We've mentioned a few times that the rules and regulations we have today normally originate from some horrible precedent. The many rules and regulations regarding air travel come together to make flying the safest mode of transportation per mile, so you know that the mistakes of early aviators and plane designers contributed to what we know about safety. However, those mistakes were tragic.
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As Aloha Flight 243, a weary, 19-year-old Boeing 737 on a short hop from Hilo, Hawaii, to Honolulu, leveled off at 24,000 ft., a large section of its fuselage blew off, leaving dozens of passengers riding in the open-air breeze. Miraculously, the rest of the plane held together long enough for the pilots to land safely. Only one person, a flight attendant who was swept out of the plane, was killed.
The National Transportation Safety Board (NTSB) blamed a combination of corrosion and widespread fatigue damage, the result of repeated pressurization cycles during the plane's 89,000-plus flights. In response, the FAA began the National Aging Aircraft Research Program in 1991, which tightened inspection and maintenance requirements for high-use and high-cycle aircraft. Post-Aloha, there has been only one American fatigue-related jet accident—the Sioux City DC-10.
Read about other accidents and how they led to greater airline safety at Popular Mechanics. -Thanks, Tim!