Parthenogenesis and "Virgin Birth"? Rhetoric and Research

Despite roadblocks, the field of stem cell research remains profoundly attractive. The idea of being able to regenerate damaged or diseased cells in the human body is appealing to nearly everyone who cares about human health.

But technical problems remain. Much has been learned in the past decade, but the pathway to medical treatments still faces many challenging problems. One worry in particular is that implanted stem cells might develop into cancer. Others challenges including getting the cells to multiply, integrate with other cells, function as they should, and avoid being rejected as an infection.

A new solution may be on the horizon, one that addresses many of these problems—moral and technical—all at once. At least that’s the claim made by a team led by Wolfram Zimmerman and colleagues at Georg-August-Universität Göttingen in Germany. Working with laboratory mice, Zimmerman’s team used mouse eggs to create what are known as parthenotes. Without being fertilized, the mouse eggs were manipulated so that they began to develop as if they were fertilized, up to a point.

PHOTO: Mouse embryonic stem cells. This image is a work of a National Science Foundation employee, taken or made as part of that person's official duties. As a work of the U.S. federal government, the image is in the public domain. This image was copied from wikipedia:en.

Parthenogenesis exists in nature. It has been observed in some plants, fish, and reptiles. Over the past decade, researchers have learned how to induce parthenogenesis in mice, monkeys, and humans. In every case, however, the resulting parthenotes fail to develop normally, which means they could never be implanted to produce a child. But they do develop for a few days, long enough for the precursors of pluripotent stem cells to develop.

What is new in the research reported on February 22, 2013 is unexpected success in the use of these stem cells derived from mouse parthenotes. These cells—parthenogenetic stem cells or PSCs—were developed and eventually implanted into damaged mouse hearts. Quite simply, they worked in ways that seem to overcome most if not all of the technical hurdles.

The research appears in the Journal of Clinical Investigation, which carried a companion article claiming that the new research “may overcome all…formidable barriers” that currently stand in the way of stem cell medicine. The original article makes this claim: “One of our key observations involved the capacity of PSCs to exhibit essentially normal cardiogenesis in vitro and in vivo.” In other words, both in the dish and in the mouse, implanted cells fully integrate into the beating heart.

Both the research article and the companion piece make another claim: PSCs are ethically acceptable. That’s because parthenotes are not embryos. Taking cells from parthenotes avoids all the moral concerns that surround the use of cells derived from embryos. Here is the claim: Research using human PSCs, derived from human parthenotes, involves “no destruction of viable embryos,” according to the research article. The companion piece simply notes that compared to embryonic stem cells, PSCs “do not have the same ethical implications.”

If only it were that simple. But plain the fact is that some who object to the use of human embryos in research are already on record as objecting to the use of human parthenotes.

Their logic is fairly straightforward. If human embryos are off limits and if parthenotes cannot be clearly and definitely distinguished from embryos, then human parthenotes are equally off limits to research.
They are not claiming that parthenotes are little people, nor are they being silly or obstructionist. They are only claiming that we do not have enough scientific clarity and certitude to proceed with moral confidence in the work of creating and destroying parthenotes, regardless of the benefit.

Just to be clear, I personally disagree with this objection. But researchers and regulators should be aware that some, at least, will balk at this new line of research, technically attractive as it may be.

For example, in a statement given to the UK Parliament, the Church of Scotland made this comment:

“We reject the suggestion made by various researchers that hybrid embryos, parthenotes and embryos that have been modified to make then non-viable would be an ethical solution to deriving stem cells from embryos. Whatever the status of such creations, it is would be at least as unethical to use methods that would create an ‘embryo’ so deformed that it could not be viable and which therefore inherently denies its potential to develop.” 

Politically more important is the response that will come from Catholics. Some Catholic scholars have defended the moral legitimacy of research using human parthenotes. There is simply no way, they argue, to equate the parthenote with the embryo. The parthenote is not a product of conception. In more popular rhetoric: If “life begins at conception,” then the parthenote is not “life.” Nor can it develop normally. It meets none standard definitions of an embryo.

Others are not so certain. They translate scientific and theological uncertainty into a moral prohibition. Creating and destroying a parthenotes requires that we know for sure that they are not embryos. Such certainty is lacking, at least for now. In the face of uncertainty, they argue, we must not proceed.

On the Catholic website www.ewtn.com, E. Christian Brugger addresses the question: Is the parthenotes enough like and embryo to be considered an embryo? His answer:

“The question presently is unsettled.” He adds this: “Although the empirical question of the status of a human parthenote is unsettled, the underlying moral principle is straightforward. Unless we have moral certainty that a dividing parthenogenetically activated human oocyte is not an embryo, we have an obligation to avoid research with human parthenotes.”

And at the end he concludes:

“Having said this, the present evidence on whether parthenotes are ever embryos seems to me inconclusive. Given the evidence to date, at least with which I am familiar, I do not think it can be established with moral certitude that parthenotes are never human embryos.”

Personally, I want to see this research go forward, and so I have some suggestions for researchers and reporterss in this field.

First, help religious scholars build the case scientifically, showing in clear terms to the wider public why parthenotes are not functionally like embryos and why a morally robust boundary separates the two. Science itself cannot create that boundary, but it can provide evidence supporting moral and philosophical arguments in favour of such a boundary.

Second, stop using provocative phrases like “virgin birth.” Regrettably, the companion piece in the Journal of Clinical Investigation is published with this title: “Virgin birth: engineered heart muscles from parthenogenetic stem cells.”

Sure, “parthenos” is Greek for virgin, so the etymology supports the use of the term “virgin birth.” But for billions of Christians around this world, this term has a very special religious meaning, one that many associate with the most tender core of their faith.

For scientists to claim they are simulating the “virgin birth” is offensive to anyone who takes the religious meaning of the phrase seriously. It is needlessly provocative, almost the worst thing that could be said if religious support for research is desired.

What’s more, associating parthenogenesis with the “virgin birth” has the bizarre effect of equating the parthenote with the embryo. Christians who hold to the “virgin birth” will claim that in one profoundly non-trivial example (Jesus), what scientists now claim they are creating turned out to be a fully viable embryo. And then they say, “But don’t worry; it’s not a human being”?

The original article, entitled "Parthenogenetic stem cells for tissue engineered heart repair," is published in the February 22, 2013 issue of the Journal of Clinical Investigation, together with the companion piece.

Engineered Eggs

Researchers in Japan have reported success in generating mouse eggs or oocytes from pluripotent stem cells. When fertilized, these induced eggs grew into live, healthy pups capable of producing their own offspring. The work is reported in the October 5 issue of the journal Science.

The research team used two different types of pluripotent cells, embryonic and induced. In both cases, they were able to produce cells that are the precursor of the cells of the ovaries, which form eggs. Once they produced these cells and grew them in clusters, they implanted them into the bodies of female mice, where they developed into cell structures that functioned like ovaries. From these reconstituted ovaries, researchers harvested mature oocytes, much as they would for in vitro fertilization (IVF).

The next step, predictably, was to fertilize these eggs and implant them in surrogate mother mice. Once born, the pups developed and were allowed to breed, producing viable offspring.

Pups from ES-oocyte. Female offspring from primordial germ cell-like cell-derived oocytes were fully fertile. Courtesy of Katsuhiko Hayashi.

The most immediate impact of this research will be to advance our understanding of the fundamentals of reproductive biology, especially the development of egg cells. If similar strategies will work with human pluripotent stem cells—especially induced cells—this research may open new approaches for reproductive medicine in the years ahead.

What other possibilities might there be? Again, if the work can be replicated in human beings, two things might happen. Somewhat more remote is the possibility that this strategy will be used for the purposes of human germline modification or so-called “designer babies.” For example, pluripotent stem cells might be genetically modified before they are induced to become the source of oocytes. The modification could be to avoid a disease or for the purposes of enhancement.

More likely, of course, is that this strategy will be used to create human oocytes for research purposes. For example, human induced ovary-like cells could be implanted into a mouse or other nonhuman animal, grown to the right stage of development, then “harvested” in order to collect a significant number of oocytes.

Today, research in certain areas is hampered because of limited supplies of human oocytes. One area that comes to mind is nuclear transfer or cloning. While “Dolly” the sheep is now only a distant memory, this advance brings closer the possibility that with an ample supply of human oocytes for experimentation, researchers will learn how to create human clones reliably.

So the big question is whether this research can be replicated in humans. On that point, here's how the article concludes: "our system serves as a robust foundatin to investige and further reconstitution femaile germline development in vitro, not only in mice, but also in other mammals, including humans."

The article, entitled "Offspring from Oocytes Derived from in vitro Primordial Germ Cell-like Cells in Mice," appears in the 5 October 2012 issue of the journal, Science.

A New Source for New Neurons

The day when stem cell research will give us treatments for common brain disorders such as Parkinson’s or Alzheimer’s just got a little closer. So, by the way, did the day when this research will be used to enhance the capacities of the normal or healthy human brain. The latest advance comes from an international team based mostly in Germany, which has figured out a way to generate new neurons from cells that already exist in the human brain.

The human brain naturally contains specialized cells called pericytes. Usually they are located at the edge of the capillaries that carry blood to the brain. They play a vital role in maintaining the blood-brain barrier.

Neurons. Photo from National Institutes of Health.

Now, thanks to the discovery reported in the October 5 issue of Cell Stem Cell, pericytes might be about to learn a new trick: forming new neurons. Using stem cell reprogramming techniques, researchers learned that two factors—Sox2 and Mash1—would induce pericytes to change their developmental state and begin to function as newly-formed neurons.

According to the article, “these induced neuronal cells acquire the ability of repetitive action potential firing and serve as synaptic targets for other neurons, indicating their capability of integrating into neuronal networks.” In other words, they do what neurons normally do. They process signals from one end of the cell to another. They form synaptic connections with other neurons. And they integrate into larger networks.

Will this become a new strategy for treating diseases or injuries to brain cells? That is the hope, but difficult challenges remain. How can living pericytes in a functioning human brain be targeted and induced to become neurons? If they generate new neurons, will they function properly? Will they integrate themselves into a functioning brain, preferably taking up the cognitive processes that are lost because of disease or injury?

The authors conclude that “much needs to be learned” but that “our data provide strong support for the notion that neuronal reprogramming of cells of pericytic origin within the damaged brain may become a viable approach to replace degenerated neurons.”

According to Benedikt Berninger of the Johannes Gutenberg University in Mainz, a leader in the research team, “The ultimate goal we have in mind is that this may one day enable us to induce such conversion within the brain itself and thus provide a novel strategy for repairing the injured or diseased brain."

That may be the goal, but it's hard to imagine this research will be limited to therapy. In fact it may turn out to be easier to use it to enhance the cognitive capacity of normal or healthy aging brains than it is to treat disease. Anything that stimulates the growth of new neurons is likely to be very appealing to aging adults.

If human stem cell research is to reach its full promise, many more advances like this will have to occur. With each advance, however, comes growing confidence that the promise of the field may be highly challenging, but it is not hype.

The article entitled “Reprogramming of pericyte-derived cells of the adult human brain into induced neuronal cells” is published in the October 4, 2012 issue of Cell Stem Cell.

Synthetic Biology: Is There Life beyond DNA?

Life as we know it is based on DNA and RNA. Could it have been otherwise? Might other worlds have life based on a different “genetic” system? We may never know for sure.

But we do know that synthetic biology is moving briskly toward the goal of engineered life beyond DNA and RNA.

Recall that in “DNA” and “RNA,” the “NA” part stands for “nucleic acids.” It’s the four nucleic acids that carry the genetic information in a chemical code. The “D” and the “R,” however, stand for sugars that hold the nucleic acids in place, allowing them to form pairs and to copy themselves. Can other sugars work as well?

Recent work in synthetic biology has led beyond DNA and RNA to xeno-nucleic acids or “XNAs.” Now, using six different forms of XNAs, an international team of researchers led by Vitor Pinheiro reports success in getting XNAs to store and propagate information. One of their XNAs actually “evolved” by responding to imposed selective constraints. Their work is published in the April 20, 2012 issue of the journal Science.

Caption: Courtesy--National Human Genome Research Institute

In a commentary on the research, Gerald F. Joyce writes in Science that this work has implications for the “understanding of life itself.” In addition, it opens new insight into the possible origins of life on our planet or else where in the cosmos.

At the same time, far more work lies ahead before synthetic biologists create XNA-based life. Pinheiro’s team was able to get their synthetic XNA “genes” to interact with DNA, but “they have not yet realized a synthetic genetic system.” One big challenge is in getting XNA sequences to copy themselves the way DNA does. Some XNAs can copy themselves to DNA and back again to XNA, but XNA-to-XNA copying is not reliable.

According to Joyce, however, “future studies are likely to yield improvements of the the various XNA-to-XNA copying reaction.” If that happens, synthetic biology will take yet another step toward “synthetic genetics.”

All this prompts a warning from Joyce: “Synthetic biologists are beginning to frolic on the worlds of alternative genetics but must not tread into areas that have the potential to harm our biology.” As ever, greater knowledge brings greater risks. More than ever, public awareness and careful thought are needed.

The research article, "Synthetic Genetic Polymers Capable of Heredity and Evolution" and the commentary, "Toward an Alternative Biology," are both published in the April 20, 2012 issue of Science, the journal of the American Association for the Advancement of Science.

Stem Cell Update: Important Research Breakthrough

Another important step has just been taken toward achieving the medical promise of stem cell research. For the first time, researchers at the Max Planck Institute for Molecular Biomedicine in Münster, Germany, have reprogrammed skin cells directly into multipotent stem cells.

Over the past five years, stem cell researchers have learned how to induce or reprogram skin cells to become pluripotent stem cells—cells capable of becoming any type of cell in the body. The result: induced pluripotent stem cells or iPSCs. Scientists have also discovered how to reprogram cells to become precursor or progenitor cells. Precursor cells have a much narrower range of potential for development. They are able to become one very specific type of cell in the body.

Expanding on previous work, the latest breakthrough achieves a kind of “goldilocks” or just-right level. Working with mice, the team led by Hans Schöler discovered how to reprogram fully differentiated skin cells into neuronal stem cells (NSC)s. Unlike pluripotent cells, NSCs are far more suitable for clinical use. And now, with this breakthrough, the Max Plank Institute team has learned how to reprogram or induce NSCs or iNSCs.

And unlike precursor or progenitor cells, iNSCs are capable of multiplying and diffentiating once they are implanted. When researchers implanted their iNSCs into mouse brains, iNSCs generated new cells that began to take on some of the characteristics of ordinary developing brain cells.

Caption: This is an immunofluorescence microscopy image of the induced neural stem cells (iNSCs) using antibodies against two neural stem cell markers SSEA1 (red color) and Olig2 (green color). Credit: MPI for Molecular Biomedicine

The field of stem cell research has faced many obstacles, some moral and some medical. The main moral objection is that the prime source of human pluripotent cells is the human embryo, and many object to the destruction of the embryo for medical purposes. One of the medical challenges is that implanted cells are likely to be rejected by the immune system, much as transplanted organs are rejected unless immunosuppressant drugs are given.

Unless, of course, the source of the cells is from the patient’s own body. That’s why this achievement is important. If this technique can be applied to human cells—and there’s no reason to think it can’t—then someday it may be possible to take a small sample of cells from a patient’s skin, convert them to iNSCs, and then implant them in the patient’s brain to repair damage from disease or injury.

Not only does the iNSC discovery use the patient’s own cells as the source. It also by-passes the pluripotent stage. That fact should help researchers avoid creating cancer or other problems.

According to Schöler, "pluripotent stem cells exhibit such a high degree of plasticity that under the wrong circumstances they may form tumours instead of regenerating a tissue or an organ."

"Our research shows that reprogramming somatic cells does not require passing through a pluripotent stage," Schöler said in a press release issued by the Max Plank Institute. "Thanks to this new approach, tissue regeneration is becoming a more streamlined—and safer—process."

The article, "Direct Reprogramming of Fibroblasts into Neural Stem Cells by Defined Factors," appears in the March 22 issue of Cell Stem Cell.

Regenerative Medicine: Repairing the Heart

A breakthrough in the use of stem cells for regenerative medicine has just been reported by researchers at Cedars-Sinai Heart Institute. Patients who suffered heart attacks were implanted with cells derived from their own hearts. Some of the scars left by the heart attacks dissolved and new heart muscle cells re-grew, according to a report in the February 14 issue of The Lancet.

Patients involved in the study had all experienced recent heart attacks that damage heart muscle. The first step in the procedure involved inserting a catheter through a vein in the neck under local anesthesia. Using the catheter, researchers withdrew a small sample of healthy heart tissue. The tissue contains some stem cells, but the key step in the procedure is to multiply and purify the small number of stem cells so that they number in the tens of millions.

These cardiac stem cells, multiplied but originally from the patient’s own heart, were then infused back into the site of the heart attack. The result seems to be a nearly 50% drop in the size of the scar and a re-growing of healthy heart muscle, at least as far as could be determined using imaging technology.

It is important to note that this study is a Phase I clinical trial. Its main purpose is to show that there is no unwarranted risk in the procedure. The outcome of this trial, however, shows a real likelihood of benefit. The evidence is strong that scaring is reduced and heart muscle regenerated. It is too soon, of course, to know the long-term benefits.

What is new in this study is the strong likelihood of actual regeneration of heart cells. Whether the implanted cells produced the new muscles or whether they acted indirectly, triggering neighboring cells to divide and regenerate tissues, is still not clear.

The lead researcher in the study, Eduardo Marbán, made this claim about the finding: "This has never been accomplished before, despite a decade of cell therapy trials for patients with heart attacks. Now we have done it. The effects are substantial, and surprisingly larger in humans than they were in animal tests." Marbán is the director of the Cedars-Sinai Heart Institute who invented the procedures and technology involved in the study, including the procedures for multiplying the stem cells.

"These results signal an approaching paradigm shift in the care of heart attack patients," said Shlomo Melmed, MD, dean of the Cedars-Sinai medical faculty and the Helene A. and Philip E. Hixon Chair in Investigative Medicine. "In the past, all we could do was to try to minimize heart damage by promptly opening up an occluded artery. Now, this study shows there is a regenerative therapy that may actually reverse the damage caused by a heart attack."

The study itself concludes with this claim: “Our study provides an initial indication that therapeutic regeneration might indeed be possible in cardiac tissue.”

The goal of regenerative medicine—the use of stem cells to help patients regrow cells and regenerate tissues or organs—has long been central to the dreams that surround stem cell research. Even though this in only a Phase I study and still must be replicated, it seems to be an important step in the development of regenerative medicine.

Many of course will be especially delighted that no embryonic stem cells were directly involved in this procedure. Those who object to the use of human embryos in research will regard these cells as “morally unproblematic.” It is also very significant to point out that because the cells come from the patients, there should be no issue of tissue rejection.

At the same time, it should be noted that the field of stem cell research advances as a whole field. Knowledge gained from one area (for example, using embryonic stem cells) opens the door for advances across the whole field.

The article, “Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial,” appears appropriately in the Valentine’s Day issue of the medical journal, The Lancet.

New Hope for Alzheimer's Patients?

Working with mice, researchers at Case Western Reserve University School of Medicine are reporting a dramatic discovery in the search for a treatment for Alzheimer’s disease (AD). They treated Alzheimer’s-prone mice with a drug called bexarotene, which is already FDA-approved and available as the anti-cancer drug Targretin®.

The result, reported in the February 10 issue of Science, is nothing short of stunning. Bexarotene appeared to dissolve the excess brain-harming amyloid beta in the mouse brain. Amyloid beta (Aβ) is produced naturally in healthy brains, mouse and human. But when Aβ builds up and forms deposits, it seems to interfere with the function of the brain, including the formation of new memories.

Researchers found that just six hours after administering bexarotene, 25% of the excess Aβ was cleared from the brains of the mice. After 72 hours, 75% of the Aβ plaque was gone and the behavior of the mice was observably different. For more on these finds, take a look at this video released by Case.

So now the big question is this: If bexarotene works like this in mice, will it work the same way in human beings with AD? According to Gary Landreth, professor of neurosciences at Case and lead author of the study, that question is already researched. “We need to be clear; the drug works quite well in mouse models of the disease. Our next objective is to ascertain if it acts similarly in humans. We are at an early stage in translating this basic science discovery into a treatment,” Landreth said in a press release issued by Case.

One interesting point about bexarotene is that it does not act directly on Aβ. What it appears to do is to stimulate the expression of gene, apolipoprotein E or apoE. Bexarotene seems to switch apoE back on to a healthy level, which produces a protein that helps clear Aβ from the cells of the brain.

This discovery about bexarotene is truly exciting news in the field of Alzheimer’s research. In the final sentence of the report in Science, the authors conclude cautiously that “The ability of bexarotene to rapidly reverse a broad range of deficits suggests that…[it] may be of therapeutic utility in the treatment of AD…”

If you know someone dealing with AD—and who doesn’t?—this is a promising advance. It is critical, however, to stress that there are still key questions that must be answered before this finding changes the way AD is treated.

On the positive side, part of the excitement is that bexarotene is already FDA-approved. What about side effect? As the study puts it, bexarotene has “a favorable safety profile.” In other words, we already know that this drug is reasonably safe for human use.

But will it work? And if so, how long will it work in an individual AD patient before the benefits of the drug are no longer strong enough to off-set the progression of the disease?

Time will tell. For now, however, there’s new reason for hope in the face of one of our most dreaded diseases.

The article entitled "ApoE-directed Therapeutics Rapidly Clear β-amyloid and Reverse Deficits in AD Mouse Models” is published in the February 10 issue of Science, the journal of the American Association for the Advancement of Science.

Designer Babies Revisited

“Designer Babies” are back in the news. Scientists and medical experts in Australia have asked the government to allow the use of a controversial technique to allow couples to conceive without passing on a genetic disease.

The technique is controversial, at least in the media accounts, because the child that is conceived would have three parents.

The truth is a little more complicated but a lot less dramatic. Most of the genes in our cells are located in chromosomes, which we get from both our parents. A very few genes are located outside the chromosomes in small structures called mitochondria. These genes—our “mitochondrial DNA”—are necessary for energy production in the cell. If they are defective, the result can be a number of diseases.

We get our mitochondria only from our mothers. That means that if a woman has a defect in her mitochondrial DNA, she will inevitably pass it on to all her children, who may be more or less ill than she has been during her lifetime.

But what if a couple could conceive a child using their own chromosomal DNA while using a donor’s mitochondria? That would give the couple the best opportunity to have a child that is almost entirely “their own” genetically while avoiding diseases associated with mitochondrial irregularities. That’s the hope that doctors in Australia are holding out.

In 2001, word leaked out that a fertility clinic in New Jersey was quietly offering this technique. The report triggered a bit of a flap, mostly over issues of safety and the utter lack of government oversight or public moral reflection. The best account of that episode is found in an essay by Erik Parens and Eric Juengst, “Inadvertently Crossing the Germ Line,” appearing in the journal Science in April of 2001.

Is the strategy safe? Should it be permitted? Is it moral? Is “germline” modification in general ethically defensible? Is it religiously objectionable?

I try to address some of these questions in my 2008 collection of essays, Design and Destiny: Jewish and Christian Perspectives on Human Germline Modification. Among other findings: Catholic teachings may object to specific techniques but not so much to the core idea. As long is “in vitro” techniques are not used, what could be wrong with helping a couple conceive a healthy child? (See my earlier post.) But for all religious people, is there a line to be drawn between germline modification aimed at avoiding disease and the very same technique that might be used to produce a “better” child—one that is smarter or healthier than normal?

To be clear, the Australian scientists are proposing no such thing. But as they know, these techniques will likely advance along a common front. The minimal modification to avoid mitochondrial disorders will help pave the way to germline modification to avoid other diseases. And those techniques will almost certainly lead in time to the possibility of enhancing our offspring.

Chimeric Monkeys? Where Do We Go From Here?

What is a “chimeric monkey”? Why would anyone want to create them? And why should anyone care?

In ancient myth, a chimera was an animal with a human head and, say, the body of a horse or a lion. That’s not what’s going on here.

In biology today, a chimera is an animal that comes from two or more embryos. This happens naturally, when twins are conceived but the two fertilized eggs fuse into one embryo, eventually producing one individual.

In research, scientists create chimeras in order to study how cells function. Mice chimeras are now commonplace in stem cell labs around the world. Researchers add stem cells to an early-stage mouse embryo (a blastocyst). If the experiment goes well, the developing mouse will have cells from two sources: the “host” embryo and the implanted cells. The implanted cells often integrate into the body and brain of the mouse pup. By this test, researchers know that the implanted cells are truly stem cells—or, more precisely, that they are pluripotent, capable of becoming any type of cell in the mouse body.

Caption: Chimero, a chimeric Rhesus monkey produced by aggregating six Rhesus blastocysts. Photo credit: OHSU.

Researchers also implant human stem cells into mice. If they multiply and are fully integrated into the body, it’s pretty clear that they are pluripotent and capable of functioning within a living biological system and not just in a dish in a lab. In that case, the mouse is an “inter-species” chimera. Two embryos, of course, but from two different species, human and mouse.

For all the ways in which mice resemble human beings, there are big differences, some of which are particularly noticeable at the earliest stages of life. So when researchers at the Oregon National Primate Research Center at Oregon Health & Science University tried to put pluripotent monkey stem cells into monkey blastocysts, they failed. At the blastocyst stage, Rhesus monkeys don’t behave like mice.

The Oregon team, led by Shoukhrat Mitalipov, kept trying other approaches, finally discovering a completely different technique. Instead of using embryonic or pluripotent stem cells and adding them to a blastocyst, they backed things up, at least in terms of embryonic development. How far back? All the way to the four-cell stage. When a Rhesus monkey egg is fertilized (in this case, in a lab dish), it divides into two cells, then four. What happens if two cells in one blastocyst were combined with two cells from another blastocyst? Success—but still only partly so.

So they tried another approach, one that seems complex and counterintuitive. Researchers “aggregated” three blastocysts—and “they” began to function as one embryo. Four blastocysts—same result. Five, even six blastocysts. They did this 29 times and produced 29 viable chimeric embryos. Or to quote the original paper: “Remarkably, all 29 aggregates developed to blastocysts…”

Just what will this mean for the field of stem cell research? At the very least, this research points to the complexity of living biological systems. It’s nice to think that researchers can extract pluripotent stem cells, keep them multiplying indefinitely, direct them to develop just the right way, and implant them into the human body to regenerate tissues. If only it were that simple. As the field advances, it is clear that what was once called “pluripotency”—the ability to become any cell type—is anything but clear or simple to define.

All the more reason, I believe, why the field needs to move forward as a whole. It’s morally and scientifically simplistic to say that the field can advance without cells from embryos.

But does the Oregon work suggest a step too far? For many, it may be morally permissible to work with cells derived from blastocysts, perhaps donated from IVF clinics and due to be discarded anyhow. But what the Oregon work seems to signal is that when it comes to primates—including human beings—the cells in the living blastocyst are significantly different from the cells derived from the blastocyst. The cells in the living blastocyst, though dynamic and changing, can be regarded as totipotent, capable of becoming any cell type including the placenta and umbilical cord. Cells derived from the blastocyst—human “embryonic” stem cells or pluripotent cells—have lost part of this potential.

Does this mean that research, in order to go forward, needs access to cells as they exist in living blastocysts? That would be a step clearly beyond federal funding guidelines (the “Dickey-Wicker Amendment”). Even with private funding, it would likely exceed what most Americans can support. In some states and many countries, it would be plainly illegal.

And yet this is exactly what lead Oregon researcher Shoukhrat Mitalipov seems to have in mind. "We need to study not just cultured embryonic stem cells but also stem cells in embryos,” Mitalipov said in a release from the journal Cell. “It's too soon to close the chapter on these cells." Is that OK as long as he sticks to non-human primates?

Mitalipov is clearly right: "We cannot model everything in the mouse." Rodents and primates are different in unexpected ways at the earliest stages. Stem cells inserted in mouse blastocysts form chimeras, but not in primate blastocysts.

Quoting Mitalipov once again: "The possibilities for science are enormous." All the more reason to think this through. As complex as the science might be, the moral and religious implications are even more complex.

I for one need time to think this through. I hope to be back here before long with some more thoughts. For now, let me recommend a statement that I helped prepare a few years ago on the question of chimeras.

The paper, "Generation of Chimeric Rhesus Monkeys," was released on January 5 and will appear in the January 20, 2012 issue of the journal, Cell.

Are You as Empathetic as a Rat?

Empathy is the capacity to share the emotional state of another. Politicians claim to have it when they say “I feel your pain.”

Even if they do not always show it, human beings are clearly capable of empathy. Other primates such as chimps have been observed acting in a way that is best explained by empathy. Rather than acting for their own benefit, they sometimes act because they share the feeling or distress of another chimp. Such behavior is said to be “empathy-driven.”

Once it was thought that only human beings could feel empathy. Now researchers are finding that empathy-driven behavior is more widespread than previously imagined. Not just other primates but even rodents, it seems, are biologically capable of empathy. For all the differences between the human and the rat brain, we share fundamental circuits that make it possible to feel the emotions of another, particularly when the other is in pain or distress.

In a simple experiment reported in the December 9 issue of the journal Science, researchers provide solid evidence that the much-maligned rat is capable of acting in a way that is most easily explained by empathy.

"This is the first evidence of helping behavior triggered by empathy in rats," said Jean Decety, a member of the research team at the University of Chicago. "There are a lot of ideas in the literature showing that empathy is not unique to humans, and it has been well demonstrated in apes, but in rodents it was not very clear. We put together in one series of experiments evidence of helping behavior based on empathy in rodents, and that's really the first time it's been seen," Decety said in a release issued by the University.

In order to act in a way that is empathy-driven, an animal must be capable of “emotional contagion.” To test whether rats have this capacity, an experiment was designed Chicago psychology graduate student Inbal Ben-Ami Bartal. Two rats were placed in an enclosure, one of them roaming freely while the other was locked inside a tube. The free rat, in time, could discover how to open the lock, but there was no reward for doing so.

The experiment was designed observe whether rats show they are capable of emotional contagion. Was the free rat biologically capable of emotional concern or what the paper defines as “an other-oriented emotional response elicited by and congruent with the perceived welfare of an individual in distress”?

PHOTO: ©Science/AAAS.

The free rats not only learned to open the container but did so repeatedly when it held another rat, something they did not do if it was empty or if it contained a stuffed animal.

Even more striking was their behavior when chocolate chips were involved. In one variation on the experiment, two enclosures were used, one with an enclosed rat and the other with five pieces of chocolate. The free rat has a choice: free the cagemate or eat the chocolate first. In the absence of empathy, the free rat will make the selfish choice. But at least half the time, the rat freed its cagemate first. According to the report, “these results show that the value of freeing a trapped cagemate is on par with that of accessing chocolate chips.”

"On its face, this is more than empathy, this is pro-social behavior," said Jeffrey Mogil of McGill University, who was not involved in the study. "It's more than has been shown before by a long shot.”

Without claiming to know what rats think, the authors conclude their report with their opinion that “the free rat was not simply empathetically sensitive to another rat’s distress but acted intentionally to liberate a trapped” member of their own species.

If rats are indeed capable of empathetic feelings, then it becomes clear that the biological substrate for shared emotion is deep in our evolutionary past and deep in the earlier parts of our brains. Far from being uniquely human, empathy seems to be widely shared. What is uniquely human, perhaps, is the way we override it with self-interest.

As I prepared this post, I was interrupted several times by others who were speaking of the history of racism in America and particularly the history of slavery. When I saw the pictures of rats in their enclosure, my mind went to chains and slave ships. If empathy is so deep in our mammalian evolution, so deeply rooted in our brains, what extraordinary rationalizations do we conjure up to negate it?

The paper, "Empathy and Pro-Social Behavior in Rats," is published Dec. 9 by the journal Science. http://www.sciencemag.org/content/334/6061/1427.abstract

Enhancing the Brain: A New Approach?

A molecule that protects you against viruses may also be slowing down your brain. That’s the startling finding just reported by researchers at the Baylor College of Medicine.

In the December 9 issue of Cell, a research team led by Mauro Costa-Mattioli report on how a key component of the immune system may also play a central role in the brain’s ability to form memories.

The molecule in question is the enzyme “protein kinase RNA-activated” or PKR for short. PKR is well-known to biomedical researchers. It is found in nearly all vertebrates and helps fight viral infections.

What was unknown is how PKR plays a pivotal role in regulating how the brain forms memories. Using mice, Costa-Mattioli’s team found that PKR actually slows down the brain’s ability to form memories. By blocking the production of PKR in mice, Costa-Mattioli’s team was able to produce mice with enhanced memory.

“The molecule PKR (the double-stranded RNA-activated protein kinase) was originally described as a sensor of viral infections, but its function in the brain was totally unknown," said Costa-Mattioli in a press release issued by Baylor Medical College.

The researchers used two methods to block PKR. They produced mice that were genetically modified so they couldn’t produce PKR. But they also used a drug that inhibits the production of PKR. In both cases, memory capacity was enhanced.

How does PKR act in the brain? Apparently by interacting with another key molecule, interferon-γ or IFN-γ, which is also best known for its role in the immune system. Researchers believe that in the brain, PKR and IFN-γ interact, keeping each other in balance. Suppressing PKR seems to increase the role of IFN-γ and the activity of the brain, particularly the neurons that are creating long-term memories.

“These data are totally unexpected, and show that two molecules classically known to play a role in viral infection and the immune response regulate the kind of brain activity that leads to the formation of long-term memory in the adult brain,” said Costa-Mattioli.

What is perhaps most startling about the report is that a drug that inhibits PKR enhances memory in mice. “It is indeed quite amazing that we can also enhance both memory and brain activity with a drug that specifically targets PKR,” according to Costa-Mattioli.

If a drug enhances memory capacity in mice, could it work in humans? That’s a big jump, one that will take much more research before anything is even tested in human beings. But researchers suggest that this is possible and worth exploring. Costa-Mattioli said, "More investigation is undoubtedly necessary to translate these findings to effective therapies but we would be delighted if our scientific studies were to contribute in some way to this ultimate goal."

“Our identity and uniqueness is made up of our memories," Costa-Mattioli said. "This molecule could hold the key to how we can keep our memories longer, but also how we create new ones.”

Will this provide a new strategy in dealing with diseases that rob us of our old memories and of our capacity to create new ones? Given the stakes, research will explore these possibilities.

If the research is applicable to human beings (and why not?) and if it provides a new path to preventing or delaying dementia, it will also open new ways to think about the enhancement of human cognition. The mice in the study were not suffering from any memory loss, but the speed at which they were able to learn a new task was enhanced nearly four-fold.

Given the wide-spread interest in cognitive enhancement, especially on university campuses and among transhumanists, we should expect to hear more about how inhibiting PKR just may make you smarter.

The article, "Suppression of PKR Promotes Network Excitability and Enhanced Cognition by Interferon-γ-Mediated Disinhibition,” appears in the December 9 issue of Cell.

Cognitive Enhancement: Campus Update

Use of drugs to boost academic performance is nothing new, but The Washington Post has just published a news story suggesting that use of these drugs is increasing on college campuses.

The story, written by Post reporter Jenna Johnson, refers to a study at the University of Maryland that suggests that students who take cognitive enhancers study less, party more, and have slightly lower grade point averages than their classmates. That suggests that their main purpose for using the drugs is stay competitive without letting studies get in the way of college.

There is little doubt, however, that the drugs are also being used by highly focused, academically competitive students in demanding programs. Their purpose: to add an edge to their hard work in order to stay in the top one or two percent of the competitive pile. As the Post reports, one name for these drugs is “Ivy League crack.”

The drugs in question are familiar enough—mostly Ritalin and Adderall. Students without prescriptions can easily buy these drugs from other students.

Should use of these drugs be treated as crimes? Or should those who wish to excel academically be allowed to use whatever means helps them achieve that end? For more on that debate, see the now-classic 2008 article in the journal Nature, in which prominent bioethicists such as Stanford’s Henry Greely argue for greater tolerance and openness.

Brain Regeneration: Mouse Brains and Human Futures

Embryonic stem cells are surprisingly capable of regenerating portions of the brains of mice according to a report published in the November 25 issue of the journal Science. What is unexpected about this report is not the extent of the repairs so much as where they occurred in the brain.

The hypothalamus, which is involved basic metabolism and complex behaviors, has usually been regarded as less open to regeneration, whether naturally or by biomedical intervention. Naturally, a limited number of neurons develop during adulthood, but these are not enough to restore this area of the brain after injury or disease. “The neurons that are added during adulthood in both regions are generally smallish and are thought to act a bit like volume controls over specific signaling,” explained Jeffrey Macklis of Harvard Medical School and one of the lead researchers in the study.

“Here we've rewired a high-level system of brain circuitry that does not naturally experience neurogenesis,” Macklis said, “and this restored substantially normal function.”

The report reached this conclusion: “these experiments demonstrate that synaptic integration… [by] donor neurons can impart an organism-level rescue of metabolic defects, thereby providing a proof of concept for cell-mediated repair of a neuronal circuit controlling a complex phenotype.”

While it is important to underscore that this work is performed on mice, the results suggest that something similar might be possible someday in human beings with brain injuries. “The finding that these embryonic cells are so efficient at integrating with the native neuronal circuitry makes us quite excited about the possibility of applying similar techniques to other neurological and psychiatric diseases of particular interest to our laboratory," according to Matthew Anderson in a press release issued by Harvard Medical School.

For now, research continues using mice as models for human disease or spinal cord injury. “The next step for us is to ask parallel questions of other parts of the brain and spinal cord, those involved in ALS and with spinal cord injuries,” according to Macklis. "In these cases, can we rebuild circuitry in the mammalian brain? I suspect that we can."

This study, coming so quickly on the heels of another report showing the functional integration of human embryonic stem cells into the mouse brain, suggests that embryonic stem cell research may indeed open new ways to treat brain disease or injury. Both studies, however, open the possibility that the use of technologies of brain regeneration will not stop with disease. As always, the growing power of medicine to treat disease is also an expansion of the possibility of human enhancement. All this if far in the future. But already, advocates of human enhancement have noticed its significance. See, for example, the re-posting of the original press release on Ray Kurweil's transhumanist blog.

The report, entitled “Transplanted Hypothalamic Neurons Restore Leptin Signaling and Ameliorate Obesity in db/db Mice,” appears in the November 25, 2011 issue of Science.

Stem Cells, Working Brains, and Human Enhancement

Research using human pluripotent stem cells—whether derived from an embryo or induced into a pluripotent state—holds great promise for regenerating parts of the human body by producing new cells to replace diseased or damaged cells. Nowhere is this potential more intriguing than in the human brain.

During the past decade, researchers have learned to turn human pluripotent cells into neurons. They have tested these neurons in cell cultures, where they seem to function like normal neurons. They have implanted these human neurons in mouse brains, where human cells thrive like normal cells. The big question is whether they do the work of brain cells. Long before cells are implanted in human brains, researchers want to know whether the cells will function properly in any working brain, starting with a mouse brain.

Now comes evidence that the implanted cells seem to be fully function, integrated in the basic process of the mouse brain. In the report published in the November 21 issue of PNAS, researchers at the University of Wisconsin report on their use of a new technology, optogenetics, to test the function of the implanted cells. This technology uses light rather than electricity to stimulate implanted neurons. The result, it is claimed, is the best evidence so far that implanted cells are integrated fully into the functioning brain, sending and receiving signals as part of living neural networks.

”We show for the first time that these transplanted cells can both listen and talk to surrounding neurons of the adult brain,” said lead author Jason P. Weick in a press release from the University.

By using optogenetics, this study provides evidence that implanted human neurons derived from pluripotent stem cells can become functionally integrated into systems of a living brain, sending and receiving signals from surrounding or “host” cells and interacting with brain circuitry in a way that is consistent with normal brain rhythms.

According to the paper published in PNAS, the neurons derived from pluripotent cells “can participate in and modulate neural network activity through functional synaptic integration, suggesting they are capable of contributing to neural network information processing…”

What’s more, the researchers discovered that optogenetics may someday have a clinical use far beyond its value as a research tool. The fact that implanted cells can be stimulated using a light signal may someday become part of the way stem cells are used on human patients. According to Su-Chun Zhang, also an author of the report, “You can imagine that if the transplanted cells don't behave as they should, you could use this system to modulate them using light.”

Still more challenges must be met before neurons derived from human pluripotent cells are implanted successfully in the human brain. But this study advances the field in a critically important way and provides strong evidence that implanted cells might one day take on the function of damaged cells in the living human brain.

If human brains can be regenerated even in highly limited ways, the consequences will be profound. The most obvious applications will be to treat patients who have lost some part of brain function due to stroke, brain injury, or disease.

And if that becomes possible, it is not hard to imagine that the same technology will be used to regenerate the brains of those whose only “disease” is aging. Furthermore, it is quite likely that at some point in the future, implanted neurons derived from pluripotent cells will be genetically modified first, perhaps to prevent disease but also perhaps to enhance the performance of the brain into which they become functionally integrated.

It is important to stress that treatment for complex disorders of the brain, such as Alzheimer’s Disease, are still a long way off. But this research is an important step, showing that the basic concept of stem cell treatment may provide one form of treatment. But is that becomes possible, it may also become possible to enhance the cognitive capacity of people without disease.

The milestone reported here is just one more step--of which there must be hundreds or thousands--leading us closer to the day when human brains might be regenerated or renewed. Few will object to the use of such treatments to restore functioning neurons to those with Huntington's disease or early onset Alzheimers. And if early onset Alzheimers, why not late onset? And if late onset dementia, why not age-related cognitive decline? At what point do we cross the line from therapy to enhancement, and does such a line even exist?

So while we stress that these treatments are not available today--and may never be--they will very likely come in time. And when they come, they will open the path for completely new ways to extend the functional lifespan of the human brain.
The report, entitled "Human embryonic stem cell-derived neurons adopt and regulate the activity of an established neural network," appeared in the Nov 21, 2011 issue of PNAS.

Resveratrol and Human Enhancement

The debate over human enhancement may just have entered a new phase. Resveratrol, the natural compound found in red wine, has now been shown to improve the metabolism of human beings. While the word "enhancement" does not appear in the published report, the research will almost certainly be read by many as evidence that the use of resveratrol enhances human health and may even increase the human lifespan.

In the more prosaic language of the report, the news is simply this: Resveratrol, the natural compound found in red wine, has now been shown to improve the metabolism of human beings.

In the 2 November 2011 issue of the journal Cell Metabolism, researchers in the Netherlands and Switzerland report that a 30-day course of resveratrol brought about significant improvement in the basic metabolic functions of obese men.

Research using animals has shown that resveratrol can have a number of benefits related to how the body uses energy. In some species, resveratrol has been shown to increase average longevity. In other experiments involving lab animals, a reduction of 30-50% in calorie intake below what the animals normally eat has been shown to benefit the metabolism and extend the lifespan. Others studies show that resveratrol seems to mimic the effects of calorie restriction.

Now come hints that resveratrol may have some of these same effects on human beings. In the Cell Metabolism article, researchers report that the men who received the 150mg/day dose of resveratrol showed a number of changes that mimic what happens with calorie reduction. 150mg is about 100 times the amount of resveratrol found in an ordinary glass of red wine.

One of the researchers, Patrick Schrauwen, commented on the study in a press release issued by Maastricht University in the Netherlands: “We saw a lot of small effects, but consistently pointing in a good direction of improved metabolic health.” The study was concluded after 30 days, and so long-term benefits or side-effects are not known.

In particular, no one knows whether resveratrol has the capacity to extend the human lifespan. But the positive results published on 2 November will surely intensify the debate over the effects and the ethics of resveratrol.

In this study, resveratrol was administered to men who were obese but otherwise healthy. One way some bioethicists distinguish between morally legitimate “therapy” and morally questionable biomedical “enhancement” is by insisting that medicine must stick to treating those with disease. It is unethical, these bioethicists argue, to “enhance” people by using medicine to benefit those who are not sick. Their views are challenged by others who believe that technology should be used for human enhancement.

While this study may have observed that moral limit of treating only those with a “disease,” there is little reason to believe that the metabolic benefits of resveratrol are limited to those who are obese. On the contrary, there is every reason to think that this study will be used by advocates of human enhancement. In particular they will see this as the best evidence yet that resveratrol can be used to extend the human lifespan.

My prediction is that this study will encourage more widespread use of resveratrol. Most who use it will be seeking some form of enhancement if not an increase in longevity.

The article, “Calorie restriction-like effects of 30 days of resveratrol (resVidaTM) supplementation on energy metabolism and metabolic profile in obese humans,” appears in the 2 Nov 2011 issue of Cell Metabolism, where it is available free to the public.

A New Approach to Enhancement?

Some people object to human germline modification because they do not like the idea of one generation messing with the DNA of future generations. Even worse, they say, is modifying the genes for the sake of…gasp!...enhancement!

But now comes a tantalizing study in tomorrow’s issue of Nature hinting at the possibility that what we do to live longer may change the lifespan of our grandchildren. It’s only a hint—the research reported here involves the faithful nematode, Caenorhabditis elegans. By exposing one generation of these tiny worms to just three proteins, researchers in Anne Brunet’s lab at Stanford produced worms that live up to 30% longer. The surprising thing is that the enhanced lifespan was passed to the next 2-3 generations. The really surprising thing is that the lifespan of the C. elegans great-grandchildren was enhanced even though no DNA sequences were modified. In other words: germline enhancement without genetic modification.

How is that possible? Epigenetics. The three proteins changed the way the DNA is structured or packed without changing the DNA code itself. Such epigenetic changes can change the way genes are expressed. The effect can be dramatic—in this case, a 30% longer lifespan. What’s more, the epigenetic change can be passed to future generations. Most often, epigenetic changes are reset during reproduction. But in some cases, epigenetic modifications are passed to the next 2-3 generations. When that happens, the structure and the expression of DNA are changed even though the DNA sequence remains unchanged. Over time, however, the effect washes out so that the great-great-grandchildren are back to the starting point.

Will this epigenetics-to-lifespan relationship be found in human beings? Who knows. Again, it must be repeated: this research involves flatworms. Humans are just a bit more complicated. Already, however, Brunet’s lab is looking for something similar in mice and in African killfish.

Whether anything similar will be found in human beings, this research already suggests a truly interesting thought experiment. Suppose this leads someday to a human-application technology. Would it be opposed by those who object to human germline modification? Sure, future human beings would be changed without their consent. But no genes are changed, and the changes are not permanent.

Perhaps the more sobering thought is this. Maybe this research will lead to a startling discovery. Never mind some new technology. Might it turn out that what health-minded human beings normally do—eat their green vegetables, get their exercise—has the effect of enhancing their offspring by modifying the expression of their genes by means of generating inheritable epigenetic changes? Could be. If just three proteins make C. elegans progeny live 30% longer, just imagine how your dinner might change your grandchildren (assuming, of course, that you’re in your reproductive years or younger).

The article, “Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans,” appears in the October 20 issue of Nature.

Embryonic Stem Cell Research Policy

Rob Stein’s article in yesterday’s Washington Post was one of the few reports to recognize that in announcing his support for federal funding for embryonic stem cell research, President Obama left several big questions unanswered.

According to Stein, NIH insiders were caught off guard. They had expected Obama to say that cell lines derived at any date from donated embryos would be eligible for research dollars. That step removes the barrier set by Pres. Bush, who made funds available but only for cells from donated embryos and derived before August 2001.

But Obama’s statement raised new questions:

First, will federal funding be available for research involving embryonic stem cells taken from embryos that were created specifically for research? Second, will funding be available for cells taken from cloned embryos?

The first of these questions is of course the more urgent of the two. A majority of Americans appear to support the view that research using cells taken from donated embryos is morally acceptable. These embryos already exists by the hundreds of thousands in storage in the nation’s fertility clinics. Most seem to think that it is better donate them for research that could lead to medical breakthroughs than destroy them.

But is it right for scientists to create the embryos, just for research that will not help the embryo but will instead destroy it? Here’s where many draw a line. It will be interesting, to put it mildly, to see if NIH agrees. What NIH will need to do, of course, is to assess carefully the impact of funding research on cells from donated embryos but not on cells from embryos created specifically for research. Will such a line really hold back science?

My own view is that, within strict limits and only if there is a need that cannot be met another way, it is permissible to create embryos for research. I believe that position can be argued on the basis of Christian theology and ethics. I also know that I am in a minority, and I am willing to recognize that policy in this field must be respectful of the deeply-held moral views of the majority. Recognizing that this area of research is contentious, I think it might be wise for NIH not to press too far in changing the guidelines. Unless it can be shown that science is seriously compromised by limiting federal funds to cells from donated embryos, it would be wise to put the limit right there.

The second question—whether federal funds will be available for research on cells from cloned embryos—is a bit more speculative. One of the great hopes for cloned embryos is that researchers could develop patient-specific stem cell lines, first to test drugs on human cell cultures but perhaps to implant in patients without provoking the immune system. Now these hopes are largely addressed with the 2006-2007 breakthroughs in induced pluripotency. Whether cloning still provides a significant scientific advantage over induced pluripotency is something that will have to be argued.

If the argument for the need for cloned stem cells is compelling, then perhaps NIH should recommend that these cells be eligible for use in federally funded studies. But if not, then it would be best, I think, for the NIH to exclude this source of cells.

In his statement yesterday, President Obama was clear that he did not wish to open the door to reproductive cloning. Reproductive cloning is, of course, a far different thing that using cloning (more precisely, nuclear transfer) to create a cloned embryo for research. Even so, many in the general public link the two and object equally to both. Perhaps the most convincing way to close the door to reproductive cloning is to exclude funding for work on cells from cloned embryos.

On top of everything else, NIH will need to consider rules for informed consent, first of all for couples who donate embryos for research, but also for anyone who donates cells that are induced to become pluripotent stem cells. If that’s not enough, NIH and other agencies need to move forward to get ready to oversee clinical trials in this field.

All this is to say that the NIH will be doing two things at once. It will be closing the first stem cell debate (the Bush-era debate over the embryo as the source) and opening a whole new era of stem cell ethics, centered around the pluripotency of cells and of what they might become—in the laboratory, in the body of patients, and in the future of regenerative medicine

Stem Cells Research and Christian Ethics

President Obama has opened a new era for stem cell research in America. He has asked the National Institutes of Health to draft new funding guidelines that will make federal research dollars available to US stem cell researchers without imposing unnecessary restrictions.

The restrictions were imposed on August 9, 2001, by Pres. George W. Bush. He approved the use of federal funds for embryonic stem cell research (something that outraged the religious right at the time), provided the cells were derived before the moment he gave the speech. Since then, the number of qualifying cell lines has shrunk while the number of new, unfunded lines has expanded.

Very few of us ever could grasp the moral difference between an embryo destroyed before August 2001 and one destroyed afterward. And most Americans favor embryonic stem cell research if it uses cells from embryos already created for fertility clinics but unused and ready to be destroyed anyway.

What's not so well known is that several religious groups support the Obama position. Jewish scholars are very clear in their support, as are experts in Islamic law. Christians are of course divided. The Vatican clearly opposes any use of embryos, but not all individual Catholics agree. Some Protestant denominations--the Presbyterian Church (USA), for example, or my own United Church of Christ--have gone on record supporting this research.

In the next few months, it will be interesting to see whether the NIH draft provides for funding for stem cell research on cell lines derived from embryos that were created especially for research. Here, more Americans are opposed, and NIH might be wise to draw a line: Offer funding for lines from donated embryos but not from embryos created expressly for research. Drawing the line at that point would also rule out cloning or nuclear transfer, since any cloned embryo is by definition created for research.

In the meantime, congratulations to Pres. Obama for recognizing the promise of this field of research, the moral complexities that lie ahead, and the need to set aside the artificial limits of the past while working toward consensus on the moral vision that guides the future.