Genetically Modified Monkeys: What's Next?

Researchers in China have used a new method to produce genetically modified monkeys.  Their purpose is to advance medical research by creating monkeys genetically predisposed to develop human diseases.  But the new method is so precise and so successful that one might imagine it leading to genetically modified humans.   

Caption: Researchers achieved precise gene modification in monkeys.  Credit: Cell, Niu et al.

According to a report published in the January 30 issue of the journal Cell, scientists used a new gene editing technique known as the CRISPR/Cas9 system.  The technique allows for very precisely targeted modification of DNA sequences. 

It also allows researchers to trigger more than one modification at a time. And it seems to avoid causing extraneous mutations where they are not wanted.  

With the CRISPR/Cas9 technique, researchers edited the DNA in monkey embryos at the one-cell stage.  As that cell multiplied, all the cells of the body contained the gene edits, probably including the cells the newborn monkeys might someday pass to their descendants. In other words, this is precise germline genetic engineering in primates.  

"Our study shows that the CRISPR/Cas9 system enables simultaneous disruption of two target genes in one step without producing off-target mutations," claimed Jiahao Sha, one of the lead authors at Nanjing Medical University.

The goal for now, Sha said, is to refine the technique and to be able to create "many disease models...in monkeys," according to the press release issued by the journal Cell.  

Just how refined will the technique become?  Consider that the first successful germline modified monkey was only reported in 2001. The current advance offers far more precision.  With enough precision, it might become possible to apply this technique to a single-cell human egg.  

The modification could be verified before the embryo is implanted, using the well-established technique of pre-implantation genetic diagnosis or PGD.  If implanted and brought to term, the human life created this way would have its germline DNA modified, meaning that the modification would pass to future generations.  

No one knows now whether this technique will offer the kind of precision that would be required to move from monkeys to humans.  But just how much precision is, in fact, required?  With PGD as a way to catch any "mistakes," might ethics committees, in a few decades or even sooner, permit couples and researchers to use this technique in order to avoid transmitting genetic problems to future generations?  Will it then be used to add something new or desirable to the genetic inheritance of our offspring?

The article, Niu et al., "Generation of gene-modified cynomolgus monkey via Cas9/RNA-mediated gene targeting in one-cell embryos," is published in the January 30, 2014 issue of Cell.  

Old DNA, New Tricks

Over the past decade, researchers have learned to reconstruct ancient DNA from fossils.  In December 2013, we were stunned to learn that refinements in techniques made it possible to restore human DNA from as far back as 400,000 years ago. 

Quickly on the heels of that advance, another new development has been announced in the 27-31 January online edition of PNAS.  Scientists at the University of Uppsala, in cooperation with the pioneering team in Leipzig, have developed a way to separate the old DNA sequences from contamination.

Photo Credit: Creative Commons, posted by Archaeogenetics, no restrictions.

Why is that important?  Because contamintion is a leading problem when it comes to reconstructing ancient DNA.  Literally thousands of fossils fill draws and shelves in museums around the world.  They contain DNA, too much of it, in fact, to be of any use.  Bits of ancient DNA are surrounded by more modern DNA from humans and from other organisms.  Now, researchers have learned to separate the old from the new. 
 
What makes the new breakthrough exciting is that now, at least some DNA information from many of these old fossils might be retreivable. 

"Many extremely interesting DNA data sets from ancient humans never see the light of day because of contamination. The idea behind this method was to change that," says Pontus Skoglund, a lead author at Uppsala University.
 
To test the new technique, the researchers used it to reconstruct the mitochondrial DNA from a previously unusuable Neandertal bone from the Altai Mountain region of Siberia.  The sample compared well with other known Neandertal DNA sequences in contrast to more modern humans.
 
It is hard to predict just where this new technology will lead.  At the very least, it seems to unlock the file boxes of museums throughout the world.  Previously discovered fossils, some of them very well dated, might be analyzed for the DNA.  Who knows what we will learn.

"There are many really interesting ancient human remains that we can rescue from severe contamination with this method. And the method is not limited to Neanderthals, even remains of anatomically modern humans that are contaminated by modern-day humans can be rescued," says co-investiagor Mattias Jakobsson in a press release from the University of Uppsala.
 
The new technique is described in a paper entitled "Separating endogenous ancient DNA from modern day contamination in a Siberian Neandertal." Skoglund, P.; Jakobsson, M.; Northoff, B.H.; Pääbo, S.; Krause, J.; Shunkov, M.V.; Derevianko, A.P; PNAS Online Early Edition the week of Jan 27-Jan31, 2014.

The Surprising Story of 400,000 Year Old Human DNA

Researchers have just announced a major advance in their quest to recover DNA from ancient humans.  400,000 year old bones contain badly damaged DNA sequences, but experts in Leipzig, Germany, have developed new techniques to extract and piece together tiny fragments until they can read at least a small portion of the genes carried by ancient humans who once lived in northern Spain.

Caption: The Sima de los Huesos hominins lived approximately 400,000 years ago during the Middle Pleistocene. Credit: Javier Trueba, Madrid Scientific Films.Usage Restrictions: None

A team led by Matthias Meyer at the Max Planck Institute for Evolutionary Anthropology in Leipzig worked together with a Spanish team of paleontologists led by Juan-Luis Arsuaga to extract tiny amounts of bone from fossil remains found at Sima de los Huesos, northern Spain’s famous “bone pit.”  This site has been excavated for more than two decades.  It has yielded at least 28 skeletons, usually classified as Homo heidelbergensis, a form of humans seen as the ancestors of the Neandertals.

 

But here is where this study broke new ground.  It turns out that the Sima de los Huesos humans were more closely related to the recently discovered Denisovans than to the Neandertals.  "The fact that the mtDNA of the Sima de los Huesos hominin shares a common ancestor with Denisovan rather than Neandertal mtDNAs is unexpected since its skeletal remains carry Neandertal-derived features," Meyer said in a press release provided by the journal Nature, which carries the report in its 4 December 2013 issue. 

What makes this finding all the more intriguing is that the Denisovans were completely unknown to us until 2010, when the Leipzig team “discovered” them by reconstructing their DNA and comparing it to Neandertals and today’s humans.  Through a spectacular technological achievement, Leipzig researchers discovered that these Denisovans lived as a distinct population some tens of thousands of years ago, when they interbred with other humans. 

"This unexpected result points to a complex pattern of evolution in the origin of Neandertals and modern humans. I hope that more research will help clarify the genetic relationships of the hominins from Sima de los Huesos to Neandertals and Denisovans" says Arsuaga. 

Caption: This is a skeleton of a Homo heidelbergensis from Sima de los Huesos, a unique cave site in Northern Spain.  Credit: Javier Trueba, Madrid Scientific Films.  Usage Restrictions: None

 

According to the most recent discovery, the Sima de los Huesos hominins seem to have shared a common ancestor with the Denisovans some 700,000 years ago.  The idea that they are more closely related to Denisovans than to Neandertals suggests that these mysterious Denisovans, totally unknown just four years ago, may have played a far bigger role in the story of human origins than ever imagined. 

It is important to point out that so far, researchers have only reconstructed the DNA of the mitochondrial.  And even there, the work is not complete.  Whether they succeed in reconstructing the DNA of the far more daunting heidelbergensis genome remains to be seen.  But if past experience is any predictor, we might look for advances not just here but in other human remains from hundreds of thousands of years ago.  Each technical achievement may fill in a page in our past, maybe even re-writing whole chapters.  When it comes to human origins, we should expect more surprises. 

Putting this most recent news in a larger context, Svante Pääbo, the director of the Leipzig research, said this in the Nature press release: "Our results show that we can now study DNA from human ancestors that are hundreds of thousands of years old. This opens prospects to study the genes of the ancestors of Neandertals and Denisovans. It is tremendously exciting."

The article, “A mitochondrial genome sequence of a hominin from Sima de los Huesos,” appears in the 4 December 2013 issue of the journal Nature. 

 

 

 

Rapamycin: Extended Lifespan, Extended Decline?

Ever since 2009, it has been known that the drug rapamycin extends the lifespan of mice.  The journal Science identified this discovery as one of the top 10 research breakthroughs for that year.  The news was all the more exciting because rapamycin already has FDA approval for other uses.

So researchers want to know just how rapamycin extends the lifespan.  Does it actually slow the entire aging process?  Or does it just slow down certain diseases, such as cancer?  

New research testing the effects of rapamycin on mice suggests that the drug probably does not slow the aging process itself.  It does slow the development of cancer and a few other diseases.  But rapamycin is no fountain of youth.  In fact, if it were used just by itself to extend the lifespan of human beings, it might merely draw out the aging process.  In other words, it might extend the lifespan but not extend the healthspan.

Photo: Public domain through Wikimedia. Thanks to Rama.

The research was conducted by a team led by Dan Ehninger and his colleagues at the German Center for Neurodegenerative Diseases. It is published in the August 2013 issue of The Journal of Clinical Investigation, which is freely available online.  In addition to the research article, the journal is publishing an expert commentary that warns about any drug that brings an increase in lifespan that “is accompanied by more disability and disease and a greater loss of physiological functions, i.e., a reduced quality of life.”  By itself, rapamycin could do just that.

On the bright side, the new study shows even more conclusively that rapamycin extends the lifespan of mice by the equivalent of almost a decade of human life.  It also provides a small benefit for cognitive function.  So despite the mixed results, the journal commentary advocates clinical trials involving human patients, perhaps those with dementia.  According to the journal article, the research supports “the feasibility of clinical trials to study the efficacy of rapamycin in treating diseases of the elderly, especially those that are debilitating and for which no current treatment is known, such as Alzheimer’s disease and other neurodegenerative diseases.”

Advocates of anti-aging research will see this new study as something of a set-back, but it is not likely to slow down basic work in the field.  Opponents of anti-aging research are likely to renew their warnings about the prospect of more years of declining health.  Any effort to enhance our humanity, whether it is by increasing cognitive ability or extending the lifespan, is always accompanied by a down-side, by side effects so costly that true enhancement is impossible.  The warning is serious, but advocates of human enhancement are not likely to be convinced.   

The research article is entitled “Rapamycin Extends Murine Lifespan but Has Limited Effects on Aging.”  The commentary is entitled “Rapamycin, Anti-aging, and Avoiding the Fate of Tithonus.”  Both are available free to the public in the August 2013 issue of The Journal of Clinical Investigation.

We Are What We Ate: Diet and Human Evolution

At a key moment in human evolution, our diet expanded and became more diverse, setting the stage for humans to draw on a wider range of food sources to feed expanding brains.

Four academic papers published together in the June 3, 2013 issue of the Proceedings of the National Academy of Sciences report on new methods of studying the carbon found in ancient teeth, going back more than 4 million years.  Ancestors living then ate pretty much what apes eat today, a diet of mostly leaves and fruits.  Then about 3.5 million years ago, a major shift occurs. 
Caption:This is an artist's representation of Paranthropus in southern Africa more than 1 million years ago.  Credit:Illustration courtesy ArchaeologyInfo.com/ScottBjelland.  Usage Restrictions: None

  

The old food sources remained in use, but new sources are added.  Researchers came to this conclusion by analyzing the carbon isotopes still present in ancient teeth.  After examining 175 specimens from 11 different species, they concluded that a key shift occurred at about 3.5 million years ago.  At that point, at least some of our ancestors were supplementing the usual foods by turning to grasses or sedges—or to the animals that graze on them.  These ancestors, including Australopithecus afarensis (best known as the famous “Lucy”), became more diverse in their food sources.

The earliest known evidence suggests that at about this same time, our human ancestors were making tools and using them to butcher large animals for food.  If these animals ate grasses, the carbon would have entered the human diet that way.  Another possibility is that human ancestors were simply learning to identify other types of plants as food sources compatible with human metabolism.

The main point, however, is that at this critical 3.5 million year transition, human ancestors were become more variable in their diet and in their behavior.  Rather than being locked into one type of food source or one way to pursue food, they were becoming more varied in their diet and behavior.  This made it possible for them to exploit more sources of food, nourish even bigger brains, travel and thrive in new niches, and survive climate change cycles, particularly ancient African cycles of wet and dry periods. 

"We don't know exactly what happened," said Matt Sponheimer of Colorado University and one of the researchers. "But we do know that after about 3.5 million years ago, some of these hominids started to eat things that they did not eat before, and it is quite possible that these changes in diet were an important step in becoming human."

If becoming more varied and adaptable is the same as becoming more human, then this study provides an important insight into this process.  One of the papers (Wynn et al.) concludes with this sentence: “This dietary flexibility implies unique landscape use patterns and malleable foraging behavior within a narrow time from of a single species.”  In other words, they were able to adjust quickly, seizing new opportunities and adapting to environmental changes. 



 

"Three-parent babies" and the Human Germline Modification Debate

Human germline modification is back in the news. The current round of public conversation was launched in the UK by the Human Fertilisation and Embryology Authority (HFEA). In the past few days, the media and the blogosphere have lit up with an intensifying debate. 

What HFEA wants people to consider is whether it is acceptable to use in vitro fertilization to try to avoid a specific category of genetic disease. Is it OK to help couples at risk for mitochondrial disorders by supplying donor mitochondria to the new embryo? If mom’s own mitochondrial DNA will lead to a disease, is it OK to add mitochondria from an outside donor?

PHOTO Transmission electron microscope image of a thin section cut through an area of mammalian lung tissue. The high magnification image shows a mitochondria. Source: Wikimedia. Credit: Louisa Howard, PhD. This work has been released into the public domain by its author.

Many refer to this as the “three-parent baby.” And for that reason alone, they object.

Others raise the stakes in the argument. They insist that the “three-parent baby” is just the tip of the looming germline modification iceberg. What’s really coming, they claim, is the era of “designer babies,” enhanced or improved versions of ourselves, a new form of high-tech eugenics.  And with that comes more mischief.

Consider what Stuart Newman (New York Medical College) had to say in his comment in The Huffington Post. Newman starts by asking whether the procedure is really as safe as it seems. Fair question. But then Newman writes that what is really going on here is “a new form of eugenics, the improvement of humans by deliberately choosing their inherited traits.” And then, a few short paragraphs later, he’s off to the Nazis, forced sterilization, and the Nurenberg Code.

Now it may be true that the “three-parent baby” is a pretty bad idea medically. But morally, is it really the fast-track to Nazi medicine?

Or consider Marcy Darnovsky’s comments in a press release from the Center for Genetics and Society:

“Changing the genes we pass on to our children is a bright ethical line that should not be crossed,” said Marcy Darnovsky, PhD, the Center's executive director. “It has been observed by scientists around the world, adopted as law by more than 40 countries, and incorporated in several international treaties. It would be wrong for the UK to disregard this global bioethical consensus, especially when there are safe alternatives available for the very few people who would be candidates for the procedures.”

The release concludes: “The Center for Genetics and Society calls for a domestic and international moratorium on approval of any procedures involving inheritable human genetic modification…”
Or consider the comment of David King of Human Genetics Alert as quoted by the BBC: 

Dr David King, the director of Human Genetics Alert, said: "Historians of the future will point to this as the moment when technocrats crossed the crucial line, the decision that led inexorably to the disaster of genetically engineered babies and consumer eugenics.

Is the “three-parent baby” really “crossing the germline barrier”? Back in 2001 when the first “three-parent babies” being created here in the US, Erik Parens and Eric Juengst wrote a response in the journal Science. They called it “Inadvertently Crossing the Germline.” Ever since then, many have agreed. Despite some really important distinctions, mitochondrial replacement is a kind of human germline modification.

A bit of a stretch, but OK, let’s call it that. But is that reason enough to condemn it? Is human germline modification itself morally wrong? It may be biomedically impossible. It may be excessively expensive considering all the other needs facing the world’s children. But is it intrinsically wrong? 

 

In 2008, I published an edited book that tried to take the temperature of religious opinions on the morality of germline modification. What I discovered surprised even me. Most religious scholars in my collection were not particularly troubled by the prospect of germline modification. Sure, they had their concerns—safety, social justice, over-controlling parents, an attitude of commodification. But in the end, almost without exception, they agreed: what can be religiously or morally wrong with wanting to use the latest technology to help parents have healthy children? For more on this, see Design and Destiny from MIT Press.

 

For many people, it comes as a total shock to hear that even some Vatican statements support the notion that germline modification is not inherently immoral—that, in fact, it could be “desirable.” The Vatican has specific constraints that must be met. No IVF, for one, so the “three-parent baby” strategy fails on that score. But if the means are acceptable, then the goal is laudable, at least according to this statement made by Pope John Paul II:

A strictly therapeutic intervention whose explicit objective is the healing of various maladies such as those stemming from chromosomal defects will, in principle, be considered desirable, provided it is directed to the true promotion of the personal well-being of the individual without doing harm to his integrity or worsening his conditions of life. Such an intervention would indeed fall within the logic of the Christian moral tradition.

I agree with the “three-parent” critics about the importance of the debate over human germline modification. For that very reason, I hope they tone down the rhetoric. This is not Nazi medicine.

 

There are sound moral reasons for wanting to move forward on human germline modification. Of course, there are incredibly important technical hurdles that must be overcome. Some of them, in fact, may prove impossible. If so, then of course human germline modification would be a bad idea because of the risks.

 

But if biomedical research can find its way through these technical barriers, what then? Yes, there are other objections, more religious or moral in nature, but there are also strong reasons for going forward. That, I suggest, is where the real discussion should focus.  

Enhancing Healthy Kids: A Warning, But Who's Listening?

The American Academy of Neurology (AAN) has just issued new guidelines calling on doctors to stop prescribing cognitive-enhancing drugs to healthy kids.

Drugs like Ritalin and Adderal are widely used, not just by adults and university students, but increasingly by children, and not just those who are appropriately diagnosed as experience difficulites with attention or focus, such as Attention Deficit Disorder. 

PHOTO: Ritalin SR (a brand-name sustained-release formulation of methylphenidate, from Wikimedia, 16 June 2006, created by Sponge. 

Perviously, the AAN raised concerns drug enhancement by adults.  It concluded that there is no moral basis for objecting, provided that the patient is acting autonomously in requesting the prescription.  But when it comes to prescribing for healthy children, the AAN report makes this claim:  "Pediatric neuroenhancement remains a particularly unsettled and value-laden practice, often without appropriate goals or justification."  

The Report notes that enhancing children is fundamentally different from enhancing adults.  For doctors, it raises concerns for "the fiduciary responsibility of physicians caring for children, the special integrity of the doctor–child–parent relationship, the vulnerability of children to various forms of coercion, distributive justice in school settings, and the moral obligation of physicians to prevent misuse of medication."

Based on these concerns, the AAN Report advises that "the prescription of neuroenhancements is inadvisable because of numerous social, developmental, and professional integrity issues."

The primary objection raised by the AAN is that children lack the competency to act as autonomous moral agents.  If they were competent, then their request for enhancement would be honored.  Sure, children can be coerced, manipulated, confused, and ambivalent about their needs.  Kind of like the rest of us. 

Whether age brings moral competence is a good question.  But perhaps what this report shows us once again is that when secular bioethics meets enhancement technology, about all it can say is this: If you want it and if you can prove your competence, you can have it. 

The AAN report, “Pediatric neuroenhancement: Ethical, legal,social, andneurodevelopmental implications,” is published in the March 13, 2013 issue of Neurology.

What a Smart Mouse Can Tell Us about Evolution

Just a few years ago, we thought that brains were all about neurons.  Sure, we also have glial cells, but the job of the lowly glia is to take care of the neurons, which do all the serious cognitive work. 

But why are the glia of humans and other primates so large and varied in their shape and structure?  Why are they so different from the simpler, smaller glia found in mice and other rodents?  Could the difference play a role in the evolution of human intelligence?

One way to compare a mouse and a human is to create a mouse that is part human.  That’s exactly what researchers at the University of Rochester did.  They implanted human cells into mouse brains.  More precisely, they implanted human glial progenitor cells into newborn mouse pups. 

What they got were chimeras, mice with human cells integrated into their brains.  When the researchers examined the brains of these chimeric mice, they found that the human cells proliferated and were widely present throughout the brain. Although interacting with mouse brain cells, the human cells remained distinctly human in their unusually large size and varied structures.

Photo credit:  A 23 week human culture astrocyte stained for GFAP.   From Wikimedia Commons.  Date: 24 February 2012.  Author: Bruno Pascal. 

Most surprising is that the chimeric mice were  smarter than unaltered mice born in the same litters.  Human glia in a mouse brain seems to make a smarter mouse.  

Why?  The answer probably involves one type of glial cell called astrocytes. Compared to other species, human brains have many more astrocytes.  Ours are larger and more varied in their structure, capable of connecting many neurons and coordinating the activity that occurs at many synapses. 

Based on this study, published in the March 7, 2013 issue of Cell Stem Cell, we now know that human astrocytes boost intelligence in chimeric mice as measured by standard testing procedures.  

This is pretty good evidence to suggest that the evolution of the larger, more complex glial cells was a critical aspect of the evolution of higher intelligence.  At least that is the conclusion drawn by one of the senior authors of the paper, Steven Goldman. “In a fundamental sense are we different from lower species,” he said, according to a press release from the University of Rochester. “Our advanced cognitive processing capabilities exist not only because of the size and complexity of our neural networks, but also because of the increase in functional capabilities and coordination afforded by human glia.”

What makes this study intriguing is that it uses stem cell technology to study brain function and to learn something important about evolution.  By implanting stem cells in create chimeric mice, researchers learn that glia play a critically important role in intelligence and that evolved changes in glial cells are a key part of the story of the rise of intelligence. 

Concerning the role of glial cells in the complex brain, Maiken Nedergaard, another senior author, had this to say:  “I have always found the concept that the human brain is more capable because we have more complex neural networks to be a little too simple, because if you put the entire neural network and all of its activity together all you just end up with a super computer.”

“But human cognition is far more than just processing data, it is also comprised of the coordination of emotion with memory that informs our higher abilities to abstract and learn,” Nedergaard added.

And concerning what chimeric mice have to teach us about evolution, Steven Goldman made this comment: “This study indicates that glia are not only essential to neural transmission, but also suggest that the development of human cognition may reflect the evolution of human-specific glial form and function.”

Or to quote the original paper: “These observations strongly support the notion that the evolution of human neural processing, and hence the species-specific aspects of human cognition, in part may reflect the course of astrocytic evolution.”

The paper does not address the interesting ethical questions raised by making smarter mice.  Over the past decade, ethicists have debated the moral legitimacy of chimeric animals.  One point of concern has been the creation of nonhuman animals with human brain cells.  To defend this practice, it is often said that a mouse brain with human cells is still a mouse brain.  It still has the structure or architecture of a mouse brain.  It may have human cells, but in no way is it a human brain or even a half mouse/half human brain.

This study suggests we should take a closer look at that line of thinking.  Maybe it is true that adding human neurons to a mouse brain does not change the mouse brain structure.  But this study implies that adding human astrocytes to a mouse brain may begin some small but significant change in structure and function. 

The study is clear about the fact these chimeric mice are more intelligent than the unmodified mice.  Their brains are quite literally faster. 

Once again, Goldman: “The bottom line is that these mice demonstrated an increase in plasticity and learning within their existing neural networks, essentially changing their functional capabilities.”

These animals have been cognitively “elevated,” to use a word sometimes found in the debate.  Probably no one will object to the idea of a slightly smarter mouse.  Researchers take special care to make sure these mice do not breed and produce pups of their own.  But even if they did, the added intelligence would not pass to future generations.  They would produce normal lab mice. 

Even so, this study—combining stem cells technology, neuroscience, and evolution in one elegant package—raises intriguing moral questions.  Are we smart enough to know how far we should go in creating smarter mice?  

The study, entitled “Forebrain engraftment by human glialprogenitor cells enhances synaptic plasticity and learning in adult mice,” appears in the March 7, 2013 issue of Cell Stem Cell. 

   

 

Brain Renewal? Enhancing Aging Brains

An aging mind may be a fountain of wisdom, but an aging brain is not very good as a source of new neurons. As we age, quite apart from diseases like Alzheimer’s, we lose our ability to remember and to concentrate. It seems that in order to remain sharp, the brain has to regenerate itself by forming new neurons. While neurogenesis continues throughout life, it declines markedly in old age.

Photo credit: published under GNU Free Documentation License, uploaded 23 Sept 2007 by Ccrai008.

Research published today may suggest a way to change that. Scientists at the German Cancer Center in Heidelberg report on their work with mice. They identified a molecule called Dickkopf-1 or Dkk1 in the brains of old mice. When they blocked the production of Dkk1, old mouse brains began to create new brain cells.

“We released a brake on neuronal birth, thereby resetting performance in spatial memory tasks back to levels observed in younger animals,” said Ana Martin-Villalba in a press release from Cell Press, which published the results.

It turns out that clinical trials are already underway involving antibodies for Dkk1. These trials are not related to neurogenesis but to prevention of osteoporosis. What is learned there, however, may be directly helpful to the possibility that blocking Dkk1 is feasible, safe, and effective in countering the effects of declining neurogenesis, which includes both memory loss and depression.

The report concludes with these comments: “Our study raises the possibility that neutralization of Dkk1 might be beneficial in counteracting depression-like behavior and improving cognitive decline in the aging population….The contribution of newly generated young neurons to memory and affective behavior opens tantalizing opportunities for the prevention of affective impairments and age-related cognitive decline.”

These words are carefully chosen, first to caution against undue optimism but also to steer away from the idea of “human enhancement.” But unless we think of aging as a disease, what is envisioned here is clearly a form of enhancement. Normally aging human beings may, someday in the future, be treated not because they have a disease such as Alzheimer’s but because their memory is not as sharp as it once was or as retentive as they would like.

But labeling this an “enhancement” is not likely to dampen public interest. On the contrary, the enhancment potential of blocking Dkk1 is the very thing that is most likely to drive public support.

And that suggests we need to consider once again just what it is we say we do not like about enhancement.

The article is entitled "Loss of Dickkopf-1 restores neurogenesis in old age and counteracts cognitive decline" and appears in the February 7, 2013 issue of Cell Stem Cell.

Asians, Europeans, and Neandertals

New research suggests that Europeans and Asians diverged at least 40,000 years ago, starting a process leading to the subtle differences that distinguish people to this day.

Working with bones discovered in 2003, researchers at the Max Planck Institute for Evolutionary Anthropology in Leipzig were able to reconstruct portions of DNA from an individual who lived in China about 40,000 years ago. Earlier analysis of the bones suggested that this individual showed “archaic” features, somewhat like Neandertal bones.

Credit: A Photograph of China's Empress Dowager, taken in the 1890s by Xunling, the Imperial Court Photographer. In the public domain.

The Max Planck team, led by Svante Pääbo, is well-known for work in producing the virtually complete Neandertal genome. In addition, using just a tiny fragment of a finger bone, this team produced the genome of a previously unknown form of humanity, called the Denisovans.

In their earlier work, they discovered that Europeans and Asians are descended in part from Neandertals, who disappeared about 30,000 years ago. In addition, some Asians, especially those living on the islands south of Asia, are partly descended from the Denisovans.

One of the reasons why the team was interested in this new sample was to look more deeply into the relationship between Europeans and Asians and to ask what role Neandertal and Denisovan interbreeding might have played.

Comparing the newly-reconstructed DNA sequence from the 40,000 year old bones, they found they were looking at an individual who also was descended from Neandertals, pretty much the way Europeans and Asians are today. And they also learned that this individual showed no evidence of Denisovan interbreeding.

What this means, they suggest, is that 40,000 years ago, an early version of anatomically modern Eurasians lived in China, near Beijing. While this human community was very much like the humans moving into Europe at about the same time, these two lineages were beginning a process of divergence.

On the basis of additional comparisons, the team concluded that the early-modern human community in China 40,000 about years ago was closely related to today’s Native Americans.

The report is also significant because it shows the power of new approaches to DNA extraction and sequencing. In their raw form, the samples extracted from the bones contained mostly DNA from microorganisms. In fact the human DNA was less than one-tenth of one percent of the total DNA. Even so, researchers were able to establish reliable human sequences, suitable for comparison with other human genomes.

What does that mean? At the very least, it means that many more discoveries like this lie ahead. The new technology means that old findings take on new significance.

The research appears online January 22, 2013, in the Proceedings of National Academy of Sciences, as "DNA analysis of an early modern human from Tianyuan Cave, China."

Neandertal Medicine

Neandertals not only ate their vegetables. They used specific plants—even ones that tasted bitter—to treat their ailments. That’s the latest finding from the international team of researchers studying Neandertal remains at in El Sidrón archeological site in northern Spain. Discovered in 1994, El Sidrón has yielded thousands of samples from at least 13 Neandertal individuals.

Using newer techniques of microanalysis, the team studied the dental plaque recovered from teeth of five individuals dating about 50,000 years ago. Lodged in the plaque were tiny microfossil remains of various plants, providing evidence that Neandertals supplemented their diet of meat with a wide range of grain, herbs, and vegetables. The study is published this week in Naturwissenschaften (The Science of Nature).

CAPTION: Researchers working in El Sidrón Cave. Credit: CSIC Comunicación.

"The varied use of plants we identified suggests that the Neanderthal occupants of El Sidrón had a sophisticated knowledge of their natural surroundings which included the ability to select and use certain plants for their nutritional value and for self-medication. While meat was clearly important, our research points to an even more complex diet than has previously been supposed," according to Karen Hardy, a leader in the research team, according to a press release from the University of York.

Neandertals disappeared from Europe and Asia somewhere around 30,000 years ago, often sharing regions with modern humans for thousands of years. Only recently has it become clear that they depended heavily on plants as well as meat for their food.

"The evidence indicating this individual was eating bitter-tasting plants such as yarrow and camomile with little nutritional value is surprising. We know that Neanderthals would find these plants bitter, so it is likely these plants must have been selected for reasons other than taste," said Dr Stephen Buckley, a member of the research team.

The clear implication of the study—that Neandertals recognized the medicinal value of certain plants—provides further evidence of the sophistication of Neanderthal culture and technology. The full scope of Neandertal cultural interaction with modern humans remains an open question.

"El Sidrón has allowed us to banish many of the preconceptions we had of Neanderthals. Thanks to previous studies, we know that they looked after the sick, buried their dead and decorated their bodies. Now another dimension has been added relating to their diet and self-medication," according to Antonio Rosas, also on the research team.

CAPTION: Microscopically visible material entrapped in dental calculus samples – filamentous and cocci bacteria. Credit: Karen Hardy/Naturwissenschaften.

The article, "Neanderthal medics? Evidence for food, cooking and medicinal plants entrapped in dental calculus," is published in the current issue of Naturwissenschafen.

Human Intelligence: Does It Depend on a Genetic Error?

What makes humans different from the great apes? What makes our brains larger and more complex? We know that our DNA is remarkable similar to other mammals. What subtle genetic changes can explain such huge behavioral differences? One surprising possibility is that our brains are bigger and more complex not so much because of new genes but because of gene duplication.

One gene in particular—SRGAP2—plays a role in how brain cells migrate. It is found widely in mammals of all sorts, from mice to humans. In the great apes, the more archaic form of SRGAP2 results in a relatively slow spread of neurons throughout the brain. Twice in the ancient past, however, SRGAP2 was duplicated, first about 3.4 million years ago and then again around 2.4 million years ago. The second duplication occurred right around the time when the genus Homo separated from Australopithecus. It appears that as a result of these duplications, brains in the Homo lineage—including our own as Homo sapiens—are both large and complex in their number of neuronal connections and in their ability to process information.

A key piece of supporting evidence comes from recent discoveries of the role of SRGAP2 in the development of the human neocortex. When the distinctly human SRGAP2 variants are missing, normal human brain development is impaired. This research appears in two papers appearing May 3, 2012 in the journal Cell. According to one of the papers, “It is intriguing that the general timing of the potentially functional copies…corresponds to the emergence of the genus Homo from Australopithecus (2-3 mya). This period of human evolution has been associated with the expansion of the neocortex and the use of stone tools, as well as dramatic changes in behavior and culture.”

Caption: A team led by Scripps Research Institute scientists has found evidence that, as humans evolved, an extra copy of a brain-development gene allowed neurons to migrate farther and develop more connections. Credit: Photo courtesy of The Scripps Research Institute Usage Restrictions: None

The uniquely human duplications work in a surprising ways, especially the second duplication. The original SRGAP2 remains present in humans today, along with the duplicated versions. The second duplication—SRGAP2C—has the effect of interfering with the original SRGAP2. The reason why SRGAP2C interferes with SRGAP2 rather than boosts it is because the duplicated version is incomplete—in other words, an advantageous copying error.

According to one of the studies, once SRGAP2C appeared about 2.4 million years ago, it created a “dominant negative interaction equivalent to a knockdown of the ancestral copy…The incomplete nature of the segmental duplication was, therefore, ideal to establish the new function by virtue of its structure,” acting in a way that was “instantaneous” in terms of evolution.

"This innovation couldn't have happened without that incomplete duplication," according to Evan Eichler, another leader in the research team. "Our data suggest a mechanism where incomplete duplication of this gene created a novel function 'at birth'."

Even though SRGAP2 duplications seem to play a significant role in distinguishing human beings from the apes, other duplications and mutations are very likely to be involved in the story of human evolution. "There are approximately 30 genes that were selectively duplicated in humans," said Franck Polleux, one of the lead researchers involved in the study, in a press release from the journal. "These are some of our most recent genomic innovations."

Rather than standard mutations, "episodic and large duplication events could have allowed for radical – potentially earth-shattering – changes in brain development and brain function," according to Eichler. For these reasons, this is one of the most intriguing areas for research into the origins of human intelligence.

Whether other duplications—including “incomplete duplications or erroneous copies—also explain our complex brains is something that will be discovered in the next few years.

But what is surprising and somewhat sobering, just based on this SRGAP2 discovery, is how our much-vaunted human uniqueness seems to hang on such a fine thread. If the SGGAP2 duplication is even partly responsible for our complex brains, should we think that our intelligence arose because of a copying error or an incomplete duplication? Is the rise of intelligence and consciousness—truly one of the great events in the story of cosmic evolution—really just based in part on a fluke of nature? Religious or not, hardly anyone is likely to think that thinking is sheer accident.

The papers, Charrier et al.: "Inhibition of SRGAP2 function by its human-specific paralogs induces neoteny during spine maturation" and Dennis et al.: "Human-specific evolution of novel SRGAP2 genes by incomplete segmental duplication," appear in the journal Cell.

Extending Healthy Lifespans? A Pill on the Horizon?

Resveratrol, the much-hyped ingredient found in red wine and sold widely as a nutritional supplement, is known to improve the health and extend the lifespan of mice. Can it do the same for humans? Without nasty side effects? And at what dose?

A study published today in Cell Metabolism helps unravel a few more of resveratrol’s mysteries. In particular, researchers have shed new light on how resveratrol works. Key to its effectiveness is a gene known as SIRT1, found in slightly different forms in species as different as yeast and humans. SIRT1 plays many roles, some tied to core metabolic processes. The new study shows that in mice, even a low dose of resveratrol interacts with SIRT1 to improve metabolism.

What makes this study especially interesting is that researchers had to create a special strain of mice in order to test whether SIRT1 is necessary for resveratrol to work. If mice have no SIRT1, they do not develop properly. So two graduate students, Nathan Price and Ana Gomes, developed a novel strain of mice with an unusual copy of the SIRT1 gene, one that could be switched off at adulthood.

By administering a drug (tamoxifen), researchers can “induce” or switch the SIRT1 gene on and off, a strategy that will likely be used in other studies. "This is a drug inducible, whole body deletion of a gene," David Sinclair, the study's senior author, said in a press release from Harvard Medical School. "This is something that's rarely been done so efficiently. Moving forward, this mouse model will be valuable to many different labs for other areas of research."

Photo by R. Cole-Turner

In this case, the switchable SIRT1 mouse provided proof that SIRT1 is key to resveratrol’s effectiveness. Why is that important? Because resveratrol is a complex molecule that interacts with the body in many unknown ways. While it may be beneficial, it may have unwanted side effects. So researchers are trying to design a more simple molecule that provides the benefits of resveratrol without all the risks. One strategy is to boost SIRT1 activity. By proving that SIRT1 is involved, this study provides support for that strategy, which is already being pursued by pharmaceutical firms.

"The results were surprisingly clear," said. "Without the mitochondria-boosting gene SIRT1, resveratrol does not work."

Are we any nearer a magic pill that slows aging or promotes longevity? Perhaps. The headline of the press release from the publisher, Cell Press, claims that this work “restores hope for anti-aging pill.” Remember, of course, that the work reported here is entirely with mice.

Even so, the paper itself concludes with this statement: “This model supports the enticing possibility of designing and developing potent small molecules that provide the health benefits of resveratrol by activating SIRT1 and downstream pathways to treat metabolic and other age-related diseases.”

The treatment of age-related diseases, including diabetes, is a huge target for pharmaceutical firms. But beyond that lies that even bigger market for human enhancement, specifically for enhancing the span of healthy decades.

The study, "SIRT1 Is Required for AMPK Activation and the Beneficial Effects of Resveratrol on Mitochondrial Function," appears in the May 1, 2012 issue of Cell Metabolism.

A Million Years of Fire

One of our newest technologies has just shed new light on one of our oldest.

When did our human ancestors learn to control and use fire? Armed with the latest high tech tools, an international team of researchers has pushed the date back to 1 million years. That’s 300,000 years earlier than previous unambiguous dates.

The massive Wonderwerk Cave is in northern South Africa on the edge of the Kalahari. Previous excavations have shown extensive human occupation. Using the new techniques of micromorphological analysis and Fourier transform infrared microspectroscopy (mFTIR), researchers analyzed cave sediments at a far more detailed level than possible before.

Caption: This is a panoramic view of the entrance to Wonderwerk Cave, South Africa. Credit: H. Ruther. Usage Restrictions: None

In the cave sediments researchers found bits of ash from plants along with fragments of burned bone. Did the wind blow burning debris into the cave? The evidence—collected about 100 feet from the current opening of the cave—supports the conclusion that the fire burned in the cave. Also part of the proof: the surrounding surfaces are discolored.

”The analysis pushes the timing for the human use of fire back by 300,000 years, suggesting that human ancestors as early as Homo erectus may have begun using fire as part of their way of life," anthropologist Michael Chazan said in a press release from the University of Toronto.

According to the paper, "Through the application of micromorphological analysis and Fourier transform infrared microspectroscopy (mFTIR) of intact sediments and examination of associated archaeological finds— fauna, lithics, and macrobotanical remains—we provide unambiguous evidence in the form of burned bone and ashed plant remains that burning events took place in Wonderwerk Cave during the early Acheulean occupation, approximately 1.0 Ma. To date, to the best of our knowledge, this is the earliest secure evidence for burning in an archaeological context."

Caption: Interior of Wonderwerk Cave. Images courtesy of M. Chazan.

"The control of fire would have been a major turning point in human evolution," says Chazan. "The impact of cooking food is well documented, but the impact of control over fire would have touched all elements of human society. Socializing around a camp fire might actually be an essential aspect of what makes us human."

How important are fire and cooking for human evolution. A recent book, Catching Fire: How Cooking Made Us Human by Richard Wrangham, argues that cooking is essential to our humanity. Now in the paper published on April 2, the team concludes that its study “is the most compelling evidence to date offering some support for the cooking hypothesis of Wrangham.”

Their work is published as “Microstratigraphic evidence of in situ fire in the Acheulean strata of Wonderwerk Cave, Northern Cape Province, South Africa,” in the April 2, 2012 issue of the Proceedings of the National Academy of Sciences.

Hope for Aging Brains

When electrical wires lose their insulation, they have to be replaced. When the nerves and brain cells in our bodies lose theirs, they regenerate it naturally.

Up to a point, that is. As the decades pass, our bodies lose the ability to regenerate themselves. The results are obvious: wrinkled skin, weak muscles, and forgetful brains.

All the more tragic for those among us with diseases that attack the very processes of regeneration. Multiple sclerosis (MS), for example, keeps the body from restoring the insulating layers that protect nerve fibers. The insulation—“myelin”—breaks down naturally. In most human brains, “remyelination” is a constant process, rebuilding the myelin that protects the brain cells and allows them to do their work. For people with MS, remyelination is under attack.

Working with mice, researchers seem to have found a way to reinstate the remyelination process. In a report in the January 6 issue of Cell Stem Cell, researchers at Harvard and Cambridge Universities show that the capacity for remyelination can be restored in aging mice.

The cells that are responsible for remyelination are still present in the aging mouse. It’s just that they have been switched off. By exposing these cells to switching signals present in a much younger mouse, researchers were able to reverse the effects of aging on the cells that do the work of remyelination.

How did they do this? They literally joined the old and the young mouse together surgically. This allows their blood to circulate together. In the young blood, apparently, were various chemical signals that reset the switches in the cells of the brains of the aging mice. The result: spontaneous remyelination.

According to Robin Franklin, one of the researchers, the study shows that “age-associated decline in remyelination is reversible. We found that remyelination in old adult mice can be made to work as efficiently as it does in young adult mice.” Franklin, who is Director of the MS Society's Cambridge Centre for Myelin Repair at the University of Cambridge, made her comments in a press release issued by her university.

What’s perhaps most interesting about this report is that it is a kind of stem cell research that doesn’t implant stem cells. It works on the principle that stem cells already exist in the patient’s body but that they’ve been silenced by age or disease. They need to be switched back on or rejuvenated. According to Franklin, “remyelination therapies do not need to be based on stem cell transplantation since the stem cells already present in the brain and spinal cord can be made to regenerate myelin - regardless of the patient's age."

As interesting as this is, it is important to stress that this is a “proof of concept” study. The techniques here are simply not applicable to human beings. They are encouraging because they suggest that perhaps some day, researchers will discover just what it is in the young body that keeps it young. What are the specific factors that keep the body’s own stem cells switched on? And if it circulates in the blood as this study shows, perhaps these factors could simply be injected.

Of course, if researchers discover how to do this, it’s not just people with diseases like MS who will be interested. One of the interesting social features about this work is that it is funded in part by the UK MS Society and the American MS Society. In other words, the funding is motivated by the search for a cure for a very specific disease. But the mice is the study were aging, not ill. That suggests to me, at least, that the larger portion of the “beneficiaries” of this work will be aging humans, not those with MS. If so, then this study is one more step in the quest of human enhancement, suggesting that it may be possible to reverse aging in the one part of the body where it is most feared—the human brain.

The journal report ends with this comment: “Moreover, this work demonstrates that the CNS maintains its responsiveness to age-regulated circulatory factors, such that age-dependent deficiencies in repair of these tissues can, in part, be reversed by circulating factors.”

The paper, “Rejuvenation of regeneration in the aging central nervous system,”' is published in the January 6 issue of Cell Stem Cell.

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.

Is Aging a Disease of Stem Cells?

Is aging a disease? And if it is a disease, what “causes” it? Is it simply natural for bodies to age over time, or is something wrong with them, something that could be “fixed”?

In a report in the January 3 issue of Nature Communications, researchers at the University of Pittsburgh School of Medicine report on work with mice that are bred especially to age quickly. The mice have a version of progeria, a disease in humans that causes children to age well before their time.

The research team looked at differences in stem cells or progenitor cells, which healthy bodies naturally keep in reserve as a source for new cells to replace worn-out cells. Not surprisingly, they found that the progeria mice had fewer progenitor cells than their healthy counterparts. What’s more, the few progenitor cells in the progeria mice failed to function normally. For example, they didn’t produce replacement cells as needed.

If that’s the problem, can it be “fixed”? The researchers, led by senior investigators Johnny Huard and Laura Niedernhofer, injected the rapidly-aging progeria mice with progenitor cells from the muscles of healthy mice. The result was pretty amazing.

"We wanted to see if we could rescue these rapidly aging animals, so we injected stem/progenitor cells from young, healthy mice into the abdomens of 17-day-old progeria mice," Dr. Huard said in a press release issued by the University of Pittsburgh. "Typically the progeria mice die at around 21 to 28 days of age, but the treated animals lived far longer—some even lived beyond 66 days. They also were in better general health."

How did this work? Did the injected cells start producing replacement cells? Possibly, but the main effect of the injected cells seems to have been to change the host cells in the body of the progeria mice. In other words, the injected healthy progenitor cells changed the progeria mouse’s own cells into more healthy, more normal cells.

"This leads us to think that healthy cells secrete factors to create an environment that help correct the dysfunction present in the native stem cell population and aged tissue," Dr. Niedernhofer said. "In a culture dish experiment, we put young stem cells close to, but not touching, progeria stem cells, and the unhealthy cells functionally improved." Fascinating!

What about mice that are aging normally? Would the injection of progenitor cells from younger mice, for example, also “rescue” non-progeria but aging mice?

Whether anything like this could be done safely in human beings is a big question that will require a lot more research. It may turn out that injecting progenitor cells into a human patient with premature aging might help stall the aging but might also create other problems, such as cancer. In time, it may be possible to get the benefits while managing the risks.

The Pitt research, although dealing with mice with progeria, opens profound questions about humanity, aging, enhancement, and the possibility of extending the human lifespan.

The biggest question of all is whether something like this would slow the aging process in normal or healthy human beings. In other words, is this yet another possible pathway to human enhancement? Could this be used to “treat aging as a disease”?

Is aging a disease? Dr. Niedernhofer’s comment is revealing: "Our experiments showed that mice that have progeria, a disorder of premature aging, were healthier and lived longer after an injection of stem cells from young, healthy animals," Dr. Niedernhofer said. "That tells us that stem cell dysfunction is a cause of the changes we see with aging." A dysfunction? A disease? A difference?

On the question of religion and the morality of extending the human lifespan, probably the best book on the market is Religion and the Implications of Radical Life Extension, edited by Calvin Mercer and Derek Maher. I have an essay in the book reflecting on the question from the standpoint of Christianity.

My take? Extending the human lifespan is not immoral or obviously wrong, but Christians hope for a transformation, not an extension. More of the same is too little.

The report appeared in the January 3 issue of Nature Communications. It is entitled Muscle-derived stem/progenitor cell dysfunction limits healthspan and lifespan in a murine progeria model and is available free to the public.