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List of unsolved problems in biology

This article lists currently unsolved problems in biology.


General biologyEdit

Evolution and origins of lifeEdit

  • Origin of life. Exactly how and when did life on Earth originate? Which, if any, of the many hypotheses is correct?
    • Extraterrestrial life. Might life which does not originate from planet Earth also have developed on other planets? Might this life be intelligent?
    • What are the chemical origins of life? How did non-living chemical compounds generate self-replicating, complex life forms?
  • Evolution of sex. What selective advantages drove the development of sexual reproduction, and how did it develop?[1]
    • Homosexuality. What is the cause of homosexuality, especially in the human species?
  • Development and evolution of brain. How and why did the brain evolve? What are the molecular determinants of individual brain development?

Biochemistry and cell biologyEdit

  • Determinants of cell size. How do cells determine what size to grow to before dividing?
  • Golgi apparatus. In cell theory, what is the exact transport mechanism by which proteins travel through the Golgi apparatus?
  • Mechanism of action of drugs. The mechanisms of action of many drugs including paracetamol, lithium, thalidomide and ketamine[2] are not completely understood.
  • Protein folding. What is the folding code? What is the folding mechanism? Can we predict the native structure of a protein from its amino acid sequence? Is it possible to predict the secondary, tertiary and quaternary structure of a polypeptide sequence based solely on the sequence and environmental information? Inverse protein-folding problem: Is it possible to design a polypeptide sequence which will adopt a given structure under certain environmental conditions?[3][4] This has been achieved for several small globular proteins in recent years.[5]
  • Enzyme kinetics: Why do some enzymes exhibit faster-than-diffusion kinetics?[6]
  • RNA folding problem: Is it possible to accurately predict the secondary, tertiary and quaternary structure of a polyribonucleic acid sequence based on its sequence and environment?
  • Protein design: Is it possible to design highly active enzymes de novo for any desired reaction?[7]
  • Biosynthesis: Can desired molecules, natural products or otherwise, be produced in high yield through biosynthetic pathway manipulation?[8]
  • What is the mechanism of allosteric transitions of proteins? The concerted and sequential models have been hypothesised but neither has been verified.
  • How many genes do we have?[9]
  • What are the endogenous ligands of orphan receptors?
  • What substance is endothelium-derived hyperpolarizing factor?


  • Why does biological aging occur? There are a number of hypotheses why senescence occurs including those that it is programmed by gene expression changes and that it is the accumulative damage of biological processes.
  • Consistency of movement. How can we move so controllably, even though the motor nerve impulses seem haphazard and unpredictable?[10]
  • How do organs grow to the correct shape and size?[11] How are the final shape and size of organs so reliably formed? These processes are in part controlled by the Hippo signaling pathway
  • Can developing biological systems tell the time?[11] To an extent, this appears to be the case, as shown by the CLOCK gene.
  • Why are babies so rarely born with cancer?[12]

Non-human biologyEdit

Ecology and paleontologyEdit

Unsolved problems relating to the interactions between organisms and their distribution in the environment include:

  • Cambrian explosion. What is the cause of the apparent rapid diversification of multicellular animal life around the beginning of the Cambrian, resulting in the emergence of almost all modern animal phyla?
  • Absence of Loricifera fossils. There are at least 100 species of this phylum of marine dwelling animals (many undescribed), but none of them is known to be present in the fossil record.
  • Adult form of Facetotecta. The adult form of this animal has never been encountered in the water, and it remains a mystery to what it grows into.


Unsolved problems relating to the behaviour of animals include:

  • Homing. A satisfactory explanation for the neurobiological mechanisms that allow homing in animals has yet to be found.
  • Butterfly migration. How do the descendants of monarch butterfly all over Canada and the US eventually, after migrating for several generations, manage to return to a few relatively small overwintering spots?
  • Blue whale. There is not much data on the sexuality of the blue whale.[13]
  • Gall wasp. It is largely unknown how gall wasps induce gall formation in plants; chemical, mechanical, and viral triggers have been discussed..

Non-human organs and biomoleculesEdit

Unsolved problems relating to the structure and function of non-human organs, processes and biomolecules include:

  • Alkaloids. The function of these substances in living organisms which produce them is not known[14]
  • Korarchaeota (archaea). The metabolic processes of this phylum of archaea are so far unclear.
  • Rotifer. What is the function of the retrocerebral organ of rotifers (pseudocoelomate animals)?
  • Glycogen body. The function of this structure in the spinal cord of birds is not known.
  • Arthropod head problem. A long-standing zoological dispute concerning the segmental composition of the heads of the various arthropod groups, and how they are evolutionarily related to each other.
  • Ovaries of basking sharks. Only the right ovary in female basking sharks appears to function, the reason is unknown.

Neuroscience and cognitionEdit


Sleep What is the biological function of sleep? Why do we dream? What are the underlying brain mechanisms? What is its relation to anesthesia?
Neuroplasticity How plastic is the mature brain?
General anesthetic What is the mechanism by which it works?
Neuropsychiatric Diseases What are the neural bases (causes) of mental diseases like psychotic disorders (e.g. mania, schizophrenia), Parkinson's disease, Alzheimer's disease, or addiction? Is it possible to recover loss of sensory or motor function?
Neural computation What are all the different types of neuron and what do they do in the brain?

Cognition and psychologyEdit

Cognition and decisions How and where does the brain evaluate reward value and effort (cost) to modulate behavior? How does previous experience alter perception and behavior? What are the genetic and environmental contributions to brain function?
Computational neuroscience How important is the precise timing of action potentials for information processing in the neocortex? Is there a canonical computation performed by cortical columns? How is information in the brain processed by the collective dynamics of large neuronal circuits? What level of simplification is suitable for a description of information processing in the brain? What is the neural code?
Computational theory of mind What are the limits of understanding thinking as a form of computing?
Consciousness What is the brain basis of subjective experience, cognition, wakefulness, alertness, arousal, and attention? Is there a "hard problem of consciousness"? If so, how is it solved? What, if any, is the function of consciousness?[15][16]
Free will Particularly the neuroscience of free will
Language How is it implemented neurally? What is the basis of semantic meaning?
Learning and memory Where do our memories get stored and how are they retrieved again? How can learning be improved? What is the difference between explicit and implicit memories? What molecule is responsible for synaptic tagging?
Noogenesis - the emergence and evolution of intelligence What are the laws and mechanisms - of new idea emergence (insight, creativity synthesis, intuition, decision-making, eureka); development (evolution) of an individual mind in the ontogenesis, etc.?
Perception How does the brain transfer sensory information into coherent, private percepts? What are the rules by which perception is organized? What are the features/objects that constitute our perceptual experience of internal and external events? How are the senses integrated? What is the relationship between subjective experience and the physical world?

See alsoEdit


  1. ^ Sherratt TN, Wilkinson DM (2009). Big questions in ecology and evolution. US: Oxford University Press. ISBN 978-0-19-954861-3.
  2. ^ Tyler MW, Yourish HB, Ionescu DF, Haggarty SJ (June 2017). "Classics in Chemical Neuroscience: Ketamine". ACS Chemical Neuroscience. 8 (6): 1122–1134. doi:10.1021/acschemneuro.7b00074. PMID 28418641.
  3. ^ "So much more to know". Science. 309 (5731): 78–102. July 2005. doi:10.1126/science.309.5731.78b. PMID 15994524.
  4. ^ King, Jonathan (2007). "MIT OpenCourseWare - 7.88J / 5.48J / 7.24J / 10.543J Protein Folding Problem, Fall 2007 Lecture Notes - 1". MIT OpenCourseWare. Archived from the original on September 28, 2013. Retrieved June 22, 2013.
  5. ^ Dill KA, Ozkan SB, Shell MS, Weikl TR (June 2008). "The protein folding problem". Annual Review of Biophysics. 37: 289–316. doi:10.1146/annurev.biophys.37.092707.153558. PMC 2443096. PMID 18573083.
  6. ^ Hsieh M, Brenowitz M (August 1997). "Comparison of the DNA association kinetics of the Lac repressor tetramer, its dimeric mutant LacIadi, and the native dimeric Gal repressor". The Journal of Biological Chemistry. 272 (35): 22092–6. doi:10.1074/jbc.272.35.22092. PMID 9268351.
  7. ^ "Archived copy". Archived from the original on 2013-04-01. Retrieved 2012-12-19.CS1 maint: Archived copy as title (link)
  8. ^ Peralta-Yahya PP, Zhang F, del Cardayre SB, Keasling JD (August 2012). "Microbial engineering for the production of advanced biofuels". Nature. 488 (7411): 320–8. Bibcode:2012Natur.488..320P. doi:10.1038/nature11478. PMID 22895337.
  9. ^ Salzberg SL (August 2018). "Open questions: How many genes do we have?". BMC Biology. 16 (1): 94. doi:10.1186/s12915-018-0564-x. PMC 6100717. PMID 30124169.
  10. ^ University of Copenhagen (24 January 2007). "Thinking With The Spinal Cord?". ScienceDaily. Retrieved 25 May 2016.
  11. ^ a b Saunders TE, Ingham PW (February 2019). "Open questions: how to get developmental biology into shape?". BMC Biology. 17 (1): 17. doi:10.1186/s12915-019-0636-6. PMC 6387480. PMID 30795745.
  12. ^ Monje M (November 2018). "Open questions: why are babies rarely born with cancer?". BMC Biology. 16 (1): 129. doi:10.1186/s12915-018-0601-9. PMC 6211449. PMID 30382924.
  13. ^ Blue Whale
  14. ^ Aniszewski, Tadeusz (2007). Alkaloids – secrets of life. Amsterdam: Elsevier. p. 142. ISBN 978-0-444-52736-3.
  15. ^ Sejnowski, Terrence J.; Hemmen, J. L. van (2006). 23 problems in systems neuroscience (PDF). Oxford [Oxfordshire]: Oxford University Press. ISBN 978-0-19-514822-0.
  16. ^ Tononi G, Koch C (May 2015). "Consciousness: here, there and everywhere?". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. Philosophical Transactions of the Royal Society London B. 370 (1668): 20140167. doi:10.1098/rstb.2014.0167. PMC 4387509. PMID 25823865.