It is often a source of wonder when a technology once deemed as ‘wishful’ thinking, the stuff of legends or part of science fiction lore is actually realised. Think self-lacing shoes that Nike recently unveiled or how we now have the Roomba, a robotic vacuum cleaner! But, the possibilities and realisations aren’t always half as harmless or cute.
A rule, now popularly known as the “fourteen-day rule” was first proposed in 1979 and has since then been incorporated into the law books and guidelines of numerous countries. Unlike building computing devices, holograms or robots, growing human embryos in-vitro has deep moral and ethical implications. Keeping that in mind, the fourteen-day rule forbids experiments on human embryos to carry on beyond fourteen days, widely recognised as the time in which an embryo develops a semblance of individuality with the start of a head-tail axis. Back then, people who formulated this law probably also believed that technology might never advance to a point to which we can produce a fully functional human baby without natural womb support – the rule will never have to be amended or challenged even. Despite rapid advances in medicine, biology and engineering, raising a foetus in a lab environment, ectogenesis, has remained a pipe dream. In this feature, we give you a lowdown on why.
Let’s start with how incredibly sophisticated and complicated the developmental process of a human foetus is. At the very onset of the above developmental process is a stage called implantation. Post-implantation is when there is self-organisation and the embryo becomes a collection of cells. This stage is critical because it is during this time when many of the developmental disorders set in. The week around implantation – when the foetus is essentially attached to the mother’s uterus, is one of the most important and yet poorly understood phases of pregnancy. Scientists have been unable to put a tab on intricate cellular interactions, primarily because it’s such a difficult system to get results out of. Growing embryo’s in a petri dish and gaining the ability to culture the embryo artificially beyond implantation is something that was possible only for simpler organisms like mice until very recently. Last year, however, two independent research groups reported successful culture of human embryo’s for thirteen days. By providing the nascent embryo with a specific cocktail of growth-supporting nutrients, the researchers found that the embryos were able to self-organise. Their results provide irrefutable evidence that a human embryo can develop beyond the implantation stage without maternal input of any sorts, in-vitro – in completely artificial conditions. Besides being a foundation setting study it has paved the way for a large number of offshoot research to study birth defects, disease and fundamentals of developmental biology. Another important point to note here is that the embryo culture continued for only thirteen days because the researchers had to pull the plug in adherence to the fourteen-day rule. However, ethical and legal issues aside, we are now in a position to culture embryos artificially for a minimum of two weeks. The next step- ensuring survival of the embryo once it begins to form structures.
Carrying out the gestation process outside a mother’s womb is difficult. Once the embryo implants to the uterus, there occurs the formation of the all important placenta and amniotic sac, filled with amniotic fluid. The placenta is basically a direct connection between the mother and the baby, allowing for exchange of nutrients, hormones and expulsion of waste. The amniotic fluid is like a shock absorbing fluid which also doubles as chemical exchange medium. Simple enough? Not really. There are plenty of uncertainties involved. What is the sequence of these developments? What exactly is transferred, when and how much? The list goes on. Besides, a single mistake in the hormone levels or genetic transfer could have consequences in the ultimate development that are impossible to predict. The current record for the survival of a premature baby is just around 21 weeks into the gestation. It is with the hope of increasing this survival rate that scientists began to originally think of creating artificial wombs. And, while there are many groups across the world now working in this area of cutting-edge biology and medicine, two groups have done seminal research.
First, an artificial womb has to provide a mechanically safe housing for the growing foetus and protect it against infection. Then scientists have to replicate the functions of the placenta, namely to remove toxins and ensure transport of oxygen and hormones. An artificial placenta will also have the capability to regulate blood sugar levels, and do other tasks that the babies newly developed organs might not be initially capable of doing. It’s also critical to ensure that the foetus is able to breathe without the support of the mother’s lung. This is a major problem in premature babies – lungs too weak to completely support themselves. Any artificial placenta will also have lung enhancement additions or perhaps make use of state of art liquid ventilation technology. Lastly, the functions of the amniotic fluid have to be replicated – which in itself is no mean task. Scientists also remark that the womb will have to mimic the sounds and rhythms of the womb.
Dr. Yoshinori Kuwabara initially lead the charge for development of artificial placenta for a long time now. His team in Japan have been able to sustain growth of goat foetuses in a ‘ectogenic chamber’. Then there is Dr. Helen Liu at Cornell university who has devised a sophisticated system for culturing mouse embryos. To sidestep the limitations imposed by the fourteen-day rule her group switched from human embryos to experimenting with mouse embryo’s. Bit by bit her group has been making additions integral in improving the viability of her artificial wombs and while there has been progress it’s a difficult road ahead.
Part of the difficulty lies also in surrounding the embryo with the right fluid, containing the correct percentages of water, hormones, proteins and other essential chemicals. Then these percentages have to be modulated according to how far the embryo is in its development. Also, while success with mouse embryo’s is a great step, scaling up to human embryo’s will need a paradigm shift in technology.
It goes without saying that this line of research can be vastly beneficial to mankind. If successful, maybe artificial wombs might even become safer than natural births in some cases. The technology will also allow couples that cannot have children by natural means to have babies – free of surrogacy. But as radical this technology is by its nature, it also raises some fundamental questions. Is the mere fusion of a sperm and egg enough to designate the resultant ‘being’ as human? Or, should go as far as to call it an instance of synthetic life? Should life, at its very elemental level be broken down to just genetic transfer?
Politicians and bioethicists have grappled with these questions for more than a decade to result into the fourteen day rule. Now that scientists have begun knocking at the door, is it the right time to revisit this rule and finally allow full-scale human embryo experiments? Maybe. It all comes down to the question that we ourselves have asked numerous times in features about CRISPR technology and designer babies – Can we trust science and scientists with such technology?
This article was first published in May 2017 issue of Digit magazine. To read Digit’s articles first, subscribe here or download the Digit app for Android and iOS. You could also buy Digit’s previous issues here.