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Wednesday, February 5, 2014

One Sensational Hand


A decade ago, Dennis Aabo Sørensen lost his hand in an accident.  Now, thanks to an international team of physicians and technicians, he can feel objects once again, this time through the use of a bionic hand that is directly connected to the nerve cells in his arm. 

Sørensen is the world's first amputee able to use his bionic hand to experience the sensation of feeling.  Because he can feel what he touches, he is able to use his bionic hand with far more agility than other amputees, knowing instantly when he is squeezing something too hard and likely to crush or harm it.

Photo Credit: Sensory feedback enabled prosthesis, close-up.  Credit: LifeHand 2/Patrizia Tocci.  LINK to Video
 
“The sensory feedback was incredible,” reports the 36 year-old amputee from Denmark according to a press release from the Ecole Polytechnique Fédérale de Lausanne.  “I could feel things that I hadn’t been able to feel in over nine years.” In a laboratory setting wearing a blindfold and earplugs, Sørensen was able to detect how strongly he was grasping, as well as the shape and consistency of different objects he picked up with his prosthetic. “When I held an object, I could feel if it was soft or hard, round or square.”

 
The bionic hand, of course, is equipped with touch sensors.  But the real key is the bi-directional or two-way connection between the hand's electronics and the brain's neurons.  Tiny, cell-size links between electrodes and nerve endings were implanted into Sørensen's arm.  Then his new hand was attached and the wires connected. 
 
Over time and with a little practice, he could feel different shapes and degrees of hardness.  The sensation was as fast as normal touch.  Signals passed from the bionic fingers to the brain and then from the brain to the hand, controlling its movements.
 
For those in need of bionic hands, this work marks a real milestone.  Ordinarily we take two-way processing for granted.  But the way things feel helps us use our hands with versatility and skill. 
 
What this means in broader terms is a little less clear.  Bionic restoration is a key frontier in today's medicine.  But the technologies of healing or restoration can quickly become the technologies of enhancement.  Perhaps someday, we will look back at Sørensen's hand as a kind of evolutionary advance, bringing not just the restoration of touch but the extension of power. 
 
The paper, entitled "Restoring NaturalSensory Feedback in Real-Time Bidirectional Hand Prostheses," is the work of an international team largely based in Italy and Switzerland.  It appears in the 5 February 2014 issue of Science Translational Medicine. 

Thursday, January 30, 2014

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.  

Monday, January 27, 2014

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.

Wednesday, December 4, 2013

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. 

 

 

 

Thursday, October 17, 2013

What a Small Brain Can Tell Us

New information about an early human skull sheds more light on the very first members of the human genus.  The skull, found in Dmanisi, Georgia in 2005, has now been freed from the stone casing that has preserved it for the past 1.8 million years. An international team led by David Lordkipanidze of the Georgian National Museum report its findings in the October 18 issue of the journal Science. 

Photo Caption: The Dmanisi D4500 early Homo cranium in situ. Photo courtesy of Georgian National Museum.

When the world first learned of early human remains in Georgia, the news came as a bit of a shock.  These early humans seemed quite similar to other remains found in Africa and dating to the same time.  That suggests they were able to travel and adapt to new settings. 

The latest analysis contains a new surprise.  The skull described in the new report has an unexpectedly small brain size, at or below the range usually seen as minimal for our genus.  At 546 cubic centimeters, its small brain widens our view of variability of humans at this time. 

Does this skull, identified as Skull 5 from Dmanisi, really measure up to being in the genus Homo at all? It is something else, like Australopithecus?  The researchers argue that it is clearly part of the genus Homo for the simple reason that Skull 5 is found with other, larger-brained skulls, all clearly part of the same community.  One Georgian brain was as large as 730 cc.  What this suggests is that Skull 5 is part of Homo but that our definition of Homo should be broadened. 

In fact, all this diversity at one site provides support for one side in an ongoing debate.  Are species defined broadly in terms of variability, or does small to moderate variation indicate separate species.  This finding supports the view that at least in terms of early humans, a species can be quite variable.      

Not too long ago, Lordkipanidze and his team took the opposite view.  They believed that these early humans from Georgia were a distinct species, what they called Homo georgicus.  The new paper retracts that claim, saying that the new evidence of variation in Georgia means that these fossils fit within the widened range variability of Homo erectus, a globally dispersed species.  More precisely, they see the Georgian samples as best classified as Homo erectus ergaster georgicus, part of the species Homo erectus but distinct because of modifications over time and because of location. 

Commenting on the variation in the skulls found almost literally on top of each other at Dmanisi, co-author Christoph Zollikofer notes that the skulls “look quite different from one another, so it's tempting to publish them as different species.  Yet we know that these individuals came from the same location and the same geological time, so they could, in principle, represent a single population of a single species,” Zollikofer said in a press release issued by the journal Science. 

The key claim advanced in the article, however, is that these samples from Georgia and Africa, together with other samples from Asia, are all part of one global species.  The report describes them as Homo erectus, seen as “a single but polymorphic lineage.” 

The diversity found in Georgia also suggests that the number of individuals in that region may have been larger than first thought, possibly numbering 10,000 or so.  And the small size of Skull 5’s brain suggests that they traveled all this way before brains began to expand.

The report, “A Complete Skull from Dmanisi, Georgia, and the Evolutionary Biology of Early Homo," is published in the 18 October 2013 issue of the journal Science, published by the American Association for the Advancement of Science.    

Monday, August 12, 2013

Is Neandertal Technology Still in Use Today?

Those primitive Neandertals may not have been so primitive after all.  Some 50,000 years ago, they were using a highly crafted bone tool virtually identical to a tool in use by human leather-workers today.

The tool is called a lissoir, was made by Neandertals living in southwestern France long before the arrival of the people we like to call “anatomically modern humans.”  The discovery, reported in the August 16, 2013 online issue of PNAS, is sure to fuel the debate over the cultural sophistication of the Neandertals.

Caption: Four views of the most complete lissoir found during excavations at the Neandertal site of Abri Peyrony.  Credit: Image courtesy of the Abri Peyrony and Pech-de-l’Azé I Projects.

Ever since their discovery over 150 years ago, Neandertals have been seen as “cavemen,” primitive in every respect compared to us “modern” humans who replaced them.


But in recent decades, the cultural achievements of Neandertals have been recognized.  Even so, the debate continues.  Did they learn more advanced technology from the modern human invaders of Europe and Asia, or did they develop it on their own?  The new findings lends support to the view that Neandertals were able to create and invent on their own. 

Neandertals were very likely the first to use sophisticated bone tools in Europe.  The tool found in France was made from the rib bone of red deer or possibly reindeer.  Making it required breaking, grinding, and polishing.  It shows evidence of being used to work leather, much like similar tools today.  When rubbed against an animal hide, it makes the leather soft, shiny, and more water resistant.

"For now the bone tools from these two sites are one of the better pieces of evidence we have for Neandertals developing on their own a technology previously associated only with modern humans", explains Shannon McPherron of the Max Planck Institute for Evolutionary Anthropology in Leipzig according to a press release from the Institute. 

Tools like this first appear in Africa much earlier.  But this new finding raising intriguing questions.  Did “modern” humans bring this technology from Africa and pass it to Neandertals prior to 50,000 years ago? Is there a technology transfer around the same time as modern/Neandertal interbreeding?  Or did Neandertals invent this technology on their own and transfer it to the modern humans who began to arrive in Europe around 40,000 years ago? 

"If Neandertals developed this type of bone tool on their own, it is possible that modern humans then acquired this technology from Neandertals. Modern humans seem to have entered Europe with pointed bone tools only, and soon after started to make lissoirs. This is the first possible evidence for transmission from Neandertals to our direct ancestors," says Marie Soressi of Leiden University in The Netherlands, part of the team of researchers who made this discovery.

"Lissoirs like these are a great tool for working leather, so much so that 50 thousand years after Neandertals made these, I was able to purchase a new one on the Internet from a site selling tools for traditional crafts," says Soressi. "It shows that this tool was so efficient that it had been maintained through time with almost no change. It might be one or perhaps even the only heritage from Neandertal times that our society is still using today."

Neandertals at this time were making sophisticated stone tools.  But these tools were made of bone because bone can is more adaptable for certain uses.  According to McPherron, "here we have an example of Neandertals taking advantage of the pliability and flexibility of bone to shape it in new ways to do things stone could not do."

The deeper question that lies behind this research is whether “modern humans” burst on the scene suddenly as a unique phenomenon of evolution, or whether the process of becoming human is more gradual and more widely distributed than we once thought.  

The research reported here was conducted by teams from Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, and the University of Leiden in the Netherlands.  The article, entitled “Neandertals made the first specialized bone tools in Europe,” appears in the August 16, 2013 online edition of the Proceedings of the National Academy of Sciences.
 




Thursday, July 25, 2013

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.