Oops, we forgot the germline

For decades, conventional medical practice had no qualms about heavily medicating pregnant women, even for anxiety caused by the price of a new crib.

The decades of the 1950s, 60s, and 70s were the heyday of prenatal pharmaceutical use.  Countless millions of us were exposed in utero to synthetic hormones, tranquilizers, amphetamines, morning sickness medications, and/or other drugs prescribed almost indiscriminately in a haze of unbridled enthusiasm for the promise of the new pharmacopeia. Until the 1970s, little thought was given to these potent chemicals' impacts on the fetus, as doctors falsely considered the placenta a fairly impenetrable barrier to the mother's medication. As we grew up, we were seldom told of our exposures, little follow-up research was done, maternal memories faded, and old medical records were thrown away.

Though many of the drugs appear to have been fairly benign, others, depending on biochemistry, timing and dosage, were teratogenic, meaning they damaged the fetus, sometimes dramatically, as is the case with thalidomide and DES, and sometimes subtly, as in the case of other sedatives and progestins.

But the damage did not stop at the fetus.  Gestational exposure affects not only the fetus itself, but also, likely to a more significant extent, its exquisitely vulnerable developing germline, those cells which develop into the child's eventual egg or sperm, and therefore, the grandchild generation.

While it's unlikely that the pharmaceutical exposures would induce classic mutations in the germline's genetic sequence, research suggests that many synthetic compounds can adulterate the more environmentally sensitive "epigenetic" programming, that is, the countless millions of tiny chemical switches that control genetic expression. Epigenetic mayhem can result in disruptions of normal development in the resulting offspring, much like early programming bugs in software can cause later computer malfunctioning. 

A generation-skipping effect

Germline damage is a tiny latent birth defect of the fetus, and results in a generation-skipping effect. While the fetus itself may appear to have escaped noticeable damage because of the relative resilience of its somatic cells, pharmaceutically-induced germline DNA instability will manifest only in the next generation. Consider for a moment that you started life as two cells no larger than the dot on this letter "i." Research shows these cells to be epigenetically vulnerable to abnormal exogenous exposures during sensitive periods of development, including when the cells are developing within the fetal gonads in utero.

Germline errors can result in abnormal brain development and behavior

Genes related to autism and brain development appear to be more susceptible than others to novel genetic alterations occurring within the germ cells themselves, and not inherited directly from the parents. (Michaelson et al. 2012). These "de novo" mutations and epimutations can be random, or can be precipitated by destabilizing exogenous factors such as the abnormal chemical/pharmaceutical exposures discussed here. (See Research page for some relevant studies). In addition, a large percentage of the genome is devoted to genes coding for proteins relating to neurological development; therefore if one was to throw darts at the genome, brain development genes would almost certainly be among those hit. Another factor to consider is that research has shown that the unfathomably complex process of human neurodevelopment is highly regulated by epigenetic factors; so when we tamper with epigenetic marks, abnormal wiring and functioning may reasonably be expected to result.

Research shows that perturbations of epigenetic instructions may result in various irregularities during the process of neurodevelopment, including the the failure of neurons to migrate or proliferate, impairment of communication at the neural synapses, and the failure of neurons to develop robust dendritic complexity. Depending on the nature and extent of the damage, irregularities may manifest in a variety of ways we see and diagnose as abnormal behavior, including:

• Autism spectrum disorders, Aspergers, pervasive development disorder
• Learning disabilities
• ADHD, ADD
• Emotional disturbance
• OCD
• Sensory processing disorders
• Anxiety, mood disorders and depression
• Mental illness
• Tourette's syndrome, tics

Incidence of these conditions, many of which were exceedingly rare before the late 1980s, has skyrocketed. For example, autism, once numbering a handful per 10,000, now affects 1 in 88 children according to the Centers for Disease Control.

Real exposure histories in real autism families

In preliminary surveys, we have found that a considerable percentage of parents of neurodevelopmentally challenged children had themselves suffered significant early in-utero exposures to pharmaceuticals (read a few of their stories on the Family Stories page), particularly synthetic hormones, mood altering medications, and anti-nausea medications. In contrast, their unexposed siblings, serving as a makeshift control group, tended to have typically developing children, lending credence to our causation hypothesis. In addition, the affected children had no genetic disorders, and no other risk factors, and the families had no histories of neurodevelopmental disorder.

What else can harm human germ cells?

Though we focus our attention here on pharmaceuticals, those chemicals are hardly the only exposures that, administered during susceptible periods of development, can wreak havoc on the human germline.  Other culprits include:

• Environmental endocrine disruptors such as Agent Orange (dioxin), pesticides, herbicides, fungicides, and flame retardants
• Maternal smoking and recreational drugs
• Various plasticizers and industrial chemicals
• Radiation
• Heavy metals

Is germline impairment the sole cause of the autism epidemic? 

Though we believe the germline exposure syndrome is likely a significant contributor to skyrocketing autism rates, the markedly abnormal neurodevelopment we call autism has many other known and suspected triggers, including:

• Prenatal (proximal, first-generation) drug exposures, including antidepressants, anticonvulsants, and terbutaline
• Epigenetic consequences (including imprinting disorders) stemming from fertility treatments such as IVF and ICSI
• Prematurity, multiple births and perinatal complications (sometimes also relating to assisted fertility)
• Prenatal infections, autoimmunity and inflammation
• Classic random de novo genetic mutations
• Familial genetic syndromes such as Fragile X
• Fetal hypothyroidism
• Post-natal events such as encephalitis and acute inflammation

How you can learn more

1.  Check out the website for the March 2013 Autism Speaks - UC Davis symposium, Environmental Epigenetics: New Frontiers in Autism Research. That website will archive videotaped presentations and other material from the event.

2. Listen to this February 25, 2013 Super Human Radio podcast with host Carl Lanore.

3. List to this April 4, 2013 Underground Wellness podcast with host Sean Croxton

4.  Read our Pages, listed at the upper right.