Pesticide link to ADHD

It’s correlation, not causation

A common pesticide and metabolites have been linked in a large study to ADHD, an attention deficit disorder characterized also by hyperactivity and impulsivity. ADHD has previously been associated with specific genes and even hailed as a one-time advantageous evolutionary adaptation. But many neurological differences likely will trace to an interaction of genes and environment, or, in fancy science talk, a multifactorial causality.

But it’s also not a surprise

This study looked at metabolites in the urine of more than 1000 children, 119 of whom had ADHD. It’s not mechanistically outre to think that pesticides designed to send a pest’s nervous system astray might have a similar effect on vertebrate systems. But this study showed links, not mechanisms, which often is a necessary first step to justify further pursuing a hypothesis. The researchers found that levels of specific metabolites of organophosphate pesticides are associated with an increased risk–by as much as two-fold–of developing ADHD.

Join the ever-expanding club

If further research does identify a mechanistic tie to this identified correlation, then these pesticides will join an ever-growing suite of chemicals we’ve introduced into the environment that influence our endocrine and neural systems. These chemicals are called endocrine disruptors.

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Let us now praise famous men

Today, my thoughts are on Louis Pasteur and Francis Crick, so I’m linking you over to a piece I wrote on the two, “Visionaries of Science: An Inescapable, Forward-moving Logic.” Both men were true polymaths who changed several fields of science in ways that continue to reverberate.

Also, I’m adding a new book to the recommended reading: Newton and the Counterfeiter: The Unknown Detective Career of the World’s Greatest Scientist. I’m reading it now. While it addresses the story the title implies, it also provides an excellent biography of Newton and his major contributions to physics. That apple story just never gets old.

Why is the sky blue? Blame rocks

Early Earth’s changing landscape…and skyscape

If you traveled back in time to about 2.5 billion years ago, you wouldn’t recognize much of what you saw. The dawning, living planet back in the day sported skies of orange, shaded by an unbreathable atmosphere awash in methane gas. But through the long Proterozoic Era, those skies changed from orange to blue. Usually, we give our thanks for this change to oxygen, but a recent review traces the original actor in the color change drama to rocks. Specifically, to the phosphorus in the rocks.

Phosphorus? Really?

Phosphorus is one of the critical of elements of life. It’s a primary component of a DNA or RNA building block (nucleotide = sugar, phosphate, base). It also happens to be the primary component of the “energy currency” of cells, ATP, or adenosine triphosphate, which is really a nucleotide with three phosphates on it. Many organisms use ATP, and all organisms use phosphorus in their genetic code and their RNA.

And, a major source of it is rocks. So, yes. Phosphorus, really. Read on.

Geochemical cycles and a whole lot of gas

Several independent lines of evidence have shown that oxygen levels rose in two lengthy bursts coincident with bursts of life on Earth. The first gassy increase happened between 2.5 to 2 billion years ago. Fittingly, scientists refer to this rise in atomspheric oxygen as the Great Oxidation Event. One of the effects of the increased oxygen is that rust started showing up in the geologic record. During this Great Event, the single-celled organisms that had thrived under a presumably orange sky grew larger, and mitochondria may have arisen as a result of endosymbiosis. These cellular powerhouses are, in fact, responsible for completing energy extraction from organic molecules and using the energy to build…ATP.

The second big burst of oxygen happened about 1 billion to 540 million years ago, this time coincident with the rise of multicellular organisms and culminating in the blast of diversificiation known as the Cambrian Explosion.

What does oxygen have to do with phosphorus?

The two often hang out together as phosphate, but the real connection here is about phosphate’s contribution to life’s explosions. It may be that geologic processes, such as erosion, caused a gradual but abundant release of phosphorus from rock into the Earth’s seas. With this influx of a key component for building life, the phosphorus facilitated the early Earth equivalent of enormous algal blooms.

And guess what those algae did…and still do? Photosynthesisis. And one of the main byproducts they release from all that busy light capturing and sugar building is…oxygen. That’s the phosphorus-oxygen connection.

So, if a child ever asks you why the sky is blue and you just can’t think of the answer, you can distract them by asking them, “Did you know that the sky used to be orange?”

For your consideration

Double-membrane organelles like mitochondria are thought to have arisen through a process called endosymbiosis. What is endosymbiosis, and how could it have led to the presence of organelles like mitochondria in cells?

The algal blooms described in this paper were enormous and their influence may literally have changed the color of the sky back in the day, but the oxygen buildup and phosphorus release happened over long stretches of geological time. Today, we experience algal blooms, too. Can you identify the causes of these blooms? How do these blooms affect today’s life on Earth? Do the effects seem to be beneficial or adverse?

Inbreeding in the Darwin dynasty?

Darwin and his wife were first cousins

Charles Darwin married his first cousin, Emma Wedgwood, and his own mother was the product of a marriage between third cousins. Given his insights into the relationship among variation, nature’s choices, and adaptation and his observations of weakening in inbred plants, it is no surprise that Darwin worried about his own family’s consanguinity. Did the inbreeding in the Darwin/Wedgwood families show up in his children?

Is marrying your first cousin really so bad?

Had the Darwin/Wedgwoods only engaged in the first-cousin marriage between Charles and Emma, the outcome would likely not have been serious. A 2002 study reported by the National Society of Genetic Counselors found that having first cousins as parents raises the risk of having a significant genetic defect from 3-4% up to about 4-7%. The group concluded that first cousins planning to reproduce require no more intense genetic counseling than unrelated couples.

Consistent consanguinity, on the other hand

But that study didn’t address serial consanguinity of the kind seen in some European royal houses or in the Darwin/Wedgwood families. And a new analysis reported in BioScience avers that the Darwin offspring did experience the repercussions of such inbreeding. Applying an inbreeding coefficient to calculate whether childhood mortality in the Darwin/Wedgwood family across several generations was related to inbreeding, the authors indeed found an association.

Three of the Darwins’ ten children died at age 10 or younger, one of tuberculosis, one of scarlet fever, and one of an unidentified disease. Studies suggest an association between childhood mortality from bacterial infection and consanguinity, and the Darwin family seems to bear that out. In addition, three of the Darwin children who did live to adulthood experienced lengthy marriages without any children, and such infertility may be another manifestation of homozygous states that interfere with reproduction. A photograph of the youngest Darwin child, Charles, who died in toddlerhood, suggests that the baby had some congenital disorder, although the nature of it remains unclear. Emma Darwin was 48 years old when she gave birth to Charles, so Down Syndrome is one likely explanation.

Successful Darwins

In spite of some of the sad facts of the Darwin family story, a few of his children experienced successes of different kinds. Three of his sons were members of the Royal Society, a long-time Darwin family tradition that skipped over the most famous member of the tribe, Charles himself. And Darwin by any measure of fitness did pretty well: in spite of the loss of three children and the infertility of three children, he nevertheless had several grandchildren.

Did Darwin himself suffer from the effects of inbreeding?

Charles Darwin experienced a variety of chronic health conditions, but they do not necessarily seem to have been related to his family’s consanguineous status. Several theories abound to explain his symptoms, which included digestive and skin problems, but no one knows for certain what afflicted the great naturalist. One of the foremost hypotheses is that he had Chagas disease, occurring after a bug bite on one of his voyages transferred an infectious protozoan that may have permanently damaged the scientist’s gut. Stress seems to have exacerbated the problem, whatever its etiology.

A drug for Fragile X syndrome?

Hopeful news but not peer-reviewed

A new report describes success in a very small trial with a new drug that targets behavioral signs of Fragile X syndrome. This syndrome, which affects about one in every five thousand children, mostly boys, usually involves some form of intellectual disability along with a suite of typical physical characteristics, including large jaws and ears and elongated faces. It is the most common known heritable cause of intellectual disability and has also been associated with autism.

Novartis has been working on an experimental drug targeting some of the behavioral manifestations of Fragile X and has just reported, via interview, positive results from a small trial. Because the results are not public and have not been peer reviewed, the nature of the improvements is unknown, as is the nature of the drug itself. All that is known is that a parameter in the treatment group improved in some, but not all, participants with Fragile X. Also, the drug targets reduction of the synaptic noise that people with Fragile X experience. This reduction in neural background noise, it is thought, may pave the way for more typical neurological development.

Why is the X fragile?

The X chromosome consists of many many genes. Some of these sequences may contain repeats of the same three nucleotides, or letters of the DNA alphabet. For example, a gene section might have 50 repeats of the sequence C-A-G. These trinucleotide repeats, as they are known, are associated with a few well-known disease states when they occur in larger numbers. At a certain low number of repeats, they may have no effect, but when the number of repeats increases, a phenomenon known as trinucleotide expansion, the result can be disease. Huntington’s disease is one well-known disorder associated with trinucleotide expansion, and the general rule is that the more repeats there are, the more severe and/or the earlier the onset of the disorder.

On the X chromosome, where these repeats achieve sufficient numbers to result in Fragile X syndrome, the X chromosome itself looks like it’s literally at a breaking point. This visual fragility is what gave the disorder its name when this chromosome characteristic was discovered in 1969. A parent who carries an X chromosome with relatively few repeats does not have Fragile X, but the gene is in a state known as a premutation. Thanks to various rearrangements and events during cell division, this premutation can expand even in a single generation to sufficient numbers of repeats to cause the disorder in an offspring.

Because the relevant gene is on the X chromosome, Fragile X is an X-linked disorder. It’s more prevalent among males than among females because males receive only one X chromosome. Without the second X chromosome backup that females have, males are stuck with whatever genes–and mutations–are present on the single X chromosome they receive.

What is the autism link?

Fragile X underlies a small percentage of diagnosed cases of autism, between 2 and 6%. Because of the usual genetic complexity underlying autism, Fragile X is also the most common known single-gene cause of autism.

These prematurely reported results have also yielded some speculation that a drug that is effective in reducing background noise and improving behaviors for people with Fragile X might do the same for autistic people, even if their autism isn’t related to Fragile X. With nothing in the way of peer-reviewed findings to consider and results available only via interview, such hopes remain in the purely speculative realm.

For your consideration

Males are born with a single X chromosome. Females have two. The X chromosome has hundreds of genes on it. How is it that women can walk around with a double dose of these genes, or conversely, men can be healthy with a half dose?

Trinucleotide expansion occurs when a trinucleotide repeat sequence expands in numbers of repeats, potentially evolving from a premutation to a full-blown disruption of a gene. What are some possible mechanisms by which this expansion might occur?

In the article related to this report, there is reference to “synaptic noise” and to the idea that a drug might reduce this noise and allow more space for typical development. What do you think “synaptic noise” is, physiologically, and how might a drug target this noise?

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