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of these species have independently acquired example, protein kinase CK2 is able to phos- There is no
immunity to glyphosate by changing the DNA phorylate more than one hundred and sixty
code such that it codes for alanine instead of substrates, and it is involved in the cell cycle naturally
glycine. This is a very minor change, introduc- and cell proliferation. It contains a glycine-rich produced
ing one extra methyl group, but it makes all the loop (GXGXXG) (where “X” stands for a “wild- amino acid
difference in the world because glyphosate only card,” i.e., any amino acid), as do many other
substitutes for glycine, not alanine. Change the protein kinases. Experiments have shown that known to
code, and you acquire complete immunity to substitution of one of the glycines in this region, mankind that
glyphosate’s effects on this protein. G48—which is conserved in 99 percent of pro- substitutes
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It’s not as if researchers are not aware that tein kinases—with a negatively charged amino
this kind of thing happens in biology. There are acid leads to increased activity. 62-65 Glyphosate for glycine.
probably over a thousand non-coding amino is negatively charged. Glyphosate is
acids that are produced naturally by biological Both AID and Nup98 can be expected to unique in this
organisms, and a few of them are known to be be susceptible to something called “pseudo-
able to substitute by mistake for specific coding phosphorylation” if glyphosate were to substi- ability, and
amino acids, generally causing extremely debili- tute for one or more of their glycine residues this is what
tating disease as a consequence. One of these by mistake. Strikingly, there is a novel version makes it so
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is another herbicide, glufosinate, which works of AID synthesized by zebrafish that does not
by substituting for glutamate during protein have the serine residue at location 38 that nor- demonic.
synthesis. Glufosinate is naturally produced by mally gets phosphorylated to convert AID into
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certain bacteria. There is also a toxin produced a dangerous protein that causes random genetic
by cyanobacteria, called β-methylamino-L- mutations. However, zebrafish AID has been
alanine (BMAA), that is an analogue of serine, shown to induce genetic mutations nonetheless.
and it causes a debilitating neurological disease Researchers have proposed that the presence
similar to ALS and Parkinson’s disease. 57,58 of a negatively charged amino acid nearby has
Another toxin produced by sugar beets caused the protein to behave as if it is perma-
under stress conditions substitutes for proline nently phosphorylated. Substitution of glypho-
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and causes multiple sclerosis and swayback sate for a nearby glycine residue would very
in lambs. 59,60 L-canavanine is an amino acid likely have a similar effect, with glyphosate’s
analogue of L-arginine, and it was probably phosphonate ion being a close approximation to
responsible for the death of Christopher Mc- a phosphate ion negative at typical cellular pH.
Candless, the protagonist of the book Into the A remarkable experiment with transgenic
Wild by John Krakauer. However, there is no mice, where the mouse DNA was modified to
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naturally produced amino acid known to man- include a constitutively expressed version of
kind that substitutes for glycine. Glyphosate, AID, demonstrated the destructive capabilities
only present because it is synthesized in the of AID if left unregulated. The mice developed
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chemistry lab, is unique in this ability, and this large numbers of point mutations in genes for
is what makes it so demonic. a number of oncogenic proteins (proteins that
In addition to inducing expression of ki- induce cancer). They later developed multiple
nases via calcium uptake, glyphosate can also be types of cancer, including lymphoma but also
expected to cause them to become hyperactive, adenomas and carcinomas in the lungs.
through substitution for glycine during protein Nup98 induces a collapse of the pore plug in
synthesis. In our first paper on glyphosate act- response to excessive phosphorylation on mul-
ing as a glycine analogue (fifth paper in our tiple serine residues within a segment known as
series), Anthony Samsel and I explained how a “phenylalanine-glycine domain” (FG domain)
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glyphosate substitution for glycine at critical because it contains many FG pairs (phenylala-
spots in kinases would be predicted to cause nine linked to glycine) within this segment.
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them to become overactive, and how glypho- Nup98 has eleven sites in this FG domain that
sate substitution in phosphatases (proteins that can be phosphorylated. In an experiment where
remove phosphates) would suppress them. For all of these sites were replaced with so-called

WINTER 2018 Wise Traditions 19