The Ethics of Embryonic Stem Cell Research

Mar 13th, 2009 | By | Category: Embryonic Stem Cell Research

What happens when a part of our body gets injured–or just wears out?

The ideal response would be to replace the tissue and cells lost with new, full-functional replacements–regeneration. For the parts of our body that are constantly turning over–skin, blood, and to a lesser extent bone for examples–this is exactly what happens. Since the cells in these tissues are always being replaced anyways, injury is little more than a very bad day.

These tissues have resident adult stem cells. Stem cells, by definition, can divide and either make more copies of themselves or give rise to new functional cells. They do not do much by themselves. It makes inherent sense that a stem cell living in a given tissue can only make cells for that tissue; you don’t want bone to be replaced skin. Tissues that are undergoing constant wear and tear have stem cells.

Run down the leading causes of death in the United States and an interesting pattern emerges. Heart disease. Stroke. Diabetes. These are caused injuries to tissues that do not turn over as a regular matter of life. Heart, brain and insulin-producing cells in the pancreas lack functional adult stem cell populations to replace them when they’re lost. After injury, the body is stuck. It does what you’d do when faced with a broken car window and no replacement glass: duct tape. When no replacement functional cells are available, the body tends to repair itself by scarring over the area–replacing what used to be functional tissue with something tough and durable.

2500 Americans die each day from heart disease. The only way, right now, to replace the heart cells lost after a heart attack (or other injury) is whole-heart transplantation. Only about 2000 transplants can be performed each year–limited mostly by the availability of donor hearts.

Which brings us to the embryonic stem cell. We need replacement cells for these tissues. Embryonic stem cells, a kind of pluripotent stem cell, can become any cell type–including heart and brain cells. Only pluripotent stem cells, to date, have an unquestioned ability to become heart cells.

blastocystThe generation of an embryonic stem cell line involves the destruction of an about 100-cell pre-implantation embryo. At this stage, the embryo looks like a beach ball filled with sand. The cells making up the hollow sphere are the trophoectoderm and can go on to become all the supporting structures of a pregnancy (placenta, amnion and such). The clump of cells at the bottom of the sphere is the inner cell mass. These are the cells that can go on to become any cell type in the body.

To generate a new embryonic stem cell line, the trophoectodermal cells are removed by immunosurgery, leaving only the inner cell mass cells behind. These cells are then placed in culture conditions that promote their division as pluripotent cells–retaining the ability to become any cell type in the body. From about fifty cells, trillions can be made. This is why most labs doing pluripotent stem cell research never work with embryos. Since the lines can divide (nearly) indefinitely, the overwhelming majority of research involves work with existing lines–not the generation of new ones.

No human embryo, to my knowledge, has been destroyed only to make an embryonic stem cell line. Every single line in existence was created from an excess IVF (in-vitro fertilization) embryo. IVF requires the mixing of human eggs and sperm in a dish. Sperm is easy enough to collect, store, freeze and thaw. Human eggs are another matter. The collection protocol is dangerous to the woman–involving massive dosages of hormones. Worse yet, there hasn’t been a reliable way to store, freeze or thaw unfertilized human eggs. Fortunately, pre-implantation human embryos can be frozen and stored. So when human eggs are collected, all must be fertilized more-or-less immediately. Some of the resultant embryos are implanted immediately, with the rest frozen for future attempts at having children.

When the couple has decided they’re done having children, the left-over excess embryos are generally destroyed. (Nobody wants to pay for their continued cryostorage.) Since IVF is unregulated, it’s hard to know how many frozen human embryos exist in the United States. Estimates hover around a half-million. A tiny number are donated to other couples seeking fertility treatment, with others donated to scientific research–to be used to create embryonic stem cell lines.

This is a key point: If these cells weren’t used to create an embryonic stem cell line, they would be destroyed anyways. And there are hundreds of thousands of embryos in storage today. Every month they spend in stasis lowers their viability.

Are these embryos, being destroyed as a consequence of in-vitro fertilization, human beings? This is, at its core, not a scientific question.

The embryos are undeniably made up of human cells. But, so are the many skin, gut, and other cells you shed or digest every day. Having the right number of human chromosomes seems a poor standard for a human being.

Nor are these embryos an individual yet. If you split a blastocyst in half, you can get identical twins. Mash two together and you can get a chimera. It seems that any standard for a human being would require the entity to be an individual. Blastocysts are not yet individuals.

These embryos, if implanted, have a potential to develop into a human being. But, it’s important to carefully consider how great this potential really is.

We can estimate there are about a half-million embryos stored in freezers around the country. Only 134 of these excess embryos have been ‘adopted’ by other couples. More are being generated every day. So, a given excess IVF embryo only has about a 1: 4,000 chance of being implanted and delivered to birth. About half of embryos attempted for IVF (again this is a very rough estimate) even manage to implant. Of those that implant, even more miscarry.

We finally come to the question of what makes a cell capable of becoming any other cell? The basic science I work on in the lab is somewhat related to this question; how does a single cell manage to become hundreds of distinct cell types–each with a unique pattern of gene expression that is maintained throughout life. It’s a huge question that I narrow by focusing on the path from anything to heart cell.

The answer is tremendously complex–much deeper and interesting than “sperm meets egg.” Part of what’s going on in that first trimester is the establishment of all those hundreds of cell types. Complex three-dimensional geometry, a dozen or so of delicate signals, precise timing and luck itself all play into this process. It often fails–in a lab dish or in the gestation of a baby.

For all these reasons, and more, I find it hard to accept that a human life starts before the end of the first trimester. Humans are not yeast or bacteria. It takes those three months to even get the vague shape of the complex machine of human life.

In fact, it’s not until deep into the third trimester when all of these cell types are formed into organs that function. Until late in gestation, independent human life is not possible; survival takes extraordinary mechanical life support.

Nor does reaching one step, in any way, mean the next is going to succeed. Very little about development is deterministic; much is subject to the whims of chance and environment.

Something else has emerged recently: induced pluripotent cells, or iPS cells. This technique–to turn some committed cells into a cell that resembles an embryonic stem cell–was developed in Japan by Dr. Yamanaka. Japan’s restrictions on embryonic stem cell research were (and are) far more restrictive than the US’s.

This reprogramming technique required, first, extensive study of human embryonic stem cells. Dr. Yamanaka used a list of potential master regulator genes that was generated based on a large amount of work done on embryonic stem cells.

And iPS cells aren’t anywhere close to perfect. My lab–and I specifically–have done experiments to compare these iPS cells to true embryonic stem cells. They aren’t the same–with a significantly hindered abilities. We’re attempting some further reprogramming techniques to make them better–but that’s still years off. For now, the best bet for making iPS cells work well enough to use for therapies is to continue studying them and embryonic stem cells–using what’s learned in the latter to improve the former.

When making an ethical judgment, I believe it’s critical for us to balance the interests of both the excess embryos produced by IVF (that I do not believe to be human beings) with those of the hundreds of millions of adult human beings that are currently suffering from horrible illnesses.

I do not believe human embryonic stem cell research should be a free-for-all. While I do not personally believe that human life starts at the moment when sperm-meets-egg, I do recognize that human blastocysts deserve serious treatment.

I believe that the donation of blastocysts and the distribution of the subsequent embryonic stem cell lines should be strictly decommercialized. The entire process should be like how we handle organ donation from adults–with oversight, and the prohibition of money changing hands in the process.

Obama’s easing of the Federal funding restrictions on human embryonic stem cell research opens the door for such a policy in a way that Bush’s restrictions never did. By preventing public funding, the destruction of human embryos was forced into the private sector. In a horrifying way, Bush’s policies made the destruction of human embryos a matter of private enterprise–a potentially for-profit venture. Anything else would be better.

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