Tiny clusters of lab-grown human brain cells provide a way to study the organ that is central to our species but is largely inaccessible in living people.

Why it matters: Brain-related disorders — from autism spectrum disorders to schizophrenia to Parkinson's disease — are a leading contributor to disability in people around the world. These purposefully grown brain-like tissues, called organoids, have the potential to help researchers better understand them.

"The biggest challenge in psychiatry today is that most disorders are still defined behaviorally," says Sergiu Pasca, a neurobiologist at Stanford University. "We don’t have molecular markers. We are very far behind in finding therapeutics."

• "For the human brain, we cannot access it at will at the molecular and cellular level. The need for creating these models comes from this frustration."

How it works: Far from being full brains, neural organoids are three-dimensional clumps of cells, typically a few millimeters in diameter, that begin in the lab as stem cells that are then chemically coaxed into becoming neurons.

• They're both a closer proxy for the human brain than the animal models researchers have traditionally used and an alternative to studying tissue from humans that can raise ethical challenges.

Brain organoids are typically grown for weeks or a few months and model the earliest stages of brain development.

• Pasca and his colleagues reported this week that organoids can be maintained for nearly two years and, after about nine months, the tissues undergo changes in gene expression that are similar to some of those in the brain after birth.
• "It opens the door to look at aspects of development that happen after birth and hopefully disorders that affect brain after birth," says Madeline Lancaster, a developmental biologist at the Medical Research Council's Laboratory of Molecular Biology in Cambridge, U.K., who pioneered brain organoid techniques.

The big picture: A recent burst of studies illustrates how scientists are honing and applying brain organoid research to probe an expanding list of questions.

Humans' evolutionary history: In a recent study, researchers grew organoids containing a genetic variant found in Neanderthals and Denisovans for a gene involved in forming synapses between neurons.

• The resulting tissues were smaller and had a different texture and the neurons fired faster compared to those of modern humans, they reported earlier this month.
• It's difficult to draw many conclusions about the brains of Neanderthals from the study, Lancaster and other experts say, but it demonstrates the breadth of studies researchers can now consider, including comparing brain organoids made from the cells of apes with those made from human cells, she adds.

How disease affects the brain: Researchers are also using the lab-grown tissues to understand how SARS-CoV-2 may infect brain cells.

The basic biology of the brain and its development: Organoids are helping researchers better understand what cells and signals direct the brain's development.

• "It allows you to almost re-create embryology," says Debra Silver, a developmental neurobiologist at Duke University who uses brain organoids to study microcephaly and other conditions.
• What's new: Pasca and other researchers are taking organoids made from brain cells that give rise to different parts of the brain and putting them together in a dish to make "assembloids." These models help them see how cells migrate to other regions of the brain during development and how different regions connect with one another.

Yes, but: Brain organoids aren't brains.

• They lack the organization of the brain and can't communicate with other brain regions.
• They lack the inputs from eyes, ears, skin and other sensory organs — in other words, a body — that shape the brain's function.
• And they don't contain the brain's other cells, including immune cells, or blood vessels.

What to watch: As brain organoids become more complex, some bioethicists say the potential ethical and legal challenges will grow.

Read the entire story.

COVID-19 survivors tend to have a roughly tenfold increase in protection against the virus, according to a government-funded study published Wednesday, Axios' Eileen Drage O'Reilly writes.

Why it matters: There have been some documented cases of reinfection, leading to concern that survivors don't gain any immunity. While questions remain about how much or how long immunity lasts and what the impact of variants will be, the study's large set of observational data bolsters evidence there's some protection.

The latest: The study, published in JAMA Internal Medicine, examined commercial SARS-CoV-2 antibody test data from 3.2 million U.S. patients from Jan. 1 and Aug. 23, 2020.

• Out of those who had tested antibody-negative initially and were later tested for active infection, they found 3% were positive for SARS-CoV-2 90 or more days later.
• Out of those who were antibody-positive initially and were later tested for active infection, they found only 0.3% were positive for SARS-CoV-2 90 or more days later.
• "There's a tenfold decrease, which is essentially a 90% reduction in risk for people who are antibody positive," says Doug Lowy, co-author and deputy director of the National Cancer Institute, which conducted the study.

Caveat: Because the study examines real-time data and was not done in a clinical trial setting, there could be "confounders," or distorting factors, that affect results, Lowy points out. This means the tenfold protection is a rough average — in actuality, "maybe it's a threefold difference, and maybe it's a twentyfold difference."

• However, the results do closely match another recent NEJM study from the U.K. that also found a roughly tenfold difference, he says.

What they're saying: Jennifer Juno, a senior research fellow at the University of Melbourne's Doherty Institute who was not part of the study, says, "several studies now suggest that prior infection does indeed provide protection against reinfection, as we would expect."

• In a different paper published last week in Nature Communications, Juno and her collaborators found people tend to have strong neutralizing antibodies initially after infection. They then rapidly decline by about 50% within 55 days, but that decline slows and plateaus.
• And then other immune system actors pick up. The level of B cells that produce antibodies to the coronavirus spike protein increased over time in their study participants, rather than declined, Juno says.
• "This is encouraging news, as it suggests that the immune system is generating a robust memory response to infection, which is likely to play a role in providing some protection from reinfection," she adds.

The big picture: Vaccination is still highly recommended for those who've been infected before, both Lowy and Juno say.

• "Early studies suggest that individuals who were previously infected show substantial boosting of their antibody levels after receiving one dose of a COVID vaccine, which points to a great benefit of receiving the vaccine even if you have been previously infected," Juno says.

"New coronavirus infections continued their sharp decline over the past week, and are now back down to pre-Thanksgiving levels," Axios' Sam Baker and Andrew Witherspoon report.

More than 500,000 people in the U.S. have died from COVID-19.

An FDA advisory panel meets tomorrow to review J&J's request for emergency use authorization of its one-dose COVID-19 vaccine. The agency reported earlier this week that the vaccine is safe and has a 66% efficacy against moderate to severe disease.

Pfizer and BioNTech are now studying the effectiveness of a third booster shot of their COVID-19 vaccine against variants of the virus.

Perseverance's first moments on Mars (Miriam Kramer — Axios)

Christian Happi: "With pathogens, we need to play offence" (Neil Munshi — FT)

The AI research paper was real. The "co-author" wasn't. (Will Knight — Wired)

Banking on bird shit (Lina Zeldovich — Hakai)

Researchers have captured the brain developing in the roundworm, C. elegans.

Why it matters: Brains — of roundworms, humans and others — contain areas of neuropil, tissue that is densely but precisely packed with the fibers of neurons and glia cells. "The structural and developmental principles that govern this nanoscale precision remain largely unknown," the authors write in Nature this week.

What they found: Daniel A. Colón-Ramos of Yale School of Medicine and his collaborators found the interconnected neurons in neuropil are organized into layers, each containing circuits of neurons associated with specific functions.

• For example, they could trace the worm's reflex to withdraw its head to circuits of cells leading to muscles.
• “When you see the architecture, you realize that all this knowledge that was out there about the animal’s behaviors has a home in the structure of the brain,” Colón-Ramos said in a press release.
• Using high-resolution microscopy and algorithms, they also tracked individual cells over time and saw "pioneer neurons" migrated to specific locations and guided the development of the neuropil.

“It has been a breathtaking experience to now be able to watch development unfold for hours, across the entire brain of the organism, and visualize this highly orchestrated dance,” study co-author Mark Moyle, a neuroscientist at Yale School of Medicine said in the press release.