before this stage, the embryos can divide in two. This has therefore been chosen as the point to draw the line for human embryo research.

In a comment piece in Nature, Insoo Hyun and co-authors argue for a relaxation of this rule, as such research could be crucial not only in the prevention of early pregnancy loss, but also in understanding early development. In revisiting the 14-day rule, the authors dissuade people from viewing it as an ethical tenet entrenched in biological fact; rather, they urge them to view it as a “public-policy tool designed to carve out a space for scientific research and simultaneously show respect for the diverse views on human embryo research.” They further advocate having discussions at the international and national levels, with researchers taking an active part.

In the context of India, the subject offers a good scope for setting up lines of discussion and informed debate, with researchers taking the initiative to educate and inform the public as well as the policymakers.

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