A running list of questions that occur to me. I often ask questions on Quora as well.



Biology

Medicine and drug discovery
  • Would use of additional dyes in routine histology improve its diagnostic capacity?
  • Can acne be treated with bacteriophage?
  • Can we infer pairs of bacteria and phage that kill each other from their covariation in metagenomic sequencing experiments?
  • Why do people have allergies to the same things?
  • Why is myopia on the rise, and what can we do about it?
  • Why are autoimmune diseases becoming more prevalent?
  • Why is obesity becoming more prevalent?
  • Do we really understand the cause of atherosclerosis, the leading killer of humans globally?
  • Are parasite-derived immunosuppressants useful as therapeutics?
  • Can T cell and B cell receptor repertoire sequencing serve as a “universal diagnostic” and enable the discovery of new drug targets?
  • How effective will NK cell therapies be in treating solid tumors?
  • Have we dismissed anything as quackery that will turn out to be a useful therapy?
  • Is rational drug design overrated?
  • How can we use experimental evolution to develop better drugs?
  • Should we care about unintended laboratory evolution in model organisms?
  • How does sugar cause pain sensation in teeth?
  • Which treatments work for chronic back pain?
  • How can we make pre-clinical assays of drug candidates more predictive?
  • How can we deal with evolved resistance to therapies?
  • How much can polygenic traits be modulated by single mutations or treatment with a single drug?
  • Which foods are the most thermogenic?
  • Which drugs enhance cognition?
  • What goes wrong when we try to freeze organs?
Aging
  • Why aren’t longevity mutations discovered in mutagenesis screens extant in wild-type populations?
  • Do diseases of aging share common causes?
    • Should we continue to address them on a disease-by-disease basis?
  • Why can’t age-associated aggregates like drusen, lipofuscin, amyloid, Lewy bodies, and glycation be degraded?
  • Why don’t artificial hearts last forever?
  • Which interventions currently reduce all-cause mortality?
  • Does evolutionary theory contradict some of the most popular theories of the cause of aging? (Read Michael Rose for an aging Theory of Everything.)
Misc. Biology
  • Why are mammalian sex ratios roughly equal?
  • How do cells adjust to cold shocks?
  • How does karyotypic speciation happen in sexual organisms, given that their karyotype must be compatible with a mate’s?
  • Is x-chromosome inactivation reversible?
  • What determines the reversibility of mitotic exit?
  • How much information is in a cell?
  • Does Muller’s ratchet make sense?
  • How does biomineral morphogenesis (growth of bones, diatoms, etc.) work?

Research institutions and culture

  • How useful is basic biology research?
  • How useful are research exercises, vs just working on a real problem?
  • Which tools can I use to enhance my thinking?
  • Should researchers be teachers?
  • How can we improve scientific education?
  • Can bureaucracies make discoveries?
  • How much of institutional excellence is feedback from good recruiting?
  • Does earmarking research grants increase or decrease capital efficiency?

Healthcare business and economics

  • Is the pace of drug discovery stagnating (a.k.a. Eroom’s law)?
  • Is the pace of medical innovation stagnating?
  • How should we interpret the RAND Health Insurance Experiment?
  • Why isn’t it profitable to develop new antibiotics?
  • Are American insulin prices a scam?
  • How can we improve electronic medical records to improve patient care and accelerate drug discovery?
  • Should we donate our electronic medical records to the public upon dying?
  • How does cash payment for treatments influence affordability and innovation in medicine?
  • Are patent protections for biologic drugs useful to society?
  • What kinds of medical innovations can be successful when intellectual property and regulatory protections are weak?
  • Why are successful biotech venture capital firms adapting a “venture creation” model, where ventures are started in-house?
  • Are discovery-phase research programs at large pharmaceutical companies productive?
  • What are the biggest secular trends in healthcare / biotech / pharma?
  • Would it be useful to be able to bet directly on the outcome of clinical trials without trading a company’s shares?
  • What are the pros and cons of medical tourism?
  • Are insurance co-pays useful?
  • Are data-centric biotech companies ever going to make any money?
  • Are there any good opportunities for veterinary-human crossover drug discovery?

Computer science

  • What is the minimum number of dimensions necessary to implement a universal classical computer?
  • Are computational kinetics provable? (i.e. can we determine analytically which processes cannot be computed faster on an alternative architectures without having to simulate them?)
  • Will homeomorphic encryption become practical anytime soon?
  • How probabilistic is software debugging? How much of it can be automated?
  • What are the potential uses of evolutionary algorithms?
  • Can more computation be memoized than we think?

Chemistry

  • Do microwaves have any non-thermal effects on reaction kinetics?
  • How useful is light in imparting enantioselectivity?
  • How well can organisms discriminate isotopes?
  • Would ice polymorphs with densities close to water allow us to freeze tissues without cryoprotectants?

Physics

  • Can the reverse of a microwave oven exist? I.e. “stimulated radiative cooling”.
Thermodynamics
  • Can some formal expression describe the minimal energetic costs of molecular quality control?
  • How does Shannon entropy relate to Boltzmann entropy? (I read answers to this one once in a while, but I don’t really get it yet. It seems like the most important and fundamental bit of science that I never encountered in school.)
  • Can we measure the information content of matter through calorimetry?
    • Thought experiment: I have one hard drive filled with random data and another that has 1s and 0s in strict alternation. I put them both in a perfect bomb calorimeter. Do they evolve different amounts of heat?

Political economy

  • What curve describes the discount rate?
  • Why do many countries tax short term capital gains at a higher rate?
  • What seemingly worthless data today will become valuable in the future?
    • What are we not recording that we should?
  • Would semi-sovereign industries solve any social or technological problems?
  • Why would someone buy a negative yield bond?
    • What are the macro / cultural implications of negative yields?

Invention

  • Are nicotine beverages effective stimulants?
  • Is it possible to enhance the light harvesting capacity of plants by engineering synthetic FRET pairs that donate to the natural chromophores?
  • Can we make bacterial nitrogen fixation cheaper than the Haber process for fertilizer production?
Cooling
  • How can we develop personal cooling devices and cooling clothing?
  • Is residential evaporative cooling cost effective?
  • Why don’t we evaporate the condensation from an air conditioner off of the condenser unit?

Philosophy

  • Why does induction work sometimes?
  • How do you know whether you should follow someone’s advice?

Sport

  • Are we using enough data in recreational sports?
  • Does weightlifting confound mainstream health recommendations?
  • How many kinds of athletic stimulus promote health?
  • How much does optimal work volume for strength training vary between individuals?
  • Does holding your breath while exercising (or while sedentary) enhance cardiovascular fitness?
  • What kind of training reduces back pain?
  • Which sports stimulate the most diverse movement patterns?
  • What are the best predictors of which sports you will be the best at?

Misc.

  • How should we decide whether to perform a destructive assay on a historical artifact?