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Parkinson’s disease is the fastest growing neurologic disease with seemingly no means for prevention. Intrinsic risk factors (age, sex, genetics) are inescapable, but environmental factors are not. We studied population attributable fraction and estimated fraction of PD that could be reduced if modifiable risk factors were eliminated. Assessing several known risk factors simultaneously in one study, we demonstrate that all were operative and independent, underscoring etiological heterogeneity within a single population. We investigated repeated blows to head in sports or combat as a potential new risk factor, and found it was associated with two-fold increased risk of PD. Considering modifiable risk factors, 23% of PD cases in females were attributable to pesticides/herbicides exposure, and 30% of PD cases in males was attributable to pesticides/herbicides, Agent Orange/chemical warfare, and repeated blows to the head. Thus, one-in-three cases of PD in males, and one-in-four cases in females could have potentially been prevented.

Prokaryotes use diverse strategies to improve fitness in the face of different environmental threats and stresses, including those posed by mobile genetic elements (e.g., bacteriophages and plasmids). To defend against these elements, many bacteria and archaea use elegant, RNA-directed, nucleic acid–targeting adaptive restriction machineries called CRISPR–Cas (CRISPR-associated) systems. While providing an effective defense against foreign genetic elements, these systems have also been observed to play critical roles in regulating bacterial physiology during environmental stress. Increasingly, CRISPR–Cas systems, in particular the Type II systems containing the Cas9 endonuclease, have been exploited for their ability to bind desired nucleic acid sequences, as well as direct sequence-specific cleavage of their targets. Cas9-mediated genome engineering is transcending biological research as a versatile and portable platform for manipulating genetic content in myriad systems. Here, we present a systematic overview of CRISPR–Cas history and biology, highlighting the revolutionary tools derived from these systems, which greatly expand the molecular biologists’ toolkit.