November 16, 2004
Will California Proposition Slow Embryonic Stem Cell Research?
The passage of California state proposition 71 to fund embryonic stem cell research may cause a backlash that brings greater federal restrictions.
The resounding victory of California's $3 billion ballot initiative for embryonic stem cell studies may have the unintended consequence of slowing research on the national level and creating a backlash from religious conservatives who feel emboldened by President Bush's reelection, say activists on both sides of the issue.
Under Proposition 71, California researchers are eligible for $295 million a year in grants to work on cell colonies -- or lines -- taken from five-day-old human embryos.
In August 2001, Bush struck a compromise, announcing he would allow federal funding for research on the limited number of cell lines that existed then. Researchers and patient groups have been frustrated by those restrictions, saying the 20-plus available lines and $24 million in federal grants have not been sufficient.
Brownback's cloning ban would make it a crime for patients treated outside the United States with therapies derived from embryonic stem cells to reenter.
Think about that last part. Some day Americans may go abroad for embryonic stem cell therapy and in the process turn themselves into permanent expatriates. If the choice is between permanent exile and death quite a few people will choose exile - at least if they can find a country that will accept them as residents.
Look at it from a purely financial standpoint: Prop. 71 will increase total money available in the United States for embryonic stem cell research even if all federal funding of embryonic stem cell research is ended. The amount California will start spending is far in excess of what the US federal government is currently spending. Also, if the federal goverment stops spending on embryonic stem cell research it will probably shift the money toward adult stem cell research. So with the California money the total amount going to stem cell research of all kinds will go up. That will speed progress overall.
Of course if Congress outlaws embryonic stem cell research entirely then embryonic stem cell research in California would be stopped regardless of what money is available. Is such an outcome possible? I would expect the more center-of-the-road Republican Senators and Congressmen from the Northeast and perhaps some from the Midwest and Northwest (e.g. Mormons from Utah) to band together with the Democrats to block such a move. But that is speculation on my part.
Whatever the United States federal and state governments do about embryonic stem cell research will affect the rate of advance of embryonic stem cell research. But it is inevitable that therapies based on embryonic stem cells will be developed in East Asian countries regardless of what the United States does.
Also, if human embryonic stem cell research is banned in the United States adult stem cell research will still produce lots of therapies. In the longer run methods will be developed to turn adult stem cells and even adult differentiated cells into any cell type that will be needed for therapy. The big advantage of embryonic stem cells is that they are pluripotent. That means they have the capability to become all other cell types. Well, eventually techniques will be discovered to turn adult cells into pluripotent cells.
Once it becomes possible to turn adult cells into pluripotent cells will most of the religious opponents of embryonic stem cell research take the position that the creation of such pluripotent cells is immoral because such cells will have the ability to develop into fetuses? Or will the religious folks decide that since the pluripotent cells were not created from an egg or an embryo that those cells do not have a soul and hence are acceptable for use in creating treatments?
Even if the embryonic stem cell research opponents remain opposed to the use of all pluripotent stem cells for research and therapy one way around restrictions against pluripotent stem cells would be to find ways to create very multipotent (capable of becoming many but not all cell types) stem cells. Basically dedifferentiate or despecialize cells almost all the way back to early embryo state but stop just short of that most flexible state. Some promising research on chemical compounds that dedifferentiate cells has been published. The search for compounds to differentiate and dedifferentiate (specialize and despecialize) stem cells is accelerating due to advances in biotechnology for growing and screening cells. So more compounds will come along that will allow scientists to basically program around restrictions on the use of embryonic stem cells. Also, it may be possible to extract highly multipotent or even fully pluripotent stem cells from the blood of pregnant women.
In the end, the ability to directly make pluripotent cells from adult differeniated cells is what everyone wants. It's still anyone's guess whether that would satisfy critics, but the technique should bypass any legislation currently being considered.
An intermediate step might be the ability to make eggs directly from differentiated adult cells. Under the proposed legislation, making ES cells from those eggs would also be illegal. The question of whether man-made embryos have a soul stretches suprenatural thinking pretty far.
Randall Parker said: "The big advantage of embryonic stem cells is that they are pluripotent." For many applications I suspect that this property can actually be a disadvantage. Consider the following quote:
"One of the problems with embryonic stem cells is, when you transplant them, they often have a tendency to form teratomas - uncontrolled growths of cells that develop into teeth, cartilage or hair, for example," said Walter C. Low, a University neurosurgery professor and the study’s principal investigator. This is something we would not want to see if we put stem cells into the brain.
Also, consider this quote:
"Replacement of dopamine neurons using embryonic stem cells has long been the holy grail," says Clive N. Svendsen, PhD. "But stem cell transplantation can introduce serious problems, including tumors and dyskinesia, or impaired, sporadic muscle movements." ... The group considered using embryonic stem cells, but realized they might lead to tumors and dyskinesia, so they tried neural stem cells. These cells don't have quite the enormous potential of embryonic stem cells, but they can become astrocytes, a type of glial cell found in the brain. Best of all, they do not induce tumors.
Perhaps the use of adult stem cells of the tissue type required for a specific application would reduce the chance of uncontrolled and inappropriate growth.
I think that adult stem cells seem to be the more promising of the two. The amount of money being spent to force embryonic stem cells on a still largely unwilling public could be spent on further developing the technologies that are already allowing great things to come from adult stem cells.
Great article, by the way. The point about pushing adult stem cell pluripotency to the edge of controversy is not an angle I had fully considered before. Thanks.
Garson, Certainly starting with more differentiated adult stem cells has the advantage over embryonic cells that the cells are less likely to shift to some other undersired cell type.
Also, yes, they are less likely to propagate excessively. That was a problem in one stem cell therapy experiment done to some Parkinson's Disease sufferers. They now have too many dopamine neurons and their muscles overreact and they are in worse shape than they were before therapy. But that is a solvable problem. Of course all these problems are solvable - but how soon?
Another advantage of adult stem cells taken from one's own body is easier to achieve immuno-compatibity.
Also, I frankly prefer my own cells in my own body. They are my cells. They are part of my identity. I want to protect my distinct identity.
Eric's initial comment is quite insightful. If scientists generate pluripotent cells from adult cells, the religious activists will be forced to declare that either these cells have a soul (and therefore that man can create souled life), or else they do not (and thus they must allow such research).
Religious and supernatural beliefs exist wherever man cannot comprehend or control the world, and we are on the threshold of controlling the generation of new lives. Barring nuclear annihilation of the scientific world (or a thunderbolt from God), we are bound to attain these supposodly "godlike" (sic) abilities.
It's unfortunate that the science-phobic confederacy of dunces has political power enough to control this kind of human advancement.
Randall Parker asked: "Once it becomes possible to turn adult cells into pluripotent cells will most of the religious opponents of embryonic stem cell research take the position that the creation of such pluripotent cells is immoral because such cells will have the ability to develop into fetuses?"
That is an interesting question. My guess would be that some religiously motivated groups would use the following rule: If a cell can be placed into a uterus and develop "naturally” into a fetus and baby then that cell has "moral significance", and it should not be destroyed without "moral justification".
It might be possible to avoid this type of religious opposition by avoiding the construction of cells with this property. For example, a collection of cells might be identified such that together they can differentiate into all the needed cell types, but so that no single cell can develop into a fetus within a uterus. Alternatively, a cell might be identified that can only generate all cell types after considerable manipulation, e.g., the cell might require special culturing procedures, growth factors, micro-injections of gene regulators, and exposure to dedifferentiate agents in order to yield all cell types. I hope that most religious individuals would find these cells unobjectionable.
One last point, there are no laws in the US against the destruction of embryos in fertility clinics so at this time the power of some religious groups to enact legislation seems to be circumscribed in this domain.
The problems with direct injection of ES cells that Garson points out is somewhat misleading. At this point, I don't see many scientists thinking they can simplying inject ES cells and get a desired result. For cell therapy, the ES cells will mostly likey have to be partially differenitated before use.
The unmentioned (unique) application of ES cells is as a platform for disease research. ES cells could be made from individuals with various diseases, and those cells could in turn be studied in vitro to understand the disease process. My guess is that that kind of research will be just as important as cell therapies, but of course it also requires cloning and destruction of an embryo with current technology.
Eric, there is an article in Proceedings of the National Academy of Sciences entitled "Will embryonic stem cells be a useful source of dopamine neurons for transplant into patients with Parkinson's disease?". The article advocates trying to use embryonic stem cells for Parkinson's, but it also mentions difficulties. For example, the article discusses an experiment in which researchers "transplanted small numbers of partially differentiated mouse ES cells from embroid bodies into a rat model of Parkinson's disease". The results included 20% lethal teratomas and 24% in which no cells survived. That is a large number of teratomas. However, the experiment was just a first step of exploratory research and the avenue still looks promising argues the author.
To reduce the probability of teratomas the author advocates just what you suggested. "For human embryonic stem (ES) cells to be useful for stem cell replacement, they should be partially differentiated into lineage-restricted stem cells to eliminate the pluripotency responsible for teratomas." I think that makes sense when using ES cells. But note that adult stem cells are typically already lineage-restricted. Adult stem cells would also provide an exact immunological match. My comment above was intended to emphasize that pluripotent cells have problems in some applications, and it is sometimes desirable to remove pluripotency.
In response to Garson's point, although ES cells are theoretically totipotent and can differentiate into every cell type, this property is not sufficient to allow a cell or cells to develop into a fetus. The contribution to development from extra-embryonic cells should not be forgotten. Thus, it becomes difficult to make a case for "the cells could develop into an embryo" without a lot of outside help. If you allow such outside assistance to widen the umbrella for "potential babies," then it is not too far in the future that skin cells (and every other cell type) would apply.
Eric, why can't adult stem cells be used for disease research? Obviously one could extract adult stem cells from individuals with various diseases and the procedures for doing those extractions will only get better in time.
CB, Yes, when every cell type becomes potentially convertible into cells that can be developed into an embryo where to draw the line on what is a human?
It even gets weirder: I can imagine a human embryo being constructed from a number of separately derived cells which have each been converted from adult cells into partially differentiated stem cells. The result would be a chimera where, say, the brain would be developed from a different cell line than the legs. There'd never be a starting cell that was in the ESC state. Yet the result would eventually be a fully functional adult human.
Another problem is going to arise with the use of birth as the alternative moment at which something becomes a human. Secular liberals who favor abortion and human embryonic stem cell research argue that this is where the line should be drawn on what can legally be killed. But birth seems an arbitrary point for drawing a line on what is a human. Once artificial wombs are developed where to draw the line of "birth"? My speculation is that when using artificial wombs there will be advantages to delaying the point at which the womb dependency is ended. Rather than bringing the baby out of the womb at 9 months from the moment a cell was first placed in the womb it might make more sense to let the baby stay in longer (10,11,12 months perhaps) and then to partially disconnect from the artificial womb in a series of steps over a period of days, weeks, or months.
Even if you do not believe we have souls or you at least doubt that we do there is not some obvious alternative point at which to draw a line on new lives to decide what is human.
CB, you make an excellent point about embryonic stem (ES) cells. I will try to clarify my earlier post. Religious opposition to ES cells is not based on the ability of an ES cell itself developing into a fetus when placed in a uterus. Instead the opposition to ES cells is based on the moral status of the cell that is used to derive the ES cell. Specifically, there is a cell that divides repeatedly and creates the blastocyst from which the ES cell is extracted. That starting cell has “moral significance” because in principle it could be placed into a uterus and develop "naturally” into a fetus and baby.
So here is my guess for the religious rule: If a cell can be placed into a uterus and develop "naturally” into a fetus and baby then that cell has "moral significance", and the cell should not be destroyed without "moral justification". In addition, the organism developing from the cell should not be destroyed without "moral justification".
The procedure used to create ES cells violates this rule and that is a moral transgression to some religious groups. On the other hand, a pluripotent stem cell that simply sits in a uterus and does not develop, or a pluripotent cell that creates a ball of cells that refuses to implant in the uterine wall might be “just another cell”, i.e., might not have “moral significance”. It might be ok to destroy or manipulate that cell from a religious standpoint.
Randall, human chimera are discussed in a fascinating article called “The Stranger Within” in New Scientist. The article is behind the subscription wall at the New Scientist website but someone made a copy http://www.katewerk.com/chimera.html ">here. Non-identical twin embryos can fuse in the womb and grow into a single body. Your example in which “the brain would be developed from a different cell line than the legs” can apparently happen naturally. A chimera is rare but microchimerism exists. (You probably already know this but some other reader might be interested in the pointer).
Short answer: you will most likely need pluipotent/multipotent cells to make a tissue culture disease model
Long answer: the disease research application of ES cells is to make a human tissue culture disease model. For example, if you could make pancreatic islet cells from diabetics, then you could study what causes the onset of the disease, and screen for drugs to reverse the process.
I don't know the complete list of hypothesized human adult stem cells, but here are a few examples: blood stem cells, skin stem cells, germ line stem cells. None of those can, given our present technology/understanding, be used to make pancreatic islet cells. But in theory that should be possible with ES cells -- may have already been done with mouse ES cells. You can imagine a technology to make a tissue from adult stem cells, but this would most likely involve the creation of ES/pluripotent cells from the adult stem cells. This is why I say that ES cells are needed for disease research.
On the topic of pancreatic islet cells, researcher Denise Faustman of Harvard has apparently been able to cure juvenile diabetes in mice and cause the islet cells to grow back. She did not use embryonic stem cells nor did she use adult stem cells. Instead she blocked the white cells that were attacking the islet cells "by supplying them with a piece of protein that signaled that the islet cells were normal cells, rather than foreign invaders." Next she administered an off-patent drug called BCG that elicits the release of tumor necrosis factor. Remarkably, the mice were cured and the islet cells grew back. This is reported in a recent New York Times article here. (The original article is entitled "A Diabetes Researcher Forges Her Own Path to a Cure" and it is behind the subscription wall so the link is to a copy.)
Another great insight from Faustman's work is the identification of the original location of the cells that were used to regrow the islets - the spleen. Faustman did an elegant experiment in which she transplanted spleens from male mice into female mice. She then showed that the regrown islet cells contained male cells. On a cautionary note the article states that "the field has been whipsawed by false hopes" in the past.
About possible moral objections that those opposed to abortion on moral grounds might have
Speaking as one of those people, I wouldn't have any problem with using adult stem cells modified to be pluripotent in curing disease. The objection to using embryonic cells has nothing to do with the qualities of the cells. The problem that I have with using embryonic cells is that a baby has to die to use them. Specifically, in most cases that death is caused by abortion; that is, the baby is killed before it's born. That is the main objection.
On the other hand, if a baby were miscarried, and the parents agreed to it, I would have no problem with using those cells; we do that all the time in the U.S. You've probably signed your organ donor card on your license, too.
Here is some background: A "potential human being" begins as a single cell. The cell divides repeatedly, and approximately four days into development, the cells begin to specialize and form a blastocyst. A blastocyst is a mostly hollow sphere of cells within which is a cluster of cells called the inner cell mass. The inner cell mass contains between 30 and 100 cells and "embryonic stem cells" are obtained from this inner cell mass. Hence, embryonic stem cells are harvested at a very early point in development.
If a woman is carrying a developing fertilized egg and a "miscarriage" occurs at the blastocyst stage then I think it would be almost undetectable by the woman. If a miscarriage occurs that is detectable by the woman then the fetus/embyro/infant would probably be much too advanced to yield embryonic stem cells. (Disclaimer: This is not my field of expertise.)
Suppose a single cell is extracted from the blastocyst and separately grown up for research without destroying the blastocsyst and without ending the pregnancy. Do religious folks object to this?
I am sure that removing a cell from a blastocyst would be generally acceptable. However, as a practical matter, we are not even close to being able to do that without destroying the blastocyst; it's just too fragile. It is possible to peel off one of the cells in a 2 or 4-cell embryo (to be used for genetic testing -- currently done, after IVF for couples with high risk of genetic disease and the money to do the testing). But this cell is capable of making a twin, so there are some that object.
Does anyone here think that, if a method to turn regular cells into pluropotent stem-cells is developed, that the religious people would still have objection to the use of such technologies for medical treatment? If this is the case, doesn't this strike all of you as being way over the top?
The day that traveling abroad for medical treatment turns me into a permanent expatriate is the day that I no longer consider myself to be an American or owe any loyalty, what so ever, to America as an institution or a concept. The day that religion is used as justification to limit access to improved health and vitality is the day that religion ought to be eliminated.
These people, who claim to believe in a right to life, certainly don't respect one's right to life enough to be free from aging and desease. They seem to think that the life of an embryo is more important the the lives of people who already exist and seek freedom and openess. I consider this sense of biomedical ethics to be warped in the extreme.
I had a discussion with a friend of mine who knows medical law. He tells me that if the Brownback law (banning therapeutic cloning) passes, it is very unlikely that someone can be prosecuted for traveling to another country to get medical treatment. This is based on precident. There are many medical therapies in places like Mexico, the Carribean, and Thailand that are illegal in the U.S. because they are considered quackery. An example of these is leatril treatment for cancer, which was popular in the 1970's. The import of these treatments are usally banned as well. Yet, many Americans travel to clinics south of the border (and other places) to receive these treatments. No one has ever been prosecuted for returning to the U.S., after receiving such treatments, even though the importation of these treatments is illegal and subject to prosecution. Once a treatment is "in the body", it is considered a part of your body and no longer a treatment.
Consult a lawyer and your mileage may vary, but I think it highly unlikely that anyone could be prosecuted for traveling abroad for medical treatment based on embryonic stem-cells.
Besides, how could they "bust" you? Give everyone who passes though immigration a comperhensive medical exam to ensure that they are not carrying any "embryonic stem cells" in their bodies? This starts to bring up privacy issues that even George Bush and his cabinet cannot overcome.
Kurt, your outrage is understandable in some ways but I think you are being oddly selective in your vehemence. Right now your access to health and vitality is artificially limited for "religious" and/or "ethical" reasons. Here is an example. Suppose you are dying because your kidneys are malfunctioning. So you decide to offer money to try and purchase a kidney from a immune-compatible and willing donor. The surgery is ready to proceed with an eager healthy non-coerced participant, but unfortunately the police arrive and arrest you because your actions are illegal in the United States (and many other countries). The law against markets in organs exists apparently because most people have a deep-seated religious/ethical sense that it is "wrong".
The result of this ban is reflected in the following quote: "The transplant waiting list currently includes 55,560 patients, and about four thousand of them will die waiting." But we know that "healthy people could conceivably sell their eyes, some skin, a few bones, a kidney, a portion of their liver, and even a lung and still survive." The restriction on markets for organs exists in countries with populations that are heavily non-religious. The questionable idea of "eliminating" religion will likely not change this.
Many people have belief systems that are nonsensical, irrational, fatuous and blinkered. This is a commonplace observation when directed at religious people. Sadly, it is also true of many non-religious people. In some cases the animating beliefs of the non-religious are even worse. Witness the record-smashing stacks of bodies during Stalin's terror.
Garson Poole - "Trapped in a world I never made." ;-)
I agree with you yet again.
Another example: What does more to slow down the rate of advance of medicine? Human embryonic stem cell research restrictions? Or liberal-supported regulations foisted by the FDA on the drug industry? The bias of regulation is skewed toward preventing unexpected harm and away from getting benefits. So, for example, a drug that prevents death from one cause but increases the risk ot death from another cause will be pilloried in the press (as is the case with Vioxx), removed from the market, and become the target of massive lawsuits by the plaintiff's bar which of the Democrats support. But I just saw a PBS news show segment where some FDA scientist lady says that even today we do not not that Vioxx has killed more people than it has saved. Of course we aren't given the choice of having Vioxx available with warnings.
Yet the liberals are all up in arms about human embryonic stem cell research while defending a regulatory system that greatly slows down the rate of drug development and that kills people as a result.
I understand what you are talking about. There are many nonsensical belief systems that result in the needless deaths of innocent people. Let me tell you about an example of which I am intimatly familier with:
I have a friend who was diagnosed with an inoperable brain cancer and was told be the diagnostic doctor that he had one to two years of life left, max. This person was actively involved in cryonics and, in fact, had cryonics arrangements and financing in place for his suspension.
As you may or may not know, you have to be legally "dead" to be cryonic suspended because the process "kills" you if you happen to be "alive" when you are suspended. Of course, current legal definition of death is based on a 5 minute cessation of brain electrical activity. We know this to be an arbitrary definition because there are occasional stories in the paper about people who fall into frozen lakes and what not who happen to be "brought back from the dead" after being "frozen" for 15-20 minutes or so. What this means is that as long as the nuerological structure of your brain is intact (synaptic connections and the like) you are theoretically alive even though you may be "dead" (by the current legal definition of death which is 5 minutes or greater perion of no brain electrical activity).
I cite all of this background to give you some insight about cryonics and why we thing it MAY work. The point is that my friend had an inoperable brain cancer that threatened to destroy much of his brains (and therefor, himself) while he was still legally alive. So, he wanted to be cryonically suspended while still legally alive. Since he knew that if he (and Alcor) did this on their own, the suspension team would be prosecuted for murder.
So, he sued for the right to be cryonically suspensed while still legally alive. The suit was filed in California court system. He lost the lawsuit because the state ruled that he need was not compeling enough to allow "assisted suicide" that the state deemed to be unacceptable for "societal" reasons (remember, this was in the late 80's).
The story, so far, has a positive ending because the cancer went into remission and he is still alive and active today (he currently lives in Australia).
I tell u
I tell you the above story to show you that such nonsensical belief systems to cost people their lives and freedom. I also want to say that I do not consider myself to owe any sense of "loyalty" what so ever to such nonsensical belief systems or the institutions that they are based on.
I lived as an expat for over 10 years and definitely enjoyed the experience. I can certainly do it again if necessary. My point is that if I became such an permanent expat (for medical or prolongevity reasons), I would no longer consider myself to be an "American" from the standpoint of owing any loyalty to the nation-state or the institutions that prevent my access to anti-aging therapies within the U.S. itself.
the problem with society, as it is currently constituted, is that it is built around the "planned obsolesence" of human beings. In otherwords, people are treated by companies, governments, and other institutions in general, as depreciating assets. This is current reality and I have to accept that it is like this.
However, I see no reason why I should feel any sense of "loyalty" or "debt" to such a society and its institutions as long as it is constituted in this manner. I am loyal to only my dreams and goals in life, nothing else.
Kurt, Your example of unjustified interference in cryonics provides an excellent illustration of the problems besetting that controversial field. (Glad to hear that your friend's cancer went into remission.) I have been reading about cryonics since the 1980s, and the most fascinating and best rationale I have seen for the approach appears in Ralph Merkle's article in the Journal "Medical Hypotheses". The paper entitled "The Molecular Repair of the Brain" is available here. (You probably already know about this paper but the link might be useful to other readers.)
Cryonics is highly speculative but coercion should not be used to frustrate the voluntary plans of an individual regarding the disposition of his or her own body in my opinion. Unfortunately, pop-science journalists like Michael Shermer have written puerile critical opinion pieces about cryonics. This web page presents Shermer's "Scientific American" slam article together with an excellent rebuttal from Dr. Steve Harris.
There are currently few nations that even have an active cryonics organization. Outside the US it might be more difficult to find a team like Alcor's that can attempt cryo-preservation. This website states that assisted suicide "remains a crime almost everywhere". Interestingly, Oregon in the US is one of the few places that now allows physician-assisted suicide. Perhaps someone with a disease such as inoperable brain cancer who is highly motivated and believes that cryonics is a "last chance" (however small) could find in Oregon two knowledgeable and sympathetic physicians (two are required) and could work out a plan of coordination with Alcor.
Here is what the web site says about Australia: "The Northern Territory of Australia actually had legal voluntary euthanasia and assisted suicide for seven months until the Federal Parliament stepped in and repealed the law in l997. ... Other states have since attempted to change the law, most persistently South Australia, but so far unsuccessfully."
Scientific American is a left-wing sheet that mascarades as a science journal.
I think that a cloning ban in the U.S. is a moot point. If the Brownback bill becomes law, the State of California will file an injunction against this law until a judicial ruling is made. It is very likely that, if passed, any cloning ban will be ruled as unconstitutional on the grounds of first amendment rights. The first amendment protects the right to scientific research in two ways. First, the freedom of scientific endevour is considered to be an aspect of the freedom of self-expression. Secondly, scientific research is protected because it is considered to be "content" of which restrictions on thereof are considered to be censorship, which is restriction of free speach.
Any attempt to restrict the development of and access to effective stem cell therapies violates both the 5th and 14th amendment because these amendments protect the right to "life" and "liberty". Any bans on effective anti-aging therapies also violate the 5th and 14th amendments to the constitution as well.
It appears that our right to "immortality" is constitutionally protected.