Natural climate shifts and from space (not asteroids but interstellar gases).
Humans are not the most successful life, bacteria is the most successful. Bacteria has survived for 3.85 billion years. Humans for 100,000 years. All other kinds of life lasted no more than 160 million years. If your numbers are not big enough and you are not diverse enough then something in nature eventually wipes you out.
I think the point is that the Enlightment and life is not just about holding past gains. Fear and lack of confidence could allow a retreat in society or make human life more fragile. Emergencies can be used as excuses for theft or rollback of gains or enable choices that increase the fragility of humanity as a whole.
We need to push forward with more confidence.
More confident projects of high risk [but with the best planning to maximize the odds of success] and high reward.
Using the nations of the world to allow the competent citizen to be as free and empowered as possible.
example. there is no approved gene therapy procedure in the USA yet. China has had a gene therapy procedure approved since 2003.
Medical tourism is something that perhaps a million people are doing.
Insurance companies are shifting to making deals with overseas hospitals to send people (expenses paid) over to the foreign country for a treatment to save money for the insurance company and the patient (no deductibles etc...)
Medical tourism is also being used to circumvent excessive restrictions.
Use jurisdictions and find ways to make them more open to create competition for more freedom and access and power for individuals.
Enable more open source, creative commons, collective research and projects.
Better and more collaboration.
Disruptions from small recessions to extinction (frequency, history and classification).