The functioning of the brain is often compared to that of a computer. Some researchers are testing this analogy to its limits, attempting to build computers containing lab-grown cultures of brain cells. In doing so, they hope to circumvent the physical limitations of the silicon-based computing hardware used for artificial intelligence today.^1,2.

The promise is there. Brain tissue combines memory and computing on the same substrate, requiring fewer components than conventional computers. Neural network theories, based on neurons and synapses, have inspired AI algorithms. Brains consume much less energy than AI machines³ and do not require large cooling systems.

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This biocomputing poses different ethical challenges. There have been intense debates about the morality of using lab-grown brain tissue and the potential for consciousness.⁴. However, until now one key issue has been absent from the debates: the lack of explicit consent for the use of human neural tissue in biocomputing.

Biocomputing research relies on voluntary donations of cells, often from people undergoing medical procedures who donate them altruistically to aid biomedical and basic biological research. However, consent forms do not ask donors what type of research they would like their cells to be used for in the future or, more importantly, all the possible ways they would not like them to be used. Donors who want to support the development of cancer treatments may not imagine that their tissues could be used to create biocomputers, possibly for commercial uses.

A more explicit and nuanced approach to donor consent is needed for bioinformatics research using laboratory-grown brain tissue. In our opinion, researchers should avoid using cell lines whose consent has been given solely for biomedical research. A system should be established to seek consent retrospectively or to review the ethics of projects when it is not possible to obtain consent again (known as reconsent).

Using brain cells to calculate

Brain-based biocomputing relies on human cortical neurons because they are larger and form more complex circuits than those of rodents or other primates. These characteristics are believed to contribute to the extraordinary information processing capabilities of the human brain.^5,6from recognizing a face to performing abstract reasoning.

Biocomputers are built using “pluripotent” stem cells, which have the potential to become most other types of cells in the body. These cells can come from donated embryos that were left over after in vitro fertilization or from engineered adult cells donated by volunteers, including people receiving medical treatment.

In the laboratory, pluripotent stem cells can be coaxed into becoming brain organoids: small three-dimensional clumps that mimic the structure, function and organization of various brain regions. Information can be encoded by neuronal stimulation, providing “computational inputs” that are processed by the organoid’s neurons, generating neuronal outputs that can be recorded via microelectronic array systems (see “Brain-based biocomputing”). It has already been shown that this setup can be used for some simple computational processes that are the basis by which hardware-based AI models identify patterns and make predictions.⁷.

A need for ethical solutions

Once generated, a pluripotent stem cell line can be cultured indefinitely and used for various experiments. But after many years, especially if the donor has died and science has advanced, it is difficult to know whether the original donor would have approved of the experiments to which his cells now contribute.

People who volunteer their tissue for biomedical research typically consent to a specific research study. At the same time, they could be asked if they are okay with others storing and using the remaining biological samples for future biomedical research. Donors who agree to the latter, known as indefinite consent, are informed that it may be difficult to predict how other researchers will use their samples. Most donors have no idea, for example, that their cells could be used to create a stem cell line that many other scientists could use in future work. But they are assured that any use will be reviewed by oversight committees to ensure the studies are scientifically meritorious.

Typically, these donations are sent to a biobank, which distributes them to researchers in accordance with strict data protection policies. Donors trust that researchers will follow those rules, protect their privacy, and handle their samples with care and respect.

Why researchers should use human embryo models with caution

Some researchers and ethicists might dismiss the ethical concerns highlighted in this article, given that the cell lines used for biocomputing would be expected to be derived from donors who have given indefinite consent.⁸. Some would say that this process strikes a balance between the autonomy of donors and the flexibility of researchers. It is impossible to obtain permission in advance for every possible future use, because science advances in ways that cannot always be predicted.

But open-ended consent can cause harm if used carelessly. When about 100 members of the Havasupai tribe in Arizona donated samples in the 1990s to researchers studying the tribe’s high prevalence of diabetes, they initially provided a type of open consent called broad consent. Two decades later, 41 donors and their families sued researchers after learning that their blood had been used in studies on mental illness and its ancestral origins that could stigmatize and harm their community. Tribal members did not anticipate this type of investigation and felt that their cultural autonomy had been violated.

The argument that indefinite consent allows researchers to use donor cells ethically might be reasonable when donated materials are used for altruistic purposes related to biomedicine. But a person donating tissues for a medical study would have no reason to consider that their cells could be used in engineering or computing.

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Some donors have expressed concern about their samples being used for commercial purposes.⁹. What’s more, a pan-European study found that many people view organoids as complicated entities: neither a living organism nor simply an object, but something in between. Brain organoids specifically were considered a more sensitive topic than other organoids¹⁰.

Research has also shown that some donors want to know about the purposes of research involving brain organoids created from their cells.^11,12. And some want the opportunity to revoke their consent if they disagree with future research that would use their donations.¹¹.

Brain-based biocomputers need strong ethical oversight because they could make donors’ concerns a reality. Biocomputers could soon be used for commercial tasks unrelated to biomedicine, such as voice or face recognition. An open consent approach is not a good ethical solution in this case.

The following changes are proposed to ensure that bioinformatics research involving laboratory-grown brain tissue is conducted responsibly. These recommendations could also be extended to other emerging fields, such as biohybrid robotics, in which human cells are used for engineering applications such as environmental monitoring.¹³.

Path to appropriate consent

Biocomputing research should be overseen by independent review committees that can evaluate both the ethical risks posed by the technology and the appropriate use of human cell lines for computing applications. Existing oversight committees for stem cell research generally do not review nonbiomedical research conducted in computer science and mechanical engineering departments, and typically do not have the technical expertise necessary to oversee the ethics of biocomputing.

New review boards could be established as needed at institutes dealing with biocomputing. Alternatively, the boards could be reconfigured from existing stem cell research oversight committees, supplemented by academics in neuroscience and computer engineering.

These review committees should instruct researchers to follow one of three paths, in a strict order of preference: establish new cell lines; obtain new consent from existing donors; or undergo an independent review of research plans.