Exposing Professor Dave’s Playground Tactics and Citation Bluffing Blitz
In a series here I have been offering a post-mortem on the recent origin-of-life Debate between Rice University chemistry professor James Tour and YouTube science educator “Professor” Dave Farina. The point of this series is that you don’t have to be a science expert to understand who won the debate. I’m presenting three observations which are strong indicators about who won the debate:
Tour focused on science, Farina focused on character assassination.
Tour posed reasonable scientific challenges which Farina refused to answer.
Farina relied heavily upon playground tactics, appeals to authority, and citation bluffing.
Blinding Us with Science?
I don’t want this series to sound like Dave Farina did not discuss science. Interspersed in his flow of personal attacks and mockery of James Tour, some science came out. For the Q&A Farina had clearly prepared a list of peer-reviewed scientific papers written by leading origin-of-life researchers that he planned to cite because he believed they answered Tour’s requests for how various chemicals could form under prebiotic conditions. That’s fine. Good for Farina — this was a step in the right direction.
It was here that Farina used a blitz approach, throwing citation after citation at Tour rather than giving a detailed description of the science. Tour would respond to some if not many of the papers but there was simply not enough time to do so for all of them.
But in a great many cases, Tour had ready answers for why those papers either did not produce what Farina claimed or did not actually model realistic prebiotic conditions. It was here that it became clear that Farina was frequently out of arguments so he would resort to unpersuasive theatrics.
Sometimes Farina would try to pre-emptively prevent Tour from challenging the paper he’d just cited by saying things like “So do you call this guy a fraud?” or “Are you calling the author a liar?” Farina began to sound like a broken record, saying this over and over. It was clear he had nothing better than to tacitly threaten Tour’s integrity if he dared to challenge Farina’s scientific authority of the moment (that is, the claims Farina was making about the authority).
Farina’s repeated framing was that if Tour criticized the paper then Tour must be calling the scientists a total “fraud” or “liars,” and he would not let Tour disagree or challenge him on this. When Tour gave details Farina would mock him. If you disagreed with Farina’s authority then you were immediately deemed a crank and intellectually deficient.
Other times, Farina would resort to ridiculing Tour with sarcasm, and would even frequently stoop to repeating Tour’s words back at him with a mocking tone — a playground tactic one might expect from a person trying to divert attention from the fact that they have no answer to the question. Similarly, whenever Tour would cite numerical statistics that challenged the origin of life, Farina would mockingly mutter things like “There you go with big numbers again,” sneering at Tour for simply making a substantive argument. These antics may please the peanut gallery but they don’t inspire confidence in Farina’s science.
The rapid-fire citation approach also raised questions about whether his papers actually backed up his claims. In fact, a little investigation after the debate showed that at least some of Farina’s papers were what we call “citation bluffs.”
Farina’s Citation Bluffs on RNA Replication
To give one important example, Farina cited a 2009 paper co-written by origin-of-life giant Gerald Joyce published in Science to claim they had produced a “fully replicating” RNA (Farina’s words) – a key step in the origin of life. This is not the first time we’ve encountered this paper — it has been answered by both Stephen Meyer and Brian Miller. A couple years ago Miller gave it an astute dissection in response to another interlocutor who cited it as a refutation of Meyer. Here’s’ what Dr. Miller wrote:
So what about Joyce’s experiments? Did they show that RNA molecules can self-replicate more than 10 percent of themselves under plausible prebiotic conditions and without intelligent intervention — the specific claim that Meyer disputes.
No, they did not. Instead, here’s what Joyce and Robertson, and earlier Joyce and Lincoln, actually did.
In these experiments, Gerald Joyce and his colleagues demonstrated that a specifically designed RNA enzyme (or “ribozyme”) that they designated as E could link together two partial strands or halves of another RNA molecule (which they called the RNA substrates A’ and B’). The resulting new RNA enzyme (designated E’) could then join together two parts of the original ribozyme (RNA substrates A and B). The longer strands fused together by this process (that is, ribozymes E and E’) could then repeatedly fuse together the two halves of the opposite ribozyme if (1) a continuous supply of the two halves (either A’ and B’ or A and B) were provided in ample amounts to the experiment and if (2) critical protein enzymes were also introduced into the experiment at specific times.
Here is a figure that depicts the entire process. … [T]he researchers themselves, give the impression that these experiments produced a self-replicating system that simulates “self-sustaining Darwinian evolution,” they in fact did no such thing. Nor did they produce an RNA molecule that could copy more than 10 percent of itself or, still less, one that could reproduce itself with “100% effectiveness” and do so under plausible prebiotic conditions.
Ligation, not Polymerization or Replication
In the first place, Joyce and colleagues did not produce a genuinely self-replicating molecule. As envisioned by RNA World proponents, the emergence of a self-replicating RNA molecule is the crucial step in the emergence of the first life on earth since only after the emergence of such a self-replicating molecule would something like natural selection and random mutation begin to occur.
Moreover, in the RNA world scenario a self-replicating RNA molecule would emerge only after (1) the chemical subunits of RNA formed on the early earth and then (2) those subunits linked together in specific ways to form an RNA molecule capable of producing copies (and near copies) of itself. RNA world researchers envision such self-replication occurring as the result of a ribozyme (specifically an RNA replicase) using a complementary copy of itself as a template to produce another copy of the original strand from free-floating RNA subunits (in particular, activated RNA nucleotides).
Nevertheless, as Meyer has repeatedly noted, the molecules in Joyce’s experiment do not demonstrate the capability for such template-directed self-replication — a capability that RNA world advocates envision as crucial to the process of life originating from RNA molecules. Such self-replication necessarily requires the ribozyme to function as a polymerase — in other words, the ribozymes need to have the ability to link many nucleotide bases together to form long RNA chains. The ribozymes in the Joyce experiments do not perform this action. Instead, they catalyze (ligate) a single linkage between two ends of two pre-made, pre-sequenced halves or sections of RNA — sections that, once linked, will become a separate RNA chain that folds into a ribozyme. Thus, the RNA enzymes in Joyce’s experiments function as simple ligases rather than polymerases or replicases.
Meyer had already critiqued these experiments showing that they lacked this capability and did so again in Return of the God Hypothesis. As he stated (on p. 309):
“The ‘self-replicating’ RNA molecules in this experiment did not copy a template of genetic information from free-standing nucleotides as protein machines (called polymerases) do in actual cells. Instead, in the experiment, a presynthesized specifically sequenced RNA molecule merely catalyzed a single chemical bond, fusing together two other presynthesized partial RNA chains. Their version of ‘self-replication,’ therefore, amounted to nothing more than joining two sequence-specific premade halves together.“
This limitation underscores why Meyer has correctly emphasized that simulations of RNA self-replication have failed to produce molecules capable of producing more than 10 percent of themselves. In Joyce’s experiments the single linkages performed by his RNA ligases provide far less than 10 percent of the total number of linkages in the resulting RNA strands (each of which include more than 60 such linkages between nucleotide bases). Indeed, Joyce himself has acknowledged that his experiment merely demonstrates the capacity of RNA molecules to perform ligation not polymerization and, thus, not genuine self-replication. As he noted, his use of “a directed evolution strategy required selecting for the ability to catalyze a simple ligation reaction, rather than replication itself.”
Thus, the paper that Farina cites as producing a “fully replicating” RNA shows no such thing: it shows that an RNA enzyme can ligate (i.e., join) two pre-existing RNA strands — but only if those RNA strands are continuously supplied in great abundance. There is no polymerization of new RNA molecules going on here; as Miller puts it there is no ability “to link many nucleotide bases together to form long RNA chains.” Miller thus notes that in a later paper commenting on these very experiments, Joyce admits this is “a directed evolution strategy required selecting for the ability to catalyze a simple ligation reaction, rather than replication itself.” This very different from the “fully replicating” result claimed by Farina.
We actually tackled this paper in a Long Story Short: Origin of Life video on replication which provided a nice discussion of what’s really going on with this paper. See the video here for details:
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Far from Explaining Replication
Biomedical engineer Robert Stadler, who helped create that Long Story Short video, further discussed this paper and the Long Story Short video’s critique on a recent episode of ID the Future, where he and Eric Anderson explained how far away this paper is from explaining the origin of replication. Their transcript is helpful to understand what’s going on:
Stadler: The analogy there is if you had a car that you cut in half, and then you had another car come along and it pushed the two halves together so that they joined and formed a functioning car. And then you claimed that you had created the world’s first self-replicating car. That’s basically what that paper is doing because it’s a ribozyme RNA, a strand of RNA, that’s able to create a single functional bond between two halves of itself to bring those together to create a full version of itself and they claimed that was self-replicating.
Anderson: Yeah I loved that example from the video because it’s really helpful for us. … They had this RNA which is able to catalyze a reaction and then they split it at the point where those particular nucleotides join. And so then you go out and buy—I mean literally buy from the polymer store — the two strands. And then you have the one that ligases or puts together those two nucleotides and then boom you get a second one and you claim that’s replication….
Stadler: A really important limitation too is that in that experiment there’s nothing hereditary being passed along, meaning that the molecule that’s doing the bonding, the ribosome, is not passing its information along to the combination of those two parts. All it’s doing is it’s bonding them together and then they go off and do their thing.
Anderson: Right. And then that reaction is just going to continue in that test tube until it runs out of reagents and then it’s done.
Stadler: Exactly.
But There’s More
How did Joyce get this continuous supply of the needed RNA strands that were being joined together? It was through modern biochemistry and intelligent design — not a simulation of unguided prebiotic conditions. Miller continues:
So, in light of all this, how did Joyce and his colleagues produce many complete copies of their original ribozymes E and E’? It turns out the production of the copies of the RNA enzymes in their experiment depends — not on the ability of the RNA molecules to copy themselves — but instead on complex protein enzymes derived from living cells. Specifically, to make more copies of the RNA enzymes Joyce and colleagues employed the reverse transcription polymerase chain reaction (RT-PCR) procedure that requires using two complex protein enzymes — a reverse transcriptase and a DNA polymerase — as well as other molecular tools such as primers. Indeed, in order to make more copies of the most efficient ribozymes (rather than making complementary RNA strands with the opposite bases at each site) this procedure requires turning RNA into DNA and then reconstituting RNA from DNA. But that procedure necessarily employs an RNA reverse transcriptase, as mentioned, and an RNA polymerase — both of which are derived from living bacteria. As Meyer has told me, “Joyce and his team did not produce a self-replicating RNA molecule. Instead, they intelligently designed a system of protein-enzyme mediated replication.” Since these proteins had to be extracted from already living cells, Meyer also commented that “these experiments lead to the paradoxical conclusion that simulating a crucial step toward the origin of the first life from non-living RNA molecules requires the use of protein enzymes derived from already living cells.” Investigator Intervention
There is another reason that these experiments do not demonstrate the capacity of the RNA molecules in the experiment to self-organize or self-replicate. Every crucial step depended upon external guidance — often in the form of inputs of functional sequence-specific information — from highly intelligent chemists, in particular, Gerald Joyce and his colleagues.
Consider first that Joyce intelligently designed the larger ribozymes designated E and E’ that could link each other’s halves together. To build a precursor ribozyme in an original 2001 experiment, Joyce started with a random crop of 100 trillion RNA molecules with many different nucleotide base sequences. He then repeatedly applied chemical screens to select out those few RNAs that could perform ligation and performed it best (Rogers and Joyce 2001).
Next, he selectively altered the base sequences in particular regions of these RNAs to enhance their ability to link together the halves of a duplicate strand. For example, he wanted the ribozymes to be able to bind strongly enough to the complementary base pairs on the substrate molecules (i.e., A and B) and yet not to bind so strongly as to prevent the larger ribozyme from breaking away once the two RNAs halves had linked together. Thus, Joyce not only used his intelligence to select molecules that could perform the function that he wanted from a random crop, he also optimized the function of these ribozymes through modifying carefully chosen regions (Paul and Joyce 2002). Joyce then altered the original RNA enzyme (which he called T) in order produce two new ribozymes (which he called E and E’) that would have the ability to link the two halves of each of these new enzymes together — where E would link together A’ and B’ to form E’, and E’ would link together A and B to form E. By his own admission, he used what he characterized as a “rational design” approach to create this mutually interdependent, cross-catalyzing system. He specifically arranged the RNA base sequences in the “paired regions” of the two enzymes so that they would bind by complementary base pairing to the substrates. In addition, the regions near the ends of the break between the two halves of E and E’ had to be engineered to ensure that a ribozyme-mediated linkage could occur (Lincoln and Joyce 2009).
All this implies that Joyce necessarily had to design the pre-made, sequence-specific halves (i.e., both A and B and A’ and B’) that his ribozymes would join together. Indeed, the break point between the two halves needed to be at just the right location in order to ensure that ligation would occur. As mentioned, the arrangement of the nucleotide bases on the pre-made halves needed to be precise so that they would bind to their opposite base on the ribozyme by complementary base pairing. Meeting these specifications required Joyce’s repeated, active, and intelligent intervention in his experiment. Once Joyce had designed this cross-catalyzing system, he used “directed evolution” in an attempt to improve the efficiency of the ligase ribozymes. His team started by altering specific positions in the original ribozymes to generate numerous variants of E and E’ in the 2009 study and to generate numerous variants of E in the 2014 version of the experiment. They then isolated the variants that demonstrated the most efficient substrate-joining (ligase) function and differentially reproduced those. The 2014 study also tested for the variants’ ability to link their own half-strands together as well as the half strands of the opposite ribozyme.
Clearly, this process also required extensive investigator guidance and intelligent design. For example, Joyce and his colleagues employed advanced laboratory techniques to generate trillions of variants of the original enzyme(s) and trillions of copies of the substrates. They then executed equally advanced procedures such as “selecting the reacted, biotinylated products by capturing them on a streptavidin-agarose resin” to tag and capture the variants that most efficiently joined substrates (Robertson and Joyce 2014). One cannot overstate the implausibility of comparable processes occurring outside of an advanced laboratory setting staffed with highly trained and intelligent technicians, let alone on the pre-biotic earth, presumably devoid of any source of intelligent guidance (here, here).
Indeed, as Meyer argued in Return of the God Hypothesis (p. 310),
“…whenever chemists set up or interfere in a reaction sequence — or whenever they otherwise apply constraints to a chemical system — to ensure one outcome and preclude others, they effectively input information into that system. In so doing, they inadvertently simulate, if anything, the need for intelligent design to generate biologically relevant chemistry and information.”
Moreover, Meyer specifically applied this critique to Gerald Joyce’s ribozyme engineering experiments in his discussion of them in in RGH (p. 309). As he notes:
“Lincoln and Joyce themselves intelligently arranged the base sequences in these RNA chains. They generated the sequence-specific functional information that made even this limited form of replication possible. Thus, the experiment not only demonstrated that even a limited capacity for RNA self-replication depends upon information-rich RNA molecules; it also lent additional support to the hypothesis that intelligent design is the only known means by which functional information arises.”
This is just one important example of a paper that Farina touted that did not show what he claimed. The paper does not show a “fully replicating” RNA system, and what was done did not occur under prebiotic conditions.
Farina’s Citation Bluffs on Prebiotically Produced “Functional RNAs”
As another example, Farina and Tour sparred over Farina’s citation of a 2013 paper by Engelhart, Powner, and Szostak in Nature Chemistry titled “Functional RNAs exhibit tolerance for non-heritable 2′-5′ versus 3′-5′ backbone heterogeneity.” In normal biology, RNAs only use bonds between 3′ and 5′ carbons between successive nucleotides along their backbones, and 2’-5’ bonds between successive nucleotides make RNAs unusable. Some experiments evidently have shown that nucleotides can link up when templated using montmorillonite clay, but the bonds are a mix of normal 3’-5’ bonds and the unwanted 2’-5’ bonds. Farina repeatedly cited language from this this paper claiming that it shows that even RNAs with 2’-5’ bonds can be “functional” — i.e., ribozymes. Tour replied that it all depends on what you mean by “functional” and that they weren’t really useful, particularly because the RNAs end up branching into non-linear structures that don’t function at all like ribozymes or modern RNAs, which are linear and orderly.
Our “Long Story Short: Origin of Life — Replication” video addressed this paper head-on, using the image below to show why these kinds of RNAs don’t look or work anything like functional biological RNAs:
The Long Story Short video provides a note explaining how poorly these ribozymes worked and that the more 2’-5’ bonds that were present, the more its efficiency dropped:
Engelhart, Powner, and Szostak took a relatively simple ribozyme that could break bonds. The correct linkage (3’-5’) made a ribozyme that could break 80% of bonds in 48 hrs (Figure 3b). Then they tried a ribosome with 10% of the wrong linkage (2’-5’). That one could break 60% of bonds in 48 hours. With 25% of the wrong linkages, it broke about 25% of the bonds in 48 hours. With 50% of the wrong linkages, it broke only a few % of the bonds in 48 hours.
Engelhart, Powner, and Szostak, the authors of the paper, are excited that they got any functionality whatsoever — but it’s clear that they were not working on a type of ribozyme that could do very much at a very rapid rate. It all comes down to how you define “functional” RNA: If the function is quite simple (i.e., nonspecific), having some inappropriate 2’-5’ linkages will be tolerated. But if the function is more specific, a bad bond could seriously interfere with the function. Could Farina’s purported (but not actual) “fully replicating” RNAs tolerate 2’-5’ linkages? It seems doubtful. One of those doubters might be Steve Benner, an authority that both Tour and Farina cited during their debate. Citing Engelhart et al. (2013), Benner wrote earlier this year:
[D]etailed analysis of the RNA formed on impact basaltic glass shows that it contains a mixture of 2’,5- and 3’,5’-links. The seriousness of this problem is still not clear. Some think that this mixture of linkages can be cured. Others not.
STEVE BENNER, “RETHINKING NUCLEIC ACIDS FROM THEIR ORIGINS TO THEIR APPLICATIONS,” PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B, 378: 20220027 (2023).
It seems that not everyone believes that functional 2’-5’ ribozymes have been created after all.
Closing Thoughts
It’s true that sometimes it can be hard to tell that serious problems remain unsolved until you drill down into the scientific details. But the rapid-fire rate and detail-poor style with which Farina was throwing papers at Tour gives you a clue that something was up. Farina further tried to impose a framing upon Tour that would not even let him challenge the paper without supposedly calling the authors a “fraud,” etc. He used playground tactics and mockery — making fun of Tour’s words without even trying to answer what he was saying. When someone resorts to mockery, won’t let an opponent speak for himself, and just throws out paper after paper without careful analysis, that shows they probably don’t have a good argument.
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