Posts Tagged ‘disease’



Dr. Leslie Norins is willing to hand over $1 million of his own money to anyone who can clarify something: Is Alzheimer’s disease, the most common form of dementia worldwide, caused by a germ?

By “germ” he means microbes like bacteria, viruses, fungi and parasites. In other words, Norins, a physician turned publisher, wants to know if Alzheimer’s is infectious.

It’s an idea that just a few years ago would’ve seemed to many an easy way to drain your research budget on bunk science. Money has poured into Alzheimer’s research for years, but until very recently not much of it went toward investigating infection in causing dementia.

But this “germ theory” of Alzheimer’s, as Norins calls it, has been fermenting in the literature for decades. Even early 20th century Czech physician Oskar Fischer — who, along with his German contemporary Dr. Alois Alzheimer, was integral in first describing the condition — noted a possible connection between the newly identified dementia and tuberculosis.

If the germ theory gets traction, even in some Alzheimer’s patients, it could trigger a seismic shift in how doctors understand and treat the disease.

For instance, would we see a day when dementia is prevented with a vaccine, or treated with antibiotics and antiviral medications? Norins thinks it’s worth looking into.

Norins received his medical degree from Duke in the early 1960s, and after a stint at the Centers for Disease Control and Prevention he fell into a lucrative career in medical publishing. He eventually settled in an admittedly aged community in Naples, Fla., where he took an interest in dementia and began reading up on the condition.

After scouring the medical literature he noticed a pattern.

“It appeared that many of the reported characteristics of Alzheimer’s disease were compatible with an infectious process,” Norins tells NPR. “I thought for sure this must have already been investigated, because millions and millions of dollars have been spent on Alzheimer’s research.”

But aside from scattered interest through the decades, this wasn’t the case.

In 2017, Norins launched Alzheimer’s Germ Quest Inc., a public benefit corporation he hopes will drive interest into the germ theory of Alzheimer’s, and through which his prize will be distributed. A white paper he penned for the site reads: “From a two-year review of the scientific literature, I believe it’s now clear that just one germ — identity not yet specified, and possibly not yet discovered — causes most AD. I’m calling it the ‘Alzheimer’s Germ.’ ”

Norins is quick to cite sources and studies supporting his claim, among them a 2010 study published in the Journal of Neurosurgery showing that neurosurgeons die from Alzheimer’s at a nearly 2 1/2 times higher rate than they do from other disorders.

Another study from that same year, published in The Journal of the American Geriatric Society, found that people whose spouses have dementia are at a 1.6 times greater risk for the condition themselves.

Contagion does come to mind. And Norins isn’t alone in his thinking.

In 2016, 32 researchers from universities around the world signed an editorial in the Journal of Alzheimer’s Disease calling for “further research on the role of infectious agents in [Alzheimer’s] causation.” Based on much of the same evidence Norins encountered, the authors concluded that clinical trials with antimicrobial drugs in Alzheimer’s are now justified.

NPR reported on an intriguing study published in Neuron in June that suggested that viral infection can influence the progression of Alzheimer’s. Led by Mount Sinai genetics professor Joel Dudley, the work was intended to compare the genomes of healthy brain tissue with that affected by dementia.

But something kept getting in the way: herpes.

Dudley’s team noticed an unexpectedly high level of viral DNA from two human herpes viruses, HHV-6 and HHV-7. The viruses are common and cause a rash called roseola in young children (not the sexually transmitted disease caused by other strains).

Some viruses have the ability to lie dormant in our neurons for decades by incorporating their genomes into our own. The classic example is chickenpox: A childhood viral infection resolves and lurks silently, returning years later as shingles, an excruciating rash. Like it or not, nearly all of us are chimeras with viral DNA speckling our genomes.

But having the herpes viruses alone doesn’t mean inevitable brain decline. After all, up to 75 percent of us may harbor HHV-6 .

But Dudley also noticed that herpes appeared to interact with human genes known to increase Alzheimer’s risk. Perhaps, he says, there is some toxic combination of genetic and infectious influence that results in the disease; a combination that sparks what some feel is the main contributor to the disease, an overactive immune system.

The hallmark pathology of Alzheimer’s is accumulation of a protein called amyloid in the brain. Many researchers have assumed these aggregates, or plaques, are simply a byproduct of some other process at the core of the disease. Other scientists posit that the protein itself contributes to the condition in some way.

The theory that amyloid is the root cause of Alzheimer’s is losing steam. But the protein may still contribute to the disease, even if it winds up being deemed infectious.

Work by Harvard neuroscientist Rudolph Tanzi suggests it might be a bit of both. Along with colleague Robert Moir, Tanzi has shown that amyloid is lethal to viruses and bacteria in the test tube, and also in mice. He now believes the protein is part of our ancient immune system that like antibodies, ramps up its activity to help fend off unwanted bugs.

So does that mean that the microbe is the cause of Alzheimer’s, and amyloid a harmless reaction to it? According to Tanzi it’s not that simple.

Tanzi believes that in many cases of Alzheimer’s, microbes are probably the initial seed that sets off a toxic tumble of molecular dominoes. Early in the disease amyloid protein builds up to fight infection, yet too much of the protein begins to impair function of neurons in the brain. The excess amyloid then causes another protein, called tau, to form tangles, which further harm brain cells.

But as Tanzi explains, the ultimate neurological insult in Alzheimer’s is the body’s reaction to this neurotoxic mess. All the excess protein revs up the immune system, causing inflammation — and it’s this inflammation that does the most damage to the Alzheimer’s-afflicted brain.

So what does this say about the future of treatment? Possibly a lot. Tanzi envisions a day when people are screened at, say, 50 years old. “If their brains are riddled with too much amyloid,” he says, “we knock it down a bit with antiviral medications. It’s just like how you are prescribed preventative drugs if your cholesterol is too high.”

Tanzi feels that microbes are just one possible seed for the complex pathology behind Alzheimer’s. Genetics may also play a role, as certain genes produce a type of amyloid more prone to clumping up. He also feels environmental factors like pollution might contribute.

Dr. James Burke, professor of medicine and psychiatry at Duke University’s Alzheimer’s Disease Research Center, isn’t willing to abandon the amyloid theory altogether, but agrees it’s time for the field to move on. “There may be many roads to developing Alzheimer’s disease and it would be shortsighted to focus just on amyloid and tau,” he says. “A million-dollar prize is attention- getting, but the reward for identifying a treatable target to delay or prevent Alzheimer’s disease is invaluable.”

Any treatment that disrupts the cascade leading to amyloid, tau and inflammation could theoretically benefit an at-risk brain. The vast majority of Alzheimer’s treatment trials have failed, including many targeting amyloid. But it could be that the patients included were too far along in their disease to reap any therapeutic benefit.

If a microbe is responsible for all or some cases of Alzheimer’s, perhaps future treatments or preventive approaches will prevent toxin protein buildup in the first place. Both Tanzi and Norins believe Alzheimer’s vaccines against viruses like herpes might one day become common practice.

In July of this year, in collaboration with Norins, the Infectious Diseases Society of America announced that they plan to offer two $50,000 grants supporting research into a microbial association with Alzheimer’s. According to Norins, this is the first acknowledgement by a leading infectious disease group that Alzheimer’s may be microbial in nature – or at least that it’s worth exploring.

“The important thing is not the amount of the money, which is a pittance compared with the $2 billion NIH spends on amyloid and tau research,” says Norins, “but rather the respectability and more mainstream status the grants confer on investigating of the infectious possibility. Remember when we thought ulcers were caused by stress?”

Ulcers, we now know, are caused by a germ.


Reprinted from The Lancet Neurology,, Trapp et al, Cortical neuronal densities and cerebral white matter demyelination in multiple sclerosis: a retrospective study, Copyright (2018), with permission from Elsevier

Bruce Trapp, Ph.D., chair of Cleveland Clinic’s Lerner Research Institute Department of Neurosciences

Cleveland Clinic researchers have discovered a new subtype of multiple sclerosis (MS), providing a better understanding of the individualized nature of the disease.

MS has long been characterized as a disease of the brain’s white matter, where immune cells destroy myelin – the fatty protective covering on nerve cells. The destruction of myelin (called demyelination) was believed to be responsible for nerve cell (neuron) death that leads to irreversible disability in patients with MS.

However, in the new findings, a research team led by Bruce Trapp, Ph.D., identified for the first time a subtype of the disease that features neuronal loss but no demyelination of the brain’s white matter. The findings, published in Lancet Neurology, could potentially lead to more personalized diagnosis and treatments.

The team’s findings support the concept that neurodegeneration and demyelination can occur independently in MS and underscore the need for more sensitive MRI imaging techniques for evaluating brain pathology in real time and monitoring treatment response in patients with the disease. This new subtype of MS, called myelocortical MS (MCMS), was indistinguishable from traditional MS on MRI. The researchers observed that in MCMS, part of the neurons become swollen and look like typical MS lesions indicative of white matter myelin loss on MRI. The disease was only diagnosed in post-mortem tissues.

“This study opens up a new arena in MS research. It is the first to provide pathological evidence that neuronal degeneration can occur without white matter myelin loss in the brains of patients with the disease,” said Trapp, chair of Cleveland Clinic’s Lerner Research Institute Department of Neurosciences. “This information highlights the need for combination therapies to stop disability progression in MS.”

In the study of brain tissue from 100 MS patients who donated their brains after death, the researchers observed that 12 brains did not have white matter demyelination. They compared microscopic tissue characteristics from the brains and spinal cords of 12 MCMS patients, 12 traditional MS patients and also individuals without neurological disease. Although both MCMS and traditional MS patients had typical MS lesions in the spinal cord and cerebral cortex, only the latter group had MS lesions in the brain white matter.

Despite having no typical MS lesions in the white matter, MCMS brains did have reduced neuronal density and cortical thickness, which are hallmarks of brain degeneration also observed in traditional MS. Contrary to previous belief, these observations show that neuronal loss can occur independently of white matter demyelination.

“The importance of this research is two-fold. The identification of this new MS subtype highlights the need to develop more sensitive strategies for properly diagnosing and understanding the pathology of MCMS,” said Daniel Ontaneda, M.D., clinical director of the brain donation program at Cleveland Clinic’s Mellen Center for Treatment and Research in MS. “We are hopeful these findings will lead to new tailored treatment strategies for patients living with different forms of MS.”

Dr. Trapp is internationally known for his work on mechanisms of neurodegeneration and repair in MS and has published more than 240 peer-reviewed articles and 40 book chapters. He also holds the Morris R. and Ruth V. Graham Endowed Chair in Biomedical Research. In 2017 he received the prestigious Outstanding Investigator award by the National Institute of Neurological Disorders and Stroke to examine the biology of MS and to seek treatments that could slow or reverse the disease.

Ionocytes (orange) extend through neighboring epithelial cells (nuclei, cyan) to the surface of the respiratory epithelial lining. This newly identified cell type expresses high levels of CFTR, a gene that is associated with cystic fibrosis when mutated.


Two independent research teams have used single-cell RNA sequencing to generate detailed molecular atlases of mouse and human airway cells. The findings, reported in two studies today (August 1) in Nature, reveal the gene-expression patterns of thousands of lung cells, as well as the existence of a previously unknown cell type that expresses high levels of the gene mutated in cystic fibrosis, the cystic fibrosis transmembrane conductance regulator (CFTR).

“These papers are extremely exciting,” says Amy Ryan, a lung biologist at the University of Southern California who was not involved in either study. “They’ve interrogated the cellular composition and the cellular hierarchy of the airways by using a single-cell RNA-sequencing technique. That kind of information is going to have a significant impact on advancing the research that we can do, and hopefully the derivation of new therapeutic approaches for any number of airway diseases.”

Jayaraj Rajagopal, a pulmonary physician at Massachusetts General Hospital and Harvard University and coauthor of one of the studies, had been studying lung regeneration and wanted to use single-cell sequencing to look at differences in the lungs’ stem-cell populations. He and his colleagues teamed up with Aviv Regev, a computational biologist at the Broad Institute of MIT and Harvard University, and together, the two groups characterized the transcriptomes of thousands of epithelial cells from the adult mouse trachea.

Rajagopal, Regev, and colleagues uncovered previously unknown differences in gene expression in several groups of airway cells; identified novel structures in the lung; and found new paths of cellular differentiation. They also described several new cell types, including one that the team has named the pulmonary ionocyte, after salt-regulating cells in fish and amphibian skin. These lung cells express similar genes as fish and amphibian ionocytes, the team found, including a gene coding for the transcription factor Foxi1, which regulates genes that play a role in ion transport.

The team also showed that pulmonary ionocytes highly express CFTR, and are in fact the primary source of its product, CFTR—a membrane protein that helps regulate fluid transport and the consistency of mucus—in both mouse and human lungs, suggesting that the cells might play a role in cystic fibrosis.

“So much that we found rewrites the way we think about lung biology and lung cells,” says Rajagopal. “I think the entire community of pulmonologists and lung biologists will have to take a step back and think about their problems with respect to all these new cell types.”

For the other study, Aron Jaffe, a biologist at Novartis who studies how different airway cell types are made, combined forces with Harvard systems biologist Allon Klein and his team. Klein’s group had previously developed a single-cell RNA-sequencing method that Jaffe describes as “the perfect technology to take a big picture view and really define the full repertoire of epithelial cell types in the airway.”

Jaffe, Klein, and colleagues sequenced RNA from thousands of single human bronchial epithelial and mouse tracheal epithelial cells. The atlas generated by their sequencing analysis revealed pulmonary ionocytes, as well as new gene-expression patterns in familiar cells. The team examined the expression of CFTR in human and mouse ionocytes in order to better understand the possible role for the cells in cystic fibrosis. Consistent with the findings of the other study, the researchers showed that pulmonary ionocytes make the majority of CFTR protein in the airways of humans and mice.

“Finding this new rare cell type that accounts for the majority of CFTR activity in the airway epithelium was really the biggest surprise,” Jaffe tells The Scientist. “CFTR has been studied for a long time, and it was thought that the gene was broadly expressed in many cells in the airway. It turns out that the epithelium is more complicated than previously appreciated.”

These studies are “very exciting work [and] a wonderful example of how new technologies that have come online in the last few years—in this case single-cell RNA sequencing—have made a very dramatic advance in our understanding of aspects of biology,” says Ann Harris, a geneticist at Case Western Reserve University who did not participate in either study.

In terms of future directions, the authors “have shown that transcription factor [Foxi1] is central to the transcriptional program of these ionocytes,” says Harris. One of the next questions is, “does it directly interact with the CFTR gene or is it working through other transcription factors or other proteins that regulate CFTR gene expression?”

According to Jennifer Alexander-Brett, a pulmonary physician and researcher at Washington University School of Medicine in St. Louis who was not involved in the studies, the possibility that a rare cell type could be playing a part in regulating airway physiology is “captivating.”

Apart from investigating the potential role for ionocytes in lung function, Alexander-Brett says that researchers can likely make broad use of the data from the studies—particularly details on the expression of genes coding for transcription factors and cell-surface markers. “One area that we really struggle with in airway biology . . . is [that] we just don’t have good markers” to differentiate cell types, she explains. But these papers are “very comprehensive. There’s a ton of data here.”

D.T. Montoro et al., “A revised airway epithelial hierarchy includes CFTR-expressing ionocytes,” Nature, doi:10.1038/s41586-018-0393-7, 2018.

L.W. Plasschaert et al., “A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte,” Nature, doi:10.1038/s41586-018-0394-6, 2018.

by Leigh Hopper

Tnew stroke-healing gel created by UCLA researchers helped regrow neurons and blood vessels in mice whose brains had been damaged by strokes. The finding is reported May 21 in Nature Materials.

“We tested this in laboratory mice to determine if it would repair the brain and lead to recovery in a model of stroke,” said Dr. S. Thomas Carmichael, professor of neurology at the David Geffen School of Medicine at UCLA. “The study indicated that new brain tissue can be regenerated in what was previously just an inactive brain scar after stroke.”

The results suggest that such an approach could some day be used to treat people who have had a stroke, said Tatiana Segura, a former professor of chemical and biomolecular engineering at UCLA who collaborated on the research. Segura is now a professor at Duke University.

The brain has a limited capacity for recovery after stroke. Unlike the liver, skin and some other organs, the brain does not regenerate new connections, blood vessels or tissue structures after it is damaged. Instead, dead brain tissue is absorbed, which leaves a cavity devoid of blood vessels, neurons or axons — the thin nerve fibers that project from neurons.

To see if healthy tissue surrounding the cavity could be coaxed into healing the stroke injury, Segura engineered a hydrogel that, when injected into the cavity, thickens to create a scaffolding into which blood vessels and neurons can grow. The gel is infused with medications that stimulate blood vessel growth and suppress inflammation, since inflammation results in scars and impedes functional tissue from regrowing.

After 16 weeks, the stroke cavities contained regenerated brain tissue, including new neuronal connections — a result that had not been seen before. The mice’s ability to reach for food improved, a sign of improved motor behavior, although the exact mechanism for the improvement wasn’t clear.

“The new axons could actually be working,” Segura said. “Or the new tissue could be improving the performance of the surrounding, unharmed brain tissue.”

The gel was eventually absorbed by the body, leaving behind only new tissue.

The research was designed to explore recovery in acute stroke, the period immediately following a stroke — in mice, that period lasts five days; in humans, it’s two months. Next, Carmichael and Segura plan to investigate whether brain tissue can be regenerated in mice long after the stroke injury. More than 6 million Americans are living with long-term effects of stroke, which is known as chronic stroke.

The other authors of the paper are Lina Nih and Shiva Gojgini, both of UCLA.

The study was supported by the National Institutes of Health.

Activating something called the behavioral immune system puts a damper on dating, new research shows.

About a decade ago, evolutionary psychologists suggested that humans have evolved a first line of defense against disease: this behavioral immune system or BIS.

The theory is that perceiving, rightly or wrongly, the threat of disease unconsciously activates this system. Although we cannot see microorganisms with the naked eye, we are nevertheless able to identify cues—such as coughs, unpleasant smells, or skin lesions—that hint at the possible presence of pathogens, whether or not these are actually present or represent real health threats.

Scientists have suggested that the activation of the BIS leads to prejudiced and avoidant attitudes and behavior towards those who display superficial cues connoting disease.

But how does this affect our dating lives, where two competing needs are pitted against one another—i.e., the potential benefits of connecting and finding a mate versus the need to protect oneself from disease? McGill University scientists set out to find out, by looking at the activation of the BIS in young, single, heterosexual Montrealers in both real speed-dating events and in experimental online dating.

The results were convincing. And not very happy.

“We found that when the behavioral immune system was activated it seemed to put the brakes on our drive to connect with our peers socially,” says first author of the study Natsumi Sawada, who holds a PhD in psychology from McGill University.

“We hadn’t expected this to be the case in real life situations like dating where people are generally so motivated to connect. The results suggest that beyond how we consciously or unconsciously think and feel about each other there are additional factors that we may not be consciously aware of, such as a fear of disease that may influence how we connect with others.”

This video explains how the experiments worked:

The findings appear in the Personality and Social Psychology Bulletin. The Social Sciences and Humanities Research Council (SSHRC) and the Fonds de Recherche sur la Société et la Culture (FRQSC) supported the work.

Saladin may not be well known in the West, but even 800 years after his death, he remains famous in the Middle East. Born in 1137, he rose to become the Sultan of an enormous area that now includes Egypt, Syria, parts of Iraq, Lebanon, Yemen and other regions of North Africa. He successfully led armies against the invading Crusaders and conquered several kingdoms. Historians have described him as the most famous Kurd ever.

Even today, however, Saladin’s death remains a mystery. The illness began in 1193, when he was 56. After two weeks, the Sultan was dead. Some have speculated that fever was a prominent symptom of the illness.

After closely examining a range of evidence about Saladin’s condition, Stephen J. Gluckman, MD, professor of medicine at the University of Pennsylvania School of Medicine, has developed a diagnosis. Dr. Gluckman theorizes that typhoid, a bacterial disease that was very common in the region at the time, is the most likely culprit. Today of course, antibiotics could have greatly helped Saladin. But in the 12th century these medicines did not exist.

Dr. Gluckman delivered his diagnosis at the 25th annual Historical Clinicopathological Conference, held Friday, May 4 at the University of Maryland School of Medicine. The conference is devoted to the diagnosis of disorders that afflicted historical figures; in the past, experts have focused on the diseases of luminaries such as Lenin, Darwin, Eleanor Roosevelt and Lincoln.

Dr. Gluckman, an expert on parasitic disorders, has provided care and taught in many countries around the world. He carefully reviewed what is known about the Sultan’s medical history. “Practicing medicine over the centuries required a great deal of thought and imagination,” he says. “The question of what happened to Saladin is a fascinating puzzle.”

Saladin is known for destroying King Guy’s army at the Horns of Hattin in 1187 and reclaiming Jerusalem for Islam after it had been ruled for nearly a century by Christian crusaders. He is also famed for treating his enemies generously.

Typhoid fever is a potentially deadly disease spread by contaminated food and water. Symptoms of typhoid include high fever, weakness, stomach pain, headache, and loss of appetite. It is common in most parts of the world except in industrialized regions such as the United States, western Europe, Australia, and Japan. About 300 people get typhoid fever in the United States each year, and most of them have recently traveled. Globally, typhoid infects about 22 million people a year, and kills 200,000.

‌Also speaking at the conference will be Thomas Asbridge, PhD, is a reader of medieval history at Queen Mary University of London. Dr. Asbridge is an expert on Saladin and the Crusades.

The conference was founded in 1995 by Philip A. Mackowiak, MD, the Carolyn Frenkil and Selvin Passen History of Medicine Scholar-in-Residence at UMSOM. “This is an intriguing piece of medical detecting,” says Dr. Mackowiak. “If antibiotics had been around in the 12th century, history may have been quite different.”

For more information on the conference, visit:

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’?”