Seven years ago, mountain biking near his home in Whitefish, Montana, Jeff Marquis felt confident enough to try for a jump he usually avoided. But he hesitated just a bit as he was going over. Instead of catching air, Marquis crashed.
Researchers' major new insight is that recovery is still possible, even years after an injury.
After 18 days on a ventilator in intensive care and two-and-a-half months in a rehabilitation hospital, Marquis was able to move his arms and wrists, but not his fingers or anything below his chest. Still, he was determined to remain as independent as possible. "I wasn't real interested in having people take care of me," says Marquis, now 35. So, he dedicated the energy he formerly spent biking, kayaking, and snowboarding toward recovering his own mobility.
For generations, those like Marquis with severe spinal cord injuries dreamt of standing and walking again – with no realistic hope of achieving these dreams. But now, a handful of people with such injuries, including Marquis, have stood on their own and begun to learn to take steps again. "I'm always trying to improve the situation but I'm happy with where I'm at," Marquis says.
The recovery Marquis and a few of his fellow patients have achieved proves that our decades-old understanding of the spinal cord was wrong. Researchers' major new insight is that recovery is still possible, even years after an injury. Only a few thousand nerve cells actually die when the spinal cord is injured. The other neurons still have the ability to generate signals and movement on their own, says Susan Harkema, co-principal investigator at the Kentucky Spinal Cord Injury Research Center, where Marquis is being treated.
"The spinal cord has much more responsibility for executing movement than we thought before," Harkema says. "Successful movement can happen without those connections from the brain." Nerve cell circuits remaining after the injury can control movement, she says, but leaving people sitting in a wheelchair doesn't activate those sensory circuits. "When you sit down, you lose all the sensory information. The whole circuitry starts discombobulating."
Harkema and others use a two-pronged approach – both physical rehabilitation and electrical stimulation – to get those spinal cord circuits back into a functioning state. Several research groups are still honing this approach, but a few patients have already taken steps under their own power, and others, like Marquis, can now stand unassisted – both of which were merely fantasies for spinal cord injury patients just five years ago.
"This really does represent a leap forward in terms of how we think about the capacity of the spinal cord to be repaired after injury," says Susan Howley, executive vice president for research for the Christopher & Dana Reeve Foundation, which supports research for spinal cord injuries.
Jeff Marquis biking on a rock before his accident.
This new biological understanding suggests the need for a wholesale change in how people are treated after a spinal cord injury, Howley says. But today, most insurance companies cover just 30-40 outpatient rehabilitation sessions per year, whether you've sprained your ankle or severed your spinal cord. To deliver the kind of therapy that really makes a difference for spinal cord injury patients requires "60-80-90 or 150 sessions," she says, adding that she thinks insurance companies will more than make up for the cost of those therapy sessions if spinal cord injury patients are healthier. Early evidence suggests that getting people back on their feet helps prevent medical problems common among paralyzed people, including urinary tract infections, which can require costly hospital stays.
"Exercise and the ability to fully bear one's own weight are as crucial for people who live with paralysis as they are for able-bodied people," Howley notes, adding that the Reeve Foundation is now trying to expand the network of facilities available in local communities to offer this essential rehabilitation.
"Providing the right kind of training every day to people could really improve their opportunity to recover," Harkema says.
It's not entirely clear yet how far someone could progress with rehabilitation alone, Harkema says, but probably the best results for someone with a severe injury will also require so-called epidural electrical stimulation. This device, implanted in the lower back for a cost of about $30,000, sends an electrical current at varying frequencies and intensities to the spinal cord. Several separate teams of researchers have now shown that epidural stimulation can help restore sensation and movement to people who have been paralyzed for years.
Epidural stimulation boosts the electrical signal that is generated below the point of injury, says Daniel Lu, an associate professor and vice chair of neurosurgery at the UCLA School of Medicine. Before a spinal cord injury, he says, a neuron might send a message at a volume of 10 but after injury, that volume might drop to a two or three. The epidural stimulation potentially trains the neuron to respond to the lower volume, Lu says.
Lu has used such stimulators to improve hand function – "essentially what defines us" – in two patients with spinal cord injuries. Both increased their grip strength so they now can lift a cup to drink by themselves, which they couldn't do before. He's also used non-invasive stimulation to help restore bladder function, which he says many spinal cord injury patients care about as much as walking again.
A closeup of the stimulator.
Not everyone will benefit from these treatments. People whose injury was caused by a cut to the spinal cord, as with a knife or bullet, probably can't be helped, Lu says, adding that they account for less than 5 percent of spinal cord injuries.
The current challenge Lu says is not how to stimulate the spinal cord, but where to stimulate it and the frequency of stimulation that will be most effective for each patient. Right now, doctors use an off-the-shelf stimulator that is used to treat pain and is not optimized for spinal cord patients, Harkema says.
Swiss researchers have shown impressive results from intermittent rather than continuous epidural stimulation. These pulses better reflect the way the brain sends its messages, according to Gregoire Courtine, the senior author on a pair of papers published Nov. 1 in Nature and Nature Neuroscience. He showed that he could get people up and moving within just a few days of turning on the stimulation. Three of his patients are walking again with only a walker or minimal assistance, and they also gained voluntary leg movements even when the stimulator was off. Continuous stimulation, this research shows, actually interferes with the patients' perception of limb position, and thus makes it harder for them to relearn to walk.
Even short of walking, proper physical rehabilitation and electrical stimulation can transform the quality of life of people with spinal cord injury, Howley and Harkema say. Patients don't need to be able to reach the top shelf or run a marathon to feel like they've been "cured" from their paralysis. Instead, recovering bowel, bladder and sexual functions, the ability to regulate their temperature and blood pressure, and reducing the breakdown of skin that can lead to a life-threatening infection can all be transformative – and all appear to improve with the combination of rehabilitation and electrical stimulation.
Howley cites a video of one of Harkema's patients, Stefanie Putnam, who was passing out five to six times a day because her blood pressure was so low. She couldn't be left alone, which meant she had no independence. After several months of rehabilitation and stimulation, she can now sit up for long periods, be left alone, and even, she says gleefully, cook her own dinner. "Every time I watch it, it brings me to tears," Howley says of the video. "She's able to resume her normal life activity. It's mind-boggling."
The work also suggests a transformation in the care of people immediately after injury. They should be allowed to stand and start taking steps as soon as possible, even if they cannot do it under their own power, Harkema says. Research is also likely to show that quickly implanting a stimulator after an injury will make a difference, she says.
There may be medications that can help immediately after an injury, too. One drug currently being studied, called riluzole, has already been approved for ALS and might help limit the damage of a spinal cord injury, Howley says. But testing its effectiveness has been a slow process, she says, because it needs to be given within 12 hours of the initial injury and not enough people get to the testing sites in time.
Stem cell therapy also offers promise for spinal cord injury patients, Howley says – but not the treatments currently provided by commercial stem cell clinics both in the U.S. and overseas, which she says are a sham. Instead, she is carefully following research by a California-based company called Asterias Biotherapeutics, which announced plans Nov. 8 to merge with a company called BioTime.
Asterias and a predecessor company have been treating people since 2010 in an effort to regrow nerves in the spinal cord. All those treated have safely tolerated the cells, but not everyone has seen a huge improvement, says Edward Wirth, who has led the trial work and is Asterias' chief medical director. He says he thinks he knows what's held back those who didn't improve much, and hopes to address those issues in the next 3- to 4-year-long trial, which he's now discussing with the U.S. Food and Drug Administration.
So far, he says, some patients have had an almost complete return of movement in their hands and arms, but little improvement in their legs. The stem cells seem to stimulate tissue repair and regeneration, he says, but only around the level of the injury in the spinal cord and a bit below. The legs, he says, are too far away to benefit.
Wirth says he thinks a combination of treatments – stem cells, electrical stimulation, rehabilitation, and improved care immediately after an injury – will likely produce the best results.
While there's still a long way to go to scale these advances to help the majority of the 300,000 spinal cord injury patients in the U.S., they now have something that's long been elusive: hope.
"Two or three decades ago there was no hope at all," Howley says. "We've come a long way."
On the morning of April 12, 1955, newsrooms across the United States inked headlines onto newsprint: the Salk Polio vaccine was "safe, effective, and potent." This was long-awaited news. Americans had limped through decades of fear, unaware of what caused polio or how to cure it, faced with the disease's terrifying, visible power to paralyze and kill, particularly children.
The announcement of the polio vaccine was celebrated with noisy jubilation: church bells rang, factory whistles sounded, people wept in the streets. Within weeks, mass inoculation began as the nation put its faith in a vaccine that would end polio.
Today, most of us are blissfully ignorant of child polio deaths, making it easier to believe that we have not personally benefited from the development of vaccines. According to Dr. Steven Pinker, cognitive psychologist and author of the bestselling book Enlightenment Now, we've become blasé to the gifts of science. "The default expectation is not that disease is part of life and science is a godsend, but that health is the default, and any disease is some outrage," he says.
The Rise and Fall of Public Trust<p>When the polio vaccine was released in 1955, "we were nearing an all-time high point in public trust," says Matt Baum, Harvard Kennedy School professor and lead author of <a href="http://www.kateto.net/covid19/COVID19%20CONSORTIUM%20REPORT%2013%20TRUST%20SEP%202020.pdf" target="_blank" rel="noopener noreferrer"><u>several</u></a> <a href="https://shorensteincenter.org/wp-content/uploads/2020/09/COVID19-CONSORTIUM-REPORT-14-MISINFO-SEP-2020.pdf" target="_blank" rel="noopener noreferrer"><u>reports</u></a> measuring public trust and vaccine confidence. Baum explains that the U.S. was experiencing a post-war boom following the Allied triumph in WWII, a popular Roosevelt presidency, and the rapid innovation that elevated the country to an international superpower.</p><p> The 1950s witnessed the emergence of nuclear technology, a space program, and unprecedented medical breakthroughs, adds Emily Brunson, Texas State University anthropologist and co-chair of the Working Group on Readying Populations for COVID-19 Vaccine. "Antibiotics were a game changer," she states. While before, people got sick with pneumonia for a month, suddenly they had access to pills that accelerated recovery. </p><p>During this period, science seemed to hold all the answers; people embraced the idea that we could "come to know the world with an absolute truth," Brunson explains. Doctors were portrayed as unquestioned gods, so Americans were primed to trust experts who told them the polio vaccine was safe. </p>
The Shift in How We Consume Information<p>In the 1950s, the media created an informational consensus. The fundamental ideas the public consumed about the state of the world were unified. "People argued about the best solutions, but didn't fundamentally disagree on the factual baseline," says Baum. Indeed, the messaging around the polio vaccine was centralized and consistent, led by President Roosevelt's successful <a href="https://files.eric.ed.gov/fulltext/EJ978264.pdf" target="_blank" rel="noopener noreferrer"><u>March of Dimes crusade</u></a>. People of lower socioeconomic status with limited access to this information were <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1551508/?page=3" target="_blank" rel="noopener noreferrer"><u>less likely to have confidence</u></a> in the vaccine, but most people consumed <a href="https://www.c-span.org/video/?506891-1/a-special-report-polio" target="_blank" rel="noopener noreferrer"><u>media that assured them</u></a> of the vaccine's safety and <a href="https://www.cbsnews.com/news/the-salk-polio-vaccine-greatest-public-health-experiment-in-history/" target="_blank" rel="noopener noreferrer"><u>mobilized them</u></a> to receive it. </p><p>Today, the information we consume is no longer centralized—in fact, just the opposite. "When you take that away, it's hard for people to know what to trust and what not to trust," Baum explains. We've witnessed an increase in polarization and the technology that makes it easier to give people what they want to hear, reinforcing the human tendencies to vilify the other side and reinforce our preexisting ideas. When information is engineered to further an agenda, each choice and risk calculation made while navigating the COVID-19 pandemic <a href="https://www.nytimes.com/2020/12/19/opinion/sunday/coronavirus-science.html?referringSource=articleShare" target="_blank" rel="noopener noreferrer"><u>is deeply politicized</u></a>. </p><p>This polarization maps onto a rise in socioeconomic inequality and economic uncertainty. These factors, associated with a sense of lost control, prime people to embrace misinformation, explains Baum, especially when the situation is difficult to comprehend. "The beauty of conspiratorial thinking is that it provides answers to all these questions," he says. Today's insidious fragmentation of news media accelerates the circulation of mis- and disinformation, reaching more people faster, regardless of veracity or motivation. In the case of vaccines, skepticism around their origin, safety, and motivation is intensified. </p><p>Alongside the rise in polarization, Pinker says "the emotional tone of the news has gone downward since the 1940s, and journalists consider it a professional responsibility to cover the negative." Relentless focus on everything that goes wrong further erodes public trust and paints a picture of the world getting worse. "Life saved is not a news story," says Pinker, but perhaps it should be, he continues. "If people were more aware of how much better life was generally, they might be more receptive to improvements that will continue to make life better. These improvements don't happen by themselves."</p>
The Future Depends on Vaccine Confidence<p>So far, the U.S. has been unable to mitigate the catastrophic effects of the pandemic through social distancing, testing, and contact tracing. President Trump has <a href="https://www.washingtonpost.com/politics/bob-woodward-rage-book-trump/2020/09/09/0368fe3c-efd2-11ea-b4bc-3a2098fc73d4_story.html" target="_blank" rel="noopener noreferrer"><u>downplayed the effects and threat of the virus</u></a>, <a href="https://www.washingtonpost.com/outlook/2020/07/14/cdc-directors-trump-politics/" target="_blank" rel="noopener noreferrer"><u>censored experts and scientists</u></a>, <a href="https://www.theatlantic.com/science/archive/2020/06/america-giving-up-on-pandemic/612796/" target="_blank" rel="noopener noreferrer"><u>given up on containing the spread</u></a>, and <a href="https://www.nytimes.com/2020/09/16/world/covid-coronavirus.html" target="_blank" rel="noopener noreferrer"><u>mobilized his base to protest masks</u></a>. The Trump Administration failed to devise a national plan, so our national plan has defaulted to hoping for the <a href="https://www.politico.com/news/2020/08/26/nation-of-miracles-pence-coronavirus-vaccine-rnc-402949" target="_blank" rel="noopener noreferrer"><u>"miracle" of a vaccine</u></a>. And they are "something of a miracle," Pinker says, describing vaccines as "the most benevolent invention in the history of our species." In record-breaking time, three vaccines have arrived. But their impact will be weakened unless we achieve mass vaccination. As Brunson notes, "The technology isn't the fix; it's people taking the technology."</p><p> Significant challenges remain, including facilitating widespread access and supporting on-the-ground efforts to allay concerns and build trust with <a href="https://www.newyorker.com/news/daily-comment/african-american-resistance-to-the-covid-19-vaccine-reflects-a-broader-problem" target="_blank" rel="noopener noreferrer"><u>specific populations with historic reasons for distrust</u></a>, says Brunson. Baum predicts continuing delays as well as deaths from other causes that will be linked to the vaccine. </p><p> Still, there's every reason for hope. The new administration "has its eyes wide open to these challenges. These are the kind of problems that are amenable to policy solutions if we have the will," Baum says. He forecasts widespread vaccination by late summer and a bounce back from the economic damage, a "Good News Story" that will bolster vaccine acceptance in the future. And Pinker reminds us that science, medicine, and public health have greatly extended our lives in the last few decades, a trend that can only continue if we're willing to roll up our sleeves. </p>
Imagine this scenario: you get an annoying cough and a bit of a fever. When you wake up the next morning you lose your sense of taste and smell. That sounds familiar, so you head to a doctor's office for a Covid test, which comes back positive.
Your next step? An anti-Covid nasal spray of course, a "trickster drug" that will clear the once-dangerous and deadly virus out of the body. The drug works by tricking the coronavirus with decoy receptors that appear to be just like those on the surface of our own cells. The virus latches onto the drug's molecules "thinking" it is breaking into human cells, but instead it flushes out of your system before it can cause any serious damage.
This may sounds like science fiction, but several research groups are already working on such trickster coronavirus drugs, with some candidates close to clinical trials and possibly even becoming available late this year. The teams began working on them when the pandemic arrived, and continued in lockdown.
Biochemist David Baker, pictured in his lab at the University of Washington.