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.

Deep Brain Cognitive Enhancement: The Latest News

The search for new methods of cognitive enhancement has just reached new depths.  Researchers in Austria and the UK report exciting new evidence that a form of noninvasive deep brain stimulation enhances the brain’s ability to do arithmetic. 

"With just five days of cognitive training and noninvasive, painless brain stimulation, we were able to bring about long-lasting improvements in cognitive and brain functions," says Roi Cohen Kadosh of the University of Oxford and lead author of the report that appears in the May 16, 2013 issue of Current Biology.  His comments were provided by the journal.

Photo Credit.  Photo by Ad Meskens of an original oil painting by Laurent de La Hyre (French, 1606-1656).  The title of the painting is Allegory of Arithmetic (Allegorie van de rekenkunde) and it dates to about 1650.  The original painting is in the Walters Art Museum, Baltimore, Maryland.  It was photographed on 18 July 2007 by Ad Meskens, who has made it freely available with proper credit.

In this study, the team used a form of noninvasive deep brain stimulation known as “transcranial random noise stimulation” or TRNS.  The TRNS input was combined with more traditional math training and drills.  Twenty-five young adults, males and females, were divided into two groups, one receiving math training with the TRNS and the other receiving math training combined with a “sham” version of TRNS, a kind of placebo. 

Not only did those who received TRNS do well immediately, but the benefits lasted for at least six months.  In addition, brain monitors detected different brain activity for those receiving TRNS.  This suggests that TRNS modifies brain function.

According to Cohen Kadosh, "If we can enhance mathematics, therefore, there is a good chance that we will be able to enhance simpler cognitive functions."

In the paper’s conclusion, the authors state that TRNS “can enhance learning with respect to high-level cognitive functions, namely algorithmic manipulation and factual recall in mental arithmetic. When this learning is based on deep-level cognitive processing, as is the case for calculation arithmetic, such enhancements are extremely long-lived both behaviorally and physiologically.

Then they sum up with these words:

Both the behavioral and physiological changes displayed extreme longevity, spanning a period of 6 months, but only when learning involved deep-level cognitive processing. By its demonstration of such longevity and, for the calculation task, generalization to new, unlearned material, the present study highlights TRNS as a promising tool for enhancing high-level cognition and facilitating learning. These findings have significant scientific and translational implications for cognitive enhancement in both healthy individuals and patients suffering from disorders characterized by arithmetic deficits.

The paper, Snowball et al.: "Long-Term Enhancement of Brain Function and Cognition Using Cognitive Training and Brain Stimulation," appears in the May 16, 2013 issue of Current Biology. 

Stem Cell Advance and Cloning Debates

An important breakthrough in stem cell medical research is likely to re-ignite an ethical debate about human cloning. 

Researchers at the Oregon Health & Science University reported on May 15 that they have succeeded for the first time in human “somatic cell nuclear transfer” or SCNT, a process that the public often refers to simply as cloning.  Oregon researchers were able to transfer the nucleus from one human cell into a donated human egg from which the nucleus had been removed, essentially the same process that led to the creation of Dolly the sheep more than fifteen years ago. 

Caption: The first step during SCNT is enucleation or removal of nuclear genetic material (chromosomal) from a human egg. An egg is positioned with holding pipette (on the left) and egg's chromosomes are visualized under polarized microscope. A hole is made in the egg's shell (zone pellucida) using a laser and a smaller pipette (on the right) is inserted through the opening. The chromosomes then sucked in inside the pipette and slowly removed from the egg.  Credit: Cell, Tachibana et al. Usage Restrictions: Credit Required.

 

While other teams have achieved nuclear transfer with human cells, none has been able to produce an embryo that developed long enough to yield human embryonic stem cells.  The Oregon team, led by Shoukhrat Mitalipov, achieved this long-desired goal.

 

Even more remarkably, the Oregon team achieved SCNT repeatedly and with high efficiency, in one case producing a stem cell line for every two donated eggs. Along with other researchers around the world, Mitalipov’s team has discovered many ways to fine-tune the nuclear transfer process, making it far more demanding technically than when Ian Wilmut’s team first created Dolly.

But just as we learned from Dolly, any major technical advance in somatic cell nuclear transfer is likely to trigger public controversy about cloning and about the social impact of science.  While nearly everyone applauds the goal of the Oregon research—better understanding and treatment of disease—not everyone will like the way they went about their work.

For one thing, the result of successful nuclear transfer is a kind of embryo.  Mitalipov’s paper, published in the June 6, 2013 issue of the journal Cell (online on May 15), repeatedly refers to this new entity as the “SCNT embryo.”  Is a “SCNT embryo” a “real” embryo?  If an embryo is the result of fertilization, then of course a “SCNT embryo” is not a normal or real embryo.  But if an embryo is defined by its potential to develop, then a SCNT embryo probably is very close to a normal or real embryo, biologically at least.

Suppose we accept that a SCNT embryo is real enough to warrant the same protection as embryos created by IVF.  Is it legitimate to create such an embryo for the express purpose of research that will destroy this SCNT embryo?  Many people object to this, and major religious institutions such as the Catholic Church have been unambiguous in their denunciation of this research. 

On the other hand, a few religious groups have specifically endorsed this research.  One of the clearest statements of support is entitled “Cloning Research, Jewish Tradition and Public Policy.”  The statement, published in 2002, speaks for all major groups within American Judaism: 

Moreover, our tradition states that an embryo in vitro does not enjoy the full status of human-hood and its attendant protections.  Thus, if cloning technology research advances our ability to heal humans with greater success, it ought to be pursued since it does not require or encourage the destruction of life in the process.

Another statement in support comes from a study committee in the United Church of Christ, which released this statement in 1997: 

...we on the United Church of Christ Committee on Genetics do not object categorically to human pre-embryo research, including research that produces and studies cloned human pre-embryos through the 14th day of fetal development.”

For more religious statements on embryo research, check out God and the Embryo, especially the appendics. 

I personally agree with the statements quoted above.  So I support the research performed in Oregon.  But I have to admit that among people with religious commitments, I am in a minority.  As much as I wish it were otherwise, I expect that many will object to the idea that Mitalipov’s group has created and destroyed embryos for research.

Some will argue that the technology of induced pluripotent stem cells (iPSCs) makes the use of embryos unnecessary.  While it is true that iPSC technology is a remarkable and promising advance, so far the field has run into unexpected technical complications in its quest to produce pluripotent stem cells that function like cells from embryonic sources.  A great attraction of iPSCs—beyond the fact that no embryos are involved—is that they are a genetic match to the donor.  What the Oregon breakthrough provides is the best of both: embryonic quality in donor-specific cells. 

Others will object because they don’t like human cloning—understood now as the use of SCNT to produce a child.  They will see the Oregon breakthrough as ushering in the era human reproductive cloning, and they will see this as reason enough to ban any further advances in SCNT technology.

Far more sensible, I think, would be a moratorium on human reproductive cloning.  What the Oregon group has achieved does make it more likely that someone somewhere might try to offer cloning as a reproductive technology.  The problem is that using Mitalipov’s techniques, they might succeed in creating an embryo that survives but that is beset by many unforeseeable health problems.

If we have learned anything in the past fifteen years, it is that SCNT is a tricky and complex process.  Just because Mitalipov’s team learned how to create the SCNT embryo that is healthy and viable through the blastocyst stage does not mean that anyone knows how to create an SCNT child.  Too many things could go wrong, and only now are we beginning to get some idea of how these potential problems might arise.

Someday, many decades in the future, we may understand these problems so well that we can solve them technically.  If that day ever comes, then those who come after us will have to ask: is a cloned child a good idea.  Right now we do not even have to ask that question because an SCNT is an unsafe idea. 

The press release from The Oregon Health and Science University that announces this advance makes this claim:

One important distinction is that while the method might be considered a technique for cloning stem cells, commonly called therapeutic cloning, the same method would not likely be successful in producing human clones otherwise known as reproductive cloning. Several years of monkey studies that utilize somatic cell nuclear transfer have never successfully produced monkey clones. It is expected that this is also the case with humans. Furthermore, the comparative fragility of human cells as noted during this study, is a significant factor that would likely prevent the development of clones.

The Oregon release then quotes Mitalipov:

"Our research is directed toward generating stem cells for use in future treatments to combat disease," added Dr. Mitalipov. "While nuclear transfer breakthroughs often lead to a public discussion about the ethics of human cloning, this is not our focus, nor do we believe our findings might be used by others to advance the possibility of human reproductive cloning."

The article is entitled "Human Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer" and appears in the May 15 issue of the journal Cell. 

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.

Art in an Age of Neandertals

The oldest confirmed date for cave art has just been pushed back again. New research re-dates paintings in caves in northern Spain to a staggering 40,800 years ago, right at the time when anatomical modern humans (AMHs) like us were just arriving in the region and encountering Neandertals.

In fact, this art is so ancient that it raises the haunting possibility that Neandertals were the painters. If so, then modern humans are not the only form of humanity to create cave art. For now, however, the question of who painted this art is a matter of speculation, something that might be settled by further research.

In work published in the June 15, 2012 issue of Science, researchers studied 50 paintings in eleven caves in the northernmost part of Spain, including the UNESCO World Heritage sites of Altamira, El Castillo and Tito Bustillo. The work was conducted by an international team led by Alistair Pike of the University of Bristol.

The Corredor de los Puntos, El Castillo Cave, Spain. Red disks here have been dated to 34,000-36,000 years ago, and elsewhere in the cave to 40,600 years, making them examples of Europe's earliest cave art. Image courtesy of Pedro Saura.

This research comes on the heels of a re-dating of cave painting in France, recently pushed back to 37,000 years. The latest study adds almost another 4,000 years to the confirmed date of the oldest art. What’s the combined effect of the two studies? In just the past month, our view of the antiquity of art has jumped by nearly 10,000 years, prompting us to wonder how much further back it might go. After all, it is known that AMHs mixed pigments as far back as 100,000 years ago.

Using a new method called uranium-thorium dating, Pike’s research team took a closer look at an old find. They extracted tiny samples of naturally forming deposits that covered the paintings. By dating the deposits, scientists are able to discover the date before which the paint was applied. The date of more than forty thousand years ago, therefore, is a minimum date, suggesting that some of the paintings—here or elsewhere—may be even older.

The specific painting that exceeds 40,800 years is a simple red disk, seemingly primitive when compared to paintings made later in the same caves. More striking are the handprint paintings on the wall of El Castillo cave, made by blowing paint and common in early cave art but now dated to 37,300 years ago.

Commenting on the age of the oldest painting, Pike pointed out the tight fit between the painting and the arrival of AMHs in northern Spain: “Evidence for modern humans in Northern Spain dates back to 41,500 years ago, and before them were Neanderthals. Our results show that either modern humans arrived with painting already part of their cultural activity or it developed very shortly after, perhaps in response to competition with Neanderthals – or perhaps the art is Neanderthal art,” Pike said in a press release issued by the University of Bristol.

The Panel of Hands, El Castillo Cave, Spain. A hand stencil has been dated to earlier than 37,300 years ago and a red disk to earlier than 40,600 years ago, making them the oldest cave paintings in Europe. Image courtesy of Pedro Saura.

Pike also speculated further on the possibility that researchers may someday identify some European cave art as Neandertal. He suggested that perhaps, “cave painting started before the arrival of modern humans, and was done by Neanderthals. That would be a fantastic find as it would mean the hand stencils on the walls of the caves are outlines of Neanderthals' hands, but we will need to date more examples to see if this is the case."

The article in entitled “U-series dating of Palaeolithic Art in 11 Caves in Spain” and appears in the June 15, 2012 issue of the journal Science.

Merging Humans and Robots--More Coffee, Please

With the help of a tiny chip implanted in the brain, human beings who cannot move their own limbs are able to move a robotic arm, in one case taking a drink of coffee on one’s own for the first time in fifteen years.

"The smile on her face was a remarkable thing to see. For all of us involved, we were encouraged that the research is making the kind of progress that we had all hoped," said the trial's lead investigator, Leigh Hochberg, M.D., Ph.D., in a press release issued by the National Institutes of Health, which provided some of the funding. Hochberg is an associate professor of engineering at Brown University and a critical care neurologist at Massachusetts General Hospital (MGH)/Harvard Medical School.

The field of brain-computer interface research is not new, but this is the first peer-reviewed report of people using brain signals to control a robotic arm, making it perform in three-dimensional space much as their natural arms once did. By imagining they were controlling their paralyzed limb, they were able to move the robotic arm. Brain activity is detected as electrical activity by the BrainGate chip, processed by an external computer, and fed into a robot that translates the signals into movement.

More research is underway, and in fact this clinical trial is recruiting more volunteers.

Caption: The BrainGate array, which is implanted on the motor cortex, comprises nearly 100 electrodes on a chip the size of a baby aspirin. Credit: www.braingate2.org Usage Restrictions: With Credit.

With future advances, researchers hope to be able to improve the quality of movement in prosthetic limbs or to restore in part the function of paralyzed limbs, perhaps by creating an electronic by-pass to normal nerves.

"This is another big jump forward to control the movements of a robotic arm in three-dimensional space. We're getting closer to restoring some level of everyday function to people with limb paralysis," said John Donoghue, Ph.D., who leads the development of BrainGate technology and is the director of the Institute for Brain Science at Brown University.

Beyond therapy, it is possible to imagine other uses as we humans and our machines co-evolve and increasingly converge, probably to do more than drink coffee.

This report is published in the May 17, 2012 issue of Nature.

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.

Planets by the Billions

New calculations suggest that there may be as many as 60 billion habitable planets just in our own Milk Way galaxy, maybe more. At least 100 of these planets may be as close as 30 light-years away.

Researchers at the European Southern Observatory (ESO) carefully sampled 102 red dwarf stars in the southern skies. Red dwarfs are very common in our galaxy. Based on observations and calculations, the ESO team estimates that approximately 40% of the red dwarf stars are orbited by planets. What’s more, these planets are in what astronomers call the “habitable zone,” meaning they are neither too close nor too far from their sun. In particular, it means that the temperature may be right for liquid water to exist on the planet’s surface.

The ESO project is the work of an international team using observations with the HARPS spectrograph on the 3.6-metre telescope at ESO's La Silla Observatory in Chile. It is published in the March 28 issue of Astronomy & Astrophysics.

Caption: This artist's impression shows a sunset seen from the super-Earth Gliese 667 Cc. The brightest star in the sky is the red dwarf Gliese 667 C, which is part of a triple star system. The other two more distant stars, Gliese 667 A and B appear in the sky also to the right. Astronomers have estimated that there are tens of billions of such rocky worlds orbiting faint red dwarf stars in the Milky Way alone. Credit: ESO/L. Calçada. Usage Restrictions: None

"Our new observations with HARPS mean that about 40% of all red dwarf stars have a super-Earth orbiting in the habitable zone where liquid water can exist on the surface of the planet," says Xavier Bonfils in a press release issued by ESO.

"Because red dwarfs are so common — there are about 160 billion of them in the Milky Way — this leads us to the astonishing result that there are tens of billions of these planets in our galaxy alone," according to Bonfils.

"The habitable zone around a red dwarf, where the temperature is suitable for liquid water to exist on the surface, is much closer to the star than the Earth is to the Sun," says Stephane Udry, another member of the ESO team.

Red dwarfs, however, may pose a special challenge to life. According to Udry, "Red dwarfs are known to be subject to stellar eruptions or flares, which may bathe the planet in X-rays or ultraviolet radiation, and which may make life there less likely." In the more technical language of the scientific publication, “The main difference from earth are a significantly higher mass and a different stellar environment, which potentially can have caused divergent evolutions.”

All the more tantalizing, of course. As one of the ESO scientists puts it, "Now that we know that there are many super-Earths around nearby red dwarfs we need to identify more of them using both HARPS and future instruments. Some of these planets are expected to pass in front of their parent star as they orbit — this will open up the exciting possibility of studying the planet's atmosphere and searching for signs of life," concludes Xavier Delfosse.

The article, "The HARPS search for southern extra-solar planets XXXI. The M-dwarf sample", by Bonfils et al. appears in Astronomy & Astrophysics on March 28.

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.

Stem Cells and Type I Diabetes

Is this just too good to be true? That’s my first reaction when I read the press release with this headline: “Stem cell therapy reverses diabetes.”

The full report was published on January 9 by an open source medical journal, BioMed Central. If the procedure it describes can be replicated, it is promising indeed. Researchers claim to have a device that “educates” the patient’s own stem cells.

The device is called a “Stem Cell Educator.” Apparently when the patient’s blood passes through the device, stem cells naturally occurring in the patient’s blood are “educated” or re-set to a more normal, functional level. The device separates the patients blood, selecting lymphocytes for special treatment by exposing them to stem cells that were originally derived from donor human umbilical cords.

No cells are exchanged or added to the patient’s blood. Instead, the patient’s own cells are reset by exposure to specific factors given off by the donor stem cells that are kept in a living culture inside the device. After two or three hours of “education,” the patient’s lymphocytes seem to perform a lot better.

The result? Researchers claim in their report that “a single treatment produces lasting improvement in metabolic control. In initial results indicate Stem Cell Educator therapy reverses autoimmunity and promotes regeneration of isletβcells.” The need for insulin was reduced and the benefits lasted at least as long as 40 weeks after the treatment.

The study also makes this claim:

Successful immune modulation by CB-SCs and the resulting clinical improvement in patient status may have important implications for other autoimmune and inflammation-related diseases without the safety and ethical concerns associated with conventional stem cell-based approaches.

Whether these findings are replicated is a key question at this point. The claims are pretty extraordinary, but the general strategy of "re-educating" rather than replacing cells seems to be showing a lot of promise. For an example, see my earlier post, "Is Aging a Disease of Stem Cells?"

The study was led Yong Zhao of the University of Illinois at Chicago, who directed an international team and prepared the report, entitled “Reversal of type 1 diabetes via islet beta cell regeneration following immune modulation by cord blood-derived multipotent stem cells.” The full text is published by the online journal BioMed Central and is freely available to the public.

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.

Eating, Aging, and the Brain

Two recent studies shed new light on the relationship between food and the brain.

The first study involves mice on a calorie-restricted diet. Restricting calories to about 70% of normal intake kept the mice—and their rodent brains—young when compared to control mice who could eat whenever they wanted. And while there’s no proof yet that this works with human beings, there is a lot of interest by researchers in finding out what is going on in the relationship between aging and eating.

The latest research is reported in the December 19 of PNAS. Researchers at the Catholic University of Sacred Heart in Rome report their finding that a naturally-occurring protein, CREB1, plays a key role in mediating between caloric restriction and the delay of aging. Caloric restriction seems to trigger CREB1, which in turn activates many other genes involved in longevity and brain function.

What is new in this research is the relationship between caloric restriction and CREB1 activity. Discovering how these molecules interact opens the possibility that the activity of CREB1 can be increased without having to keep to a fairly austere diet.

According to Giovambattista Pani, one of the lead researchers, “Our hope is to find a way to activate CREB1, for example through new drugs, so to keep the brain young without the need of a strict diet.”

“This discovery has important implications to develop future therapies to keep our brain young and prevent brain degeneration and the aging process. In addition, our study shed light on the correlation among metabolic diseases as diabetes and obesity and the decline in cognitive activities,” according to Dr. Pani.

The second study is published in the December 28 issue of Neurology and does involve human beings. Just in time for New Year’s resolutions, researchers at Oregon State University report on the brains and the diets of 104 seniors with an average age of 87. The result is pretty sobering. Those who ate fast foods and snack loaded with trans-fats scored much worse on cognitive tests than those who ate diets rich in the healthy oils commonly found in fish or consumed high levels of vitamins B, C, D, and E.

How much worse? The fast-food seniors scored 17% lower on thinking and memory tests and had a shocking 37% lower active brain size based on an MRI. And that’s after other factors such as age or education level are removed. Diet alone, it appears, makes a significant difference. Eating the right food seems to help slow down the age-related shrinkage of the brain.

Someday there might be a pill that makes us and our brains resist aging. For now, it’s what we eat that counts. These results need to be confirmed, but obviously it is very exciting to think that people could potentially stop their brains from shrinking and keep them sharp by adjusting their diet," according to Gene Bowman of the Oregon Health & Science University in Portland and author of the study.

This would not have surprised Saint Athanasius, bishop of Alexandria in the mid-4th century. Like many of his age, Athanasius was fascinated by the story of Saint Anthony of Egypt, one of the earliest Christian ascetics. Athanasius wrote a spiritual biography of Anthony, interpreting his life and turning him into the prototype of Christian monks.

Anthony gave away the family fortune and lived in isolation in the Egyptian desert, eating almost nothing. The result? He lived to 105 and was known for his wisdom to the very end.

Todd Daly has written about Athanasius and Anthony, including an essay in my recent book, Transhumanism and Transcendence. Daly makes it clear that Anthony’s purpose was not longevity or a youthful brain. This is no science experiment, and if Anthony is the first monk, he’s not the first transhumanist. But according to Athanasius (and to Daly), Anthony is conducting a spiritual experiment. His question is whether it is possible to regain some small portion of the original human condition…humanity as God intended, in other words, rather than the fallen humanity we experience. By denying his body, he sought to expand his soul. Without realizing it, he kept his brain from shrinking.

The amazing thing is that by asking a seemingly arcane theological question—and by sticking with it for decades—Anthony anticipates today’s research.

The PNAS article was published on December 19. The Oregon study was published online on December 28 by the journal Neurology.

Searching for Life on Other Planets

This post is a little bit out of my usual orbit. Literally. It has to do with newly discovered planets that orbit other suns. They’re called “extra-solar planets” or simply “exoplanets.”

Over the past twenty years, scientists have discovered nearly 700 such planets. Most of these are too big and too hot for life. Their powerful gravity and their vaporizing heat make it unlikely that any form of life could arise, much less evolve.

PHOTO CAPTION: Scientists are now starting to identify potential habitable exoplanets after nearly twenty years of the detection of the first planets around other stars. This image shows all known examples using 18 mass and temperature categories similar to a periodic table, including confirmed and unconfirmed exoplanets. Only 16 in the Terrans groups are potential habitable candidates. PHOTO CREDIT: PHL copyright UPR Arecibo

A few exoplanets may have the right conditions for life. So far, at least two exoplanets seem to have roughly “earth-like” conditions, making them what researchers call “habitable exoplanets.”

More will surely be discovered. So many more, in fact, that some sort of catalog is needed. Enter the “Habitable Exoplanets Catalog,” hosted at the University of Puerto Rico. The Catalog is being introduced on December 5, 2011 to astronomers at the Kepler Science Conference in California.

The Catalog is an online database of habitable worlds. There’s no proof yet that life exists on any of them, but many researchers believe that some forms of life will be discovered once our detection technology advances just a bit further, with probes such as NASA’s Kepler.

”New observations with ground and orbital observatories will discover thousands of exoplanets in the coming years. We expect that the analyses contained in our catalog will help to identify, organize, and compare the life potential of these discoveries,” said Abel Méndez, Director of the PHL and principal investigator of the project in a press release issued by the University of Puerto Rico.

One nice feature of the Catalog is its “periodic table of exoplanets.” Everyone remembers the periodic table of elements that hangs in every science classroom. Just as that table organizes elements by their properties, so the table of exoplanets organizes them by habitability. What’s more, because it is an online database, new discoveries are included and organized as they occur.

To achieve this, the Catalog uses data from other databases, such as the Extrasolar Planets Encyclopedia,Exoplanet Data Explorer, the NASA Kepler Mission, and other sources.

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.

New Book on “Transhumanism and Transcendence”

My latest book is Transhumanism and Transcendence: Christian Hope in an Age of Technological Enhancement. It is a collection of essays from leading Christian theologians responding to various aspects of transhumanism and of the growing potential for technology to “enhance” human beings. The book is on display for the first time at the book exhibits at the American Academy of Religion, 19-22 November 2011 in San Francisco. The publisher is Georgetown University Press.

On the back cover of the book, Philip Clayton comments:

This is the most important Christian debate on transhumanism that I have ever read. Those who prefer fawning acceptance or frightened rejection of human enhancement can find simplistic monographs aplenty. But if you want to think theologically about the transformation of humanity through technology—what's already here, and what lies ahead of us—this collection is mandatory reading.

I wrote the first and the last chapters of the book, framing the argument and summarizing the findings.
The eleven chapters in between are written by established scholars and younger thinkers, some of whom were finishing doctoral studies on transhumanism just as the book was being written.

Michael Burdett, for example, drew upon his studies at Oxford in writing about Francis Bacon, N. F. Fedorov, and Teilhard as early examples of transhumanist thinking. David Grumett, an emerging expert on Teilhard, follows Burdett with a deeper look at this pioneering theologian and scientist.

J. Jeanine Thweatt-Bates drew upon her doctoral work to criticize transhumanist thinking on gender, while Stephen Garner and Todd Daly provided fresh thinking about themes of cyborgs and extended lifespans in traditional Christian theology. Michael Spezio, a theologian who does advanced research in neuroscience, engages some of the projects of the Defense Advanced (DARPA).

Established scholars such as Ted Peters, Karen Lebacqz, Gerald McKenny, Brent Waters, and Celia Deane-Drummond also contribute chapters to this book. While all of them raise criticisms of transhumanism and of the growing use of technology for human enhancement, all recognize that transhuman poses a challenge for Christian theology.

Here’s one way to think about the challenge. Religion promises but technology delivers, so who needs religion anymore? For example, Christian theology holds up a promise of some form of life beyond the present. Technology, on the other hand, sees aging as a problem to be overcome, and it sets out to slow or even reverse it.

Whether it will truly succeed is, of course, debatable. But that’s not that point. The key question is where we place our hopes and what form of life do we hope for.

Through technology, transhumanists hope to transcend the limits of our biology. But is this the truest and highest form of human transcendence? It is not that technology is rejected or feared. But does teach us to settle for too little?

Studying Transhumanism and Religion

For several years now, the American Academy of Religion has included a “Transhumanism and Religion Group.” The next session of the group will be on Saturday, November 19, during the annual meeting of the AAR in San Francisco.

During our session, we will hear four papers. Brian Green will address the question, “Could Transhumanism Change Natural Law?” He will be followed by Michael Burdett, speaking on “New Jerusalem or the Tower of Babel?: Transhumanist Visions of the Future in Kurzweil, Rees, and Bostrom.”

The third paper will be presented by Amy Michelle DeBaets, addressing “The Transhuman Mystique: Feminism and the Discourses of Democratic Transhumanism.” Finally, Abbas Rattani will speak on “Transhumanism, Cosmetic Neurology, and Suffering.”

Following the discussion, Calvin Mercer will conduct a business meeting to make plans for next year’s session. Stay tuned here for a report on what happens on Saturday.

Archaic Interbreeding? So What?

Later this week, I will be speaking at the University of South Florida—Saint Petersburg in their lecture series, a Celebration of the Genome.” My topic is “Finding the Human in the Genome.”

I start with the obvious: Our knowledge of human biology is increasing rapidly, thanks in large part to the Human Genome Project. We can now compare the DNA of one human being with another and ask questions about similarities and differences. We can compare human DNA with the full genomes of chimps and other species.

Most interesting to me is that we can also compare the genome of anatomically modern humans with that of extinct forms of humanity, such as Neandertals or their recently discovered cousins, the Denisovans. What we have found is that in a real sense, they are not extinct at all because their DNA lives on in us.

That leads to something less obvious but more profound. The more we know about human biology, the less we know about human nature. Put another way, the more information we have, the less confident we are that we really know what we mean when we talk about “humanity.”

So what is going on here? Does it really bother anyone—besides me, that is, and perhaps only because I am, after all, a “theologian”? I am asking myself this question a lot these days. Does it really matter that our ancestors interbred with Neandertals and Denisovans and, as time will probably tell, many other forms of archaic humanity?

So what’s the big deal? In some ways I guess it’s like the high school student who runs a paternity test and learns that daddy isn’t daddy.

Or maybe it’s more like this. Years ago, I remember hearing Kári Stefánsson speaking to a roomful of scientists and introducing deCODE Genetics, the Iceland DNA database. He explained the reasons for the project, such as excellent health records, small genetic diversity, and superb genealogical records going back 1,000 years. We Icelanders need to sell more than fish, he said. We want to mine our DNA for all kinds of gene-disease information. Then Stefánsson mentioned that the information sometimes disproved the genealogies. Everyone laughed when he said: “We are not responsible for what our Viking ancestors did back then during the long Icelandic winters.”

Is that it? Is that all that’s happened here, just some forced revisions of the family tree? So what if my ancient ancestors were not exactly what I thought? It happened, after all, some 40,000-100,000 years ago. I am not responsible.

But I am affected. My biology is different from what I once thought. Perhaps I am healthier as a result of the ancient interbreeding, as at least one report has suggested.

More than that, I am coming to see human beings as biologically more diverse and more complicated that we once thought. The diversity part is a bit scary. We have not done well as a species in dealing with our differences.

The complexity part—that’s more of a mystery than a fear. I don’t claim to hear the voices of my Neandertal ancestors calling out from my DNA or reverberating through my metabolic processes. At least not yet.

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.

Complicating the Family Tree

Our view of our past keeps getting more complicated. Our family tree, it turns out, is more of a twisted vine than a neatly linear branch.

Evidence keeps building by the day that our anatomically modern human (AMH) ancestors interbred with earlier forms of “archaic” humans. In the 31 Oct 2011 early online issue of PNAS, Pontus Skoglund and Mattias Jakobsson present evidence for the view that the genetic legacy of the Denisovans is wider than ever thought before.

First is was the Neandertals. This branch of the human family diverged from our own somewhere around 500,000 years ago. Somewhere between 100,000 and just 50,000 years ago, however, AMHs and Neandertals interbred successfully. The result lives on today in our genes. For many of us, our DNA is 2-3% from our Neanderthal ancestors. The Neandertals may be extinct, but their DNA lives on in every cell in the human body.

Then it was the Denisovans, a recently discovered branch of the human family more closely related to Neandertals than to us. What about AMH-Denisovan iInterbreeding? An international team of researchers led by Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Leipzig was able to extract Denisovan DNA from tiny fragments of remains. From the extracts, they reconstructed the Denisovan genome and compared it with the human genome. What they found was clear evidence of interbreeding. Some living human beings—those identified as Melanesians—carry Denisovan genes. That was reported in December 2010.

In September, however, Pääbo was joined by David Reich and Mark Stoneking and other colleagues in reporting that the legacy of Denisovan DNA extends beyond the Melanesians. It’s all over the islands that extend below Southeast Asia, including Australia. Not just Aboriginal Australians but Near Oceanians, Polynesians, Fijians, east Indonesians, and other groups as far as the Philippines are carriers of the Denisovan legacy.

According to this study, the genetic legacy of AMH-Denisovan admixture does not include East Asians. This led the authors to conjecture that there are at least two main waves of AMH migration into southeast Asia. The first wave interbred with Denisovans while the second, apparently, did not.

Their work appeared in the 7 Oct 2011 issue of the American Journal of Human Genetics. Reich discusses these findings in a video. Hint: start at minute 22:30.

But now a study published in the online early edition of the Proceedings of the National Academy of Sciences for the week of 31 Oct 2011 presents evidence that East Asians are also descended in part from the Denisovans. In the paper, the authors (Pontus Skoglund and Mattias Jakobsson) write that “we found a significant affinity between East Asians, particularly Southeast Asians, and the Denisova genome.”

Experts in the field will no doubt debate these findings. Just how widespread is the effect of AMH-Denisovan interbreeding? How widely did AMHs and archaic humans interbreed? To what extent does admixture provide any benefit? Does it shed any light on observable differences between different groups within the human family today?

According to Skoglund and Jakobsson, the “history of anatomically modern and archaic humans might be more complex than previously proposed.”

If our past is more complex than we thought, so is our present. What does it mean to be human? It no longer seems to mean that we are all part of a biological species. Whether we like to call ourselves "anatomically modern humans" (AMHs) or Homo sapiens, we are learning that the very concept of species is becoming unfocused by research. Should we speak of AMH-Denisovan "interbreeding" or "hybridization"? Does it matter? Are we separate species or one slightly-tangled humanity?