After reading the article entitled Topoisomerases Facilitate Transcription of Long Genes Linked to Autism, published in the September, 2013 issue of Nature – – I wrote the following post on Collective Evlolution –

A writer for the Simons Foundation Autism Research Initiative (SFARI.ORG) wrote this post about the same article –  It was republished on the Scientific American web site –  Basically, I think that the writer asked the wrong questions, drew the wrong conclusions and mis-read the Nature article.  Here is a letter to the editor that I wrote to both the SFARI and the Scientific American folks.

Dear Editor,

In the SFARI article entitled “Autism genes are surprisingly large, study finds” written by Virginia Hughes and published on September 16, 2013, Ms. Hughes did a disservice to those who are interested in finding out a cause for the marked increase in Autism rates over the past 30 years by focusing on the less consequential aspects of the study entitled “Topoisomerase Facilitates Transcription of Long Genes Linked to Autism” published in the September 2013 issue of Nature. The significant finding of the study was not, as Ms. Hughes focused on, that Autism genes are larger than other genes. The significant finding of the study was that pharmaceuticals that interfere with topoisomerase “profoundly affect the expression of long ASD candidate genes.” The conclusion of the study is:

Our data suggest that chemicals or genetic mutations that impair topoisomerases, and possibly other components of the transcription elongation machinery that interface with topoisomerases, have the potential to profoundly affect the expression of long ASD candidate genes. Length-dependent impairment of gene transcription, particularly in neurons and during critical periods of brain development, may thus represent a unifying cause of pathology in in many individuals with ASD and other neurodevelopmental disorders.”

In focusing on the interesting fact that ASD related genes are unusually large instead of on the important finding that pharmaceutical drugs are influencing the expression of these genes, Ms. Hughes steered the reader away from the implications of the study. She quoted Dr. James Sutcliffe, “the implications are really quite fascinating.” Too bad none of the questions that would lead us to uncover fascinating implications were asked by Ms. Hughes.

The drug studied in “Topoisomerase Facilitates Transcription of Long Genes Linked to Autism,” Topotecan, a TOP1 inhibitor, is the chemical that impairs topoisomerases and “profoundly affect(s) the expression of long ASD candidate genes.” According to the study, a pharmaceutical is influencing the expression of ASD candidate genes. None of the potentially fascinating implications of a drug being indicated in triggering the expression of ASD related genes was explored in the article.

Here are some potentially interesting questions that could have been raised in an article covering the study:

  • Do topoisomerase interrupting drugs change gene expression of the person who takes them, the offspring of the person who takes them, or both?
  • Do topoisomerase interrupting drugs increase a person’s chances of having a child with Autism? How?
  • If a person takes a topoisomerase interrupting drug, is their DNA altered? If so, how?
  • Are some people’s genes affected by these drugs more than others? What factors determine whether or not an individual’s genes are affected?
  • Are DNA/gene alterations triggered by pharmaceuticals reversible? If so, how?
  • What, if anything, can people who have taken these drugs do to discourage the expression of the ASD related genes?
  • When would the administration of the drug happen to influence genes in a way that could trigger the genes associated with Autism – when a mother is pregnant or at any point before the child is conceived?
  • How is the mitochondrial DNA affected vs. how is the rest of the DNA affected? Do topoisomerase interrupting drugs influence both mitochondrial DNA and the rest of DNA or one or the other?
  • Do these drugs change gene expression in the ways that diet and music change gene expression or do they adduct to DNA like Agent Orange?

And, the most important question of all:

  • What drugs, other than Topotecan, are topoisomerase interrupters that also may have an influence on expression of ASD genes?

Answer: Fluoroquinolone Antibiotics. Per the FDA datasheet on Ciprofloxacin (Cipro – a Bayer pharmaceutical), the mechanism for action for Ciprofloxacin, a fluoroquinolone antibiotic, is “The bactericidal action of ciprofloxacin results from inhibition of the enzymes topoisomerase II (DNA
gyrase) and topoisomerase IV (both Type II topoisomerases), which are required for bacterial DNA
replication, transcription, repair, and recombination.” Other fluoroquinolones, including Levofloxacin (Levoquin – Johnson & Johnson) and Moxifloxacin (Avelox – Bayer) have the same mechanism for action.

The study notes that the UNC researchers examined TOP2 inhibitors (fluoroquinolones are TOP2 and TOP4 inhibitors, as noted in the FDA insert) have the same effects as the TOP1 inhibitor studied, Topotecan. The study notes that “Thus, TOP1 (topoisomerase I) and TOP2 (topoisomerase II) enzymes regulate the expression of many of the same genes.”

Of course, the precise influence on Fluoroquinolone Antibiotics on ASD related genes needs to be verified, but putting together the findings of the study with the basic mechanism for action of Fluoroquinolone Antibiotics should raise all of the questions listed above for anyone who has ever taken a Fluoroquinolone Antibiotic. (26.9 million prescriptions for fluoroquinolone antibiotics were filled in 2011 alone. It is quite important that these questions be answered.)

Ms. Hughes and the editors at SFARI, along with the editors of Scientific American who republished Ms. Hughes’ article as is, FAILED to ask the questions that would point readers toward the interesting and consequential implications of the UNC study. In doing so, they disregarded a study that may have profound implications for determining at least one of the causes (admittedly, Autism is an incredibly complex disorder) of the drastic increase of ASD rates in the last 30 years.

I highly recommend that both SFARI and Scientific American revisit the study and communicate the important implications entailed in it. Topoisomerase inhibiting drugs are passed out like candy. If we are being genetically altered by them in ways that are affecting our children, we deserve to know about it.


Lisa Bloomquist

Lakewood, Colorado


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