A singular scientist

Science has become the realm of specialists, and I am by nature a thoroughgoing generalist.  (Less kind words like "dilettante" and "dabbler" have also been applied to me.)  The result is that although I have a decent background in a good many areas of science, my knowledge of most of them is shallow at best by today's standards.  Even though I taught biology for over three decades, papers in peer-reviewed journals in most realms of biological science -- immunology and biochemistry come to mind -- lose me after the first couple of sentences.

One exception is the field of evolutionary biology and its sibling, evolutionary genetics.  These subjects have been something of a fascination of mine since I was in college, and looking back, I rather wish I had pursued them as a career.  My AP Biology students always reacted with tolerant amusement at my obvious excitement once we got to those topics, so at least my background was put to some good use.

This love for evolution and genetics is why I was absolutely thrilled when I heard that the winner of this year's Nobel Prize in Medicine and Physiology was the eminent Swedish researcher Svante Pääbo.  Pääbo is the founder of the field of paleogenetics -- the use of DNA from fossils to reconstruct the evolutionary history of a species.

[Image licensed under the Creative Commons The Royal Society, Professor Svante Paabo ForMemRS, CC BY-SA 4.0]

Pääbo is best known for his accomplishing something no one thought was possible: extracting DNA from fossilized bones.  His attitude when told something is impossible is, "Watch me."  Working at the Max Planck Institute for Evolutionary Genetics in Leipzig, Germany, he developed a pioneering technique to extract DNA from bones, first the mt (mitochondrial) DNA, which is passed only through the maternal line, and finally the nuclear DNA.

It was Pääbo's technique that allowed researchers to determine the placement of our near relatives the Neanderthals and Denisovans, the latter using only eight fossil fragments from sites in Russia, China, and northern Laos.  Without Pääbo's work, much of what we know about our own prehistory would still be a mystery.

Pääbo is also a remarkably humble, genial man.  When he received the call of his win, he was incredulous, and thought he was the victim of a prank by his friends.  A bit of questioning established that no, he had in fact clinched the highest honor in the scientific world.  Characteristically, in a press conference shortly afterward, he directed the attention outward from himself to the subject he loves.  "The thing that is amazing to me," he said, "is that we now have some ability to go back in time and actually follow genetic history and genetic changes over time."

Others were more effusive about the contributions of this soft-spoken gentleman.  "Nobody believed him [about extracting fossil DNA]," said Leslie Vosshall, neuroscientist at Rockefeller University.  "Everyone thought it was contamination or broken stuff  from living people.  Just the mere fact that he did it was so improbable.  That he was able to get the complete genome sequence of a Neanderthal was viewed, even up until he did it, as an absolutely impossible feat...  He's a singular scientist."

Indeed.  I remember reading papers by Pääbo and his colleague, the late Luigi Luca Cavalli-Sforza, when I was in graduate school, and being absolutely fascinated by the light they shone on the genetic underpinnings of evolutionary biology.  That one of my science heroes won the Nobel Prize makes me very, very happy.  

I congratulate him, and wish him many more years of blowing our minds with his groundbreaking research into our own deep past.

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Peering into the Neanderthal brain

Despite having taught genetics for 32 years, it still is astonishing to me that all of the genetic diversity of the 7.7-odd-billion humans on Earth is accounted for by differences amounting to only a tenth of a percent of the genome.

Put a different way, if you were to find the person who is the most genetically different from you, the two of you would still have a 99.9% overlap in your DNA.  A lot of that additional tenth of a percent is made up of genes for obvious appearance-related features -- eye color and shape, hair color and texture, skin color, body build, and so on.  But even these characteristics, which are usually considered to determine race, don't really tell you all that much.  A San man and his Tswana neighbor in Botswana were both called "black" by the white European colonists, but those same white Europeans were genetically closer to people in Japan than the San and Tswana were to each other.  There is, in fact, more human genetic diversity on the continent of Africa than there is in the entire rest of the world put together -- unsurprising, perhaps, given that our species originated there.

Race, then, is a social construct, not really a biological one.  There are some distinct genetic signatures in different ethnic groups, which is what allows the "percent composition" you get if you have your DNA analyzed by Ancestry or 23 & Me, and within their limitations, they don't have bad accuracy.  My own DNA test lined up almost perfectly with what I know of my family tree; something like two-thirds from western and northwestern France, a good chunk of the rest from Scotland and England, and an interesting (and spot-on) 6% of my DNA from my Ashkenazi Jewish great-great-grandfather.

Even more surprising, perhaps, is that the average difference between the human genome and that of our closest non-human relatives -- chimps and bonobos -- is still only 1.2%.  So all of the lineages that split off from our line of descent after the chimps and bonobos did, on the order of five million years ago, would be closer than that to us genetically.  This has been confirmed by analysis of DNA in those now-extinct groups of hominins -- Neanderthals, Denisovans, and so on.

Here, we're talking about way bigger physical differences than there are between any two races of modern humans you might pick.  Bone structure, brain size and structure, body proportions -- some pretty major stuff.  Still, the Neanderthals, Denisovans, and us are all the same species, by the rather mushy definition of a species as being a group of organisms capable of reproduction that results in fertile offspring; modern humans have a good chunk of Neanderthal and Denisovan DNA, also at least in part detectable by genetic testing.

[Image licensed under the Creative Commons Stefan Scheer, Neandertaler reconst, CC BY-SA 3.0]

Why all this comes up is a study in Science this week by a huge team led by Alysson Muotri of the University of California - San Diego in which geneticists tinkered with human stem cells, altering their DNA to reflect one of 61 genes that have been identified as differences between ourselves and our Neanderthal and Denisovan kin.  They then allowed those cells to proliferate and form organoids -- mini-brains that can form connections (synapses) just as a developing brain in an embryo would.

Well, my first thought was, "Haven't these people ever watched a science fiction movie?"  Because scientists always try shit like this in movies, and it always ends up with a giant brain-blob that goes rogue, escapes the lab, and proceeds to eat Tokyo.  But Dr. Muotri assures us that that's not possible in this case.  He explains that organoids are incapable of living all that long because they don't have all the support structures that real brains have -- a circulatory system for example -- so they'd never be capable of surviving outside the petri dish.

To which I say: of course, Dr. Muotri.  That's what you would say.  Just realize that in those same science fiction movies, it's always the scientist who says, "Wait, stand back!  Let me try to communicate with it!" and ends up being the first one to get devoured.

So don't say I didn't warn you.

In any case, what is kind of amazing is that these organoid brains with a single gene altered to what our Neanderthal cousins had developed in a way that was completely unlike our own.  As the press release in Science Daily explained it:

The Neanderthal-ized brain organoids looked very different than modern human brain organoids, even to the naked eye.  They had a distinctly different shape.  Peering deeper, the team found that modern and Neanderthal-ized brain organoids also differ in the way their cells proliferate and how their synapses -- the connections between neurons -- form.  Even the proteins involved in synapses differed.  And electrical impulses displayed higher activity at earlier stages, but didn't synchronize in networks in Neanderthal-ized brain organoids.

All of that, from a single gene.

"This study focused on only one gene that differed between modern humans and our extinct relatives. Next we want to take a look at the other sixty genes, and what happens when each, or a combination of two or more, are altered," Muotri said.  "We're looking forward to this new combination of stem cell biology, neuroscience and paleogenomics.  The ability to apply the comparative approach of modern humans to other extinct hominins, such as Neanderthals and Denisovans, using brain organoids carrying ancestral genetic variants is an entirely new field of study."

So that "less than a percent" label on the differences between ourselves and our nearest non-modern-human kin is a little misleading, because apparently some of that less-than-a-percent are really critical.

In any case, that's our view of the cutting edge of science for today.  One can't help but be impressed with studies like this, which accomplish feats of genetic messing-about that would have been themselves in the realm of science fiction twenty years ago.  I wonder what the next twenty years will bring?  Hopefully not brain blobs eating Tokyo.  I mean, I'm all for scientific advancement, but you have to draw the line somewhere.

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 Many of us were riveted to the screen last week watching the successful landing of the Mars Rover Perseverance, and it brought to mind the potential for sending a human team to investigate the Red Planet.  The obstacles to overcome are huge; the four-odd-year voyage there and back, requiring a means for producing food, and purifying air and water, that has to be damn near failsafe.

Consider what befell the unfortunate astronaut Mark Watney in the book and movie The Martian, and you'll get an idea of what the crew could face.

Physicist and writer Kate Greene was among a group of people who agreed to participate in a simulation of the experience, not of getting to Mars but of being there.  In a geodesic dome on the slopes of Mauna Loa in Hawaii, Greene and her crewmates stayed for four months in isolation -- dealing with all the problems Martian visitors would run into, not only the aforementioned problems with food, water, and air, but the isolation.  (Let's just say that over that time she got to know the other people in the simulation really well.)

In Once Upon a Time I Lived on Mars: Space, Exploration, and Life on Earth, Greene recounts her experience in the simulation, and tells us what the first manned mission to Mars might really be like.  It makes for wonderful reading -- especially for people like me, who are just fine staying here in comfort on Earth, but are really curious about the experience of living on another world.

If you're an astronomy buff, or just like a great book about someone's real and extraordinary experiences, pick up a copy of Once Upon a Time I Lived on Mars.  You won't regret it.

[Note: if you purchase this book using the image/link below, part of the proceeds goes to support Skeptophilia!]

A journey with the Denisovans

Every once in a while, I'll run across a piece of research that will make me think, "Ha!  How will the creationists explain that?  They'll have to admit that the evolutionary model is correct now!"

I am always wrong.

Assuming your conclusion, apparently, means never having to say you're sorry.

Take, for example, the recent study by Emilia Huerta-Sánchez et al., that showed that altitude adaptation in the Tibetan people was likely to be due to the presence of a specific gene from a group of Siberian proto-hominins called the Denisovans.  The gene, called EPAS1, protects the individuals who have it against hypoxia when the oxygen concentrations are low, is are not found in surrounding groups (the Han Chinese) but is found in the DNA of the now-extinct Denisovans.  Huerta-Sánchez et al. write:

As modern humans migrated out of Africa, they encountered many new environmental conditions, including greater temperature extremes, different pathogens and higher altitudes.  These diverse environments are likely to have acted as agents of natural selection and to have led to local adaptations.  One of the most celebrated examples in humans is the adaptation of Tibetans to the hypoxic environment of the high-altitude Tibetan plateau. A hypoxia pathway gene, EPAS1, was previously identified as having the most extreme signature of positive selection in Tibetans, and was shown to be associated with differences in haemoglobin concentration at high altitude.

Re-sequencing the region around EPAS1... we find that this gene has a highly unusual haplotype structure that can only be convincingly explained by introgression of DNA from Denisovan or Denisovan-related individuals into humans. Scanning a larger set of worldwide populations, we find that the selected haplotype is only found in Denisovans and in Tibetans, and at very low frequency among Han Chinese.  Furthermore, the length of the haplotype, and the fact that it is not found in any other populations, makes it unlikely that the haplotype sharing between Tibetans and Denisovans was caused by incomplete ancestral lineage sorting rather than introgression.

Put more simply, the scientists found that because of the distribution of the gene, the presence of EPAS1 in Tibetans was much more likely to be due to introgression (hybridization between two distinct species followed by repeated backcrossing to one of the parent species) rather than common ancestry followed by strong selection for phenotype.

Given that the Denisovans are otherwise genetically distinct from modern humans -- work by paleontologist Svante Pääbo supports the conclusion that the Denisovans represent a group whose ancestors left Africa, and have been separate from, both Neanderthals and modern humans for half a million years -- you'd think this would lead anyone who thinks that all humans come from a single family who miraculously survived the Great Flood less than 6,000 years ago to have some serious second thoughts.

Denisova Cave, southern Siberia [image courtesy of the Wikimedia Commons]

Nope.  Should have known better.  Turns out the creationists, for some reason, love the Denisovans, although I'm still at a loss for why.  Take, for example, what they have to say about all of this over at Creation.com:

It was easy to compare the [Denisovan DNA] to modern man, but in order to make comparisons to Neanderthal they needed more and better Neanderthal DNA to be sequenced.  The results were startling, for the Neanderthals turned out to be very close relations to each other, and this includes individuals from Spain, Germany, Russia and Croatia.  They were closer as a group than any of the modern populations used in the study.  That is a very large area for a very closely related group of people to cover.  The authors used the phrase “drastic bottleneck” to describe what they believe must have happened in the early years of the Neanderthal family line.  We do not feel it is ‘drastic’ to believe the Neanderthals were one family group who spread out into western Eurasia in the years after the Flood, who intermingled with other people groups as they also spread out, and who eventually died out as many other people groups have done in history... 

As with Neanderthals (from whom these Denisovans probably were a further splitoff), the evidence from hybridization scotches any notion that these were other than post-Babel descendants of Adam.

Or if you've a taste for even more bizarre pretzel logic, there's this, over at New Discoveries & Comments About Creationism:

How could have ancient humans who lived in a Siberian cave who were considered lower than Neanderthals interbreed with modern humans?  Before the sequencing of the genome took place it would have been considered, impossible!  But in human evolution, falsifications are confirmations... 

Rather than admitting their evolutionary story had been wrong with real-time observations, it’s now a race to get to the finish line. Not only that but it is implausible that this bone contained 70% of its original DNA after 82,000 years!  Who would believe such preservation of soft tissue?  It’s a stretch to say the least.  It’s much more likely that this individual lived a few thousand years ago at most... 

While a new sequencing technique now available to researchers that can be used to discern a genome from one DNA strand rather than both is quite remarkable but trying to explain it in historical terms which is forced into a particular framework known as human evolution, is not remarkable, it’s not even science. 

We live in an exciting time, since the earth is actually thousands of years old, we are able to learn more about the past rather than loosing [sic] valuable information which comes from DNA if the earth was older!

So... because the Denisovans interbred with some human populations, they had to be modern humans, and therefore less than 6,000 years old, and therefore god and the bible and the flood and all the rest of it.

Pardon me for a moment while I recover from the headdesk I just did.

I always expect, somehow, that logic and science and rationality will reach people.  Science remains our best tool for understanding the universe, and has a proven track record of uncovering the deepest, subtlest mechanisms of the world around us.

And what's odd is that the creationists pretty much buy all of it except evolution and cosmology.  Anything else is awesome -- chemistry, medical science, atmospheric science, most of physics, much of geology, and damn near all of the technological manifestations of scientific research.  Science and the scientific method, apparently, work just fine in all of those realms.

But not in biology and paleogeology, apparently.  The same scientific method that gives right answers in chemistry gives answers in biology and paleogeology that are off by three to four orders of magnitude (six orders of magnitude if you're talking about cosmology and the Big Bang).

So I'm probably engaging in a forlorn hope to think that the recent work on the Denisovans will have any effect on that.  Call me foolish, but I keep believing that one day, this will change, that the habit of teaching Bronze-Age creation myths to children as if they were fact will be over for good.

But to quote Aragorn, that day is not today.  As I said earlier, if you assume your conclusion, magic happens.  It's just that in this case, the magic has to do with insulating you from reality.