Post by ArkalenPost by MarkEHere is further evidence that OoL research is really only at base
camp, if that. Excitement and optimism over reported progress needs to
"Explaining isolated steps on the road from simple chemicals to
complex living organisms is not enough. Looking at the big picture
could help to bridge rifts in this fractured research field."
https://www.nature.com/articles/d41586-024-00544-4
snip
Okay you know what I've now seen three different sources describing this
article as confirming ID/debunking OoL research and that *look* like
they read it (as in, they quote from it & claim to have read the full
thing) so I'd really like to see for myself what it says. Anybody have a
subscription to Nature & feel generous with PDFs?
Got my hands on the paper! (thanks mom :)) And I can confirm... that it
is hilarious. Let me give you an extremely bad-faith reading between the
lines that I am sure Nick Lane would repudiate in the most indignant terms.
First, I'll say my overall bet on the paper was wrong - it isn't telling
everyone the hydrothermal vent theory is correct and while it is asking
the field to get on with a program that program isn't quite "do the
alkaline hydrothermal vent theory". It's also, needless to say, not at
all saying OoL research is in a rut and I think my description of it
firing a starting pistol is still correct.
Now first, to reveal to you all what follows the "here are all the
issues that make abiogenesis a seemingly intractable problem" quote mine:
"None of this precludes understanding the
origin of life, but it does make competing
hypotheses hard to prove or disprove unam-
biguously. Combine that with the overarch-
ing importance of the question and it’s clear
why the field is beset with over-claims and
counter-claims, which in turn warp funding,
attention and recognition.
This context has splintered the field.
Strongly opposed viewpoints have coexisted
for decades over basic questions such as the
source of energy and carbon, the need for light
and whether selection acts on genes, chemical
networks or cells.
To understand how life might have begun,
researchers must stop cherry-picking the
most beautiful bits of data or the most appar-
ently convincing isolated steps, and explore
the implications of these deep differences in
context. Depending on the starting point, each
hypothesis has different testable predictions.
For example, if life started in a warm pond on
land, the succession of steps leading from
prebiotic chemistry to cells with genes is sur-
prisingly different from those that must be
posited if the first cells emerged in deep-sea
hydrothermal vents.
Building coherent frameworks — in which
all the steps in the continuum fit together — is
essential to making real progress."
=> Hmm, I wonder what parts of the field have been highlighting
beautiful bits of data and convincing isolated steps, and who's been
building a coherent framework in which all the steps in the continuum
fit together.
"To see why,
here we highlight two of the most prominent
frameworks, which propose radically distinct
environments for the origin of life."
=> Oh how uncharitable of me! There are two such competing frameworks
equal in dignity, fair enough. So what's the first one?
"Prebiotic soup"
=> Nicholas Herbert Lane (not his real name) I have watched your talks I
know what you think of "soup".
"This chemistry can produce relevant
products, such as the nucleotide building
blocks of genes, in high yields — although dif-
ferent reactions occur in distinct environments,
ranging from laboratory equivalents of the
atmosphere to geothermal ponds and streams."
"Meteorite impacts might be one source, but there is
little agreement about that among geologists."
"Nor does this approach explain just how these
“reservoirs of material ... come to life when
conditions change”"
"The problems are that there is
little evidence that RNA can catalyse many of
the reactions attributed to it (such as those
required for metabolism)"
"copying ‘naked’
RNA (that is not enclosed in compartments
such as cells) favours the RNA strands that rep-
licate the fastest. Far from building complex-
ity, these tend to get smaller and simpler over
time."
"Worse, by regularly drying everything
out, wet–dry cycles keep forming random
groupings of RNA (in effect, randomized
genomes). The best combinations, which hap-
pen to encode multiple useful catalysts, are
immediately lost again by re-randomization
in the next generation, precluding the ‘verti-
cal inheritance’ that is needed for evolution
to build novelty."
" Evolution would therefore need
to replace each and every step in metabolism,
and there is no evidence that such a wholesale
replacement is possible."
"Can genes that encode
multiple metabolic pathways have arisen at
once? The odds against this are so great that
the astrophysicist Fred Hoyle once compared
it to a tornado blowing through a junkyard and
assembling a jumbo jet."
=> Wow that's a lot of pretty severe problems you point out there Nick
(and Joana, sorry for erasing you like that)
"On balance, we would say that prebiotic
chemistry starting with cyanide can produce
the building blocks of life, but most of the
downstream steps predicted by this frame-
work remain problematic"
=> Hmm, sounds like that would be an issue for a coherent framework in
which all the steps in the continuum fit together
Okay now "Hydrothermal systems":
"There are plenty of prob-
lems here, too, but they differ from those in
the prebiotic soup framework."
=> I see, different but equal in dignity, of course of course
"The first problem is that H2 and CO2 are
not particularly reactive"
=> Nickleby Tiberius Lane did you not solve that problem? Let me check
your publication page hmmm "CO2 reduction driven by a pH gradient"
Hudson et al 2020, surely you're aware of it you're fifth author after all
"Research in the past few years shows
that these conditions can drive the synthesis
of carboxylic acids and long-chain fatty acids,
which can self-assemble into cell-like struc-
tures bounded by lipid bilayer membranes."
=> Oh yeah you know it does
"But many chemists are troubled by the
idea that, in the absence of enzymes to serve
as catalysts, hydrothermal flow could drive
scores of reactions through a network that
prefigures metabolism, from CO2 right up to
nucleotides"
=> LOL don't you love how the previous section presented issues as "This
is an issue" but this section is all "Many chemists [that aren't us] are
troubled..."
"The chemist Leslie Orgel once dis-
missed this scenario as an “appeal to magic”."
=> That's a fun parallel to the previous section's quote of Hoyle. That
previous one was followed by a sentence hammering the point: "It is not
good enough to counter that evolution will find a way: a real
explanation needs to specify how.". What sentence follows this one?
"Certainly, further data are required, support-
ing or otherwise."
=> LMAO so the most empty concession possible, okay oh wait the
paragraph isn't over:
"Certainly, further data are required, support-
ing or otherwise. Multiple steps have now been
shown to occur spontaneously in core meta-
bolic pathways (such as the Krebs cycle and
amino-acid biosynthesis) without being driven
by enzymes, but this is still far from demon-
strating flux through the entire network."
=> That... Seems like a certain amount of supporting data you have
already, Joana Charybdis Xavier!
The next paragraph I just appreciate with no sarcasm whatsoever, I think
it presents a legitimate difficulty in a fair way:
"Polymerization is another stumbling block.
Nucleotides have been polymerized in water
on mineral surfaces, but this raises similar
questions to those noted for wet–dry cycles
about how selection could act. If the problem
is solved by polymerizing nucleotides inside
growing protocells, mineral surfaces would
not have been available. Polymerization would
then have needed to happen in cell-like (aque-
ous gel) conditions, but without enzymes. If
serious attempts to synthesize RNA under
those conditions fail, the overall framework
would need to be modified."
=> I mean, it actually presents a number of difficulties most of which
they have hypotheses to handle (the selection aspect most notably), but
the "mineral surfaces would not have been available inside a protocell"
does seem like a real problem. A *tantalizing research problem* even, do
young, dynamic early-stage researchers or PhD students read "Nature" by
any chance?
"Conversely, if these difficult problems are
resolved, then the hydrothermal scenario
offers a promising route to the emergence
of genetic information, overcoming Hoyle’s
jumbo-jet argument. "
=> Hoyle's jumbo-jet argument? The one that was mentioned as a big
problem with the first framework? Man this second framework just seems
to be racking up points compared to the other one doesn't it?
[Blah blah running up the score with the patterns in the genetic code
thing and the ability for random RNA sequences to template non-random
peptides to conlude with: ]
"Thus, in short, the two frameworks have
different advantages and disadvantages, and
it is premature to dismiss either"
=> IS IT, JOANA CAROLINE XAVIER? IS THIS YOUR TRUE OPINION NICOLAS
MIDDLENAME LANE? Cause I don't know I'm a newborn babe in the woods
reading this article and the second one seemed much better than the
first one, and again - I'VE SEEN YOUR TALKS AND READ YOUR PAPERS I KNOW
WHAT YOU REALLY THINK (for NL at least but JCX seems to be in the same
world)
"Findings can be true but irrelevant"
=> Oh that's true there's also all the hypotheses that don't even rise
to the vaguely-but-mostly-not framework of the cyanide prebiotic soup
one that you also need to take out back and shoot
[summary execution of the organic molecules from space, coacervates,
eutectic freezing & the Miller-Urey experiment by pointing out that
showing those things can happen doesn't tell us life started that way]
[I'll note by the way a VERY INTERESTING statement this makes about the
field, and could be the shooting of a starting pistol. Because the
reason people were looking at all of these disparate things was that we
were so clueless and at sea about the origin of life that any straw that
*could* happen was worth grasping. Lane & Xavier are saying here that
this is no longer the state of the field; they are now in a position to
narrow down the search to what *did* happen]
"If none of these scenarios is ‘wrong’, then
there is space in the field to pursue multiple
frameworks"
=> Oh honey honey honey, is there?
"No one needs to abandon their
favoured positions (yet). "
=> HAHAHAHAHAHAHAHAHAHA wheeze HAHAHAHAHAHAHAHAHAHAHAHA (yet) HAHAHAHAHA
"But brash claims for
a breakthrough on the origin of life are unhelp-
ful noise if they do not come in the context of
a wider framework. The problem is ultimately
answerable only if the whole question is taken
seriously."
=> Bad-faith read: right, like yours, the hypothesis with the best and
possibly only wider framework
=> Serious read: hear the starting pistol!
"An important feature of these competing
frameworks is that they must ultimately con-
verge on cells with genes and proteins — on life
as we know it on Earth. This convergence offers
new possibilities for collaboration, because
any answer will probably feature aspects of
more than one framework. "
=> Aw I feel bad for my bad faith now, that's true different frameworks
could contribute ! (and to be serious again, they obviously do - RNA
World in particular contributes to anything RNA-related even if its
strongest claims are false)
"Cofactors offer a possible convergence
point. "
=> Ooooh this one is new to me - maybe JC Xavier works on this?
"These might prove hard to make
when starting with CO2. Could it be that cofac-
tors were initially synthesized from cyanide,
but, once in circulation, tended to catalyse CO2
chemistry, now driving a lifelike protometabo-
lism that included their own synthesis?"
=> Very interesting, and proves me wrong because that's a genuine
contribution from the cyanide prebiotic soup framework!
"Perhaps, but this idea also shows how impor-
tant it is to test predictions within a specific
framework first. In the simplest scenario, all of
biochemistry begins from CO2 in a hydrother-
mal system, whereas the alternative scenario
calls for at least two places and two types of
chemistry — adding up to much more uncer-
tainty. Occam’s razor says that the simplest
scenario should be tested thoroughly first. If
the simplest chemistry is shown not to work —
that is, if it is not possible to synthesize cofac-
tors from CO2 without cofactors — then the
alternative can be taken seriously"
=> PSYCH!
"the best way
to make progress is to test the simplest idea to
destruction first. If it can be shown not to work,
then the convergence point might be real, and
should be explored seriously"
=> Sure, sure, this will definitely become relevant when the simplest
idea that you actually believe is definitely true is shown not to work
which you know it won't because it's definitely true
The last section "Towards an answer" has the actual
recommendations/pleas to the field at large that the paper is ostensibly
about:
"The origins-of-life field faces the same prob-
lems with culture and incentives that afflict all
of science — overselling ideas towards publica-
tion and funding, too little common ground
between competing groups and perhaps too
much pride: too strong an attachment to
favoured scenarios, and too little willingness to
be proved wrong."
=> Strong "no seriously guys the alkaline hydrothermal vent theory is
correct stop refusing to accept the obvious" vibes under the thin veil
of "haha don't *we* all love our pet theories" there
"Changing this culture will take some work,
given the political reality of science — the
relentless pressure to publish, to secure fund-
ing, tenure or promotion — but it is necessary
if the field wishes to continue attracting stu-
dents. "
=> That's interesting, I wonder if this is a platitude or if they have
actual issues with the student pipeline
" We highlight four priorities to
begin to move in the right direction.
*Train interdisciplinary scientists.* Pursuing
hypotheses across conventional disciplinary
boundaries calls for a new generation of scien-
tists — PhD students, postdoctoral researchers
and early-career principal investigators (PIs) —
with wide-ranging expertise and a willingness
to test specific hypotheses within coherent
wider frameworks. The field will clearly benefit
from doctoral training that stresses collegial-
ity, interdisciplinarity and the rigorous, open-
minded testing of competing hypotheses
*Foster good communication.* To promote
such a culture, one of us ( J.C.X.) co-founded the
Origin of Life Early-career Network (OoLEN)
in 2020, which has grown to more than
200 international researchers, from students
to early-career PIs. It is run by volunteers and
has no institutional ties, financial or otherwise.
Members engage in debates through regular
meetings (online or in-person), disseminate
research and write articles together. There is
still no shortage of disagreements, but that is
part of scientific research and OoLEN promotes
a healthy approach to them.
For later-career researchers, conferences
could help to reach across divides in similar
ways. Physics meetings have provided exam-
ples. In one, proponents of loop quantum
gravity and string theory switched sides in a
debate, framing good-humoured but strong
arguments against their own position in a con-
structive form of ‘steel manning’."
=> Ah so like... The people working on PAH world or cyanide get to
actually find out that the alkaline hydrothermal vent hypothesis is the
way to go! Sarcasm aside, if the field isn't already doing that then
yeah no duh it's time to start. And the AHVH does need genuine, serious
pushback from people who aren't working on it that I haven't seen so far.
"*Embrace open science*. Accepting that specific
hypotheses will be disproved and that frame-
works will be reshaped requires the publication
of negative results — too often undervalued
and unpublished. But it is clearly important
for the field to know whether, for example,
attempts to synthesize cofactors from CO2
fail — and, specifically, under what conditions."
=> Oh nice J&N, this time you managed to not only write words that
suggest the idea your hypothesis could maybe be wrong - but you even
managed to not immediately undermine it the next sentence!
"*Improve publishing practices*.
(...)
Journal editors and grant-awarding bodies
should also consider how polarized the field is
to ensure fair reviews. One way to improve the
peer-review process would be to enlist more
early-career researchers, who tend to be less
entrenched in their positions. Transparent
peer review (in which anonymous reports
are published with a paper) could also curb
bias, because it enables constructive criticism
without concealing prejudice."
=> Ooooh have someones been having their AHVH papers spiked by unfair
reviews by inhabitants of the other silos? Yikes
=> Also, lots of early researcher love here isn't there? Is someone
looking for students ? :)
"It is too soon to aim for consensus or unity,
and the question is too big; the field needs
constructive disunity. Embracing multiple
rigorous frameworks for the origin of life, as
we advocate here, will promote objectivity,
cooperation and falsifiability — good science
— while still enabling researchers to focus
on what they care most about. Without that,
science loses its sparkle and creativity, never
more important than here. With it, the field
might one day get close to an answer"
=> Beautiful conclusion to a paper that is absolutely advocating for
"*constructive* disunity" and "embracing multiple *rigorous* frameworks"
and definitely NOT calling anyone out or promoting one hypothesis above
another - or more accurately it's trying SO SO HARD to not do that in
order to get its actual message across and it's just cute how
ambiguously it succeeds. But then I'd wager the actual audience is the
youth, not the entrenched.