January 03, 2003
The Coming Demystification Of Embryonic Stem Cells

Another piece of the puzzle of what defines embryonic stem cells falls into place.

Scientists have identified a gene that is required during early mammalian embryogenesis to maintain cellular pluripotency the ability of an embryonic cell to develop into virtually any cell type of the adult animal. This discovery by Dr. Robin Lovell-Badge and colleagues at the MRC National Institute for Medical Research (London, UK) that the Sox2 gene is necessary to sustain the developmental plasticity of embryonic cells sheds new light on the molecular cues that direct early embryogenesis, as well as the genetic requirements for embryonic stem cell maintenance. The report is published in the January 1 issue of Genes & Development.

"Stem cells must have specific genes that give them their characteristic properties. Our work describes one such gene, Sox2, that appears essential for multipotent stem cell types in the early embryo," explains Dr. Lovell-Badge.

Early in mammalian development, a pre-implantation stage embryo called a blastocyst forms. The cells of the blastocyst are at a developmental fork in the road: The cells on the surface of the blastocyst become trophoblast cells, while the cells on the inside of the blastocyst become the inner cell mass (ICM). The ICM is further specified into epiblast and hypoblast cells, which, together with trophoblast cells, give rise to the entire embryo and its associated tissues: epiblast cells differentiate into all the cell types of the embryo, hypoblast cells differentiate into the yolk sac, and trophoblast cells differentiate into the chorion and much of the placenta, including a range of specialized cell types.

Dr. Lovell-Badge and colleagues have identified Sox2 as one of the only two known transcription factors (master gene regulators) to be involved in the specification of these three embryonic cell lineages.

I'm reporting this because it is an example that illustrates the on-going demystification of embryonic stem cells (ESCs hereafter) and cell differentiation (differentiation is the process by which cells change to become cells dedicated to specific end purposes such as organ cells). There are many more pieces of the puzzle yet to come. Most of what makes ESCs have their unique quality of pluripotency (the ability to become any other cell type) is still unknown. These unknowns help fuel the ethics debate about ESC use. The debate over the use of embryonic stem cells is, for the most part, a debate about whether there is something ethically unique about embryonic stem cells.

As science progresses a large number of advances such as the one excerpted above will show at a molecular level what exactly makes embryonic stem cells different from other cell types including other stem cell types. All or almost all of the differences will turn out to be different regulatory states for genes (slightly complicated by the fact that some of the regulatory states will be caused by concentrations of some regulatory molecules floating around). There will be a unique combination (or a unique set of combinations) of genes that must be activated and inactivated to make an embryonic stem cell.

When all those details of genetic regulation of stem cell state get worked out and published in scientific journals the effect this will have on some (though not all) observers will be to rob embryonic stem cells of a spiritual dimension. Embryonic stem cells (ESCs) will be defined by a list of genes that are on or off. The genes will have obscure names such as Sox2 and perhaps FoxM1B. It will become possible to send chemicals or perhaps gene therapy plasmids into a differentiated cell and order it to become an ESC. Therefore it will no longer be necessary to use fertilization or cloning to create an ESC. Note that this ability to instruct any cell type to become any other cell type will effectively make other cell types pluripotent (albeit with the requirement of advanced biotech tools to manage the transition into other cell types). At the same time, it will become possible to directly and quickly turn an ESC into any other cell type.

Even as ESCs become demystified the necessity of their use will decline as well. The genetic regulatory state that uniquely defines each and every cell type will become known. With that knowledge and with knowledge about how cells change genetic regulatory states will come knowledge of how to manipulate the regulatory mechanisms of the genome to instruct a cell to change its cell type. Techniques for turning any cell type into any other cell type will become available. Therefore there will be far less need for ESCs as a starting point for the creation of cell therapies and replacement organs.

When it becomes possible to use non-ESC cells to accomplish anything that can be done with ESCs many conservative commentators may breathe a sigh of relief and argue that the medical use of ESC can now be banned without any harm. They will think that there will be no need to challenge conception as the starting point of a rights-possessing legally protected being. However, this sort of view misses the real ethical challenge that biotechnology poses for humanity: a bright line definition of human life as starting at the moment of conception using traditional mating to combine sperm and egg is not a defensible position from which to define a human life. One can't simply ban any technology that makes that bright line inadequate. Such technologies are, by their very possibility, an intellectual challenge to traditional definitions of humanity. But their ethical challenge is not just an abstract one. Technologies will be used even if their use is criminalized (as is demonstrated by the massive illegal industries that run illegal factories for making illicit narcotics).

If some human teenagers step forward 25 years from now out of a secret cult in the Amazon and claim their bodies were grown separately from their head using specially engineered cells that never were embryonic stem cells and which were never even cloned using an egg we are still going to be faced with the question of whether to treat those people as fully human and accorded of all the rights of a human. It is inevitable that when faced with these beings we will resort to asking questions about what they are like as fully developed beings regardless of how they came to be created.

As biotechnology advances many new methods for creating humans will be developed that are different than the ways new humans have been made naturally. Using these technologies it will become possible to create humans who feel and think in ways that are well within the range of how existing humans think now. These technologies will make it possible to create humans that will not be able to be visibly distinguished from humans made from normal sexual reproduction. But it will also become possible to create sentient beings that differ from humans in an assortment of ways with such things as chimeric bodies, enhancements of muscles, coordination, eyesight, and other abilities and even to create disembodied fully sentient minds that live in a vat. Even if the creation of such beings are outlawed by every nation on the planet (which I think unlikely) and even if the people who do such things are caught and punished after they have created such beings we will still have to judge whether the sentient beings that they create have rights as humans.

The practical and ethical challenge that biotechnology poses is the question of what are the attributes of a rights-possessing being. Sexual reproduction between the egg and sperm of two existing humans is an inadequate definition of how a rights-possessing human being comes into existence. So many kinds of sentient beings will be able to be created via other pathways that we will need to come up with workable practical criteria for what sorts of beings will be allowed to live, which of those will be allowed to roam free in our societies, which will be allowed to enter into contracts, and which will be accorded full rights as members of a society. It is quite possible that there will come to be creatures that are sentient yet bioengineered to be such a threat to society that they will be shot on sight. At the same time it may become possible to create sentient beings that, while not dangerous, may be missing some essential quality that make them able to, say, serve on a jury or to fulfill some other obligation of society. Therefore there may be categories of beings whose rights will be restricted in a variety of ways. Even if one holds that such beings are an abomination whose creation should be outlawed we will still need to decide what should be done about them should a group or individual manage to create them.

Pandora's Box is opening. There is no appeal to supernatural authority or to tradition that will let us close it back up again. We can not deal with the ethical challenges that biotechnology poses simply by outlawing any manipulation of cells that challenges long-standing definitions of humanity that are based on how reproduction happens naturally. We have to face the question of what are the essential qualities of a rights possessing being and even whether there are types of beings that possess lesser sets of rights.

Share |      Randall Parker, 2003 January 03 12:50 PM  Biotech Society


Comments
Vinay said at January 26, 2004 11:06 PM:

Hi

Its an interesting site

If any body knows abt the function and exact role of the gene Hex in Embyonic stem cell please let me know. Hex is a homeodomain transcription factor and believed to regulate the maturation of morphogenesis of organiser in stem cells

Michael Little said at July 21, 2004 9:55 PM:

I'm a supporter of embryonic stem cell research, but I would be less than candid if I were to say that Randall Parker's article did not send chills down my spine. While I can relate to the concept that it may be possible to create sentient beings that are so markedly different than the "old fashioned" strain (that's us), that restrictions may be placed upon their activities, a disturbing thought refuses to leave my mind: Humans created them.

monica said at November 12, 2004 11:12 AM:

I am interested in the difference between embryonic and adult stem cell.

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