Svante Pääbo awarded Nobel Prize for studies of extinct human ancestors | Hacker News Reader

Svante Pääbo awarded Nobel Prize for studies of extinct human ancestors

quantamagazine.org

If anyone wants to understand the huge impact paleogenomics is having on writing human history a very good book is "Who We Are and How We Got Here" by David Reich.

It describes the seminal work of Dr. Paabos and many others. The main focus are the 3 big migrations of hominids to Europe (early nomadic settlers, farmers from Anatolia and the corded culture/horse riders from South-Central Asia).

The book also discusses the inter-breeding of Neanderthals and Sapiens, Denisovarian and Sapiens, the migrations and castes/class system that shaped the ethnic diversity on the Indian subcontinent and the surprising genetic evidence of colonization of South America by Pacific islanders.

It is mind blowing stuff...

I'm surprised that the prize wasn't awarded jointly with Reich.

The Nobel Prize tends to favor initial breakthroughs. Svante's lab sequenced the very first complete Neandertal genome, showing it was possible to reconstruct genomes from ancient DNA, with high-throughput sequencers, and developing the necessary lab protocols and software to put it all together (with his lab). Svante was senior author on the Denisova paper as well. So, I am not surprised. There was no major advance needed for Reich to do his work further elucidating the origin and dispersion of various hominin species and ancient human populations.

Paabo told me (when he visited to give a talk at my institution) that the first few years of Neandertal sequencing, he was just sequencing his own genome accidentally, since he didn't have truly stringent lab technique. He was out ahead of everybody else for at least 2-3 years at the time, and could demonstrate to people trying to replicate his results that they were just using contaminated samples. Sequencing is absurdly sensitive- it can pick up a real signal from just a few individual molecules.

Seriously? Nobody was verifying that end to end?

This reminds me of another story - BGI was sequencing the chicken genome, and for a while, a lot of people who did other sequencing projects kept receiving chicken DNA in their sequencing data files (as contamination).

As it turns out, paleogenomics takes next level cleanliness, far more than anyone expected, particularly when you're trying to sequence something so close to human DNA.

Sometimes verifying the little details can get in the way of publication velocity. It's a risk many advanced scientists take because the chance of getting caught (publishing something that is later shown to be obviously false using careful control experiments) is low, and the risk to your career of being second to publish.

Does this mean that inexpensive DNA tests you can buy online are likely to contain contaminated samples? As the person taking the sample at home hardly has stringent lab tech available?

No, tests like that work with an abundance of DNA and so contamination is less likely. A DNA test typically works with saliva or blood which contains a ton of DNA> That DNA can then be amplified, which amplifies both the signal and the noise, but the noise is very low and can be trivially ignored after the fact.

With paleogenomics, you're collecting a tiny amount of DNA, mostly degraded, from ancient samples, and so the "noise" (contamination DNA) ends up being close to or more than the signal you get from the sample.

Details here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3926038/

The issue with paleo DNA is that the target is much lower in concentration than potential contaminants from the lab worker. etc. This wouldn't be the case in DNA tests where the concentration of the sample would be comparatively high.

That was a common problem in Paabo's early work. He also "sequenced an Egyptian mummy" that turned out to be himself as well.

My feelings exactly. (That aside - delighted that Pääbo and his field are getting this recognition.)

Here, have a UTF8 code point for the next comment: ä

You're welcome!

>"Who We Are and How We Got Here" by David Reich

IMHO, I'd take the conclusions offered here with a grain of salt. It's applying statistical methods to very improbable events (ancient bones surviving with DNA) to determine other very improbable events (evolutionary DNA change). The conclusions at least somewhat rest on the assumption that those two things have relatively consistent probabilities. That could be true but it's probably not and if it's not it's somewhat unclear how that would bias the results that the book draws its conclusions from.

> statistical methods to very improbable events

What is the alternative?

If I had one I'd be clearing a space on my shelf for my Nobel Prize

Seriously though, I don't think there's any way to know for sure. Like imagine if it were dice rolls. You can look at the results and draw conclusions to see if it's a weighted dice. But what if my table biased rolls or if some results were lost? It's probably reasonable to conclude that they weren't but no way that I can see to be sure.

Random walks.

> other very improbable events (evolutionary DNA change)

Sorry, I don't understand this part.

Are you suggesting that evolution is a "very improbable event"?

Among serious scientists evolution is already settled and beyond dispute.

I don't see any basis for an argument if you're suggesting that.

Denying evolution belongs to religion, not science.

No, they are referring to the fact that the events that lead to permanent changes in the genome are extremely rare- the vast majority of mutations are not fixed.

I recently started reading that book have been constructing a drinking game based on it. I'd definitely recommend the book so far, but wouldn't necessarily recommend this drinking game:

* Every time a new process is described as being a factor of x times faster/cheaper/better than its predecessor, take log(x) sips of your drink

* Take a sip of your drink for every unique 3-Population Test or a 4-Population test that is described (where uniqueness is defined as the set of populations going into the test).

* Take a shot every time the difference between Population X's DNA and East Asian DNA is used as a unit of measure. Take an additional shot for the quantity if it's more than one, e.g. "The difference between Denisovan and European Hunter Gatherer DNA is twice as large as the difference between Denisovan and modern East Asian DNA." would result in two shots.

* Take a shot every time certain events are described as happening in sequence, but the years also have overlapping error bars

I read Svante Pääbo’s autobiography, which is basically a story of him continually getting the scientific equivalent of promoted, and thought it was interesting that he refuses to give his discoveries Latin species names like “Homo denisova” on the basis that they’re pretentious. So Denisovans still don’t have one.

Also, at one point he steals his labmate’s wife, and then later hires them both for his own lab.

It's a good book and his work is very significant - this is a well deserved prize.

That was interesting. I looked what Wikipedia says

"Denisovans may represent a new species of Homo or archaic subspecies of Homo sapiens (modern humans), but they are known from too few fossils to erect a proper taxon. Proactively proposed species names for Denisovans are H. denisova[2] or H. altaiensis.[3]"

It is illegal to own people in Sweden, so you can't steal them.

Do you know another verb for being the person someone is cheating on their spouse with?

The wife of his labmate got bored of her current partner and instead went for someone less boring?

Congrats Svante Pääbo! I saw his lecture in person a year or two ago, it's really fascinating how the new genetic analysis tools revolutionized the study of human evolution and migration.

I thought he was Finnish, judging by the last name, but according to Wikipedia, "Pääbo was born in Stockholm and grew up with his mother, Estonian chemist Karin Pääbo."

Also interesting, "His father was biochemist Sune Bergström, who shared the Nobel Prize in Physiology or Medicine with Bengt I. Samuelsson and John R. Vane in 1982"

It's even more remarkable that Paabo never really had much of a relationship with his father but still managed to follow him in getting a Nobel Prize. Something to fuel nature-nurture debates...

Are you underestimating the choices of his mother and her capacity for creating an unprecedented intellectual atmosphere?

so this guy had nature and nurture on his side, nice!

That is the clear and smart way of phrasing it, I did not have enough clarity to make the point, thanks!

Please try not to be tedious. If you want to stir the pot, bring up the fact his mother selected a Nobel prize winner to have kids with, so clearly had bias, or something more creative.

Your statement leaves little doubt to my unsettling question, thanks for the clarity!

Or, I just pointed out that you went into the conversation with a boring assumption. It's transparent.

Yes yes, we know the problem.

Moral of the story : choose your parents wisely.

Karin Pääbo is a WW2 Estonian child refugee.

I had the similar pleasure of attending a Svante Pääbo lecture at Princeton. A bit after the Cell paper was published. The entire team seemed like scientists genuinely chagrined at the attention. Of course it should surprise no one that Neanderthal / Homo Sapiens "gene flow" would spark imaginations ;)

It's the Year 2022, and it appears we've evolved technologically to the point that Nobel calibre bioinformatics can be done on consumer laptops. It should be enough to literally calculate a personal Neanderthal / Denisovian admixture ratio on your own, provided you have access to your own sequence. With prices dropping on an Illumina machines, gene sequencers could be as ubiquitous as the PC shortly. Which, it's quite easy to see, results in the private sector human gene hacking industry, where humans in competitive play seek to "amp" their hominid characteristics for performance advantage ;)

https://github.com/PrincetonUniversity/IBDmix

Leipzig... he's a colleague of McElreath (of Statistical Rethinking).

Atrocious that David Reich and Nick Patterson were not recognized, although this is typical of the Nobel committee.

I hadn't considered that Reich and Patterson might have deserved recognition. I think a case could possibly be made for that, especially if the prize-winning work had been defined more broadly as ancient DNA research in general rather than sequencing archaic hominins and identifying introgression into modern humans more specifically. Reich and Patterson were after all heavily involved in the analysis identifying gene flow from Neanderthals into modern non-Africans. But Reich's and Patterson's (very successful and important) careers have focused on more recent, within-sapiens population history, and I think their role in archaic hominin work was less "irreplaceable" than Paabo's. There are plenty of very important archaic hominin papers from Paabo and collaborators which did not involve Reich and Patterson at all: the earliest Neanderthal mtDNA and autosomal sequences, Denisovan mtDNA (which came out before the autosomal paper), much of the biochemically focused work on gene expression differences between species and so on, Sima de los Huesos... Reich and Patterson also came into the picture quite a bit after Paabo initiated the whole ancient DNA field - I think about 10 years later. So, even though I would have for personal reasons preferred that Reich and Patterson be recognised too, I think Paabo's contributions in the more narrowly defined field of archaic hominin research are very clearly much more comprehensive and vital than theirs.

My greatest contribution to scientific progress came in 2010 when I was having lunch with Nick. He described an admixture problem to me, summarizing: "I've got observed populations and I want to build a tree where I pick points for unobserved populations such that it minimizes the edge length of the tree. I can't seem to come up with a good algorithm for it."

"Nick, that's the Steiner Tree problem! It's NP-complete!" He probably would've wasted a few more days going down that rabbit hole.

Edit: Nick has some great Cold War spy games stories that I've only heard him tell in broad strokes.

Any hope of solving it using quantum computing?

NP-complete isn't necessarily bad, depending on the size of inputs, right?

Most problems in this space have reasonable-time approximations that get you close to the right answer for far less computational complexity. Even without ever having looked at Steiner trees before, I guess that there were reasonable approximations, and confirmed that was true without looking too hard. Letting Patterson know about the problem mapping ("your problem is an instance of <X>") is typically enough for a person of his calibre to research approximate solutions good enough for him to run some experiments.

(many people say the protein folding problem is NP-complete, but the community generally believes you can predict the folding pathways of all proteins without explicitly running such calculations).

> typically enough for a person of his calibre to research approximate solutions good enough for him to run some experiments

And it's hard to overstate his caliber. For those of you who are unfamiliar with the name, Nick mentored Clifford Cocks at GCHQ and pushed him in the direction of inventing public key cryptography.

Looks like there's a quantum speedup: https://arxiv.org/abs/1904.03581 IIRC there's no epsilon approximation.

No. Theory offers you a quadratic speed-up of the exponential worst-case running time. And this is the theory. In practice, it looks worse. ....and: exponential worst-case running time is almost never observed in any kind of practical NP-hard optimization problem when using state-of-the-art algorithms on digital computers... and talking about the Steiner tree problem: It is basically solved for all practical matters. Same for the famous travelling salesman problem. Look at this solver: https://www.math.uwaterloo.ca/tsp/concorde.html

Or look at these amazing results: https://www.math.uwaterloo.ca/tsp/star/index.html

Sorry, but this was a somewhat bad advise. You can solve huge Steiner tree problems (up to a million of edges) in practice to optimality. See for example this solver: https://scipjack.zib.de/

There is a wide-spread misconception of the meaning of NP-complete, unfortunately. Also, it should probably be NP-hard, not NP-complete, the latter is for a decision problem only.

I thought the latter name sounded familiar and then I realized I met with him at the Broad Insitute and he told an off color joke about getting DNA from mosquito's testicles. Interesting guy who worked on UK crypto before genomics.

wikipedia already updated, quite impressive always: https://en.wikipedia.org/w/index.php?title=Svante_P%C3%A4%C3...

Is there enough extant Neanderthal DNA in some Homo Sapiens lineages to restore Homo Neanderthalensis by back crossing? Actually doing so would almost certainly be highly unethical, but I still wonder if it’s possible.

Probably not.

But I think we have pretty complete Neanderthal DNA from fossils, so, with a few more decades of gene engineering, they could probably be created.

Then I guess we'd have to ask them if their creation was ethical :)

This is important work, and this award choice is a good one.

https://www.nobelprize.org/prizes/medicine/2022/press-releas...

(via https://news.ycombinator.com/item?id=33065326, but we merged that thread hither)

Love Paabos work, but spinning the work as giving “huge insights into human physiology” is a bit of a stretch. If the bar were insights in human physiology there would be a lot more people who have done more important work.

Forgive me, but can you expand a bit on this? I am completely uninformed in this area and like to have a holistic view when endeavoring to learn anything new.

I've recently begun reading Harari's Sapiens. Does Dr. Pääbo's research throw any light unto the interbreeding/replacement debate regarding extinct humans?

Yes, it does.

The most interesting aspect it brings are numbers. It allows to measure how much of our DNA comes from which group of humans (Neanderthals, Denisovarians, etc). It also shows that the migratory currents had a lot of details that we barely got to understand.

To understand Dr. Paabo's (and others) work, I suggested above "Who We Are and How We Got Here" by David Reich.

Read it. It is easy reading. If you liked Sapiens I guarantee you will like that book too.

Thank you for the info, much appreciated!

Nice! One of those areas of science which I think really capture the public imagination.

Katalin Karikó was robbed, unless they are giving mRNA vaccines as chemistry.

Why Katalin Karikó and not Robert Malone? [0]

[0] https://en.wikipedia.org/wiki/Robert_W._Malone

From your link:

The New York Times, in an article about Malone, reported: "While he was involved in some early research into the technology, his role in its creation was minimal at best, say half a dozen Covid experts and researchers, including three who worked closely with Dr. Malone."

I know nothing about this, but this passage in the Wiki article that you linked points at some controversy:

>While Malone promotes himself as an inventor of mRNA vaccines,[1][7] credit for the distinction is more often given to the lead authors on the major papers he contributed to (such as Felgner and Wolff), later advances by Katalin Karikó and Drew Weissman,[3][19] or Moderna co-founder Derrick Rossi.[13] Ultimately, mRNA vaccines were the decades-long result of the contributions of hundreds of researchers, including Malone.[3][20] The New York Times, in an article about Malone, reported: "While he was involved in some early research into the technology, his role in its creation was minimal at best, say half a dozen Covid experts and researchers, including three who worked closely with Dr. Malone."[7]

Addon: I do not promote that Malone get Nobel price (just first google hit). What I meant to ask was what Karinó did that is special related to all other work in this field.

The Nobel Committees sometimes take quite a while to get around to deserving researchers. It is not a rapid-response organization.

The only exception I'm aware of in modern times is the high-Tc superconductor prize in Physics. Results announced in March, prize awarded in October -- it was so obviously important and trivially demonstrated as correct.

LIGO is another example

GW150914 was detected in September of 2015 -- the associated prize wasn't awarded until 2017. That award followed the very important detection of GW170817 in August 2017, which featured the critical detection of an optical signature in parallel with the GW signal.

mRNA is definitely in a similar regime today. A promising technology led to vaccines in trials by autumn 2020, and oodles of shots-in-arms by autumn 2021. In 2022, the mRNA technology is on very solid footing for having saved millions of lives. The Committees definitely could award one or more mRNA prizes this year, but they may have other prizes they need to award before a worthy recipient passes away.

No COVID-19 vaccination breakthrough awarded?

The ones most likely to receive the prize isn't that old yet, also since the DDT scandal they do prefer to wait a bit to hedge on delivering prize before side-effects are known (Often one wishes the ones awarding the peace prize had kept that in mind).

TIL

> Müller was awarded the Nobel Prize in Physiology or Medicine in 1948 "for his discovery of the high efficiency of DDT as a contact poison against several arthropods".

The lobotomy guy too was awarded the prize I think.

Wait another 30 years, it would be hailed a miracle just like the small-pox vaccine. Like they say, the victors (re)write the history.

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