Magnetic resonance imaging of the brain.
This past March, headlines suddenly flooded the Internet about a startup company called Nectome. Founded by two graduates of the Massachusetts Institute of Technology, the new company was charging people $10,000 to join a waiting list to have their brains embalmed, down to the last neuron, using an award-winning chemical compound.
While the lay public presumably burnt their wills and grew ever more excited about the end of humanity's quest for immortality, neurologists let out a collective sigh.
Essentially, participants' brains would turn to a substance like glass and remain in a state of near-perfect preservation indefinitely. "If memories can truly be preserved by a sufficiently good brain banking technique," Nectome's website explains, "we believe that within the century it could become feasible to digitize your preserved brain and use that information to recreate your mind." But as with most Faustian bargains, Nectome's proposition came with a serious caveat -- death.
That's right, in order for Nectome's process to properly preserve your connectome, the comprehensive map of the brain's neural connections, you must be alive (and under anesthesia) while the fluid is injected. This way, the company postulates, when the science advances enough to read and extract your memories someday, your vitrified brain will still contain your perfectly preserved essence--which can then be digitally recreated as a computer simulation.
Almost immediately this story gained buzz with punchy headlines: "Startup wants to upload your brain to the cloud, but has to kill you to do it," "San Junipero is real: Nectome wants to upload your brain," and "New tech firm promises eternal life, but you have to die."
While the lay public presumably burnt their wills and grew ever more excited about the end of humanity's quest for immortality, neurologists let out a collective sigh -- hype had struck the scientific community once again.
The truth about Nectome is that its claims are highly speculative and no hard science exists to suggest that our connectome is the key to our 'being,' nor that it can ever be digitally revived. "We haven't come even close to understanding even the most basic types of functioning in the brain," says neuroscientist Alex Fox, who was educated at the University of Queensland in Australia. "Memory storage in the brain is only a theoretical concept [and] there are some seriously huge gaps in our knowledge base that stand in the way of testing [the connectome] theory."
After the Nectome story broke, Harvard computational neuroscientist Sam Gershman tweeted out:
"Didn't anyone tell them that we've known the C Elegans (a microscopic worm) connectome for over a decade but haven't figured out how to reconstruct all of their memories? And that's only 7000 synapses compared to the trillions of synapses in the human brain!"
Hype can come from researchers themselves, who are under an enormous amount of pressure to publish original work and maintain funding.
How media coverage of Nectome went from an initial fastidiously researched article in the MIT Technology Review by veteran science journalist Antonio Regalado to the click-bait frenzy it became is a prime example of the 'science hype' phenomenon. According to Adam Auch, who holds a doctorate in philosophy from Dalhousie University in Nova Scotia, Canada, "Hype is a feature of all stages of the scientific dissemination process, from the initial circulation of preliminary findings within particular communities of scientists, to the process by which such findings come to be published in peer-reviewed journals, to the subsequent uptake these findings receive from the non-specialist press and the general public."
In the case of Nectome, hype was present from the word go. Riding the high of several major wins, including having raised over one million dollars in funding and partnering with well-known MIT neurologist Edward Boyden, Nectome founders Michael McCanna and Robert McIntyre launched their website on March 1, 2018. Just one month prior, they were able to purchase and preserve a newly deceased corpse in Portland, Oregon, showing that vitrifixation, their method of chemical preservation, could be used on a human specimen. It had previously won an award for preserving every synaptic structure on a rabbit brain.
The Nectome mission statement, found on its website, is laced with saccharine language that skirts the unproven nature of the procedure the company is peddling for big bucks: "Our mission is to preserve your brain well enough to keep all its memories intact: from that great chapter of your favorite book to the feeling of cold winter air, baking an apple pie, or having dinner with your friends and family."
This rhetoric is an example of hype that can come from researchers themselves, who are under an enormous amount of pressure to publish original work and maintain funding. As a result, there is a constant push to present science as "groundbreaking" when really, as is apparently the case with Nectome, it is only a small piece in a much larger effort.
Calling out the audacity of Nectome's posited future, neuroscientist Gershman commented to another publication, "The important question is whether the connectome is sufficient for memory: Can I reconstruct all memories knowing only the connections between neurons? The answer is almost certainly no, given our knowledge about how memories are stored (itself a controversial topic)."
The former home page of Nectome's website, which has now been replaced by a statement titled, "Response to recent press."
Furthermore, universities like MIT, who entered into a subcontract with Nectome, are under pressure to seek funding through partnerships with industry as a result of the Bayh-Dole Act of 1980. Also known as the Patent and Trademark Law Amendments Act, this piece of legislation allows universities to commercialize inventions developed under federally funded research programs, like Nectome's method of preserving brains, formally called Aldehyde-Stabilized Cryopreservation.
"[Universities use] every incentive now to talk about innovation," explains Dr. Ivan Oransky, president of the Association of Health Care Journalists and co-founder of retractionwatch.com, a blog that catalogues errors and fraud in published research. "Innovation to me is often a fancy word for hype. The role of journalists should not be to glorify what universities [say, but to] tell the closest version of the truth they can."
In this case, a combination of the hyperbolic press, combined with some impressively researched expose pieces, led MIT to cut its ties with Nectome on April 2nd, 2018, just two weeks after the news of their company broke.
The solution to the dangers of hype, experts say, is a more scientifically literate public—and less clickbait-driven journalism.
Because of its multi-layered nature, science hype carries several disturbing consequences. For one, exaggerated coverage of a discovery could mislead the public by giving them false hope or unfounded worry. And media hype can contribute to a general mistrust of science. In these instances, people might, as Auch puts it, "fall back on previously held beliefs, evocative narratives, or comforting biases instead of well-justified scientific evidence."
All of this is especially dangerous in today's 'fake news' era, when companies or political parties sow public confusion for their own benefit, such as with global warming. In the case of Nectome, the danger is that people might opt to end their lives based off a lacking scientific theory. In fact, the company is hoping to enlist terminal patients in California, where doctor-assisted suicide is legal. And 25 people have paid the $10,000 to join Nectome's waiting list, including Sam Altman, president of the famed startup accelerator Y Combinator. Nectome now has offered to refund the money.
Founders McCanna and McIntyre did not return repeated requests for comment for this article. A new statement on their website begins: "Vitrifixation today is a powerful research tool, but needs more research and development before anyone considers applying it in a context other than research."
The solution to the dangers of hype, experts say, is a more scientifically literate public—and less clickbait-driven journalism. Until then, it seems that companies like Nectome will continue to enjoy at least 15 minutes of fame.
A movie still from the 1966 film "Fantastic Voyage"
"Chemotherapy is delivered systemically," Bionaut-founder and CEO Michael Shpigelmacher says. "Often only a small percentage arrives at the location where it is actually needed."
But what if it was possible to send a tiny robot through the body to attack a tumor or deliver a drug at exactly the right location?
Several startups and academic institutes worldwide are working to develop such a solution but Bionaut Labs seems the furthest along in advancing its invention. "You can think of the Bionaut as a tiny screw that moves through the veins as if steered by an invisible screwdriver until it arrives at the tumor," Shpigelmacher explains. Via Zoom, he shares the screen of an X-ray machine in his Culver City lab to demonstrate how the half-transparent, yellowish device winds its way along the spine in the body. The nanobot contains a tiny but powerful magnet. The "invisible screwdriver" is an external magnetic field that rotates that magnet inside the device and gets it to move and change directions.
The current model has a diameter of less than a millimeter. Shpigelmacher's engineers could build the miniature vehicle even smaller but the current size has the advantage of being big enough to see with bare eyes. It can also deliver more medicine than a tinier version. In the Zoom demonstration, the micorobot is injected into the spine, not unlike an epidural, and pulled along the spine through an outside magnet until the Bionaut reaches the brainstem. Depending which organ it needs to reach, it could be inserted elsewhere, for instance through a catheter.
"The hope is that we can develop a vehicle to transport medication deep into the body," says Max Planck scientist Tian Qiu.
Imagine moving a screw through a steak with a magnet — that's essentially how the device works. But of course, the Bionaut is considerably different from an ordinary screw: "At the right location, we give a magnetic signal, and it unloads its medicine package," Shpigelmacher says.
To start, Bionaut Labs wants to use its device to treat Parkinson's disease and brain stem gliomas, a type of cancer that largely affects children and teenagers. About 300 to 400 young people a year are diagnosed with this type of tumor. Radiation and brain surgery risk damaging sensitive brain tissue, and chemotherapy often doesn't work. Most children with these tumors live less than 18 months. A nanobot delivering targeted chemotherapy could be a gamechanger. "These patients really don't have any other hope," Shpigelmacher says.
Of course, the main challenge of the developing such a device is guaranteeing that it's safe. Because tissue is so sensitive, any mistake could risk disastrous results. In recent years, Bionaut has tested its technology in dozens of healthy sheep and pigs with no major adverse effects. Sheep make a good stand-in for humans because their brains and spines are similar to ours.
The Bionaut device is about the size of a grain of rice.
Bionaut Labs
"As the Bionaut moves through brain tissue, it creates a transient track that heals within a few weeks," Shpigelmacher says. The company is hoping to be the first to test a nanobot in humans. In December 2022, it announced that a recent round of funding drew $43.2 million, for a total of 63.2 million, enabling more research and, if all goes smoothly, human clinical trials by early next year.
Once the technique has been perfected, further applications could include addressing other kinds of brain disorders that are considered incurable now, such as Alzheimer's or Huntington's disease. "Microrobots could serve as a bridgehead, opening the gateway to the brain and facilitating precise access of deep brain structure – either to deliver medication, take cell samples or stimulate specific brain regions," Shpigelmacher says.
Robot-assisted hybrid surgery with artificial intelligence is already used in state-of-the-art surgery centers, and many medical experts believe that nanorobotics will be the instrument of the future. In 2016, three scientists were awarded the Nobel Prize in Chemistry for their development of "the world's smallest machines," nano "elevators" and minuscule motors. Since then, the scientific experiments have progressed to the point where applicable devices are moving closer to actually being implemented.
Bionaut's technology was initially developed by a research team lead by Peer Fischer, head of the independent Micro Nano and Molecular Systems Lab at the Max Planck Institute for Intelligent Systems in Stuttgart, Germany. Fischer is considered a pioneer in the research of nano systems, which he began at Harvard University more than a decade ago. He and his team are advising Bionaut Labs and have licensed their technology to the company.
"The hope is that we can develop a vehicle to transport medication deep into the body," says Max Planck scientist Tian Qiu, who leads the cooperation with Bionaut Labs. He agrees with Shpigelmacher that the Bionaut's size is perfect for transporting medication loads and is researching potential applications for even smaller nanorobots, especially in the eye, where the tissue is extremely sensitive. "Nanorobots can sneak through very fine tissue without causing damage."
In "Fantastic Voyage," Raquel Welch's adventures inside the body of a dissident scientist let her swim through his veins into his brain, but her shrunken miniature submarine is attacked by antibodies; she has to flee through the nerves into the scientist's eye where she escapes into freedom on a tear drop. In reality, the exit in the lab is much more mundane. The Bionaut simply leaves the body through the same port where it entered. But apart from the dramatization, the "Fantastic Voyage" was almost prophetic, or, as Shpigelmacher says, "Science fiction becomes science reality."
This article was first published by Leaps.org on April 12, 2021.
In 2013, the Human Brain Project set out to build a realistic computer model of the brain over ten years. Now, experts are reflecting on HBP's achievements with an eye toward the future.
Scholars have found that the project did help advance neuroscience more than some detractors initially expected, specifically in the area of brain simulations and virtual models. Using an interdisciplinary approach of combining technology, such as AI and digital simulations, with neuroscience, the HBP worked to gain a deeper understanding of the human brain’s complicated structure and functions, which in some cases led to novel treatments for brain disorders. Lastly, through online platforms, the HBP spearheaded a previously unmatched level of global neuroscience collaborations.
Simulating a human brain stirs up controversy
Right from the start, the project was plagued with controversy and condemnation. One of its prominent critics was Yves Fregnac, a professor in cognitive science at the Polytechnic Institute of Paris and research director at the French National Centre for Scientific Research. Fregnac argued in numerous articles that the HBP was overfunded based on proposals with unrealistic goals. “This new way of over-selling scientific targets, deeply aligned with what modern society expects from mega-sciences in the broad sense (big investment, big return), has been observed on several occasions in different scientific sub-fields,” he wrote in one of his articles, “before invading the field of brain sciences and neuromarketing.”
"A human brain model can simulate an experiment a million times for many different conditions, but the actual human experiment can be performed only once or a few times," said Viktor Jirsa, a professor at Aix-Marseille University.
Responding to such critiques, the HBP worked to restructure the effort in its early days with new leadership, organization, and goals that were more flexible and attainable. “The HBP got a more versatile, pluralistic approach,” said Viktor Jirsa, a professor at Aix-Marseille University and one of the HBP lead scientists. He believes that these changes fixed at least some of HBP’s issues. “The project has been on a very productive and scientifically fruitful course since then.”
After restructuring, the HBP became a European hub on brain research, with hundreds of scientists joining its growing network. The HBP created projects focused on various brain topics, from consciousness to neurodegenerative diseases. HBP scientists worked on complex subjects, such as mapping out the brain, combining neuroscience and robotics, and experimenting with neuromorphic computing, a computational technique inspired by the human brain structure and function—to name just a few.
Simulations advance knowledge and treatment options
In 2013, it seemed that bringing neuroscience into a digital age would be farfetched, but research within the HBP has made this achievable. The virtual maps and simulations various HBP teams create through brain imaging data make it easier for neuroscientists to understand brain developments and functions. The teams publish these models on the HBP’s EBRAINS online platform—one of the first to offer access to such data to neuroscientists worldwide via an open-source online site. “This digital infrastructure is backed by high-performance computers, with large datasets and various computational tools,” said Lucy Xiaolu Wang, an assistant professor in the Resource Economics Department at the University of Massachusetts Amherst, who studies the economics of the HBP. That means it can be used in place of many different types of human experimentation.
Jirsa’s team is one of many within the project that works on virtual brain models and brain simulations. Compiling patient data, Jirsa and his team can create digital simulations of different brain activities—and repeat these experiments many times, which isn’t often possible in surgeries on real brains. “A human brain model can simulate an experiment a million times for many different conditions,” Jirsa explained, “but the actual human experiment can be performed only once or a few times.” Using simulations also saves scientists and doctors time and money when looking at ways to diagnose and treat patients with brain disorders.
Compiling patient data, scientists can create digital simulations of different brain activities—and repeat these experiments many times.
The Human Brain Project
Simulations can help scientists get a full picture that otherwise is unattainable. “Another benefit is data completion,” added Jirsa, “in which incomplete data can be complemented by the model. In clinical settings, we can often measure only certain brain areas, but when linked to the brain model, we can enlarge the range of accessible brain regions and make better diagnostic predictions.”
With time, Jirsa’s team was able to move into patient-specific simulations. “We advanced from generic brain models to the ability to use a specific patient’s brain data, from measurements like MRI and others, to create individualized predictive models and simulations,” Jirsa explained. He and his team are working on this personalization technique to treat patients with epilepsy. According to the World Health Organization, about 50 million people worldwide suffer from epilepsy, a disorder that causes recurring seizures. While some epilepsy causes are known others remain an enigma, and many are hard to treat. For some patients whose epilepsy doesn’t respond to medications, removing part of the brain where seizures occur may be the only option. Understanding where in the patients’ brains seizures arise can give scientists a better idea of how to treat them and whether to use surgery versus medications.
“We apply such personalized models…to precisely identify where in a patient’s brain seizures emerge,” Jirsa explained. “This guides individual surgery decisions for patients for which surgery is the only treatment option.” He credits the HBP for the opportunity to develop this novel approach. “The personalization of our epilepsy models was only made possible by the Human Brain Project, in which all the necessary tools have been developed. Without the HBP, the technology would not be in clinical trials today.”
Personalized simulations can significantly advance treatments, predict the outcome of specific medical procedures and optimize them before actually treating patients. Jirsa is watching this happen firsthand in his ongoing research. “Our technology for creating personalized brain models is now used in a large clinical trial for epilepsy, funded by the French state, where we collaborate with clinicians in hospitals,” he explained. “We have also founded a spinoff company called VB Tech (Virtual Brain Technologies) to commercialize our personalized brain model technology and make it available to all patients.”
The Human Brain Project created a level of interconnectedness within the neuroscience research community that never existed before—a network not unlike the brain’s own.
Other experts believe it’s too soon to tell whether brain simulations could change epilepsy treatments. “The life cycle of developing treatments applicable to patients often runs over a decade,” Wang stated. “It is still too early to draw a clear link between HBP’s various project areas with patient care.” However, she admits that some studies built on the HBP-collected knowledge are already showing promise. “Researchers have used neuroscientific atlases and computational tools to develop activity-specific stimulation programs that enabled paraplegic patients to move again in a small-size clinical trial,” Wang said. Another intriguing study looked at simulations of Alzheimer’s in the brain to understand how it evolves over time.
Some challenges remain hard to overcome even with computer simulations. “The major challenge has always been the parameter explosion, which means that many different model parameters can lead to the same result,” Jirsa explained. An example of this parameter explosion could be two different types of neurodegenerative conditions, such as Parkinson’s and Huntington’s diseases. Both afflict the same area of the brain, the basal ganglia, which can affect movement, but are caused by two different underlying mechanisms. “We face the same situation in the living brain, in which a large range of diverse mechanisms can produce the same behavior,” Jirsa said. The simulations still have to overcome the same challenge.
Understanding where in the patients’ brains seizures arise can give scientists a better idea of how to treat them and whether to use surgery versus medications.
The Human Brain Project
A network not unlike the brain’s own
Though the HBP will be closing this year, its legacy continues in various studies, spin-off companies, and its online platform, EBRAINS. “The HBP is one of the earliest brain initiatives in the world, and the 10-year long-term goal has united many researchers to collaborate on brain sciences with advanced computational tools,” Wang said. “Beyond the many research articles and projects collaborated on during the HBP, the online neuroscience research infrastructure EBRAINS will be left as a legacy even after the project ends.”
Those who worked within the HBP see the end of this project as the next step in neuroscience research. “Neuroscience has come closer to very meaningful applications through the systematic link with new digital technologies and collaborative work,” Jirsa stated. “In that way, the project really had a pioneering role.” It also created a level of interconnectedness within the neuroscience research community that never existed before—a network not unlike the brain’s own. “Interconnectedness is an important advance and prerequisite for progress,” Jirsa said. “The neuroscience community has in the past been rather fragmented and this has dramatically changed in recent years thanks to the Human Brain Project.”
According to its website, by 2023 HBP’s network counted over 500 scientists from over 123 institutions and 16 different countries, creating one of the largest multi-national research groups in the world. Even though the project hasn’t produced the in-silico brain as Markram envisioned it, the HBP created a communal mind with immense potential. “It has challenged us to think beyond the boundaries of our own laboratories,” Jirsa said, “and enabled us to go much further together than we could have ever conceived going by ourselves.”