As per a research study, titled ‘Exutero Mouse Embryogenesis from Pre-gastrulation to Late Organogenesis’, published in the journal Nature in March 2021, Israeli scientists have successfully grown 250-cell embryos into mouse foetuses with fully formed organs using artificial wombs, under the stem cell biologist Prof. Jacob Hanna, at the Weizmann Institute of Science, Israel. The experiment took seven years to be successful.
According to Jacob Hanna, this is considered as a major development in life science as the idea of growing early embryos outside a uterus has been around since the 1930s, but experiments based on these proposals had limited success for a very short period, i.e., few hours or one-to-two days only and the embryos tended to be abnormal.
The research was conducted to observe how a tiny ball of identical cells becomes a mammalian embryo. The researchers wanted to know how mammals develop, and how gene mutations, nutrients, and environmental conditions may affect the fetus. It was necessary to understand how the early embryo first attaches to an awaiting uterine wall. Then how it develops nervous system, heart, stomach, and limbs. This has been beyond comprehension for nearly 100 years.
Whatever scientists know even today about mammalian embryonic development comes either from observing the process in non-mammals like frogs or fish that lay transparent eggs, or by obtaining static images from dissected mouse embryos and adding them together.
Experiment
Jacob Hanna and his team took great pains through trial error, fine-tuning and double-checking and came up with a two-step process in which they were able to grow normally developing mouse embryos outside the uterus. For this, they took mouse embryos from the pregnant mice at day five of development having just 250 cells. Then they placed them on a lab dish and attached the ball of cells with it which acted like uterine walls. They put them in the incubator from day five until day 11, by which point the embryos were about halfway though their development as the full gestation period is 20 about days. At this stage, a human embryo is called a fetus. These scientists have so far grown over 1,000 embryos in this way.
It was observed that by day 11 the foetuses were able to make their own blood having a normal beating heart (170 beats per minutes) and a fully developed brain. They looked like a mouse foetus with all the characteristics of a mouse. The early-foetus changed from being a ball of cells to an advanced foetus. The embryos had grown too large to survive without blood supply. They had a placenta and a yolk sack, but the nutrient solution that fed them through diffusion was no longer sufficient. They were healthy but died at 11 days. This is currently the longest survival of mammal foetus in an artificial womb. But they could not be transplanted back into a mice uterus.
Methodology
The method involved placing the embryos in a special liquid to nourish embryo cells in a laboratory dish and getting them to float on the liquid. With this step, the researchers succeeded in duplicating the first stage of embryonic development, in which the embryo grows tenfold. The key to success goes to a special incubator system in which each embryo was in a bottle with liquid, and the bottle was spinning to ensure it did not attach to the side. The incubator created all the right conditions for the embryo development. The liquid in the bottle provided all the nutrients, hormones, and sugars needed for the development of embryos. Moreover, the incubator, a custom-made electronic device, controlled gas concentration, pressure, and temperature to provide the required atmosphere.
The method also involved adding blood serum from the human umbilical cords, agitating the embryos in glass jars, and fuelling them in a pressurised oxygen mixture. The process is similar to putting a COVID-19 patient on a ventilator which, forces oxygen into the cells. Once the oxygen is sent in, the embryo has a blood system; so all the major organs work.
Importance of the Study
The artificial womb will help scientists understand the development programme encoded in the genes. This understanding will provide detailed insights into birth and developmental defects as well as those involved in embryo implantation. It will also provide information on how mammals develop and how gene mutations, nutrients, and environmental conditions may affect the foetus. The artificial womb may allow researchers to learn more about why pregnancies end in miscarriages or why fertilised eggs fail to implant. It also opens a new window onto how gene mutations or deletions affect foetal development. This will help the developmental biologists in understanding the mechanism of how a single cell, a fertilised egg, can make all the specific cell types in the human body and grow into 40 trillion cells.
Ethical Concerns
The experiment could lead to artificial embryonic development of human beings which is a matter of ethical concern and is prohibited by international laws. There is a 14-day rule, past which cultured human embryos are not to continue developing outside the body. Twelve countries support this rule, including the United Kingdom; five countries take this law as a guideline, including the USA. This rule had been created in 1978, shortly after the birth of Louise Brown, the first in-vitro fertilisation (IVF) baby. Jacob believes that the lab-grown embryos could be a research replacement for tissue derived from abortions, and possibly a source of tissue for medical treatment as well. Besides, the research also collides with the debate regarding women’s abortion rights.
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