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.
Swiss researchers have found a type of brain cell that appears to be a hybrid of the two other main types — and it could lead to new treatments for brain disorders.
A new brain cell: Researchers at the Wyss Center for Bio and Neuroengineering and the University of Lausanne believe they’ve definitively proven that some astrocytes do actively participate in neurotransmission, making them a sort of hybrid of neurons and glial cells.
According to the researchers, this third type of brain cell, which they call a “glutamatergic astrocyte,” could offer a way to treat Alzheimer’s, Parkinson’s, and other disorders of the nervous system.
“Its discovery opens up immense research prospects,” said study co-director Andrea Volterra.
The study: Neurotransmission starts with a neuron releasing a chemical called a neurotransmitter, so the first thing the researchers did in their study was look at whether astrocytes can release the main neurotransmitter used by neurons: glutamate.
By analyzing astrocytes taken from the brains of mice, they discovered that certain astrocytes in the brain’s hippocampus did include the “molecular machinery” needed to excrete glutamate. They found evidence of the same machinery when they looked at datasets of human glial cells.
Finally, to demonstrate that these hybrid cells are actually playing a role in brain signaling, the researchers suppressed their ability to secrete glutamate in the brains of mice. This caused the rodents to experience memory problems.
“Our next studies will explore the potential protective role of this type of cell against memory impairment in Alzheimer’s disease, as well as its role in other regions and pathologies than those explored here,” said Andrea Volterra, University of Lausanne.
But why? The researchers aren’t sure why the brain needs glutamatergic astrocytes when it already has neurons, but Volterra suspects the hybrid brain cells may help with the distribution of signals — a single astrocyte can be in contact with thousands of synapses.
“Often, we have neuronal information that needs to spread to larger ensembles, and neurons are not very good for the coordination of this,” researcher Ludovic Telley told New Scientist.
Looking ahead: More research is needed to see how the new brain cell functions in people, but the discovery that it plays a role in memory in mice suggests it might be a worthwhile target for Alzheimer’s disease treatments.
The researchers also found evidence during their study that the cell might play a role in brain circuits linked to seizures and voluntary movements, meaning it’s also a new lead in the hunt for better epilepsy and Parkinson’s treatments.
“Our next studies will explore the potential protective role of this type of cell against memory impairment in Alzheimer’s disease, as well as its role in other regions and pathologies than those explored here,” said Volterra.
In a recent research trial, patients with Parkinson's disease reported that their symptoms had improved after stem cells were implanted into their brains. Martin Taylor, far right, was diagnosed at age 32.
For years, there's been little improvement in the standard treatment. Patients are typically given the drug levodopa, a chemical that's absorbed by the brain’s nerve cells, or neurons, and converted into dopamine. This drug addresses the symptoms but has no impact on the course of the disease as patients continue to lose dopamine producing neurons. Eventually, the treatment stops working effectively.
BlueRock Therapeutics, a cell therapy company based in Massachusetts, is taking a different approach by focusing on the use of stem cells, which can divide into and generate new specialized cells. The company makes the dopamine-producing cells that patients have lost and inserts these cells into patients' brains. “We have a disease with a high unmet need,” says Ahmed Enayetallah, the senior vice president and head of development at BlueRock. “We know [which] cells…are lost to the disease, and we can make them. So it really came together to use stem cells in Parkinson's.”
In a phase 1 research trial announced late last month, patients reported that their symptoms had improved after a year of treatment. Brain scans also showed an increased number of neurons generating dopamine in patients’ brains.
Increases in dopamine signals
The recent phase 1 trial focused on deploying BlueRock’s cell therapy, called bemdaneprocel, to treat 12 patients suffering from Parkinson’s. The team developed the new nerve cells and implanted them into specific locations on each side of the patient's brain through two small holes in the skull made by a neurosurgeon. “We implant cells into the places in the brain where we think they have the potential to reform the neural networks that are lost to Parkinson's disease,” Enayetallah says. The goal is to restore motor function to patients over the long-term.
Five patients were given a relatively low dose of cells while seven got higher doses. Specialized brain scans showed evidence that the transplanted cells had survived, increasing the overall number of dopamine producing cells. The team compared the baseline number of these cells before surgery to the levels one year later. “The scans tell us there is evidence of increased dopamine signals in the part of the brain affected by Parkinson's,” Enayetallah says. “Normally you’d expect the signal to go down in untreated Parkinson’s patients.”
"I think it has a real chance to reverse motor symptoms, essentially replacing a missing part," says Tilo Kunath, a professor of regenerative neurobiology at the University of Edinburgh.
The team also asked patients to use a specific type of home diary to log the times when symptoms were well controlled and when they prevented normal activity. After a year of treatment, patients taking the higher dose reported symptoms were under control for an average of 2.16 hours per day above their baselines. At the smaller dose, these improvements were significantly lower, 0.72 hours per day. The higher-dose patients reported a corresponding decrease in the amount of time when symptoms were uncontrolled, by an average of 1.91 hours, compared to 0.75 hours for the lower dose. The trial was safe, and patients tolerated the year of immunosuppression needed to make sure their bodies could handle the foreign cells.
Claire Bale, the associate director of research at Parkinson's U.K., sees the promise of BlueRock's approach, while noting the need for more research on a possible placebo effect. The trial participants knew they were getting the active treatment, and placebo effects are known to be a potential factor in Parkinson’s research. Even so, “The results indicate that this therapy produces improvements in symptoms for Parkinson's, which is very encouraging,” Bale says.
Tilo Kunath, a professor of regenerative neurobiology at the University of Edinburgh, also finds the results intriguing. “I think it's excellent,” he says. “I think it has a real chance to reverse motor symptoms, essentially replacing a missing part.” However, it could take time for this therapy to become widely available, Kunath says, and patients in the late stages of the disease may not benefit as much. “Data from cell transplantation with fetal tissue in the 1980s and 90s show that cells did not survive well and release dopamine in these [late-stage] patients.”
Searching for the right approach
There's a long history of using cell therapy as a treatment for Parkinson's. About four decades ago, scientists at the University of Lund in Sweden developed a method in which they transferred parts of fetal brain tissue to patients with Parkinson's so that their nerve cells would produce dopamine. Many benefited, and some were able to stop their medication. However, the use of fetal tissue was highly controversial at that time, and the tissues were difficult to obtain. Later trials in the U.S. showed that people benefited only if a significant amount of the tissue was used, and several patients experienced side effects. Eventually, the work lost momentum.
“Like many in the community, I'm aware of the long history of cell therapy,” says Taylor, the patient living with Parkinson's. “They've long had that cure over the horizon.”
In 2000, Lorenz Studer led a team at the Memorial Sloan Kettering Centre, in New York, to find the chemical signals needed to get stem cells to differentiate into cells that release dopamine. Back then, the team managed to make cells that produced some dopamine, but they led to only limited improvements in animals. About a decade later, in 2011, Studer and his team found the specific signals needed to guide embryonic cells to become the right kind of dopamine producing cells. Their experiments in mice, rats and monkeys showed that their implanted cells had a significant impact, restoring lost movement.
Studer then co-founded BlueRock Therapeutics in 2016. Forming the most effective stem cells has been one of the biggest challenges, says Enayetallah, the BlueRock VP. “It's taken a lot of effort and investment to manufacture and make the cells at the right scale under the right conditions.” The team is now using cells that were first isolated in 1998 at the University of Wisconsin, a major advantage because they’re available in a virtually unlimited supply.
Other efforts underway
In the past several years, University of Lund researchers have begun to collaborate with the University of Cambridge on a project to use embryonic stem cells, similar to BlueRock’s approach. They began clinical trials this year.
A company in Japan called Sumitomo is using a different strategy; instead of stem cells from embryos, they’re reprogramming adults' blood or skin cells into induced pluripotent stem cells - meaning they can turn into any cell type - and then directing them into dopamine producing neurons. Although Sumitomo started clinical trials earlier than BlueRock, they haven’t yet revealed any results.
“It's a rapidly evolving field,” says Emma Lane, a pharmacologist at the University of Cardiff who researches clinical interventions for Parkinson’s. “But BlueRock’s trial is the first full phase 1 trial to report such positive findings with stem cell based therapies.” The company’s upcoming phase 2 research will be critical to show how effectively the therapy can improve disease symptoms, she added.
The cure over the horizon
BlueRock will continue to look at data from patients in the phase 1 trial to monitor the treatment’s effects over a two-year period. Meanwhile, the team is planning the phase 2 trial with more participants, including a placebo group.
For patients with Parkinson’s like Martin Taylor, the therapy offers some hope, though Taylor recognizes that more research is needed.
BlueRock Therapeutics
“Like many in the community, I'm aware of the long history of cell therapy,” he says. “They've long had that cure over the horizon.” His expectations are somewhat guarded, he says, but, “it's certainly positive to see…movement in the field again.”
"If we can demonstrate what we’re seeing today in a more robust study, that would be great,” Enayetallah says. “At the end of the day, we want to address that unmet need in a field that's been waiting for a long time.”