New RNA-Based Tool Could Assess Preeclampsia Risk


Transcripts circulating in the blood provide real-time information about maternal, fetal, and placental health.

by Amanda Heidt

Preeclampsia, a potentially fatal complication that affects roughly 5 percent of pregnancies worldwide, can only be diagnosed after the onset of symptoms such as high blood pressure, so treatment is always reactive. “The next really big need is better methods to diagnose or predict risk of pregnancy complications such as preeclampsia,” says Fiona Kaper, a senior director of scientific research at the biotech company Illumina.

To identify possible biomarkers of the condition, Kaper and her colleagues drew blood from 40 pregnant women with early-onset severe preeclampsia and 73 unaffected expecting mothers. Circulating in the blood of each mom-to-be is her own RNA, as well as transcripts from the placenta and the fetus. Studying these circulating RNAs (cRNAs), the team identified 30 maternal, fetal, or placental genes with altered expression patterns in women with preeclampsia compared with controls. A machine algorithm also identified 49 genes with altered expression, including 12 that overlapped with the earlier list, suspected of being linked to preeclampsia.

To test the ability of the 49 suspect genes to predict preeclampsia, the researchers classified an independent cohort of two dozen women, half with early-onset preeclampsia and half without signs of the condition. The model predicted which women had preeclampsia with 85 percent to 89 percent accuracy.

While large-scale, prospective studies are still needed, cRNA screening represents a step toward earlier preemptive diagnosis, says Kathryn Gray, an obstetrician at Brigham and Women’s Hospital who was not involved in the study. She notes that researchers have been doing something similar in detecting circulating tumor DNA for cancer screening. “It’s really exciting that we’re applying some of these . . . strategies that have been used in cancer to pregnancy. We’re always a bit behind in women’s health and pregnancy in applying the most cutting-edge technologies.”

S. Munchel et al., “Circulating transcripts in maternal blood reflect a molecular signature of early-onset preeclampsia,” Sci Transl Med, 12:eaaz0131, 2020.

https://www.the-scientist.com/the-literature/new-rna-based-tool-could-assess-preeclampsia-risk-67873?utm_campaign=TS_DAILY%20NEWSLETTER_2020&utm_medium=email&_hsmi=95863075&_hsenc=p2ANqtz-8H-ikdjnvKrmnzwtrGHlOIath9Qs78m–DSqudO6tO-Y6Y2DAvu65i9JT3SBSgMACaMx4xfNiVpw5StKx8sw1URGXMeg&utm_content=95863075&utm_source=hs_email

Blood from coronavirus survivors might save lives

Hospitals in New York City are gearing up to use the blood of people who have recovered from COVID-19 as a possible antidote for the disease. Researchers hope that the century-old approach of infusing patients with the antibody-laden blood of those who have survived an infection will help the metropolis — now the US epicentre of the outbreak — to avoid the fate of Italy, where intensive-care units (ICUs) are so crowded that doctors have turned away patients who need ventilators to breathe.

The efforts follow studies in China that attempted the measure with plasma — the fraction of blood that contains antibodies, but not red blood cells — from people who had recovered from COVID-19. But these studies have reported only preliminary results so far. The convalescent-plasma approach has also seen modest success during past severe acute respiratory syndrome (SARS) and Ebola outbreaks — but US researchers are hoping to increase the value of the treatment by selecting donor blood that is packed with antibodies and giving it to the patients who are most likely to benefit.

A key advantage to convalescent plasma is that it’s available immediately, whereas drugs and vaccines take months or years to develop. Infusing blood in this way seems to be relatively safe, provided that it is screened for viruses and other infectious agents. Scientists who have led the charge to use plasma want to deploy it now as a stopgap measure, to keep serious infections at bay and hospitals afloat as a tsunami of cases comes crashing their way.

“Every patient that we can keep out of the ICU is a huge logistical victory because there are traffic jams in hospitals,” says Michael Joyner, an anaesthesiologist and physiologist at the Mayo Clinic in Rochester, Minnesota. “We need to get this on board as soon as possible, and pray that a surge doesn’t overwhelm places like New York and the west coast.”

On 23 March, New York governor Andrew Cuomo announced the plan to use convalescent plasma to aid the response in the state, which has more than 25,000 infections, with 210 deaths. “We think it shows promise,” he said. Thanks to the researchers’ efforts, the US Food and Drug Administration (FDA) today announced that it will permit the emergency use of plasma for patients in need. As early as next week, at least two hospitals in New York City — Mount Sinai and Albert Einstein College of Medicine — hope to start using coronavirus-survivor plasma to treat people with the disease, Joyner says.

After this first rollout, researchers hope the use will be extended to people at a high risk of developing COVID-19, such as nurses and physicians. For them, it could prevent illness so that they can remain in the hospital workforce, which can’t afford depletion.

And academic hospitals across the United States are now planning to launch a placebo-controlled clinical trial to collect hard evidence on how well the treatment works. The world will be watching because, unlike drugs, blood from survivors is relatively cheap and available to any country hit hard by an outbreak.

Scientists assemble

Arturo Casadevall, an immunologist at Johns Hopkins University in Baltimore, Maryland, has been fighting to use blood as a COVID-19 treatment since late January, as the disease spread to other countries and no surefire therapy was in sight. Scientists refer to this measure as ‘passive antibody therapy’ because a person receives external antibodies, rather than generating an immune response themselves, as they would following a vaccination.

The approach dates back to the 1890s. One of the largest case studies occurred during the 1918 H1N1 influenza virus pandemic. More than 1,700 patients received blood serum from survivors, but it’s difficult to draw conclusions from studies that weren’t designed to meet current standards.

During the SARS outbreak in 2002–03, an 80-person trial of convalescent serum in Hong Kong found that people treated within 2 weeks of showing symptoms had a higher chance of being discharged from hospital than did those who weren’t treated. And survivor blood has been tested in at least two outbreaks of Ebola virus in Africa with some success. Infusions seemed to help most patients in a 1995 study in the Democratic Republic of the Congo, but the study was small and not placebo controlled. A 2015 trial in Guinea was inconclusive, but it didn’t screen plasma for high levels of antibodies. Casadevall suggests that the approach might have shown a higher efficacy had researchers enrolled only participants who were at an early stage of the deadly disease, and therefore were more likely to benefit from the treatment.

Casadevall corralled support for his idea through an editorial in the Wall Street Journal, published on 27 February, which urged the use of convalescent serum because drugs and vaccines take so long to develop. “I knew if I could get this into a newspaper, people would react, whereas if I put it into a science journal, I might not get the same reaction,” he says.

He sent his article to dozens of colleagues from different disciplines, and many joined his pursuit with enthusiasm. Joyner was one. Around 100 researchers at various institutes self-organized into different lanes. Virologists set about finding tests that could assess whether a person’s blood contains coronavirus antibodies. Clinical-trial specialists thought about how to identify and enroll candidates for treatment. Statisticians created data repositories. And, to win regulatory clearance, the group shared documents required for institutional ethical-review boards and the FDA.

Tantalizing signs

Their efforts paid off. The FDA’s classification today of convalescent plasma as an ‘investigational new drug’ against coronavirus allows scientists to submit proposals to test it in clinical trials, and lets doctors use it compassionately to treat patients with serious or life-threatening COVID-19 infections, even though it is not yet approved.

“This allows us to get started,” says Joyner. Physicians can now decide whether to offer the therapy to people with very advanced disease, or to those that seem to be headed there — as he and other researchers recommend. He says hospitals will file case reports so that the FDA gets a handle on which approaches work best.

Researchers have also submitted to the FDA three protocols for placebo-controlled trials to test the plasma, which they hope will take place at hospitals affiliated with Johns Hopkins, the Mayo Clinic and Washington University in St. Louis, along with other universities that want to take part.

Future directions

The US tests of convalescent plasma aren’t the first. Since early February, researchers in China — where the coronavirus emerged late last year — have launched several studies using the plasma. Researchers have yet to report on the status and results of these studies. But Liang Yu, an infectious-disease specialist at Zhejiang University School of Medicine in China, told Nature that in one preliminary study, doctors treated 13 people who were critically ill with COVID-19 with convalescent plasma. Within several days, he says the virus no longer seemed to be circulating in the patients, indicating that antibodies had fought it off. But he says that their conditions continued to deteriorate, suggesting that the disease might have been too far along for this therapy to be effective. Most had been sick for more than two weeks.

In one of three proposed US trials, Liise-anne Pirofski, an infectious-disease specialist at Albert Einstein College of Medicine, says researchers plan to infuse patients at an early stage of the disease and see how often they advance to critical care. Another trial would enrol severe cases. The third would explore plasma’s use as a preventative measure for people in close contact with those confirmed to have COVID-19, and would evaluate how often such people fall ill after an infusion compared with others who were similarly exposed but not treated. These outcomes are measurable within a month, she says. “Efficacy data could be obtained very, very quickly.”

Even if it works well enough, convalescent serum might be replaced by modern therapies later this year. Research groups and biotechnology companies are currently identifying antibodies against the coronavirus, with plans to develop these into precise pharmaceutical formulas. “The biotech cavalry will come on board with isolating antibodies, testing them, and developing into drugs and vaccines, but that takes time,” says Joyner.

In some ways, Pirofski is reminded of the urgency she felt as a young doctor at the start of the HIV epidemic in the early 1980s. “I met with medical residents last week, and they are so frightened of this disease, and they don’t have enough protective equipment, and they are getting sick or are worried about getting sick,” she says. A tool to help to protect them now would be welcomed.

Since becoming involved with the push for blood as a treatment, Pirofski says another aspect of the therapy holds her interest: unlike a pharmaceutical product bought from companies, this treatment is created by people who have been infected. “I get several e-mails a day from people who say, ‘I survived and now I want to help other people’,” she says. “All of these people are willing to put on their boots and brush their teeth, and come help us do this.”

https://www.nature.com/articles/d41586-020-00895-8?utm_source=fbk_nnc&utm_medium=social&utm_campaign=naturenews&fbclid=IwAR08dlcqj_ixR5eJxFxrlI4UikMrTpBLLA4_aYTxfD5CfjRLi8lli2DB3gI&utm_source=Nature+Briefing&utm_campaign=7fdc8b2aa7-briefing-dy-20200325&utm_medium=email&utm_term=0_c9dfd39373-7fdc8b2aa7-44039353

Stressed Blood Cells Could Be a Biomarker for Chronic Fatigue, also known as myalgic encephalomyelitis

by Shawna Williams

A distinguishing characteristic of the disease myalgic encephalomyelitis/chronic fatigue syndrome appears to be the electrical response of patients’ blood cells when under stress, researchers report today (April 29) in PNAS. The team hopes the finding will speed diagnoses for people with the condition and facilitate research on it.

The University of California, San Diego’s Robert Naviaux, a genetics professor who was not involved in the research, tells the San Francisco Chronicle, “It’s a major milestone. If it holds up in larger numbers, this could be a transformative advance.”

Up to 2.5 million Americans are thought to have myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), whose symptoms can include severe fatigue that isn’t explained by exertion, pain, and difficulties concentrating or remembering. It is currently diagnosed based on symptoms, as no biomarker for it exists.

To see whether the blood cells of ME/CFS patients respond differently to stress than those of healthy people, researchers exposed cells from a patient’s blood sample to salt to stress them, then ran them through a device that measures electrical impedance—a proxy for energy use. After the test picked up differences between the patient’s blood and that of healthy people, the research team used the test to compare blood cells from 20 patients with ME/CFS and 20 healthy people, and found that it reliably distinguished members of the two groups.

“We don’t know exactly why the cells and plasma are acting this way, or even what they’re doing. But there is scientific evidence that this disease is not a fabrication of a patient’s mind,” Ron Davis, a biochemist at Stanford University who began studying ME/CFS after his son became bedridden with the disease, tells The Sacramento Bee. “We clearly see a difference in the way healthy and chronic fatigue syndrome immune cells process stress.”

Research on ME/CFS has been controversial, with scientists who test talk therapy and exercise for the condition facing harassment from activists who see such treatments as harmful and rooted in a mistaken idea that the illness is psychological, according to a report last month in Reuters. Davis tells the San Francisco Chronicle that he hopes the discovery of a biomarker “will help the medical community accept that this is a real disease.”

Simon Wessely, a psychiatrist at King’s College London’s Institute of Psychiatry, Psychology & Neuroscience who works with ME/CFS patients, writes in an email to Reuters that the study was unable to solve two key issues: “The (first) issue is, can any biomarker distinguish CFS patients from those with other fatiguing illnesses? And second, is it measuring the cause, and not the consequence, of illness?”

https://www.the-scientist.com/news-opinion/stressed-blood-cells-could-be-a-biomarker-for-chronic-fatigue-65816

Gut Bacteria Hold the Key to Creating Universal Blood

gut-bacteria-hold-the-key-to-creating-universal-blood-307955

 

In January, raging storms caused medical emergencies along the U.S. East Coast, prompting the Red Cross to issue an urgent call for blood donations. The nation’s blood supply was especially in need of O-type blood that can be universally administered in an emergency. Now, scientists say they have identified enzymes — from the human gut — that can turn type A and B blood into O, as much as 30 times more efficiently than previously studied enzymes.

The researchers will present their results today at the 256th National Meeting & Exposition of the American Chemical Society (ACS). ACS, the world’s largest scientific society, is holding the meeting here through Thursday. It features more than 10,000 presentations on a wide range of science topics.

A brand-new video on the research is available at http://bit.ly/acsblood.

“We have been particularly interested in enzymes that allow us to remove the A or B antigens from red blood cells,” Stephen Withers, Ph.D., says. “If you can remove those antigens, which are just simple sugars, then you can convert A or B to O blood.” He says scientists have pursued the idea of adjusting donated blood to a common type for a while, but they have yet to find efficient, selective enzymes that are also safe and economical.

To assess potential enzyme candidates more quickly, Withers collaborated with a colleague at his institution, the University of British Columbia (UBC), who uses metagenomics to study ecology. “With metagenomics, you take all of the organisms from an environment and extract the sum total DNA of those organisms all mixed up together,” Withers explains. Casting such a wide net allows Withers’ team to sample the genes of millions of microorganisms without the need for individual cultures. The researchers then use E. coli to select for DNA containing genes that code for enzymes that can cleave sugar residues. So instead of using metagenomics as a means of learning about microbial ecology, Withers uses it to discover new biocatalysts. “This is a way of getting that genetic information out of the environment and into the laboratory setting and then screening for the activity we are interested in,” he says.

Withers’ team considered sampling DNA from mosquitoes and leeches, the types of organisms that degrade blood, but ultimately found successful candidate enzymes in the human gut microbiome. Glycosylated proteins called mucins line the gut wall, providing sugars that serve as attachment points for gut bacteria while also feeding them as they assist in digestion. Some of the mucin sugars are similar in structure to the antigens on A- and B-type blood. The researchers homed in on the enzymes the bacteria use to pluck the sugars off mucin and found a new family of enzymes that are 30 times more effective at removing red blood cell antigens than previously reported candidates.

Withers is now working with colleagues at the Centre for Blood Research at UBC to validate these enzymes and test them on a larger scale for potential clinical testing. In addition, he plans to carry out directed evolution, a protein engineering technique that simulates natural evolution, with the goal of creating the most efficient sugar-removing enzyme.

“I am optimistic that we have a very interesting candidate to adjust donated blood to a common type,” Withers says. “Of course, it will have to go through lots of clinical trails to make sure that it doesn’t have any adverse consequences, but it is looking very promising.”

The researchers acknowledge support and funding from the Canadian Institutes of Health Research.

https://www.acs.org/content/acs/en/pressroom/newsreleases/2018/august/gut-bacteria-provide-key-to-making-universal-blood-video.html

Blood serum study reveals networks of proteins that impact aging

by Bob Yirka

A team of researchers from several institutions in Iceland and the U.S. has conducted a unique blood serum investigation and discovered multiple protein networks that are involved in the aging process. In their paper published in the journal Science, the group describes their study and what they found.

Prior research has shown that when older mice have their blood systems connected to younger mice, the older mice experience improvements in age-related organ deterioration. This finding has led scientists to suspect that aging might be caused by something in the blood. In this new effort, the researchers sought to test this idea by studying proteins in the circulatory system.

The study consisted of analyzing blood samples from 5,457 people living in Iceland, all of whom were over the age of 65 and who were participants in an ongoing study called Age, Gene/Environment Susceptibility. The volunteers had also been chosen specifically to represent a cross section of the people living in Iceland. The major part of the blood analysis involved creating a panel of DNA aptamers (short sequences that bind to proteins) that could be used to recognize proteins, both known and unknown. Blood serum from the volunteers was then compared against the panels and the results were analyzed by a computer looking for patterns.

The researchers report that they discovered 27 networks that showed evidence of coordinated pattern expression. These networks, or modules, as the researchers call them, were different from one another in size and form and were made of proteins from both tissue and organs. They also report that many of the modules had expression patterns that have in the past been associated with age-related diseases such as heart disease and metabolic syndrome—and there were some that were also associated with mortality in the years after the samples were taken from the volunteers. The group suggests their findings offer more evidence of the role blood serum plays in the aging process.

The researchers report that they also looked for the means by which the networks they discovered are regulated and found that approximately 60 percent of mechanisms involved are unknown.

More information: Valur Emilsson et al. Co-regulatory networks of human serum proteins link genetics to disease, Science (2018). DOI: 10.1126/science.aaq1327

https://m.medicalxpress.com/news/2018-08-blood-serum-reveals-networks-proteins.html

Giant neurons in the brain may play similarly giant role in awareness and cognition, and uniquely control their own blood supply.


Researchers believe that large cells called nucleus gigantocellularis neurons, pictured here, modulate blood flow by releasing nitric oxide.

There is no shortage of wonders that our central nervous system produces—from thought and language to movement to the five senses. All of those dazzling traits, however, depend on an underappreciated deep brain mechanism that Donald Pfaff, head of the Laboratory of Neurobiology and Behavior at The Rockefeller University, calls generalized arousal, or GA for short. GA is what wakes us up in the morning and keeps us aware and in touch with ourselves and our environment throughout our conscious hours.

“It’s so fundamental that we don’t pay attention to it,” says Pfaff, “and yet it’s so important that we should.”

Pfaff and his team of researchers certainly do. Now, in a series of experiments involving a particular type of brain cell, they have advanced our understanding of the roots of consciousness. Their work may potentially prove relevant in the study of some psychiatric diseases.

The big cells in the black box

The findings, published this month in Proceedings of the National Academy of Sciences, shed light on an area of the brainstem that is so little understood the first author of the paper, Inna Tabansky, a research associate in Pfaff’s lab, calls it “the black box.” That term is certainly simpler than its actual name—the nucleus gigantocellularis (NGC), which is part of a structure called the medullary reticular formation.

In her work, using mice, Tabansky focused on a subtype of extremely large neurons in the NGC with links to virtually the entire nervous system, including the thalamus, where neurons can activate the entire cerebral cortex. “If you just look at the morphology of NGC neurons, you know they’re important,” Pfaff says. “It’s just a question of what they’re important for. I think they’re essential for the initiation of any behavior.”

To discover what role the NGC neurons might play in GA, Tabansky and her colleagues, including Joel Stern, a visiting professor in the Pfaff lab, began by identifying the genes that these neurons express. They used a technique known as “retro-TRAP,” developed in the lab of Rockefeller scientist Jeffrey Friedman.

To Tabansky’s surprise, the NGC neurons were found to express the gene for an enzyme, endothelial nitric oxide synthase (eNOS), which produces nitric oxide, which in turn relaxes blood vessels, increasing the flow of oxygenated blood to tissue. (No other neurons in the brain are known to produce eNOS.) They also discovered that the eNOS-expressing NGC neurons are located close to blood vessels.

In Pfaff’s view, the neurons are so critical for the normal functions of the central nervous system that they have evolved the ability to control their own blood supply directly. ‘“We’re pretty sure that if these neurons need more oxygen and glucose, they will release nitric oxide into these nearby blood vessels in order to get it,” he says.

The circumstances that would prompt such a response were the subject of further experiments. The scientists found evidence that changes in the environment, such as the introduction of novel scents, activated eNOS in the NGC neurons and produced increased amounts of nitric oxide in mice.

“There is some low level of production when the animal is in a familiar setting,” says Tabansky, “which is what you expect as they maintain arousal. But it is vastly increased when the animal is adapting to a new environment.” This activation of the NGC neurons supports the case for their central role in arousal, Tabansky says.

From cells to psychiatry

Going forward, Tabansky says she’s interested in exploring if their findings might help fill a gap in the understanding of certain disorders, such as bipolar disorder, suicidality, and ADHD. Some genetic research has implicated a role for the neurons she studied in these diseases, but the mechanism behind this link is not known.

“By showing that this gene and its associated pathways have a particular role, at least in the rodent brain, that relates to a fundamental function of the nervous system, is a hint about how this gene can cause psychiatric disease,” she says. “It’s very preliminary, and there is a lot more work to be done, but it potentially opens a new way to study how this gene can alter an individual’s psychology.”

https://www.rockefeller.edu/news/23275-giant-neurons-in-the-brain-may-play-similarly-giant-role-in-awareness-and-cognition/

Lab mini-brains now growing their own blood vasculature systems

THE FIRST HUMAN brain balls—aka cortical spheroids, aka neural organoids—agglomerated into existence just a few short years ago. In the beginning, they were almost comically crude: just stem cells, chemically coerced into proto-neurons and then swirled into blobs in a salty-sweet bath. But still, they were useful for studying some of the most dramatic brain disorders, like the microcephaly caused by the Zika virus.

Then they started growing up. The simple spheres matured into 3D structures, fusing with other types of brain balls and sparking with electricity. The more like real brains they became, the more useful they were for studying complex behaviors and neurological diseases beyond the reach of animal models. And now, in their most human act yet, they’re starting to bleed.

Neural organoids don’t yet, even remotely, resemble adult brains; developmentally, they’re just pushing second trimester tissue organization. But the way Ben Waldau sees it, brain balls might be the best chance his stroke patients have at making a full recovery—and a homegrown blood supply is a big step toward that far-off goal. A blood supply carries oxygen and nutrients, allowing brain balls to grow bigger, complex networks of tissues, those that a doctor could someday use to shore up malfunctioning neurons.

“The whole idea with these organoids is to one day be able to develop a brain structure the patient has lost made with the patient’s own cells,” says Waldau, a vascular neurosurgeon at UC Davis Medical Center. “We see the injuries still there on the CT scans, but there’s nothing we can do. So many of them are left behind with permanent neural deficits—paralysis, numbness, weakness—even after surgery and physical therapy.”

Last week, it was Waldau’s group at UC Davis that published the first results of vascularized human neural organoids. Using brain membrane cells taken from one of his patients during a routine surgery, the team coaxed them first into stem cells, then some of them into the endothelial cells that line blood vessels’ insides. The stem cells they grew into brain balls, which they incubated in a gel matrix coated with those endothelial cells. After incubating for three weeks, they took a single organoid and transplanted it into a tiny cavity carefully carved into a mouse’s brain. Two weeks later the organoid was alive, well—and, critically, had grown capillaries that penetrated all the way to its inner layers.

Waldau got the idea from his work treating a rare disorder called Moyamoya disease. Patients have blocked arteries at the base of their brain, keeping blood from reaching the rest of the organ. “We sometimes lay a patient’s own artery on top of the brain to get the blood vessels to start growing in,” says Waldau. “When we replicated that process on a miniaturized scale we saw these vessels self-assemble.”

While it wasn’t clear from this experiment whether or not there was rodent blood coursing through its capillaries—the scientists had to flush them to accomplish fluorescent staining—the UC Davis team did demonstrate that the blood vessels themselves were comprised of human cells. Other research groups at the Salk Institute and the University of Pennsylvania have successfully transplanted human organoids into the brains of mice, but in both cases, blood vessels from the rodent host spontaneously grew into the transplanted tissue. When brain balls make their own blood vessels, they can potentially live much longer by hooking them up to microfluidic pumps—no rodent required.

That might give them a chance to actually mature into a complex computational organ. “It’s a big deal,” says Christof Koch, president of the Allen Institute for Brain Science in Seattle, “but it’s still early days.” The next problem will be getting these cells wired into circuits that can receive and process information. “The fact that I can look out at the world and see it as spatially organized—left, right, near, far— is all due to the organization of my cortex that reflects the regularity of the world,” says Koch. “There’s nothing like that in these organoids yet.”

Not yet, maybe, but it’s not too soon to start asking what happens when they do. How large do they have to be before society has a moral mandate to provide them some kind of special protections? If an organoid comes from your cells, are you then its legal guardian? Can a brain ball give its consent to be studied?

Just last week the National Institutes of Health convened a neuroethics workshop to confront some of these thorny questions. Addressing a room filled with neuroscientists, doctors, and philosophers, Walter Koroshetz, director of the NIH’s National Institute of Neurological Disorders and Stroke, said the time for involving the public was now, even if the technology takes a century to become reality. “The question here is, as those cells come together to form information processing units, when do they get to the point where they’re as good as what we do now in a mouse? When does it go beyond that, to information processing you only see in a human? And what type of information processing would be to a point where you would say, ‘I don’t think we should go there’?”

https://www.wired.com/story/mini-brains-just-got-creepiertheyre-growing-their-own-veins/