Ethical issues related to stem cell research

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I want to start this entry in a controversial way and claim that in my opinion there is no major ethical issue related to stem cell research. Of course, there are ways to exploit this field in a bad way but who could give me an example of a research field where this is not the case. Where there are people, there are issues that need to be dealt with, without any exceptions.  As always, we just have to be reasonable! But that is, of course, easier to say than to do. So let me just list some of the reasons why I do not think that stem cell research confronts us with an exceptional bunch of extraordinarily new ethical issues:

–        When it comes to embryonic stem cells, people are concerned about messing with something that could potentially become a complete human being. One has problems to deal with something as “divine” as the embryo. But let me clarify something: a single cell or a clump of cells are not the same as a human being! And being worried about potentials means to be overly sensitive and scholastic. We are always confronted with potentials. Every step we take in daily life is a reduction of potentials and the creation of new ones. So why do we see embryonic stem cell research only as a destruction of a potential human being, rather than the creation of new potentials if all that we are doing is to deal with actual problems, such as the regeneration of a whole organ for a suffering individual? Who’s got more rights? The potential human being whose existence is in no way guaranteed even if the embryo was not touched at all or the actual human being lying in front me that would do anything to improve his condition?

–        Consider the following situation: a child suffers from incurable leukaemia and requires an appropriate bone marrow/stem cell donor to get a last chance to live. Would it pose a big ethical problem if the parents decided to undergo IVF by pre-selecting embryos that perfectly matches the needs of the sick child in order to obtain a perfect donor (given that the whole process of donation is rather harmless and does not represent a major risk for the donor )? I understand that many people would probably feel uncomfortable to immediately give “no” as an answer.  The reason for that might be due to the feeling that the yet unborn child was only meant to be living to serve the needs of another child. But is that really a necessary corollary of the whole situation? People usually have got all kinds of “reasons” to get a baby, some are better and some are worse. But that does not really matter, I think, as long as they do their best to take care and educate their child in the best way they can when it entered their lives. Pure love between a couple might be the noblest reason we can think of to get a child, but the noblest love cannot compensate for the neglect a child has to cope with as soon as the original passionate love fades and the grand idea of getting a child suddenly seems to have been a big mistake. On the other side of the spectrum, getting a child due to purely practical reasons, such as the need for a stem cell donor, does not preclude the amount of love and care a child can experience when born. What I want to say is that no one can ever monitor the love and care that every newborn child actually deserves from their parents, no matter under which conditions it is conceived. In the end, we all have to proof and somehow rely that we are responsible and moral human beings that carry the heart at the right spot! But no ethical system can guarantee that these conditions are ever fulfilled.

I discussed two arguments/scenarios that can be frequently encountered when dealing with ethical issues around stem cell research. There is, of course, much more to discuss but I just wanted to give a short introduction. Our world develops continuously, we have to deal with new situations constantly and therefore it is natural that we find ourselves before situations that raise difficult questions. But this is the case for everything! No two situations are exactly the same. Our moral standards, however, should somehow be stable. What a fruitful discussion should be about is to cover all aspects that need to be taken into account to finally be able to make a good and sensible decision.

Something about Stem Cells

I wish this post might be a very short introduction to the basic terminology of the field (i.e. words you can find in popular science magazines; this does not pretend to be conprehensive or complete anyway). I hope this will be either a trigger of further questions and a link between Mario’s (past) and Mathias’ (next) discussions. I provide interesting links below for those who wish to have detailed reviews on this topic.

One year before getting his MD (at solely 20 years) Giulio Bizzozero (1846-1901) provided evidences supporting the hemopoietic role of bone marrow – this was the first of an impressive list of experimental achievements (including the association of platelets with hemostasis) which crowned Bizzozero as one of the fathers of scientific medicine in Italy. Being involved in the teaching of histology and (experimental) pathology, he suggested one classification of the cells that reside in animal tissues: these were supposed to be labile (it. labili), stable (it. stabili) and permanent (it. perenni). Although its simplistic form, he recognized through this classification one essential biological truth: that is, the degree of regenerative capacity among different tissues varies greatly and can occasionally be triggered by specific stimuli (e.g. hepatocytes –stable cells- can start dividing upon hepatectomy in order to eventually reconstitute a [fully] functional organ). This intrinsic regenerative capacity is actually due to special cells called stem cells. It indirectly refers to the stamen –the reproductive organ in plants- and then to fertility, which is the capacity to generate. This is the first and most important concept to keep in mind: stem cells are able to generate more differentiated (i.e. endowed with specific physiological function) cells through a process of sequential change in the expression of [their] genes. This process is in turn due to exposure to tissue-related growth and differentiating factors and take place both in fetal and –although differently- in adult life. Isolated stem cells (or supposed to be stem cells) can be defined experimentally by using surface molecular markers (i.e. molecules expressed on their plasma membrane) and challenging through a variety of assays their capacity to multiplicate indefinitely or to differentiate. The capacity to generate one or more differentiated cell types is called potency and –according to the degree of potency- stem cells can be considered to be pluri-potent (e.g. able to generate cell types belonging to all three germ layers) or multi-potent (progenitors or precursors; think of hematopoietic stem cells [HSCs]). The ‘most potent’ (say toti-potent) array of stem cells is the embryo itself; indeed, one general distinction is made between embryonic stem cells (derived from different anatomical structures of the developing embryo and the fetus) and adult stem cells, which usually reside in specialized niches (a homely place in which the stemness is uniquely preserved) in their tissue of destination. The source of stem cells for research and/or curative intents is argument of ethical, social and scientific debate and much can be found either in the web and books on it (further issues will be developed in the blog, too). The most intriguing observation –I guess- is that wether what I have briefly described seems a one-way process, actually it is not exactly the case. Manipulation of adult differentiated cells (e.g. fibroblast in the paper by Szavo et al.; see “The plasticity of stem cells”) is a powerful tool to induce genetic reprogramming of cells toward a different phenotipyc identity from the original one. Anyway, further experimental proof (especially long-term monitoring of induced phenotype) is needed in order to apply this tricky biological game to cure disases. As we wait for that proof, the field of regenerative medicine grows prolific and promise to approach a variety of pathologic conditions. In spite of Bizzozero’s classification of cell types (which was insightful and innovative at the time), the harnessing of the physiologic potential for auto-reparation of the organism to improve our own condition –together with its corollary pro’s and con’s- is a necessary step, I guess.

1. Here a very well-done web pages dedicated to basic knowledge about stem cells:

http://stemcells.nih.gov/info/basics/

www.medicalnewstoday.com/info/stem_cell/

2. Paolo Mazzarello, Alessandro L. Calligaro & Alberto Calligaro (2001) Timeline: Giulio Bizzozero: a pioneer of cell biology Nature Reviews Molecular Cell Biology 2, 776-784.

Lista di cosa piacerebbe ai ricercatori/List of what (Italians) researchers would like

Lista di cosa piacerebbe ai ricercatori

Vorrei fare una professione che venga considerata una professione

Vorrei  avere la maternità quando sono incinta

Vorrei poter stare in Italia a fare il mio lavoro

Vorrei avere I soldi per curare le malattie altrui, ma anche per pagare il dentista

Vorrei avere I soldi per scoprire energie alternative.

Vorrei essere pagato, anche poco, e solo per pagare le spese della benzina, quando vado ad insegnare

Vorrei poter aprire un conto in banca senza aver bisogno della garanzia dei I miei genitori.

Vorrei avere la possibilità di aprire un mutuo per comprare una casa con mia moglie.

Vorrei poter pagare I contributi prima dei 40 anni.

Vorrei essere considerata prima di tutto una persona e non un arrogante assetata di soldi che viola I valori dettati da Dio.

Vorrei che le banche mi considerassero un lavoratore e non un borsista.

Vorrei poter pianificare progetti più lunghi di 1 anno.

Vorrei poter ridare ricchezza al mio paese che ha speso tanto per darmi un istruzione.

 

List of what (Italians) researchers would like:

I would like a job that is considered as a job;

I would like to have the maternity leaves;

I would like to stay in Italy;

I would like have funding to cure diseases;

I would like to be paid, although a little bit and just for the fuel, when I teach;

I would like to have funding to discover renewable energies;

I would like to open a bank account without the help of my parents;

I would like to have a pension scheme before the 40’s;

I would like to be considered first of all as a person and not as an arrogant being looking for money that destroys the ethical values defined by god;

I would like to be considered a worker, with a normal job, from the banks;

I would like to plan scientific projects longer than 1 year;

I would like to give back all the resources that my country invested on my education.

The plasticity of Stem Cell

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There’s no better way than start our blog talking about the progenitors of all the cells in pluricellular living organisms: the Stem Cells

A recent paper by Szavo and colleagues described a protocol to obtain blood cells starting from skin fibroblast (the cells that produce extracellular matrix). It sounds like a science fiction tail but it is actually the result of many years of research that step by step, in different laboratories around the world, build up this technology. But let have a quick look at the recent evidences that brought to this discovery.

One of the most important challenges in medicine is the ability to regenerate an entire tissue or organ to replace the non-functional one, situation that can occur after numerous different injuries such as genetic disorder, cancer, stroke, multiple sclerosis, etc. This branch of medicine/biology research is called regenerative medicine. This field of study is based on the ability of  Stem Cells (multipotent/pluripotent progenitor cells) to proliferate and differentiate in many different types of cells such neurons, erythrocytes, muscle cells, etc (Dr Davide Torti will give soon a more general introduction about stem cell and the correlated principles). However, it is often very difficult to isolate a big number of pluripotent stem cell. It is therefore necessary to find innovative strategies to obtain them.

Isolating cells from embryos is an excellent approach to obtain a big number of high quality stem cells. Although using murine 8-cell embryos for research is commonly accepted, the use of human 8-cell embryos is still under ethical debate (Dr Mathias Zech will soon explore this issue). Conscious of the ethical limits, the scientific community moved on to define the adult pluripotent stem cells. These cells are present in the body of the adult individuals and they are responsible for the maintenance of our organs and tissues. The haematopoietic stem cells (HSC), which are present in the bone marrow and in the fetal cord blood, are the most known example. The HSC have been extensively used in the clinical environment: transplantation of bone marrow is still a fundamental treatment for patients affected by Leukemia.

The adult stem cells are often rare and difficult to isolate. Techniques, that allow to take a terminally differentiated cell (like fibroblast or neurons) and to invert its genetic program back to its progenitor and over to pluripotent cells, will overcome that limit. This is what has been done by Takahashi and Yamanaka (Nature 2006; http://www.ncbi.nlm.nih.gov/pubmed/16904174): using a retroviral vector (a viral vehicle for the transport of selected genes to be expressed within a target cell) they induced the expression of Oct3/4, Sox2, Klf4, and c-Myc genes (the so called Yamanaka factors) in fibroblasts. These factors triggered a genetic program in the target cells resulting in dedifferentiation of fibroblasts to pluripotent stem cells, thereafter called induced pluripotent stem cells (iPS). This was an astonishing result that finally confirmed what has been partially shown before by experiments of nuclear transfer into oocyte for cloning purpose: according to this technique it is possible to obtain a whole organism starting from its own differentiated/somatic cell. As shown in the scheme below, once the iPS are produced it is possible to obtain cells of different tissues by exposing them to cell-specific growth factors. This allows the production without theoretical limit of cells that can be used to regenerate patients’ organs in a patient-specific cell therapy way.

However some issues rise from the previous approach:

1) Feasibility: the protocol to obtain iPS cells is very laborious and still requires optimisation.

2) Biosafety: iPS can cause teratomas, an embryonic cancer that presents many tissues in the same tumour mass, typical of pluripotent cells when transplanted into mice.

In the attempt to solve these issues, first Vierbuchen et al and Ieda et al with murine cells and then Szabo et al. in human, demonstrated the possibility to directly induce fibroblasts to become blood cells without first inducing pluripotent stem cell-like status. Their researched started from the observation that while inducing iPS cells from fibroblast, a small proportion of intermediates express the protein CD45, a marker of haematopoietic cells. They also determine that the gene OCT4 was responsible for induction of Fibroblast CD45 positive (CD45+Fib).

The experimental design of this paper was as follow:

Therefore, Svabo and colleagues define an in vitro protocol for the induction of haematopoietic progenitor able to repopulate the peripheral blood population of sub-lethally irradiated immune-deficient mice.

Limits:

1)    They didn’t show the long-term repopulation ability of CD45+Fib^oct4 in the in vivo model. The epigenetic status of the cell together with a limited telomerase activity may impact on their ability in surviving and to proliferate.

2)    The protocol requires 37 days to obtain haematopoietic cells. Quite long for clinical approach in which the viable cells number and the time to obtain them are 2 critical factors.

Do you observe any other limitations in this model? Which direction future research should take: direct differentiation (as shown by Svabo) or indirect differentiation (shown by Yamanaka)?

Let’s play

Let me quickly tell you my ideas about the blog: how I imagine it to be, why I want to keep a blog and what science/philosophy means to me.

I want to pursue 2 different interests with our project e-ducereX (name of blog):

1. The first reason why I want to discuss different topics is simply because I am enjoying it. Too often we tend to ask: what purpose does it serve, why should I invest time in certain things, what output do I get, how do I profit, etc. What I want to say is that too often we are aiming to “achieve “ something, be it in our profession or even in our hobbies (“Why are you doing sports?” “Because I need to stay healthy/good looking…!” etc.). This tendency has led our culture to invent the idea of “holidays” and “recreation centres” where we can all take a break from being “effective” and just lay back. But even then it can occur that we feel bad about doing nothing. We keep thinking at least to read a book, explore some touristic sites or do something for our health. After these few thoughts, let me again ask the question: why should we keep a blog? My answer will not be: because it serves a good cause, it serves to educate ourselves and to inform people, it trains our communication skills. My answer will be: because it’s fun and it’s good! First and foremost: it does not serve any specific purpose, it is a purpose by itself (one might argue, it serves to make us feel well, therefore the purpose is our well-being; but “good” is a transcendental term [in the Kantian sense] that guides our general behaviour; all our behaviour is driven by the idea of “goodness”, even the behaviour of murderers; it is something different if the actual outcome is not as good as expected! Therefore I would go with classical ancient philosophers and say that doing the good makes us feel well and therefore just doing it is the actual purpose we are aiming for and not that we are doing the good because it serves a different and better purpose which is to make us feel well! A complex matter and worth a discussion on its own). Of course, as a very positive and most welcome side effect, we do educate ourselves and we will be able to inform people and maybe we can also train our communication and argumentation skills. But it should not be our first goal! We should use this platform as a playing ground, dealing with scientific and philosophical topics like toys. This is our internal impulse and every good pedagogue will tell you that this is the best way to education: doing it because you enjoy it. Let’s finish this part with a quote by Friedrich Schiller (1759-1805), a German poet and philosopher: “Man is only human when at play.” So let’s play!

2. I consider myself to be the philosopher in our blog. That does not mean that I am wise or that I know an awful lot about philosophy, I just enjoy studying it, reading it, thinking about it. Socrates once said (see Platos “Apology”) that he considers himself to be a bee that keeps stinging the big horse Athens to keep it awake. Why did he feel the need to do that? Because people were not radical enough to ask questions and to admit that they actually knew very little about themselves, the world they are living in and other basic questions of life. They lived in a very advanced culture, they were intelligent and successful but that made them also too self-confident. I think Socrates is a historical phenomenon! He dared to question things radically and we should take this spirit and carry it on. Why now and why here, in this blog? I think science is a very powerful tool to explain lots of different things, to deal with our surrounding and to provide stability in a world that is actually not stable. We live in a constant thermo-dynamical imbalance, both strictly physically but also metaphorically, viz. culturally spoken! But science is just one approach to this world, it is, so to say, one-sided, despite its beauty and versatility. Its success is also its danger! Let’s not forget: the whole big world still consists of one big question mark! I critically observe that scientists tend to forget that, they are very often too self-confident about what science can achieve (see Richard Dawkins who claims that god does not exist or Stephen Hawking who thinks philosophy is dead). I see my role as a bee stinging scientists to reconsider their position. Philosophy, for me, is an admiration for the big riddles of life. When I am in a proper philosophical mood, I always stand completely stunned before this world. This mood very often comes with passionate discussions. It can be scary but it instils you with a deep respect for all that is in this world which can never be fully embraced by science. I want to infect people with this mood and therefore I am very motivated to work on e-ducereX. Let me close this part with two theses stated by Karl Popper, an Austrian philosopher of the 20^th century:

First thesis: We have a fair amount of knowledge. Moreover, we know not only details of doubtful intellectual interest, but also, and more especially, things that are not only of considerable practical importance, but may, in addition, provide us with deep theoretical insight, and with a surprising understanding of the world.

Second thesis: Our ignorance is boundless and sobering. Indeed, it is precisely this overwhelming progress of the natural sciences (to which my first thesis alludes) that continually reminds us of our ignorance, even in the field of the natural sciences themselves.

I Wish Everyone Could Experience a Creative Leap

I wondered what I may write as the very first post when I remembered a cartoon I had seen some years ago in a book I found in the library of my college (www.sssup.it). The book was one Albert Einstein’s biography and the cartoon was a reproduction of a diagram drawn by the scientist in a letter written to his lifelong friend Maurice Solovine -a romanian phylosopher and mathematician- to eventually explain his view of the scientific process (the picture is reproduced below). I feel that the remarks one can derive from it are very consistent with the mission and intents of our blog EducereX, firstly because it offers a comprehensive view –although in abstract form- of what we call science. The germanborn physicist explained himself the meaning of the drawing: the lower horizontal line represents the real (i.e. the material) word with phenomena scientists wish to investigate. The curve line on the left figures the ‘creative leap’ one shall make to interpret phenomena; This ‘idea’ may be very consistent and insightful but is pre-scientific -if not scientific at all. The final output of the creative leap is an axiom (indicated by the letter A), from which a number of consequences (or predicitons: the smaller circles in the diagram) can be sorted out. The scientific process begins when the scientist challenges the real word with the consequences (let’s say: try to falsificate by doing experimentation). If there is no match between the consequences and the real word (dotted vertical arrows), then the idea may not be worth enough (in other words falsification has occurred). On the contrary, when the scientist obtains proof that the consequences of his original idea are correct, the idea can have merit with particular regards to those phenomena it aimed to explain. Each time an experimental work is published and thus shared with the scientific community, the community itself shall enter the process. I find this summary of tremendous beauty: its powerful abstraction recapitulate a complicated set of events and it’s applicable almost to any field in science. Although the dynamic that rule the sequence of experimental achievements is not as linear as represented in Einstein’s diagram, it suggests a more general principle in designing and performing experiments: theories (i.e. ideas) must adhere to data, not the contrary. Due to overwhelming pressures related to economic issues scientists are often induced to force the interpretation of their results, forgetting that if not accompanied by intellectual honesty, curiosity is not sufficient to drive scientific inquiry. One can also figure out that science (for the sake of the science!) is a double-faceted stuff in which either a creative flavour and an analytical mind are equally important. However, if analytical skills shall be exercised through application and experience, creative mood can not be summarized in books and that’s exactly why I wish everyone –myself included- could experience a creative leap!



The idea behind EducereX

Can Science contribute to improve human condition?

This question may sound easy to answer when we think about how technology improves human life. However, this is just part of the answer. Someone may recall that some of the most important physicists contributed to create the atomic bomb, which may have extinguished human kind from the earth.

So, is science good or bad?

I personally think that this simple question is an important one in the modern society. Although nobody would ever criticize the kind of research that aims to cure cancer, many discussions rise when in vitro fertilization, genetic modified organisms (GMO) or evolution are debated. Science and scientists are still pointed at suspiciously by the society. This is because the scientific knowledge, which often is not fully understood by the community, impacts against some established ethical values originated in the past when certain knowledges were not available. As all scientists know, science is not bad or good but it’s objective. Science is looking for answers. The true science is inspired by curiosity. Science describes the nature as it is. Science doesn’t demonstrate ethical principle. What makes science good or bad is how human being uses that knowledge.

Can scientific knowledge help to postulate ethical principles?

In the preface of “Chance and Necessity”, Jacques Monod pointed out the importance to distinguish between the ideas suggested by science and science itself. As previously said, science objectively describes reality without judging if it is good or bad: “The first scientific postulate is the objectivity of nature: nature does not have any intention or goal”. But knowing the reality allows us to propose ideas and ethical principles that are based on objective knowledge. These ideas may crash against the common view of ethics, politics and religion, but give more responsibility to the human being that is author of his good or his bad.

EducereX is the place where I would like to develop the ideas based on knowledge: the ethics of knowledge (so well introduced by Jacques Monod). I would like to explain the scientific achievements to the community and expand together the conclusions, even if they will impact against establishments and prejudices . This will be hard and long (as Einstein said: it’s easier to break an atom than a prejudice) but I’m confident that the power of  justified ideas will be approached by men, which will be responsible of their destiny.

Here I leave you with an interview of Jacques Monod that has been done after he was awarded with the Nobel Prize:

http://www.vega.org.uk/video/real/156

“Science is the poetry of reality”

 

Since the homo sapiens started being aware of his existence, the human being try to answer to many questions: Who am I? Why am I here? Which is the origin of the man and more general of life? How has the universe  been formed? How does nature work? Which is the right way of living?

At first man try to answer to this questions through 2 different approaches: the rational approach of philosophy where the rational argumentations are the fundamental basis, and the spiritual approach of the religion.

It was clear since the beginning that not all the answers can be given by a single approach. However, without an alternative approach, many efforts has been done to use philosophy and religion for answering to this questions. Both these approaches failed in giving optimal answer to naturalistic issues: the Greek philosophy was an astonishing piece of human history where many and fundamental progress in understanding has been done (as Bertrand Russel said: the modern philosophy is a revival of Plato’s). Despite the great achievements, Greeks failed in their lack of experimental evidence. Their rationalism was based only on rational argumentation, without testing if the reality was actually following the same pattern. In the Asimov book of physics, he explained how the Greek philosophy failed in describing the nature because it was based on axiōma that were considered true although their were not exact. Only with empirical observation was possible to correct those model.
The religions satisfy the need of spirituality of the human being, providing also explanations of the real world. Usually, most of religions state the existence of a God with great power, able to create the man, the world and the universe. At first, religions not only try to satisfy the spiritual needs but also try to explain the beginning of the universe, the natural mechanism and the creation of life. However most of these knowledge on natural system resulted to be false and inconsistent with human observation.
Therefore, science come into the scene to provide answers on how the world works, the mechanistic origin of life and human being and the origin of the Universe. The scientific knowledge have revolutioned the entire view we have of the world. On this basis it is now possible to go deep in understanding ourself and to find answer to the most ancient questions. Some religious organization recognize in the science an enemy. We don’t. We think that science is just explaining what God have done. The existence of God is something that we all have to deal with in our own consciousness.As I started with an amazing citation of Richard Dawkins,  I would like to terminate this first post of our blog by a citation of Einstein: “ I want to know God thoughts…all the rest are details”.