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.
Beyond Henrietta Lacks: How the Law Has Denied Every American Ownership Rights to Their Own Cells
A 2017 portrait of Henrietta Lacks.
The common perception is that Henrietta Lacks was a victim of poverty and racism when in 1951 doctors took samples of her cervical cancer without her knowledge or permission and turned them into the world's first immortalized cell line, which they called HeLa. The cell line became a workhorse of biomedical research and facilitated the creation of medical treatments and cures worth untold billions of dollars. Neither Lacks nor her family ever received a penny of those riches.
But racism and poverty is not to blame for Lacks' exploitation—the reality is even worse. In fact all patients, then and now, regardless of social or economic status, have absolutely no right to cells that are taken from their bodies. Some have called this biological slavery.
How We Got Here
The case that established this legal precedent is Moore v. Regents of the University of California.
John Moore was diagnosed with hairy-cell leukemia in 1976 and his spleen was removed as part of standard treatment at the UCLA Medical Center. On initial examination his physician, David W. Golde, had discovered some unusual qualities to Moore's cells and made plans prior to the surgery to have the tissue saved for research rather than discarded as waste. That research began almost immediately.
"On both sides of the case, legal experts and cultural observers cautioned that ownership of a human body was the first step on the slippery slope to 'bioslavery.'"
Even after Moore moved to Seattle, Golde kept bringing him back to Los Angeles to collect additional samples of blood and tissue, saying it was part of his treatment. When Moore asked if the work could be done in Seattle, he was told no. Golde's charade even went so far as claiming to find a low-income subsidy to pay for Moore's flights and put him up in a ritzy hotel to get him to return to Los Angeles, while paying for those out of his own pocket.
Moore became suspicious when he was asked to sign new consent forms giving up all rights to his biological samples and he hired an attorney to look into the matter. It turned out that Golde had been lying to his patient all along; he had been collecting samples unnecessary to Moore's treatment and had turned them into a cell line that he and UCLA had patented and already collected millions of dollars in compensation. The market for the cell lines was estimated at $3 billion by 1990.
Moore felt he had been taken advantage of and filed suit to claim a share of the money that had been made off of his body. "On both sides of the case, legal experts and cultural observers cautioned that ownership of a human body was the first step on the slippery slope to 'bioslavery,'" wrote Priscilla Wald, a professor at Duke University whose career has focused on issues of medicine and culture. "Moore could be viewed as asking to commodify his own body part or be seen as the victim of the theft of his most private and inalienable information."
The case bounced around different levels of the court system with conflicting verdicts for nearly six years until the California Supreme Court ruled on July 9, 1990 that Moore had no legal rights to cells and tissue once they were removed from his body.
The court made a utilitarian argument that the cells had no value until scientists manipulated them in the lab. And it would be too burdensome for researchers to track individual donations and subsequent cell lines to assure that they had been ethically gathered and used. It would impinge on the free sharing of materials between scientists, slow research, and harm the public good that arose from such research.
"In effect, what Moore is asking us to do is impose a tort duty on scientists to investigate the consensual pedigree of each human cell sample used in research," the majority wrote. In other words, researchers don't need to ask any questions about the materials they are using.
One member of the court did not see it that way. In his dissent, Stanley Mosk raised the specter of slavery that "arises wherever scientists or industrialists claim, as defendants have here, the right to appropriate and exploit a patient's tissue for their sole economic benefit—the right, in other words, to freely mine or harvest valuable physical properties of the patient's body. … This is particularly true when, as here, the parties are not in equal bargaining positions."
Mosk also cited the appeals court decision that the majority overturned: "If this science has become for profit, then we fail to see any justification for excluding the patient from participation in those profits."
But the majority bought the arguments that Golde, UCLA, and the nascent biotechnology industry in California had made in amici briefs filed throughout the legal proceedings. The road was now cleared for them to develop products worth billions without having to worry about or share with the persons who provided the raw materials upon which their research was based.
Critical Views
Biomedical research requires a continuous and ever-growing supply of human materials for the foundation of its ongoing work. If an increasing number of patients come to feel as John Moore did, that the system is ripping them off, then they become much less likely to consent to use of their materials in future research.
Some legal and ethical scholars say that donors should be able to limit the types of research allowed for their tissues and researchers should be monitored to assure compliance with those agreements. For example, today it is commonplace for companies to certify that their clothing is not made by child labor, their coffee is grown under fair trade conditions, that food labeled kosher is properly handled. Should we ask any less of our pharmaceuticals than that the donors whose cells made such products possible have been treated honestly and fairly, and share in the financial bounty that comes from such drugs?
Protection of individual rights is a hallmark of the American legal system, says Lisa Ikemoto, a law professor at the University of California Davis. "Putting the needs of a generalized public over the interests of a few often rests on devaluation of the humanity of the few," she writes in a reimagined version of the Moore decision that upholds Moore's property claims to his excised cells. The commentary is in a chapter of a forthcoming book in the Feminist Judgment series, where authors may only use legal precedent in effect at the time of the original decision.
"Why is the law willing to confer property rights upon some while denying the same rights to others?" asks Radhika Rao, a professor at the University of California, Hastings College of the Law. "The researchers who invest intellectual capital and the companies and universities that invest financial capital are permitted to reap profits from human research, so why not those who provide the human capital in the form of their own bodies?" It might be seen as a kind of sweat equity where cash strapped patients make a valuable in kind contribution to the enterprise.
The Moore court also made a big deal about inhibiting the free exchange of samples between scientists. That has become much less the situation over the more than three decades since the decision was handed down. Ironically, this decision, as well as other laws and regulations, have since strengthened the power of patents in biomedicine and by doing so have increased secrecy and limited sharing.
"Although the research community theoretically endorses the sharing of research, in reality sharing is commonly compromised by the aggressive pursuit and defense of patents and by the use of licensing fees that hinder collaboration and development," Robert D. Truog, Harvard Medical School ethicist and colleagues wrote in 2012 in the journal Science. "We believe that measures are required to ensure that patients not bear all of the altruistic burden of promoting medical research."
Additionally, the increased complexity of research and the need for exacting standardization of materials has given rise to an industry that supplies certified chemical reagents, cell lines, and whole animals bred to have specific genetic traits to meet research needs. This has been more efficient for research and has helped to ensure that results from one lab can be reproduced in another.
The Court's rationale of fostering collaboration and free exchange of materials between researchers also has been undercut by the changing structure of that research. Big pharma has shrunk the size of its own research labs and over the last decade has worked out cooperative agreements with major research universities where the companies contribute to the research budget and in return have first dibs on any findings (and sometimes a share of patent rights) that come out of those university labs. It has had a chilling effect on the exchange of materials between universities.
Perhaps tracking cell line donors and use restrictions on those donations might have been burdensome to researchers when Moore was being litigated. Some labs probably still kept their cell line records on 3x5 index cards, computers were primarily expensive room-size behemoths with limited capacity, the internet barely existed, and there was no cloud storage.
But that was the dawn of a new technological age and standards have changed. Now cell lines are kept in state-of-the-art sub zero storage units, tagged with the source, type of tissue, date gathered and often other information. Adding a few more data fields and contacting the donor if and when appropriate does not seem likely to disrupt the research process, as the court asserted.
Forging the Future
"U.S. universities are awarded almost 3,000 patents each year. They earn more than $2 billion each year from patent royalties. Sharing a modest portion of these profits is a novel method for creating a greater sense of fairness in research relationships that we think is worth exploring," wrote Mark Yarborough, a bioethicist at the University of California Davis Medical School, and colleagues. That was penned nearly a decade ago and those numbers have only grown.
The Michigan BioTrust for Health might serve as a useful model in tackling some of these issues. Dried blood spots have been collected from all newborns for half a century to be tested for certain genetic diseases, but controversy arose when the huge archive of dried spots was used for other research projects. As a result, the state created a nonprofit organization to in essence become a biobank and manage access to these spots only for specific purposes, and also to share any revenue that might arise from that research.
"If there can be no property in a whole living person, does it stand to reason that there can be no property in any part of a living person? If there were, can it be said that this could equate to some sort of 'biological slavery'?" Irish ethicist Asim A. Sheikh wrote several years ago. "Any amount of effort spent pondering the issue of 'ownership' in human biological materials with existing law leaves more questions than answers."
Perhaps the biggest question will arise when -- not if but when -- it becomes possible to clone a human being. Would a human clone be a legal person or the property of those who created it? Current legal precedent points to it being the latter.
Today, October 4, is the 70th anniversary of Henrietta Lacks' death from cancer. Over those decades her immortalized cells have helped make possible miraculous advances in medicine and have had a role in generating billions of dollars in profits. Surviving family members have spoken many times about seeking a share of those profits in the name of social justice; they intend to file lawsuits today. Such cases will succeed or fail on their own merits. But regardless of their specific outcomes, one can hope that they spark a larger public discussion of the role of patients in the biomedical research enterprise and lead to establishing a legal and financial claim for their contributions toward the next generation of biomedical research.
Is a Successful HIV Vaccine Finally on the Horizon?
The HIV virus (yellow) infecting a human cell.
Few vaccines have been as complicated—and filled with false starts and crushed hopes—as the development of an HIV vaccine.
While antivirals help HIV-positive patients live longer and reduce viral transmission to virtually nil, these medications must be taken for life, and preventative medications like pre-exposure prophylaxis, known as PrEP, need to be taken every day to be effective. Vaccines, even if they need boosters, would make prevention much easier.
In August, Moderna began human trials for two HIV vaccine candidates based on messenger RNA.
As they have with the Covid-19 pandemic, mRNA vaccines could change the game. The technology could be applied for gene editing therapy, cancer, other infectious diseases—even a universal influenza vaccine.
In the past, three other mRNA vaccines completed phase-2 trials without success. But the easily customizable platforms mean the vaccines can be tweaked better to target HIV as researchers learn more.
Ever since HIV was discovered as the virus causing AIDS, researchers have been searching for a vaccine. But the decades-long journey has so far been fruitless; while some vaccine candidates showed promise in early trials, none of them have worked well among later-stage clinical trials.
There are two main reasons for this: HIV evolves incredibly quickly, and the structure of the virus makes it very difficult to neutralize with antibodies.
"We in HIV medicine have been desperate to find a vaccine that has effectiveness, but this goal has been elusive so far."
"You know the panic that goes on when a new coronavirus variant surfaces?" asked John Moore, professor of microbiology and immunology at Weill Cornell Medicine who has researched HIV vaccines for 25 years. "With HIV, that kind of variation [happens] pretty much every day in everybody who's infected. It's just orders of magnitude more variable a virus."
Vaccines like these usually work by imitating the outer layer of a virus to teach cells how to recognize and fight off the real thing off before it enters the cell. "If you can prevent landing, you can essentially keep the virus out of the cell," said Larry Corey, the former president and director of the Fred Hutchinson Cancer Research Center who helped run a recent trial of a Johnson & Johnson HIV vaccine candidate, which failed its first efficacy trial.
Like the coronavirus, HIV also has a spike protein with a receptor-binding domain—what Moore calls "the notorious RBD"—that could be neutralized with antibodies. But while that target sticks out like a sore thumb in a virus like SARS-CoV-2, in HIV it's buried under a dense shield. That's not the only target for neutralizing the virus, but all of the targets evolve rapidly and are difficult to reach.
"We understand these targets. We know where they are. But it's still proving incredibly difficult to raise antibodies against them by vaccination," Moore said.
In fact, mRNA vaccines for HIV have been under development for years. The Covid vaccines were built on decades of that research. But it's not as simple as building on this momentum, because of how much more complicated HIV is than SARS-CoV-2, researchers said.
"They haven't succeeded because they were not designed appropriately and haven't been able to induce what is necessary for them to induce," Moore said. "The mRNA technology will enable you to produce a lot of antibodies to the HIV envelope, but if they're the wrong antibodies that doesn't solve the problem."
Part of the problem is that the HIV vaccines have to perform better than our own immune systems. Many vaccines are created by imitating how our bodies overcome an infection, but that doesn't happen with HIV. Once you have the virus, you can't fight it off on your own.
"The human immune system actually does not know how to innately cure HIV," Corey said. "We needed to improve upon the human immune system to make it quicker… with Covid. But we have to actually be better than the human immune system" with HIV.
But in the past few years, there have been impressive leaps in understanding how an HIV vaccine might work. Scientists have known for decades that neutralizing antibodies are key for a vaccine. But in 2010 or so, they were able to mimic the HIV spike and understand how antibodies need to disable the virus. "It helps us understand the nature of the problem, but doesn't instantly solve the problem," Moore said. "Without neutralizing antibodies, you don't have a chance."
Because the vaccines need to induce broadly neutralizing antibodies, and because it's very difficult to neutralize the highly variable HIV, any vaccine will likely be a series of shots that teach the immune system to be on the lookout for a variety of potential attacks.
"Each dose is going to have to have a different purpose," Corey said. "And we hope by the end of the third or fourth dose, we will achieve the level of neutralization that we want."
That's not ideal, because each individual component has to be made and tested—and four shots make the vaccine harder to administer.
"You wouldn't even be going down that route, if there was a better alternative," Moore said. "But there isn't a better alternative."
The mRNA platform is exciting because it is easily customizable, which is especially important in fighting against a shapeshifting, complicated virus. And the mRNA platform has shown itself, in the Covid pandemic, to be safe and quick to make. Effective Covid vaccines were comparatively easy to develop, since the coronavirus is easier to battle than HIV. But companies like Moderna are capitalizing on their success to launch other mRNA therapeutics and vaccines, including the HIV trial.
"You can make the vaccine in two months, three months, in a research lab, and not a year—and the cost of that is really less," Corey said. "It gives us a chance to try many more options, if we've got a good response."
In a trial on macaque monkeys, the Moderna vaccine reduced the chances of infection by 85 percent. "The mRNA platform represents a very promising approach for the development of an HIV vaccine in the future," said Dr. Peng Zhang, who is helping lead the trial at the National Institute of Allergy and Infectious Diseases.
Moderna's trial in humans represents "a very exciting possibility for the prevention of HIV infection," Dr. Monica Gandhi, director of the UCSF-Gladstone Center for AIDS Research, said in an email. "We in HIV medicine have been desperate to find a vaccine that has effectiveness, but this goal has been elusive so far."
If a successful HIV vaccine is developed, the series of shots could include an mRNA shot that primes the immune system, followed by protein subunits that generate the necessary antibodies, Moore said.
"I think it's the only thing that's worth doing," he said. "Without something complicated like that, you have no chance of inducing broadly neutralizing antibodies."
"I can't guarantee you that's going to work," Moore added. "It may completely fail. But at least it's got some science behind it."