Lab-Grown "Mini-Brains" Could Revolutionize Drug Research

Technician at the Johns Hopkins Institute
Technician at the Johns Hopkins Institute
Nathalie Jollien

LAUSANNE â€" Imagine a brain the size of the tip of a ballpoint pen. Now imagine that this brain can spontaneously generate an electric charge, just like a human brain could. Well, imagine no more because this tiny human brain replica, a so-called mini-brain, actually exists.

Over the past five years, techniques to manufacture these tiny organs called organoids have developed rapidly. Organoids could revolutionize pharmacological research and limit the use of animal testing. And they’re about to hit the market for the first time.

It all started with a discovery that earned Shinya Yamanaka and John Gurdon a Nobel Prize in 2012. They found they could reprogram mature cells to become immature “pluripotent” cells that can then develop into any type of tissue in the human body, provided it gets enough stimulation. A three-dimensional organoid can be created from stem cells suspended in a suitable liquid. As the cells used are mature, the method dodges the ethical issues that plague stem cell research from embryos.

Thomas Hartung, a professor at the Johns Hopkins Bloomberg School of Public Health in Baltimore is one of the many researchers in the field of mini-organs. He said he believes that "organoids are the cell cultures of the 21st century. An organoid can tell us more than a simple two-dimensional in vitro cell culture, such as the interaction between cells and an organ's functions. But this remains a negotiation between complexity and feasibility.”

Organoids, which don’t have the complexity of a real organ, have so far been unable to recreate all the functions of an organ.

Hartung has developed mini-brains just 350 micrometers in size by stimulating pluripotent cells into nerve cells. Deprived of fresh blood, organoid cells have no access to the nutrients and oxygen they need to grow. Since this must be provided from an external environment, it can't reach the inner cell mass. That's why organoids are so small.

While mini-brains don't have the same anatomy as a real brain, they do have part of the same functionality. Cells can communicate with one another just like in a real brain.

Since we can observe stem cells transform into organoids, we can study diseases that result from a development flaw or from the degradation of a specific organ and understand what causes them. A number of studies are being carried out on the brain alone: multiple sclerosis, Alzheimer's and Parkinson's disease. Mini-brains are also being used for research on viral infections and traumas.

A mini-brain study published in the journal Cell on April 22 confirmed that the Zika virus causes microcephaly in fetuses of infected mothers. By infecting mini-brains at different development stages, scientists were able to identify the deficient cells.

Section of a brain organoid â€" Photo: Madeline A. Lancaster

Cancer cells are hosted in organoids at QGel, a spin-off from the Switzerland-based École Polytechnique Fédérale de Lausanne. Whether they are from the lungs, the colon or the ovaries, each tumor is cultivated on an industrial scale in a specific environment developed by the company.

"With one single biopsy, our technology allows us to cultivate more than 2,000 identical tumors in three dimensions in small test tubes," says Colin Sanctuary, QGel's co-founder. "This makes it possible to compare quickly the efficiency of drugs on these thousands of tumors, each of which represents a mini-patient."

QGel now sells its growth kits for tumorous organoids to other research laboratories.

Each tumor is tested with different versions or combinations of new medicines being developed. While organoids are a quick and profitable tool for pharmacological tests, they could also accelerate the development of personalized medicine over the next few years. "Being able to test potential drugs on a patient's cells would preserve his health while giving him the most efficient treatment," Sanctuary explains.

In the long run, organoids could also remove the need for animal testing. John Frampton, a researcher at the Dalhousie University in Canada, thinks that organoids are still "a long way away from completely replacing animals. They're generally not whole organs. Mini-brains, for example, are just balls of cortical cells and as such don't reflect the complexity of the entire brain."

Moreover, scientists still need to recreate the way drugs reach the brain in real-life conditions. Research projects on organoids are mushrooming to answer those questions.

Hartung doesn't see the new laboratories as competition. "We all benefit from everybody else's experience. We share all our "recipes." Our interest is to drive science forward," he says.

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Air Next: How A Crypto Scam Collapsed On A Single Spelling Mistake

It is today a proven fraud, nailed by the French stock market watchdog: Air Next resorted to a full range of dubious practices to raise money for a blockchain-powered e-commerce app. But the simplest of errors exposed the scam and limited the damage to investors. A cautionary tale for the crypto economy.

Sky is the crypto limit

Laurence Boisseau

PARIS — Air Next promised to use blockchain technology to revolutionize passenger transport. Should we have read something into its name? In fact, the company was talking a lot of hot air from the start. Air Next turned out to be a scam, with a fake website, false identities, fake criminal records, counterfeited bank certificates, aggressive marketing … real crooks. Thirty-five employees recruited over the summer ranked among its victims, not to mention the few investors who put money in the business.

Maud (not her real name) had always dreamed of working in a start-up. In July, she spotted an ad on Linkedin and was interviewed by videoconference — hardly unusual in the era of COVID and teleworking. She was hired very quickly and signed a permanent work contract. She resigned from her old job, happy to get started on a new adventure.

Others like Maud fell for the bait. At least ten senior managers, coming from major airlines, airports, large French and American corporations, a former police officer … all firmly believed in this project. Some quit their jobs to join; some French expats even made their way back to France.

Share capital of one billion 

The story began last February, when Air Next registered with the Paris Commercial Court. The new company stated it was developing an application that would allow the purchase of airline tickets by using cryptocurrency, at unbeatable prices and with an automatic guarantee in case of cancellation or delay, via a "smart contract" system (a computer protocol that facilitates, verifies and oversees the handling of a contract).

The firm declared a share capital of one billion euros, with offices under construction at 50, Avenue des Champs Elysées, and a president, Philippe Vincent ... which was probably a usurped identity.

Last summer, Air Next started recruiting. The company also wanted to raise money to have the assets on hand to allow passenger compensation. It organized a fundraiser using an ICO, or "Initial Coin Offering", via the issuance of digital tokens, transacted in cryptocurrencies through the blockchain.

While nothing obliged him to do so, the company owner went as far as setting up a file with the AMF, France's stock market regulator which oversees this type of transaction. Seeking the market regulator stamp is optional, but when issued, it gives guarantees to those buying tokens.

screenshot of the typo that revealed the Air Next scam

The infamous typo that brought the Air Next scam down

compta online

Raising Initial Coin Offering 

Then, on Sept. 30, the AMF issued an alert, by way of a press release, on the risks of fraud associated with the ICO, as it suspected some documents to be forgeries. A few hours before that, Air Next had just brought forward by several days the date of its tokens pre-sale.

For employees of the new company, it was a brutal wake-up call. They quickly understood that they had been duped, that they'd bet on the proverbial house of cards. On the investor side, the CEO didn't get beyond an initial fundraising of 150,000 euros. He was hoping to raise millions, but despite his failure, he didn't lose confidence. Challenged by one of his employees on Telegram, he admitted that "many documents provided were false", that "an error cost the life of this project."

What was the "error" he was referring to? A typo in the name of the would-be bank backing the startup. A very small one, at the bottom of the page of the false bank certificate, where the name "Edmond de Rothschild" is misspelled "Edemond".

Finding culprits 

Before the AMF's public alert, websites specializing in crypto-assets had already noted certain inconsistencies. The company had declared a share capital of 1 billion euros, which is an enormous amount. Air Next's CEO also boasted about having discovered bitcoin at a time when only a few geeks knew about cryptocurrency.

Employees and investors filed a complaint. Failing to find the general manager, Julien Leclerc — which might also be a fake name — they started looking for other culprits. They believe that if the Paris Commercial Court hadn't registered the company, no one would have been defrauded.

Beyond the handful of victims, this case is a plea for the implementation of more secure procedures, in an increasingly digital world, particularly following the pandemic. The much touted ICO market is itself a victim, and may find it hard to recover.

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