Stress turns ordinary cells into pluripotent stem cells

February 19, 2014

PÄR SEGERDAHL Associate Professor of Philosophy and editor of The Ethics BlogTissues of the body originally form when “naïve” undifferentiated embryonic stem cells differentiate to form the “mature” cells of specific tissues: liver cells, brain cells, skin cells, and so on.

The mature cells are then locked in their differentiated forms, as if they met their fate.

I recently mentioned that Yamanaka and Gurdon were awarded the Nobel Prize in Medicine in 2012 for their surprising findings about dedifferentiation. Through direct genetic modification of nuclear function, mature cells can be reprogrammed to return to naïve stem-cell states. These dedifferentiated cells are pluripotent and can differentiate again and form a variety of mature cell types.

The rejuvenated cells regain the naïve properties of embryonic stem cells!

In January this year, an article published in Nature reported that the genetic reprogramming can be achieved more easily, without direct nuclear manipulation.

All you need to do to dedifferentiate mature cells, according to this article, is to subject them to stress: like an acid environment. Not all but some of the mature cells will be freed from their fate as liver or skin cells and return to naïve pluripotent states.

An easy to read summary can be found in BioEdge, and here is a link to the article:

Using mature cells to create stem cells with properties of embryonic stem cells might thus be easier than expected. In fact, the new findings weren’t even made in a stem-cell laboratory.

The ethical responses to the findings are not as thrilling as the findings. Some welcome the possibility of creating “ethical stem cells” that avoid the controversy about embryonic stem cells. Others see “new ethical issues” on the horizon.

These responses are characteristic of a routine view of ethical assessment as a static one-way process: ethicists assess others. But these findings indicate that processes in the opposite direction are possible as well, since they seem to challenge ethical assumptions about the unique function of the embryo.

I’m tempted to extend Thomas Kuhn’s notion of scientific revolutions to ethics. The new findings could function as anomalies for ethically paradigmatic ways of thinking about the embryo.

As stress turns mature cells into naïve pluripotent stem cells, these findings could stress some ethicists to return to more open-minded states that in the future can differentiate in new and unexpected directions.

Pär Segerdahl

We like challenging findings - The ethics blog

Scholastic reasoning versus modern cell biology

January 30, 2014

PÄR SEGERDAHL Associate Professor of Philosophy and editor of The Ethics BlogEmbryonic stem cell research can find effective treatments for a wide range of currently untreatable diseases. No wonder embryonic stem cell research can be perceived as an important practice.

A human embryo can develop into someone’s child, who breathes, talks and lives. No wonder embryonic stem cell research can be perceived as a controversial practice.

What interests me here is how these two in my view humanly comprehensible perceptions of stem cell research are translated into an intellectual arena called “ethical debate.”

On this arena, forms of reasoning with different historical roots meet to combat each other. The idea is that here finally the issue shall be settled: is embryonic research, as a matter of fact, morally controversial, or is it not?

Or are we rather debating Aristotle versus modern cell biology?

Attempts to prove that the research is controversial bear witness of a legacy from the metaphysics of Aristotle. The human embryo is supposed to have a unique potentiality to become a person: a potentiality so actively present in the embryo that the embryo is to be understood as a “prenatal person” or as a “potential person.”

Attempts to disprove such scholastic claims instead rely on the latest scientific evidence in cell biology. In 2012, Shinya Yamanaka and John B. Gurdon were awarded the Nobel Prize in Medicine for their work on what is called “dedifferentiation.” Stem cells derived not from embryos but from, for example, skin cells can be genetically induced to regress into less differentiated states that in turn can differentiate into various directions.

These findings are invoked in an article in The American Journal of Bioethics to finally take leave of the argument from potentiality:

  • “Technically speaking, fertilized egg cells (earliest embryos), iPSCs (induced pluripotent stem cells), and skin cells are all potential ‘baby-precursors,’ in part due to modern cell biology.”

So much for the unique potentiality of the human embryo: a skin cell will suffice.

To what extent do such debates concern the two perceptions of stem cell research in their human comprehensibility?

Pär Segerdahl

We think about bioethics :

What are absolute borders made of?

December 17, 2013

I return to the question in my previous post. I was wondering why biotechnological developments repeatedly invite moral responses in terms of borders that shouldn’t be transgressed by humans. (Think of stem cell research using human embryos.)

What is fundamental in these responses? Is it the absolute border? Do people already have stable notions of borders that shouldn’t be transgressed by humans, as part of semi-metaphysical views of life? Do they respond, “Controversial!”, because they deem some new practice to be transgressing a border that already is in place within their view of life?

Or is the notion of the border itself part of the reaction? Is “the absolute border” reactive rather than the source of the reaction?

I’m inclined to say that the “absolute border” arises with and through the reaction. Let’s call it the intellectual part of the reaction. It is how the reaction presents itself as legitimate; it is how the reaction transforms itself into a reason against the new developments.

The notion of an “absolute border” is how the reaction translates itself into the “space of reasons.”

If so, the recurrent reaction is almost bound to misunderstand itself in accordance with my first suggestion: the border will be perceived as basic, and the reaction will present itself as rational verdict: “The absolute border is being transgressed here; therefore, a moral response is in order!”

We must not forget that entire views of life can be reactive. Even when they are beautiful and admirable human achievements, their function can be that of digesting reactions and providing them with meaning.

My conclusion is that if we want to understand these recurrent reactions, we must not be fooled by how they spontaneously translate themselves into “the space of reasons.” We need a practice of back-translation.

We seem bound to repeatedly misunderstand ourselves. Our much praised faculty of understanding easily becomes a faculty of misunderstanding.

Pär Segerdahl

We challenge habits of thought : the Ethics Blog

Absolute limits of a modern world?

June 21, 2012

A certain form of ethical thinking would like to draw absolute limits to human activity. The limits are often said to be natural: nature is replacing God as ultimate moral authority.

Nature is what we believe we still can believe in, when we no longer believe in God.

God thus moves into the human embryo. As its nature, as its potential to develop into a complete human being, he continues to lay down new holy commandments.

The irony is that this attempt to formulate nature’s commandments relies on the same forms of human activity that one wants to delimit. Without human embryo research, no one would know of the existence of the embryo: no one could speculate about its “moral status” and derive moral commandments from it.

This dependence on modern research activities threatens the attempt to discover absolute moral authority in nature. Modern research has disassociated itself from the old speculative ambition to stabilize scientific knowledge as a system. Our present notion of “the embryo” will be outdated tomorrow.

Anyone attempting to speculate about the nature of the embryo – inevitably relying on the existence of embryo research – will have to acknowledge the possibility that these speculations already are obsolete.

The changeability of the modern world thus haunts and destabilizes the tendency to find absolute moral authority in nature.

Pär Segerdahl

We challenge habits of thought : the Ethics Blog

The patentability of inventions requiring destruction of embryos

November 25, 2011

A month ago the European Court of Justice banned patents that require destroying human embryos at and after the blastocyst stage. A month later, the company Geron decided to stop their unique clinical trial concerning a treatment of spinal cord injury with neural cells derived from human embryonic stem cells. The company cited lack of financial resources as their reason. Yet, the termination of their trial illustrates possible consequences of the ruling of the European Court of Justice. Patient groups with, for example, spinal cord injury may less likely hope for efficient treatments.

Bioethics groups, such as the Anscombe Bioethics Centre in Oxford, saw the ruling as a victory of ethics over greed (here is an interview with the director). I want to ask, though: what kind of ethics really won here? And what was defeated?

According to the philosopher Christian Munthe, the argumentation preceding the ruling was unusually bad. Among the many deficiencies he identifies, there is an important missing premise that moreover is false.

I believe that Munthe is right about the missing premise. But perhaps the most important question is WHY the premise began to haunt the argumentation and implicitly steer it towards the ruling. The missing premise contained a comparison of the destruction of human embryos when stem cells are isolated with killings of prisoners in former Yugoslavia to make money on their organs. Obviously, patents for procedures that involve actions that resemble this crime should be banned. But does isolating stem cells from embryos have such resemblances to the brutalities of civil war?

Evidently, the judge working on the issue speculated about established customs and shared moral views in Europe (“ordre public and morality”). People understand the relevant facts of war sufficiently well to react morally to acts of cruelty against prisoners. This moral view is grounded in an unclouded perception of reality. The development of stem cell treatments, however, is unknown to most of us. When we respond to hearing about such procedures, we easily react to IMAGINARY PICTURES of what isolating embryonic stem cells might be like. These pictures often resemble a chamber of horrors with which the new and unknown is compared… like killing victims of war to sell their organs: a “tech noir” image of the future fundamentally stuck in the past.

Notice that we are not dealing with two known procedures and their perceivable similarity. One of the procedures, the isolation of embryonic stem cells, is unknown to most people. When the judge speculated that people in Europe would see a similarity between isolating stem cells and killing prisoners, this meant speculating about how people might speculate about the unknown, using the known as a pattern. As a result of this speculation about speculations about the unknown, treatments of serious conditions like spinal cord injury are now less likely.

Was the ruling a victory of ethics over greed? Or was ethics defeated by speculations about fantasies about the not yet understood?

Instead of being merely a case of bad logical reasoning, the missing premise exemplifies a tremendous moral difficulty in modern societies. Ethics in these rapidly developing societies demand that we are open to learning about NEW notions and facts. If we are not, we risk responding “morally” to imageries rooted in the past rather than to the new realities.

I admit that developments in medicine pose considerable challenges for moral thought today. An example of the efforts that may be required to avoid questionable comparisons and imaginations is an article in Stem Cells, written by Mats G. Hansson at CRB with Gert Helgesson, Richard Wessman and Rudolf Jaenisch. The article is technically advanced and I’m pondering whether the relevant facts could be explained in simpler terms.

While waiting for future posts that may summarize the thoughts less technically, I recommend it as a warning against temptations to compare new facts with a cabinet of old threats.

Pär Segerdahl

We challenge habits of thought : the Ethics Blog

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