How dozens of men across Alaska (and their dogs) teamed up to save one town from a deadly outbreak
In 1925, health officials in Alaska came up with a creative solution to save a remote fishing town from a deadly disease outbreak.
During the winter of 1924, Curtis Welch – the only doctor in Nome, a remote fishing town in northwest Alaska – started noticing something strange. More and more, the children of Nome were coming to his office with sore throats.
Initially, Welch dismissed the cases as tonsillitis or some run-of-the-mill virus – but when more kids started getting sick, with some even dying, he grew alarmed. It wasn’t until early 1925, after a three-year-old boy died just two weeks after becoming ill, that Welch realized that his worst suspicions were true. The boy – and dozens of other children in town – were infected with diphtheria.
A DEADLY BACTERIA
Diphtheria is nearly nonexistent and almost unheard of in industrialized countries today. But less than a century ago, diphtheria was a household name – one that struck fear in the heart of every parent, as it was extremely contagious and particularly deadly for children.
Diphtheria – a bacterial infection – is an ugly disease. When it strikes, the bacteria eats away at the healthy tissues in a patient’s respiratory tract, leaving behind a thick, gray membrane of dead tissue that covers the patient's nose, throat, and tonsils. Not only does this membrane make it very difficult for the patient to breathe and swallow, but as the bacteria spreads through the bloodstream, it causes serious harm to the heart and kidneys. It sometimes also results in nerve damage and paralysis. Even with treatment, diphtheria kills around 10 percent of people it infects. Young children, as well as adults over the age of 60, are especially at risk.
Welch didn’t suspect diphtheria at first. He knew the illness was incredibly contagious and reasoned that many more people would be sick – specifically, the family members of the children who had died – if there truly was an outbreak. Nevertheless, the symptoms, along with the growing number of deaths, were unmistakable. By 1925 Welch knew for certain that diphtheria had come to Nome.
In desperation, Welch tried treating an infected seven-year-old girl with some expired antitoxin – but she died just a few hours after he administered it.
AN INACCESSIBLE CURE
A vaccine for diphtheria wouldn’t be widely available until the mid-1930s and early 1940s – so an outbreak of the disease meant that each of the 10,000 inhabitants of Nome were all at serious risk.
One option was to use something called an antitoxin – a serum consisting of anti-diphtheria antibodies – to treat the patients. However, the town’s reserve of diphtheria antitoxin had expired. Welch had ordered a replacement shipment of antitoxin the previous summer – but the shipping port that was set to deliver the serum had been closed due to ice, and no new antitoxin would arrive before spring of 1925. In desperation, Welch tried treating an infected seven-year-old girl with some expired antitoxin – but she died just a few hours after he administered it.
Welch radioed for help to all the major towns in Alaska as well as the US Public Health Service in Washington, DC. His telegram read: An outbreak of diphtheria is almost inevitable here. I am in urgent need of one million units of diphtheria antitoxin. Mail is the only form of transportation.
FOUR-LEGGED HEROES
When the Alaskan Board of Health learned about the outbreak, the men rushed to devise a plan to get antitoxin to Nome. Dropping the serum in by airplane was impossible, as the available planes were unsuitable for flying during Alaska’s severe winter weather, where temperatures were routinely as cold as -50 degrees Fahrenheit.
In late January 1925, roughly 30,000 units of antitoxin were located in an Anchorage hospital and immediately delivered by train to a nearby city, Nenana, en route to Nome. Nenana was the furthest city that was reachable by rail – but unfortunately it was still more than 600 miles outside of Nome, with no transportation to make the delivery. Meanwhile, Welch had confirmed 20 total cases of diphtheria, with dozens more at high risk. Diphtheria was known for wiping out entire communities, and the entire town of Nome was in danger of suffering the same fate.
It was Mark Summer, the Board of Health superintendent, who suggested something unorthodox: Using a relay team of sled-racing dogs to deliver the antitoxin serum from Nenana to Nome. The Board quickly voted to accept Summer’s idea and set up a plan: The thousands of units of antitoxin serum would be passed along from team to team at different towns along the mail route from Nenana to Nome. When it reached a town called Nulato, a famed dogsled racer named Leonhard Seppala and his experienced team of huskies would take the serum more than 90 miles over the ice of Norton Sound, the longest and most treacherous part of the journey. Past the sound, the serum would change hands several times more before arriving in Nome.
Between January 27 and 31, the serum passed through roughly a dozen drivers and their dog sled teams, each of them carrying the serum between 20 and 50 miles to the next destination. Though each leg of the trip took less than a day, the sub-zero temperatures – sometimes as low as -85 degrees – meant that every driver and dog risked their lives. When the first driver, Bill Shannon, arrived at his checkpoint in Tolovana on January 28th, his nose was black with frostbite, and three of his dogs had died. The driver who relieved Bill Shannon, named Edgar Kalland, needed the owner of a local roadhouse to pour hot water over his hands to free them from the sled’s metal handlebar. Two more dogs from another relay team died before the serum was passed to Seppala at a town called Ungalik.
THE FINAL STRETCHES
Seppala and his team raced across the ice of the Norton Sound in the dead of night on January 31, with wind chill temperatures nearing an astonishing -90 degrees. The team traveled 84 miles in a single day before stopping to rest – and once rested, they set off again in the middle of the night through a raging winter storm. The team made it across the ice, as well as a 5,000-foot ascent up Little McKinley Mountain, to pass the serum to another driver in record time. The serum was now just 78 miles from Nome, and the death toll in town had reached 28.
The serum reached Gunnar Kaasen and his team of dogs on February 1st. Balto, Kaasen’s lead dog, guided the team heroically through a winter storm that was so severe Kaasen later reported not being able to see the dogs that were just a few feet ahead of him.
Visibility was so poor, in fact, that Kaasen ran his sled two miles past the relay point before noticing – and not wanting to lose a minute, he decided to forge on ahead rather than doubling back to deliver the serum to another driver. As they continued through the storm, the hurricane-force winds ripped past Kaasen’s sled at one point and toppled the sled – and the serum – overboard. The cylinder containing the antitoxin was left buried in the snow – and Kaasen tore off his gloves and dug through the tundra to locate it. Though it resulted in a bad case of frostbite, Kaasen eventually found the cylinder and kept driving.
Kaasen arrived at the next relay point on February 2nd, hours ahead of schedule. When he got there, however, he found the relay driver of the next team asleep. Kaasen took a risk and decided not to wake him, fearing that time would be wasted with the next driver readying his team. Kaasen, Balto, and the rest of the team forged on, driving another 25 miles before finally reaching Nome just before six in the morning. Eyewitnesses described Kaasen pulling up to the town’s bank and stumbling to the front of the sled. There, he collapsed in exhaustion, telling onlookers that Balto was “a damn fine dog.”
A LIVING LEGACY
Just a few hours after Balto’s heroic arrival in Nome, the serum had been thawed and was ready to administer to the patients with diphtheria. Amazingly, the relay team managed to complete the entire journey in just 127 hours – a world record at the time – without one serum vial damaged or destroyed. The serum shipment that arrived by dogsled – along with additional serum deliveries that followed in the next several weeks – were successful in stopping the outbreak in its tracks.
Balto and several other dogs – including Togo, the lead dog on Seppala’s team – were celebrated as local heroes after the race. Balto died in 1933, while the last of the human serum runners died in 1999 – but their legacy lives on: In early 2021, an all-female team of healthcare workers made the news by braving the Alaskan winter to deliver COVID-19 vaccines to people in rural North Alaska, traveling by bobsled and snowmobile – a heroic journey, and one that would have been unthinkable had Balto, Togo, and the 1925 sled runners not first paved the way.
“Virtual Biopsies” May Soon Make Some Invasive Tests Unnecessary
Patient Dan Chessin met recently in Dr. Lee Ponsky's office at University Hospitals, discussing Chessin's history with prostate cancer.
At his son's college graduation in 2017, Dan Chessin felt "terribly uncomfortable" sitting in the stadium. The bouts of pain persisted, and after months of monitoring, a urologist took biopsies of suspicious areas in his prostate.
This innovation may enhance diagnostic precision and promptness, but it also brings ethical concerns to the forefront.
"In my case, the biopsies came out cancerous," says Chessin, 60, who underwent robotic surgery for intermediate-grade prostate cancer at University Hospitals Cleveland Medical Center.
Although he needed a biopsy, as most patients today do, advances in radiologic technology may make such invasive measures unnecessary in the future. Researchers are developing better imaging techniques and algorithms—a form of computer science called artificial intelligence, in which machines learn and execute tasks that typically require human brain power.
This innovation may enhance diagnostic precision and promptness. But it also brings ethical concerns to the forefront of the conversation, highlighting the potential for invasion of privacy, unequal patient access, and less physician involvement in patient care.
A National Academy of Medicine Special Publication, released in December, emphasizes that setting industry-wide standards for use in patient care is essential to AI's responsible and transparent implementation as the industry grapples with voluminous quantities of data. The technology should be viewed as a tool to supplement decision-making by highly trained professionals, not to replace it.
MRI--a test that uses powerful magnets, radio waves, and a computer to take detailed images inside the body--has become highly accurate in detecting aggressive prostate cancer, but its reliability is more limited in identifying low and intermediate grades of malignancy. That's why Chessin opted to have his prostate removed rather than take the chance of missing anything more suspicious that could develop.
His urologist, Lee Ponsky, says AI's most significant impact is yet to come. He hopes University Hospitals Cleveland Medical Center's collaboration with research scientists at its academic affiliate, Case Western Reserve University, will lead to the invention of a virtual biopsy.
A National Cancer Institute five-year grant is funding the project, launched in 2017, to develop a combined MRI and computerized tool to support more accurate detection and grading of prostate cancer. Such a tool would be "the closest to a crystal ball that we can get," says Ponsky, professor and chairman of the Urology Institute.
In situations where AI has guided diagnostics, radiologists' interpretations of breast, lung, and prostate lesions have improved as much as 25 percent, says Anant Madabhushi, a biomedical engineer and director of the Center for Computational Imaging and Personalized Diagnostics at Case Western Reserve, who is collaborating with Ponsky. "AI is very nascent," Madabhushi says, estimating that fewer than 10 percent of niche academic medical centers have used it. "We are still optimizing and validating the AI and virtual biopsy technology."
In October, several North American and European professional organizations of radiologists, imaging informaticists, and medical physicists released a joint statement on the ethics of AI. "Ultimate responsibility and accountability for AI remains with its human designers and operators for the foreseeable future," reads the statement, published in the Journal of the American College of Radiology. "The radiology community should start now to develop codes of ethics and practice for AI that promote any use that helps patients and the common good and should block use of radiology data and algorithms for financial gain without those two attributes."
Overreliance on new technology also poses concern when humans "outsource the process to a machine."
The statement's leader author, radiologist J. Raymond Geis, says "there's no question" that machines equipped with artificial intelligence "can extract more information than two human eyes" by spotting very subtle patterns in pixels. Yet, such nuances are "only part of the bigger picture of taking care of a patient," says Geis, a senior scientist with the American College of Radiology's Data Science Institute. "We have to be able to combine that with knowledge of what those pixels mean."
Setting ethical standards is high on all physicians' radar because the intricacies of each patient's medical record are factored into the computer's algorithm, which, in turn, may be used to help interpret other patients' scans, says radiologist Frank Rybicki, vice chair of operations and quality at the University of Cincinnati's department of radiology. Although obtaining patients' informed consent in writing is currently necessary, ethical dilemmas arise if and when patients have a change of heart about the use of their private health information. It is likely that removing individual data may be possible for some algorithms but not others, Rybicki says.
The information is de-identified to protect patient privacy. Using it to advance research is akin to analyzing human tissue removed in surgical procedures with the goal of discovering new medicines to fight disease, says Maryellen Giger, a University of Chicago medical physicist who studies computer-aided diagnosis in cancers of the breast, lung, and prostate, as well as bone diseases. Physicians who become adept at using AI to augment their interpretation of imaging will be ahead of the curve, she says.
As with other new discoveries, patient access and equality come into play. While AI appears to "have potential to improve over human performance in certain contexts," an algorithm's design may result in greater accuracy for certain groups of patients, says Lucia M. Rafanelli, a political theorist at The George Washington University. This "could have a disproportionately bad impact on one segment of the population."
Overreliance on new technology also poses concern when humans "outsource the process to a machine." Over time, they may cease developing and refining the skills they used before the invention became available, said Chloe Bakalar, a visiting research collaborator at Princeton University's Center for Information Technology Policy.
"AI is a paradigm shift with magic power and great potential."
Striking the right balance in the rollout of the technology is key. Rushing to integrate AI in clinical practice may cause harm, whereas holding back too long could undermine its ability to be helpful. Proper governance becomes paramount. "AI is a paradigm shift with magic power and great potential," says Ge Wang, a biomedical imaging professor at Rensselaer Polytechnic Institute in Troy, New York. "It is only ethical to develop it proactively, validate it rigorously, regulate it systematically, and optimize it as time goes by in a healthy ecosystem."
How Emerging Technologies Can Help Us Fight the New Coronavirus
A security officer in a protective mask checks the temperature of a passenger following the outbreak of a new coronavirus, at an expressway toll station on the eve of the Chinese Lunar New Year celebrations, in Xianning.
In nature, few species remain dominant for long. Any sizable population of similar individuals offers immense resources to whichever parasite can evade its defenses, spreading rapidly from one member to the next.
Which will prove greater: our defenses or our vulnerabilities?
Humans are one such dominant species. That wasn't always the case: our hunter-gatherer ancestors lived in groups too small and poorly connected to spread pathogens like wildfire. Our collective vulnerability to pandemics began with the dawn of cities and trade networks thousands of years ago. Roman cities were always demographic sinks, but never more so than when a pandemic agent swept through. The plague of Cyprian, the Antonine plague, the plague of Justinian – each is thought to have killed over ten million people, an appallingly high fraction of the total population of the empire.
With the advent of sanitation, hygiene, and quarantines, we developed our first non-immunological defenses to curtail the spread of plagues. With antibiotics, we began to turn the weapons of microbes against our microbial foes. Most potent of all, we use vaccines to train our immune systems to fight pathogens before we are even exposed. Edward Jenner's original vaccine alone is estimated to have saved half a billion lives.
It's been over a century since we suffered from a swift and deadly pandemic. Even the last deadly influenza of 1918 killed only a few percent of humanity – nothing so bad as any of the Roman plagues, let alone the Black Death of medieval times.
How much of our recent winning streak has been due to luck?
Much rides on that question, because the same factors that first made our ancestors vulnerable are now ubiquitous. Our cities are far larger than those of ancient times. They're inhabited by an ever-growing fraction of humanity, and are increasingly closely connected: we now routinely travel around the world in the course of a day. Despite urbanization, global population growth has increased contact with wild animals, creating more opportunities for zoonotic pathogens to jump species. Which will prove greater: our defenses or our vulnerabilities?
The tragic emergence of coronavirus 2019-nCoV in Wuhan may provide a test case. How devastating this virus will become is highly uncertain at the time of writing, but its rapid spread to many countries is deeply worrisome. That it seems to kill only the already infirm and spare the healthy is small comfort, and may counterintuitively assist its spread: it's easy to implement a quarantine when everyone infected becomes extremely ill, but if carriers may not exhibit symptoms as has been reported, it becomes exceedingly difficult to limit transmission. The virus, a distant relative of the more lethal SARS virus that killed 800 people in 2002 to 2003, has evolved to be transmitted between humans and spread to 18 countries in just six weeks.
Humanity's response has been faster than ever, if not fast enough. To its immense credit, China swiftly shared information, organized and built new treatment centers, closed schools, and established quarantines. The Coalition for Epidemic Preparedness Innovations, which was founded in 2017, quickly funded three different companies to develop three different varieties of vaccine: a standard protein vaccine, a DNA vaccine, and an RNA vaccine, with more planned. One of the agreements was signed after just four days of discussion, far faster than has ever been done before.
The new vaccine candidates will likely be ready for clinical trials by early summer, but even if successful, it will be additional months before the vaccine will be widely available. The delay may well be shorter than ever before thanks to advances in manufacturing and logistics, but a delay it will be.
The 1918 influenza virus killed more than half of its victims in the United Kingdom over just three months.
If we faced a truly nasty virus, something that spreads like pandemic influenza – let alone measles – yet with the higher fatality rate of, say, H7N9 avian influenza, the situation would be grim. We are profoundly unprepared, on many different levels.
So what would it take to provide us with a robust defense against pandemics?
Minimize the attack surface: 2019-nCoV jumped from an animal, most probably a bat, to humans. China has now banned the wildlife trade in response to the epidemic. Keeping it banned would be prudent, but won't be possible in all nations. Still, there are other methods of protection. Influenza viruses commonly jump from birds to pigs to humans; the new coronavirus may have similarly passed through a livestock animal. Thanks to CRISPR, we can now edit the genomes of most livestock. If we made them immune to known viruses, and introduced those engineered traits to domesticated animals everywhere, we would create a firewall in those intermediate hosts. We might even consider heritably immunizing the wild organisms most likely to serve as reservoirs of disease.
None of these defenses will be cheap, but they'll be worth every penny.
Rapid diagnostics: We need a reliable method of detection costing just pennies to be available worldwide inside of a week of discovering a new virus. This may eventually be possible thanks to a technology called SHERLOCK, which is based on a CRISPR system more commonly used for precision genome editing. Instead of using CRISPR to find and edit a particular genome sequence in a cell, SHERLOCK programs it to search for a desired target and initiate an easily detected chain reaction upon discovery. The technology is capable of fantastic sensitivity: with an attomolar (10-18) detection limit, it senses single molecules of a unique DNA or RNA fingerprint, and the components can be freeze-dried onto paper strips.
Better preparations: China acted swiftly to curtail the spread of the Wuhan virus with traditional public health measures, but not everything went as smoothly as it might have. Most cities and nations have never conducted a pandemic preparedness drill. Best give people a chance to practice keeping the city barely functional while minimizing potential exposure events before facing the real thing.
Faster vaccines: Three months to clinical trials is too long. We need a robust vaccine discovery and production system that can generate six candidates within a week of the pathogen's identification, manufacture a million doses the week after, and scale up to a hundred million inside of a month. That may be possible for novel DNA and RNA-based vaccines, and indeed anything that can be delivered using a standardized gene therapy vector. For example, instead of teaching each person's immune system to evolve protective antibodies by showing it pieces of the virus, we can program cells to directly produce known antibodies via gene therapy. Those antibodies could be discovered by sifting existing diverse libraries of hundreds of millions of candidates, computationally designed from scratch, evolved using synthetic laboratory ecosystems, or even harvested from the first patients to report symptoms. Such a vaccine might be discovered and produced fast enough at scale to halt almost any natural pandemic.
Robust production and delivery: Our defenses must not be vulnerable to the social and economic disruptions caused by a pandemic. Unfortunately, our economy selects for speed and efficiency at the expense of robustness. Just-in-time supply chains that wing their way around the world require every node to be intact. If workers aren't on the job producing a critical component, the whole chain breaks until a substitute can be found. A truly nasty pandemic would disrupt economies all over the world, so we will need to pay extra to preserve the capacity for independent vertically integrated production chains in multiple nations. Similarly, vaccines are only useful if people receive them, so delivery systems should be as robustly automated as possible.
None of these defenses will be cheap, but they'll be worth every penny. Our nations collectively spend trillions on defense against one another, but only billions to protect humanity from pandemic viruses known to have killed more people than any human weapon. That's foolish – especially since natural animal diseases that jump the species barrier aren't the only pandemic threats.
We will eventually make our society immune to naturally occurring pandemics, but that day has not yet come, and future pandemic viruses may not be natural.
The complete genomes of all historical pandemic viruses ever to have been sequenced are freely available to anyone with an internet connection. True, these are all agents we've faced before, so we have a pre-existing armory of pharmaceuticals and vaccines and experience. There's no guarantee that they would become pandemics again; for example, a large fraction of humanity is almost certainly immune to the 1918 influenza virus due to exposure to the related 2009 pandemic, making it highly unlikely that the virus would take off if released.
Still, making the blueprints publicly available means that a large and growing number of people with the relevant technical skills can single-handedly make deadly biological agents that might be able to spread autonomously -- at least if they can get their hands on the relevant DNA. At present, such people most certainly can, so long as they bother to check the publicly available list of which gene synthesis companies do the right thing and screen orders -- and by implication, which ones don't.
One would hope that at least some of the companies that don't advertise that they screen are "honeypots" paid by intelligence agencies to catch would-be bioterrorists, but even if most of them are, it's still foolish to let individuals access that kind of destructive power. We will eventually make our society immune to naturally occurring pandemics, but that day has not yet come, and future pandemic viruses may not be natural. Hence, we should build a secure and adaptive system capable of screening all DNA synthesis for known and potential future pandemic agents... without disclosing what we think is a credible bioweapon.
Whether or not it becomes a global pandemic, the emergence of Wuhan coronavirus has underscored the need for coordinated action to prevent the spread of pandemic disease. Let's ensure that our reactive response minimally prepares us for future threats, for one day, reacting may not be enough.