In the latest wave of extraordinary computer development, tiny \u2018brains\u2019 are being grown in dishes and connected to digital interfaces to perform tasks. In Cosmos Print March 20205, Ken Eastwood took us to the lab to meet the brains behind the research.<\/p>\n
In season 2 of Star Trek, released in 1966, on a fictional planet called Treskelion, a fresh-faced William Shatner comes across a large bowl-like structure with 3 alive, connected brains encased inside it. Almost 60 years later, Professor Thomas Hartung of Johns Hopkins University in the USA points to this in an online forum on organoid computing, as an example of how teams like his are making the unbelievable come true.<\/p>\n
\u201cCaptain Kirk encountered in 1966 a computer built on brains, which was actually biological computing, which at the time was pure science fiction and now we try to make this a reality,\u201d says Hartung.<\/p>\n
Around the world, progress is rapidly being made in organoid or biological computing \u2013 the meshing of specially grown brain cells with digital platforms. <\/p>\n
In 2022, Australian researchers at Cortical Labs successfully got their \u2018Dishbrain\u2019 to play the simple computer game of Pong. <\/p>\n
Last year, Chinese researchers revealed that their open-source biocomputer MetaBOC is using human brain cells to control robots. Companies such as the Swiss Final Spark and Cortical Labs are now developing commercial hardware \u2013 plug-in brain computer systems \u2013 that you can buy or use via the cloud. <\/p>\n
And, at Johns Hopkins University in the US, and other institutions around the world, researchers are rapidly developing everything from ethical frameworks for experimenting on these new biocomputers through to new methods to engage with and \u2018teach\u2019 them.<\/p>\n
Proponents say the practical uses for organoid computers could be legion. Imagine, for example, if you were testing a new drug, say for Alzheimer\u2019s, epilepsy or dementia, and being able to directly ask an organoid computer how the drug was affecting it.<\/p>\n
Researchers are excited by other advantages too: potential computing speed, processing and energy efficiency. Human brains may be slower than machines at processing simple information, such as a maths problem, but they far surpass machines in processing complex information, particularly when there is uncertain data.<\/p>\n
Unlike silicon constructions, humans can perform parallel processing (running separate parts of an overall task at the same time). It takes supercomputers many minutes to model even a fraction of a human brain, and they use massive amounts of power to do so \u2013 roughly a million times more energy. It would take the construction of huge new power plants to digitally replicate the activity of even one human brain.<\/p>\n
\u201cThe potential for [organoid computing] is massive and there\u2019s nothing really we can compare it to,\u201d says scientific futurist, tech influencer and author Dr Catherine Ball. \u201cThe human neuron always beats the silicon creation \u2013 it\u2019s always the best way. So, using the best kind of cognition \u2013 the human brain \u2013 in a tiny form just seems logical. It makes so much sense.\u201d<\/p>\n
The DishBrain chip, containing human cells. Credit: Courtesy of Cortical Labs.<\/p>\n
Organic development<\/p>\n
Professor David Gracias, Johns Hopkins University. Credit: Courtesy of Professor David Gracias.<\/p>\n
Professor David Gracias, from the Department of Chemical and Biomolecular Engineering, is one of 20\u201330 lead researchers at Johns Hopkins working directly or indirectly on biocomputing. <\/p>\n
He points out organic computing hasn\u2019t just developed in isolation, but has progressed at this time because a whole suite of technologies have come together simultaneously \u2013 the ability to keep cells alive in a dish for months at a time, the power of AI to help run multiple experiments and interpret the masses of data they produce, and micro wiring at the digital interface to connect to the organoids.<\/p>\n
Gracias says that the Johns Hopkins researchers began working on organic computing a few years ago. \u201cIf humans are trying to emulate the brain in a silicon chip in modern day neuromorphic computing, why not just emulate the brain with the brain itself, right, instead of trying to mimic it?\u201d he asks.<\/p>\n
The organoids he works on have about 10,000 human brain cells \u2013 which together make up a tiny ball up to about 0.5mm across. Elsewhere in the world smaller or larger organoids are being used. But even the process of keeping the organoids alive is time-consuming and thought-provoking.<\/p>\n
\u201cIf you don\u2019t have blood vessels, you cannot grow things that are bigger than a few hundred microns across,\u201d Gracias says. \u201cIf they get bigger then the centre starts to die. So, we and others are trying very hard and we are developing instrumentation to see how to make blood vessels in them [to keep them alive].\u201d<\/p>\n
In addition, the organoids are \u2018wetware\u2019 \u2013 they need to be kept in a liquid medium to survive, which makes connecting digital computers with electricity to them a challenge. \u201cWater is the enemy of computers because it shorts the circuit,\u201d he says. <\/p>\n
\u201cThis is going to be a paradigm shift in computers, which is to learn how to build computers which have water in them, which can keep the media \u2018perfusing\u2019 [or flowing].\u201d<\/p>\n
Another challenge that Gracias has been specifically working on is how best to digitally connect to the organoids. The connections are used both to stimulate the organoid (e.g., putting a current into a neuron) and to receive any electrical response.<\/p>\n
In simple organic computing models, the organoids are kept as small, 2D structures, making it relatively easy to connect wires to neurons. However, to better create the multitude of activity that can occur in a brain as multiple neurons interact with each other, 3D structures are required. Placing one of these little brain balls of activity on a 2D interface limits the digital contact with the structure to just a couple of points \u2013 not an ideal outcome when you are trying to monitor what is going on throughout the structure.<\/p>\n
\u201cWe\u2019re going after the tough Holy Grail problems,\u201d Gracias says. \u201cOne is to stimulate and monitor every cell in the organoid in real time.\u201d Taking inspiration from an EEG skull cap used to measure brain activity, Gracias worked on a tiny shell that could wrap around the miniscule 3D brain organoids, recording activity at many points.<\/p>\n
\u201cOne of the problems with the mini EEG cap is there are a lot of wires on them,\u201d he says. \u201cSo, we\u2019re now also thinking of electronic tattoos or non-contact or wireless, so we don\u2019t need all the wires\u2026 Maybe we can use light or we can use electromagnetic fields.\u201d<\/p>\n
Of course, merely sending and receiving signals from the organoids doesn\u2019t mean we necessarily know what those signals mean, so many current studies involve sending millions of signals into the organoids in order to understand how they respond, and how those responses change over time, i.e., how they \u2018learn\u2019 to respond to something like a game of Pong. <\/p>\n
\u201cYou and I speak in English, but the brain speaks in a language of chemical and electrical signals,\u201d Gracias says. \u201cWe have to learn the language of the brain, and that is not a trivial thing. We can stimulate and we can record, but then we don\u2019t know what to stimulate and we don\u2019t know how to interpret the recording. So, we are learning this language. There\u2019s a lot of data that comes out of it, which is why we need data scientists, because brain organoids fire on the timescale of milliseconds, so you get a lot of data very fast.\u201d<\/p>\n
Gracias says teaching the organoid computers a task is a bit like teaching a small child, with rewards and punishment. \u201cBasically, we have to find out what the brain organoid likes. And you give it a pattern and if it repeats the pattern, you give it a reward of some kind. It could be an electrical spike or it could be a chemical. Then if it does something you don\u2019t want it to repeat, you kind of give it something it doesn\u2019t like.\u201d<\/p>\n
Some of the current research Gracias is involved in includes giving the organoids neurochemicals such as dopamine. \u201cSo, we are trying to create a multi-modal shell which can stimulate and record both chemical and electrical stimuli. We\u2019ve made a lot of progress there.\u201d<\/p>\n
Measuring activity in organoids: A tiny shell can be wrapped around organoids to detect their activity (in microvolts, \u03bcV). Wrapping 3D organoids with a shell allows researchers to detect activity at multiple points at once. <\/p>\n
Source: Gracias Lab, JHU Image reprinted by Huange et al. Sci Adv 2022 (top)
Source: Image reprinted from Smirnova et al. Frontiers in Science, 2023<\/p>\n
Scaling up<\/p>\n
Dr Brett Kagan, Cortical Labs. Credit: Courtesy of Cortical Labs.<\/p>\n
After making a splash with their Pong-playing \u2018Dishbrain\u2019, Dr Brett Kagan and the team at Cortical Labs pivoted the company\u2019s goals to extend beyond pure research, and instead, provide a viable, commercial organoid computing product that others could use.<\/p>\n