Uploaded August 2026 | Updated September 2026, 2 weeks ago
In where????? In vitro, in vivo, ex vivo, in situ, & in silico – when it comes to what happens where, here’s what there is to know!
thebumblingbiochemist.com/365-days-of-science/in-where-in-vitro-in-vivo-ex-vivo-in-situ-in-silico-when-it-comes-to-what-happens-where-heres-what-there-is-to-know
Scientists must choose from a variety of experimental systems to investigate questions. Each system has pros and cons. (More on those here: thebumblingbiochemist.com/365-days-of-science/choosing-an-experimental-system-in-vitro-in-cell-culture-in-vivo-etc/)
From most control to least control (and least realism to most realism): in vitro (outside of cells), in cell culture, in vivo (inside of organisms)
We can broaden that a little to encompass more systems… reconstituted, lysate-based, in cell culture, in organoids, in tissue, in vivo
* In vitro – outside of cells, “in a test tube*” – most experimental control but least realistic – best for dissecting mechanisms – how do things work?
* Latin: in glass
* *doesn’t have to literally be in a tube, just outside of a cellular and organismal context
* Often involves using purified components, sometimes uses cellular lysates (the content of broken open cells) or in cell culture (work with cells adapted to grow in the lab)
* In vitro cell culture (in cells/in cellulo)* – medium level of control & realism, more variability
* Such experiments are typically done on culture-adapted cells outside of an organism in a highly controlled system.
* *Sometimes people refer to cell culture as “in vivo” but, if you’re working with single cells, it’s only really in vivo if you’re working with a unicellular organism like bacteria or yeast - but some people don't even consider that "in vivo" if you're doing it in the lab.
* In vivo – inside of organisms – least experimental control but most realistic*
* Latin: within the living
* * at least for the organism studied – but are the findings directly transferable to the system you care about? (i.e. a mouse isn’t a human)
These days, “in vivo” and “ex vivo” are heard a lot in reference to gene editing. With In vivo gene editing, the treatment machinery (e.g. CRISPR/Cas and guide RNA or the instructions for the cells to make them) are delivered into the body to fix cells in place. With ex vivo editing, in contrast, cells or are removed, treated outside of the person to “fix” them or give them new abilities, then returned to the body. This is sometimes done with blood-forming, hematopoietic stem cells (HPSCs) and can be used to treat blood disorders (e.g. by editing the cells to make them produce more fetal hemoglobin to compensate for faulty adult hemoglobin). In other forms of ex-vivo editing, leukapheresis is used to remove white blood cells (immune cells) to equip cells with new abilities to do things like fight cancers (e.g. with CAR-T cells).
Other systems:
* Ex vivo: outside of the source organism
* Latin: out of the living
* Experiments or work done on tissue from a living organism worked on outside of that living organism, but with minimal disruption and as natural of conditions as possible.
* Note: This contrasts with in vitro cell culture work, where scientists break tissues up into individual cells and use highly artificial conditions in order to allow them to survive for a long time
* In situ: in the original place
* Latin: on site
* For example:
* In Fluorescence In Situ Hybridization, FISH, scientists bind fluorescent probes to molecules inside of cells to see where those molecules are hanging out.
* There are also increasing technological advancements leading to in situ sequencing to do things like localize mRNA transcripts inside of cells to see what’s being made where.
* In silico: in computer land
* “Dry work” techniques that typically depend on data collected through physical “wet lab” experiments, often by many scientists.
* For example:
* Molecular docking can be used to predict whether molecules might bind to a protein of interest by seeing if their structures could theoretically fit together nicely & molecular dynamics can be used to predict how molecules wiggle.
* Genetic sequences can be analyzed to predict potential off-target binding locations of guide RNAs used to direct CRISPR/Cas gene editing machinery.
Note: the above phrases (in vivo, etc.) do not need to be italicized in most style guides.
Additional strategies include things like “organoids” that try to mimic tissues and organs in vitro, sometimes starting from iPSCs (induced Pluripotent Stem Cells). iPSCs are stem cells made from non-stem cells (e.g. skin cells) taken from an organism and treated to revert back to stemness so they can then be treated with cell-type-specific signals to get them to differentiate into desired cell types.
In where????? In vitro, in vivo, ex vivo, in situ, & in silico – when it comes to what happens where, here’s what there is to know!
thebumblingbiochemist.com/365-days-of-science/in-where-in-vitro-in-vivo-ex-vivo-in-situ-in-silico-when-it-comes-to-what-happens-where-heres-what-there-is-to-know
Scientists must choose from a variety of experimental systems to investigate questions. Each system has pros and cons. (More on those here: thebumblingbiochemist.com/365-days-of-science/choosing-an-experimental-system-in-vitro-in-cell-culture-in-vivo-etc/)
From most control to least control (and least realism to most realism): in vitro (outside of cells), in cell culture, in vivo (inside of organisms)
We can broaden that a little to encompass more systems… reconstituted, lysate-based, in cell culture, in organoids, in tissue, in vivo
* In vitro – outside of cells, “in a test tube*” – most experimental control but least realistic – best for dissecting mechanisms – how do things work?
* Latin: in glass
* *doesn’t have to literally be in a tube, just outside of a cellular and organismal context
* Often involves using purified components, sometimes uses cellular lysates (the content of broken open cells) or in cell culture (work with cells adapted to grow in the lab)
* In vitro cell culture (in cells/in cellulo)* – medium level of control & realism, more variability
* Such experiments are typically done on culture-adapted cells outside of an organism in a highly controlled system.
* *Sometimes people refer to cell culture as “in vivo” but, if you’re working with single cells, it’s only really in vivo if you’re working with a unicellular organism like bacteria or yeast - but some people don't even consider that "in vivo" if you're doing it in the lab.
* In vivo – inside of organisms – least experimental control but most realistic*
* Latin: within the living
* * at least for the organism studied – but are the findings directly transferable to the system you care about? (i.e. a mouse isn’t a human)
These days, “in vivo” and “ex vivo” are heard a lot in reference to gene editing. With In vivo gene editing, the treatment machinery (e.g. CRISPR/Cas and guide RNA or the instructions for the cells to make them) are delivered into the body to fix cells in place. With ex vivo editing, in contrast, cells or are removed, treated outside of the person to “fix” them or give them new abilities, then returned to the body. This is sometimes done with blood-forming, hematopoietic stem cells (HPSCs) and can be used to treat blood disorders (e.g. by editing the cells to make them produce more fetal hemoglobin to compensate for faulty adult hemoglobin). In other forms of ex-vivo editing, leukapheresis is used to remove white blood cells (immune cells) to equip cells with new abilities to do things like fight cancers (e.g. with CAR-T cells).
Other systems:
* Ex vivo: outside of the source organism
* Latin: out of the living
* Experiments or work done on tissue from a living organism worked on outside of that living organism, but with minimal disruption and as natural of conditions as possible.
* Note: This contrasts with in vitro cell culture work, where scientists break tissues up into individual cells and use highly artificial conditions in order to allow them to survive for a long time
* In situ: in the original place
* Latin: on site
* For example:
* In Fluorescence In Situ Hybridization, FISH, scientists bind fluorescent probes to molecules inside of cells to see where those molecules are hanging out.
* There are also increasing technological advancements leading to in situ sequencing to do things like localize mRNA transcripts inside of cells to see what’s being made where.
* In silico: in computer land
* “Dry work” techniques that typically depend on data collected through physical “wet lab” experiments, often by many scientists.
* For example:
* Molecular docking can be used to predict whether molecules might bind to a protein of interest by seeing if their structures could theoretically fit together nicely & molecular dynamics can be used to predict how molecules wiggle.
* Genetic sequences can be analyzed to predict potential off-target binding locations of guide RNAs used to direct CRISPR/Cas gene editing machinery.
Note: the above phrases (in vivo, etc.) do not need to be italicized in most style guides.
Additional strategies include things like “organoids” that try to mimic tissues and organs in vitro, sometimes starting from iPSCs (induced Pluripotent Stem Cells). iPSCs are stem cells made from non-stem cells (e.g. skin cells) taken from an organism and treated to revert back to stemness so they can then be treated with cell-type-specific signals to get them to differentiate into desired cell types.
