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Indeed.

In post 227 tallhappy attempts again to be the smartest guy in the room while flattering me by appreciating my comments. While completely ignoring the fact that I'd understood completely his fabrication of the 1/3 odds of ERV insertion loci.

The thing that really burns me is that obviously he's looked at this issue long enough and deep enough to understand completely that he's misleading on the ERV insertion odds. I really, really dislike being deliberately misled.

It's partly my fault for not thinking about the process of ERV insertion. I knew better, but didn't think of it, and tallhappy took advantage of it. So I'm mad at myself for missing it, but madder at him for successfully misleading me.

I appreciate the meaning of ERV insertion "randomness". And I understand the meaning of "not quite" randomness, and "almost never" randomness. Although there are lots of other points that still support DNA verification of common ancestry, damage to the randomness issue would have weakened it. I'm glad to see that the smoking gun of common ancestry has a few extra orders of magnitude of certainty provided by "almost" random insertion points in the ancestral line.

Actually, it's *worse* than that.

Here's his key passage again:

Given that this insertion in to the same site happen not in two genomes, as you asked for, but in three out of only nine integrations, the targetted nature of integration, which is not understood, is apparent. Addressing this targetting is an active area of current research.

As you and I have already noted, he has very dishonestly claimed (in the blue-highlighted text) that the same-site retroviral integration has occurred in "three out of only nine integrations", when *actually* it has occurred in "three out of [a vast number of integrations throughout millions of cells in the bodies of] nine patients". This is *extremely* dishonest.

By how much is it dishonest? Well let's look at the research paper (linked below), shall we?

"...the total number of injected transduced cells — 92 x 10⁶ and 133 x 10⁶ for patients P4 and P5, respectively..."

So it's not actually "3 of only 9 integrations", as tallhappy falsely claims, since just *two* out of the nine total patients had TWO HUNDRED TWENTY FIVE MILLION retrovirus-treated cells pumped into their bodies...

Even leaving aside the other seven patients, tallhappy has understated the number of retroviral integrations by a factor of 25,000,000... Maybe more, since in other studies I've read, treated cells often have more than a single integration per cell.

But wait, there's more!

Note the passage highlighted in red... He claims that in these three patients, the retroviral integration was found at "the same site" (i.e., at the same basepair location in the genome, as is the case for shared ancestral endogenous retroviruses, which we have been discussing).

Well, it turns out that he was dishonest about *THAT* as well. "Same site", eh? Um, sorry, no -- I haven't found any data on the third patient yet, but in patient#4 and patient#5 (the two who actually came down with leukemia), it turns out that the disruptive integrations in the LMO2 gene were actually almost FIVE THOUSAND BASEPAIRS APART.

From LMO2-Associated Clonal T Cell Proliferation in Two Patients after Gene Therapy for SCID-X1, by S. Hacein-Bey-Abina et al, we find:

In the V ${gamma}$ 9V ${delta}$ 1 P4 clone, the single copy of the retrovirus vector was mapped to the short arm of chromosome 11, close to the distal (hematopoietic) promoter of the LMO2 locus (Fig. 2C). It was found inserted at position 46,229 (the first nucleotide of exon 1 is 44,218), within the first intron in reverse orientation. Sorted populations of the different T cell clones from patient P5 (i.e., Vß1, Vß2, and Vß23) possessed a unique integration site also located in the LMO2 locus, at position 41,253, 3 kbp upstream of the first LMO2 exon in forward orientation (Fig. 2C).

Um, "same site", as tallhappy claims? Not hardly. They were on OPPOSITE SIDES of Exon1 of the gene, oriented in OPPOSITE DIRECTIONS, nearly FIVE THOUSAND BASEPAIRS apart. Gosh, Mr. Wizard, that doesn't sound like the "same site" to *me*...

But hey, as he keeps trying to tell us, *I'm* the one who "doesn't understand" this subject...

Uh huh. Sure. I understand it well enough to catch it when tallhappy lies *twice* in the same sentence.

The final delicious irony is that although he has brought up this case study in an attempt to demonstrate that retroviral integration is "not random", and to claim a "targetted nature of integration", the authors of THIS SAME STUDY disagree with him:

Taken together, our data suggest that the following scenario might account for occurrence of the lymphocyte proliferations observed in these patients. LMO2 targeting suggests either that there is a "physical hotspot" of integration at this locus, or more likely, that random, activating, LMO2 integrants are selected simply by the growth advantage conferred on them. The chance of integration of any active gene is assumed to be $~$ 1 x 10^–5 (a rough estimate of a random hit within 10 kbp among the estimated transcriptionally active 1 x 10⁹ base pairs. It is likely that each patient received at least 1 to 10 LMO2-targeted cells, because the patients received 1 x 10⁶ or more transduced T lymphocyte precursors (estimating that at least 1% of the total number of injected transduced cells—92 x 10⁶ and 133 x 10⁶ for patients P4 and P5, respectively — could give rise to T cells).

So there you have it -- the case study that TALLHAPPY HIMSELF introduced in order to "demonstrate" that retroviral integrations were somehow "targeted" to a location (in this case the LMO2 gene) actually has the authors pointing out that they would expect between one and ten LMO2 integrations per patient BY RANDOM CHANCE ALONE, due to the large number of retroviral-treated cells, and the number of sites occupied by the LMO2 gene.

I'd say that this has "hoist on his own petard" written all over it...