Biocomputing: the promise of biological computing

Advances in neu­ro­science are paving the way for the con­struc­tion of bio­log­i­cal com­put­ers using neu­rons and brain tis­sue. This inven­tion was both a break­through for com­put­ing and a tool for fun­da­men­tal research and the study of human diseases.

They are some­times called mini-brains. These cere­bral organoids are in fact 3‑dimensional cul­tures of cere­bral tis­sue. They could lead to the next rev­o­lu­tion in com­put­ing, the birth of organoid intel­li­gence (OI).

As a reminder, and con­trary to what its name sug­gests, arti­fi­cial intel­li­gence (AI) does not mim­ic human intel­li­gence. In fact, it works in a com­plete­ly dif­fer­ent way. Just watch it play chess: it sac­ri­fices far more pieces than any human play­er¹. Anoth­er dif­fer­ence is its ener­gy con­sump­tion. In June 2022, the record capac­i­ty of the Fron­tier super­com­put­er, housed at Oak Ridge Nation­al Lab­o­ra­to­ry in the Unit­ed States, was 1.1 exaflops (i.e. it per­forms up to 1.1 1018 oper­a­tions per sec­ond), a per­for­mance equiv­a­lent to the human brain. Except that the human brain oper­ates on 20 Watts, where­as the Amer­i­can super­com­put­er requires 10MW…

Organoid intel­li­gence (OI), on the oth­er hand, promis­es to bring the two sys­tems clos­er togeth­er, by repro­duc­ing the com­pu­ta­tion­al per­for­mance of the best com­put­ers and the ener­gy effi­cien­cy of a human brain. This tech­nol­o­gy is being devel­oped at the cross­roads of three tech­no­log­i­cal break­throughs: elec­tro­phys­i­ol­o­gy, arti­fi­cial intel­li­gence, and cere­bral organoids.

The first is essen­tial for com­mu­ni­cat­ing with cere­bral organoids. The chal­lenge? Find­ing a non-inva­sive sys­tem that takes into account the mul­ti­ple elec­tro­chem­i­cal sig­nals that occur every sec­ond in the small mass of tis­sue in cul­ture. Researchers at Amer­i­can uni­ver­si­ties are propos­ing the use of cage-shaped elec­trodes², an ini­tial solu­tion for direct com­mu­ni­ca­tion with the organoid in culture.

The devel­op­ment of the bio­log­i­cal com­put­er is still in its infancy.

The ques­tion of elec­trodes is also impor­tant for the devel­op­ment of brain tis­sue. With­out sig­nals, cere­bral organoids can­not be con­struct­ed in three dimen­sions and remain inop­er­a­tive. Nerve tis­sue has to work to func­tion and brain mech­a­nisms require more than a sim­ple elec­tro­chem­i­cal sig­nal. Mem­o­ry involves the reor­gan­i­sa­tion of neu­ron net­works and the inter­ven­tion of oth­er brain cells, such as those that make up microglia, the immune sys­tem of the brain. To devel­op, organoid intel­li­gence must inte­grate all these parameters.

The sec­ond tech­no­log­i­cal break­through that makes OI pos­si­ble is AI. It is essen­tial for explor­ing what these bio­log­i­cal sys­tems can do. Brain tis­sue cul­tures pro­duce very large vol­umes of data, both spa­tialised and struc­tured over time. Inter­pret­ing this data is a chal­lenge that recent advances in algo­rithms will be able to meet. 

The last tech­nol­o­gy on which the devel­op­ment of OI is based has yet to prove itself, and that is the one that will enable brain organoids to change scale. At present, the largest brain tis­sue cul­tures mea­sure just a few mil­lime­tres and con­tain a max­i­mum of 15,000 neu­rons. Mak­ing them big­ger means pro­tect­ing them against oxy­gen depri­va­tion, to which neu­rons are very sen­si­tive. To do this, they need to be per­fused, to ensure that each cell is con­nect­ed to a sup­ply of oxy­gen and nutri­ents, just as the blood­stream does in vivo.  Microflu­idics seems capa­ble of pro­vid­ing this per­fu­sion. But this tech­nol­o­gy has not yet been trans­posed to cere­bral organoids. This tech­no­log­i­cal trans­fer will make it pos­si­ble to go from a cul­ture the size of a fly’s brain to one com­pa­ra­ble to that of a mouse.

Will these sys­tems replace our com­put­ers? Not in the near future. In 2019, a Japan­ese team suc­ceed­ed in get­ting two cere­bral organoids to com­mu­ni­cate³. It is dif­fi­cult to pre­dict what will hap­pen next, giv­en the large num­ber of teams work­ing on the sub­ject. Nev­er­the­less, there is hope that the first OI sys­tems will be tools for neu­ro­science research. Bio­log­i­cal com­put­ers could help to explain how a brain man­ages to process incom­plete infor­ma­tion, for example.

They could also help to elu­ci­date the mech­a­nisms of demen­tia, Asperger’s syn­drome, or oth­er com­mon human brain con­di­tions. It is cur­rent­ly very dif­fi­cult to have accept­able lab­o­ra­to­ry mod­els for these issues. Eth­i­cal con­sid­er­a­tions, for exam­ple, nat­u­ral­ly for­bid study­ing the effect of a mol­e­cule that dis­rupts mem­o­ry on humans… Cere­bral organoids offer an alter­na­tive for such research.

OI also rais­es eth­i­cal ques­tions in its own right: Which sys­tems could be at risk of suf­fer­ing pain? What pro­to­cols will be used to assess the intel­li­gence of a cul­ture? These issues need to be antic­i­pat­ed, and OI spe­cial­ists have com­mit­ted to incor­po­rat­ing them into the devel­op­ment of tech­ni­cal aspects by sign­ing the Bal­ti­more Con­ven­tion in 2022⁴. The devel­op­ment of the bio­log­i­cal com­put­er is still in its infancy.

Agnès Vernet