List of unsolved problems in biology

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This article lists notable

unsolved problems in biology
.

General biology

Evolution and origins of life

  • Origin of life. Exactly how, where, and when did life on Earth originate? Which, if any, of the many hypotheses is correct? What were the metabolic pathways used by the earliest life forms? How did genetic code originate? What was the molecular mechanism that allows the association of the amino acids with their triplet codons?[1] What were the biochemical paths from individual bio-building blocks like amino acids or nucleic acids to functional polymers such as proteins and DNA? [2]
  • Origin of sexual reproduction. What were the fundamental selective forces responsible for the origin of sexual reproduction?
  • Maintenance of sexual reproduction. What are the fundamental selective forces maintaining sexual reproduction?
  • Origins of viruses. Exactly how and when did different groups of viruses originate?
  • Morphology problem. How are neural tissues formed in specific ways in different species? The formation of neural tissues in a certain way is necessary for the formation of certain goal-directed behavior for certain species. Developmental psychobiology posed this question since the lack of knowledge about the precise coordination of all cells, even those not related anatomically, in space and time during the embryonic period does not allow us to understand what forces at the cellular level coordinate four very general classes of tissue deformation, namely: tissue folding and invagination, tissue flow and extension, tissue hollowing, and, finally, tissue branching. [3][4]
  • molecular
    determinants of individual brain development?
  • Origin of Eukaryotes (Symbiogenesis). How and why did cells combine to form the eukaryotic cell? Did one or more random events lead to the first eukaryotic cells, or can the formation of eukaryotic cells be explained by physical and biological principles? How did the mitochondria's mitosis cycle come in sync with its host cell? Did the mitochondria or the nucleus develop first in eukaryotes?
  • Last universal common ancestor. What were the characteristics of the Last Universal Common Ancestor of Archaea and Bacteria?
  • The
    lipid divide: How did archaea end up using membrane glycerophospholipids of the opposite chirality compared to bacteria?[5] Why do eukaryotes have bacteria-type membrane lipids?[6]

Biochemistry and cell biology

See also: Hypothetical types of biochemistry
  • Biological homochirality. What is the origin of homochirality in living organisms? In biological organisms, amino acids appear almost exclusively in the left-handed form and sugars in the right-handed form. Homochirality is an obvious characteristic of life on Earth, yet extraterrestrial samples contain largely racemic compounds.[7] It is not known whether homochirality existed before life, whether the building blocks of life must have this particular chirality, or whether life must be homochiral at all.[8][9]
  • What do all the unknown proteins do? Two decades since the first eukaryotes were sequenced, the "biological role" of around 20% of proteins are still unknown.[10] Many of these proteins are conserved across most eukaryotic species and some are conserved in bacteria, indicating a role fundamental for life.[10][11][12]
  • 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 lithium, thalidomide and ketamine[13]
    are not completely understood.
  • polypeptide sequence based solely on the sequence and environmental information?[14][15]
    • Prediction of native structure has turned out to be the easiest of the questions, as the variety of known structures have allowed the development of prediction methods such as Rosetta (since 1998) and the AlphaFold neural network of 2020. AlphaFold is capable of predicting a protein's final shape based solely on its amino-acid chain with an accuracy of around 90% on a test sample of proteins used by the team.[16] Accurate prediction of quaternary structure was achieved by AlphaFold3 in 2024.[17]
    • Inverse protein-folding problem (protein design): Is it possible to design a polypeptide sequence which will adopt a given structure under certain environmental conditions? This turned out to be tractable given a good structual prediction method, starting with the success of the small globular protein Top7 from the Rosetta team in 2002.[18] The use of structure-prediction neural networks afforded even more complex designs.[19] Large language models trained on protein sequences seem to learn a "grammar"; they represent yet another approach to the protein-design problem.[20]
    • The success of prediction and design methods still skip over how proteins end up in the final shape (folding mechanism and kinetics; protein dynamics). Wet lab methods of the 2020s allow for microsecond-level changes to be observed and quantified. 2020s molecular dynamics techniques can be used to simulate the folding behavior at the atomic level to this same timescale, though a specialized computer is needed for the simulation to finish in a reasonable amount of time.[21] See also Folding@home.
    • The study of intrinsically disordered proteins is also not as advanced as the study of globular proteins: some sequences do not fold into a fixed shape yet still have a function.
  • Enzyme kinetics: Why do some enzymes exhibit faster-than-diffusion kinetics?[22]
  • 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?[23]
  • Biosynthesis: Can desired molecules, natural products or otherwise, be produced in high yield through biosynthetic pathway manipulation?[24]
  • What is the mechanism of allosteric transitions of proteins? The
    concerted and sequential models
    have been hypothesised but neither has been verified.
  • What are the endogenous ligands of orphan receptors?
  • What substance is endothelium-derived hyperpolarizing factor?
  • Mechanism of Golgi's method: Why does this specific method stain nerve tissues? Why does it only color a random portion of the cells?

Other

  • Why does
    biological aging occur? There are a number of hypotheses as to why senescence occurs including those that it is programmed by gene expression changes and that it is the accumulative damage of biological structures, particularly damage to DNA.[25][26][27]
  • How do organs grow to the correct shape and size?[28] 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?[28] To an extent, this appears to be the case, as shown by the CLOCK gene.
  • Star jelly. A complete explanation about its origins is still lacking.
  • Forest rings. The origin of forest rings is not known, despite several mechanisms for their creation having been proposed. Such hypotheses include radially growing fungus, buried kimberlite pipes, trapped gas pockets, and meteorite impact craters.

Human biology

  • Handedness: It is unclear how handedness develops, what purpose it serves, why right-handedness is far more common, and why left-handedness exists.
  • Laughter: While it is generally accepted that laughing evolved as a form of social communication, the exact neurobiological process that leads humans to laugh is not well understood.
  • Yawning: It is yet to be established what the biological or social purpose of yawning is.[29]
  • Heritable components of homosexuality: How to reconcile evolution with the heritable components of human homosexuality? Homosexuality is prevalent across human societies, past and present. These facts constitute an evolutionary puzzle.[30][non-primary source needed]
  • Decline in average human body temperature since the 19th century: Medical data suggests that the average body temperature has declined 0.6 °C since the 19th century. The cause is unclear although it has been suggested that it has some relation with reduced inflammation from reduced exposure to microorganisms.[31]
  • Why are there
    blood types? It is unclear what the origin and purpose of having blood types is. It is thought that O blood may be an adaptation to malaria and that different blood types respond to different diseases but this hypothesis has yet to be proven. Why did these antigens develop in the first place? What accounts for the differences in blood type? How ancient are the differences in blood types? What accounts for the large number of rare non ABO blood types? What role do blood types have in fighting disease?[32]
  • Photic sneeze effect
    :     What causes the photic sneeze effect? Why is it so common yet not universal?
  • Human sex pheromones: There is contradictory evidence on the existence of human pheromones. Do they actually exist, and if so, how do they affect behavior?[33]
  • Existence of the
    Grafenberg spot (G-spot): Does the G-spot actually exist? If so is it present in all women? What exactly is it?[34]
  • Extinction of
    Homo sapiens the only surviving species of humans?[35]
  • selection pressure) romantic love evolved.[36]

Neuroscience and cognition

Neurophysiology

Sleep What is the biological function of sleep? What is the purpose of dreaming? 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 psychology

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
subjective experience, cognition, wakefulness, alertness, arousal, and attention? What is the precise mechanism behind how phenomenal binding occurs? Is there a "hard problem of consciousness"? If so, how is it solved? What, if any, is the function of consciousness, and what is the mechanism behind the function of consciousness?[37][38]
Free will Particularly the neuroscience of free will
Language How is it implemented neurally? What is the basis of
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?
The emergence and evolution of intelligence What are the laws and mechanisms - of new
ontogenesis
, etc.?
Perception How does the
senses integrated? What is the relationship between subjective experience and the physical
world?

Non-human biology

Ecology, evolution, and paleontology

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

Ethology

Unsolved problems relating to the behaviour of animals include:

Non-human organs and biomolecules

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

  • Korarchaeota
    (archaea). The metabolic processes of this phylum of archaea are so far unclear.
  • 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.[47]
  • Brightly colored bird eggs. It is unknown what evolutionary process would lead birds to having brightly colored eggs given the increased visibility to predators.[48]
  • Stegosaur
    osteoderms/scutes. There is a long-standing debate over whether the primary function of the osteoderms/scutes of stegosaurs is protection from predators, sexual display, species recognition, thermoregulation, or other functions.
  • Function of vanadocytes, a type of blood cells found in some tunicates. Vacuoles of vanadocytes are notable for high levels of the metal vanadium and their low pH.
  • aerobic respiration
    .
  • mitochondria
    .

Artificial life

Unsolved problems in artificial life include:[49][50]

  • How does life arise from the non-living?
  • What are the potentials and limits of living systems?
  • How is life related to mind, machines, and culture?

See also

References

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  4. ^ Collinet, C., Lecuit, T.(2021) “Programmed and self-organized flow of information during morphogenesis.” Nature Reviews Molecular Cell Biology.;22(4):245-65.(2021) https://doi.org/10.1038/s41580-020-00318-6
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  26. ^ Niedernhofer, L. J.; Gurkar, A. U.; Wang, Y.; Vijg, J.; Hoeijmakers JHJ; Robbins, P. D. (2018). "Nuclear Genomic Instability and Aging". Annual Review of Biochemistry. 87: 295–322. doi:10.1146/annurev-biochem-062917-012239. PMID 29925262. S2CID 49343005
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  49. ^ "Libarynth". Retrieved 2015-05-11.
  50. ^ "Caltech" (PDF). Retrieved 2015-05-11.
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