ANCHORAGE, Alaska; Braunschweig, Germany––
A German immunologist, funded by People for the Ethical Treatment of Animals, has reportedly made a scientific discovery that may scratch horses from the substance of the Iditarod serum run legend.
Horses in the Iditarod Trail Race, the 938-mile world’s most famous and most controversial dog sled race?
Yes, tens of thousands of horses, far more than all the dogs who ever ran the Iditarod, including the 150-odd dogs who have died along the route.
Horses made the 1925 serum run to Nome possible
Horses were used to produce the horse-blood-based anti-diphtheria antitoxin that was central to the Iditarod legend. Horses are still used, in growing numbers, to combat a global resurgence of diphtheria resulting from declining childhood vaccination rates.
Just six weeks from the March 7, 2020 start of the 48th annual running of the Iditarod Trail Race, commemorating the role of dog sled teams in stopping a 1925 diphtheria outbreak that menaced the snowbound city of Nome, Alaska, comes word via the peer-reviewed journal Scientific Reports that the use of horses to make the anti-diphtheria antitoxin may no longer be necessary.
The Iditarod story originated in the late 19th century, at a time when the toxin-producing Cornybacterium diphteriae bacterium responsible for causing diphtheria was a leading cause of childhood death.
“The ‘strangling angel, as it was called, killed hundreds of thousands of children worldwide each year,” recalled Science reporter Kai Kupferschmidt, in describing the breakthrough by Michael Hust of the Technical University of Braunschweig, funded by the PETA International Science Consortium in 2016 to develop a non-animal-based anti-diphtheria antitoxin.
Polish/German bacteriologist Emil von Behring (1854-1917) in 1901 received the very first Nobel Prize in Physiology or Medicine for discovering the horse-blood-based anti-diphtheria antitoxin used for more than 120 years now.
“Routine childhood immunizations with an inactivated form of the toxin reduced the number of cases to several thousand annually—mostly in children who missed their vaccinations,” continued Kupferschmidt.
Vaccine production itself does not harm horses––but neglect by developing world laboratories does
“But today, the [production] method—which harvests antibody-rich serum after injecting the diphtheria toxin into horses—is widely seen as antiquated, and some find it cruel, given how the animals used are sometimes treated. The toxin itself does not seem to seriously harm the horses,” Kupferschmidt observed.
However, horses used in vaccine production are often stabled for excessively long hours, and sometimes underfed and otherwise neglected, especially in the developing world––as ANIMALS 24-7 documented in a 2001 exposé of conditions at the King Institute in Guindy, Chennai, India, which helped to bring about the closure of the horse serum collection operation in early 2002.
“Another downside: In up to 5% of cases, the patient’s immune system reacts against the horse antibodies, a life-threatening side effect called ‘serum sickness,’ reported Kupferschmidt.
The Hust approach to producing anti-diphtheria antitoxin uses “lab-grown cells to make human antibodies that could finally replace the ones produced in horse serum,” Kupferschmidt summarized. “Several of the new antibodies combined protected guinea pigs from the effects of the diphtheria toxin injected into the skin; the scientists,” Hust and partners, “hope trials in humans will be next.”
The guinea pig testing, Kupferschmidt mentioned, was not funded by PETA. But PETA did fund immunizing three human volunteers against diphtheria using the von Behring vaccine, Kupferschmidt explained, and then collecting blood to isolate the immune cells that make antibodies that target the toxin.
The antibodies were then isolated and tested.
“Even the best antibody alone did not protect the animals from the effects of diphtheria toxin, but when researchers combined two or three of the antibodies, they did,” Kupferschmidt explained.
$5 billion market emerging
“The antibodies,” having originated in humans, “will [nonetheless] have to be tested in humans, however,” Kupferschmidt said, “a procedure that will take years and cost millions of dollars. Given that diphtheria cases are rare, companies have shown minimal interest in the past.”
That may rapidly change, however, On the very same day that Hust et al described their findings in Scientific Reports, the business journal Fior Markets, of Pune, Maharashtra, India, projected that “the global diphtheria, pertussis, and tetanus vaccine market is expected to grow from $2.97 billion in 2018 U.S. dollars to $5.07 billion by 2026.
“Growing incidence of diphtheria, tetanus and pertussis coupled with rising worldwide governmental support for vaccination programs are anticipated to drive” the anticipated near-doubling of anti-diphtheria vaccine revenue, Fior Markets explained.
“A great piece of work”
“This is a great piece of work that responds to the international need for a replacement” for horse serum, MassBiologics researcher Mark Klempner told Kupferschmidt.
MassBiologics, a nonprofit organization based at the University of Massachusetts Medical School, “is also developing a horse-free way to make diphtheria antitoxin,” Kupferschmidt said.
The single-antibody treatment “developed through directly screening human antibodies by MassBiologics appears to be further ahead,” Kupferschmidt wrote. “It has just been tested in a phase I clinical trial, which typically establishes safety, not efficacy.
19th century antiserum now called “experimental therapy”
“Although the data from that trial aren’t published yet,” Kupferschmidt specified, “Klempner says discussions are already ongoing with the U.S. Food and Drug Administration to replace an aging stockpile of diphtheria antiserum from horses kept at the U.S. Centers of Disease Control & Prevention. The stockpile is officially expired and doses are only offered as an experimental therapy.”
Finished Kupferschmidt, “MassBiologics’s antibody, called S315, has been tested in more stringent animal models than the German team used, Klempner says. And one advantage of having a single antibody is that it will be cheaper than a combination of two or three antibodies, he says, adding that it should also be comparable in cost or less expensive than the horse serum treatment.”
Annual “re-enactment” to start on March 7
Whichever non-horse anti-diphtheria antitoxin replaces the von Behring version, the replacement research and development is likely to excite scientists and physicians more than Iditarod Trail Race followers.
The 58 mushers scheduled to participate in 2020 include previous winners Martin Buser, Peter Kaiser, Lance Mackey, Mitch Seavey, and Joar Leifseth Ulsom, along with at least one medical doctor, Robert Bundtzen, 66, of Anchorage.
The Iditarod dog sled race, begun in 1973, is touted as a quasi-re-enactment of the serum run undertaken from January 27 to February 1, 1925, during the coldest, darkest, windiest days of a fierce Alaskan winter, when 20 mushers and their 400 dogs relayed a packet of anti-diphtheria serum 674 miles northwest from the nearest railhead.
Bad weather had already thwarted an attempt to fly the anti-diphtheria serum to Nome.
“Always ready” Togo
Two dogs in particular won distinction during the serum run.
Togo, 12, was already an Alaskan legend for racing exploits and a surprising number of other acts of heroism. Deemed a poor prospect to become a sled dog as a pup, he was given away to a lady who wanted a lap dog, but escaped through a window and ran back to sled racer and courier Leonhard Seppala’s dog yard.
Togo followed Seppala’s team for a time, and then at age eight months began running in front of the team.
Putting Togo in harness, Seppala, who had already trained several legendary dogs, soon discovered that the pup was a natural leader, even of much older and larger dogs.
Crossed the Norton Sound
Togo led Seppala’s team 170 miles to meet the serum relay, then led them 91 miles back toward Nome with the serum, charging through a headwind across the frozen and often treacherous Norton Sound––an audacious shortcut that saved the team 200 miles of running along the rocky shoreline.
That was by far the longest part of the relay, but Togo wasn’t done. After Seppala handed off the serum, Togo still had enough energy left to lead the team in a mass break from harness in hot pursuit of a herd of reindeer.
Seppala soon recaptured the others, but Togo and another dog were lost in a blizzard and presumed dead until they trotted into Nome a week later––and were photographed as they sauntered down the main street as if they owned it.
Balto, age 6, a dog also once considered a poor sledding prospect, brought the serum into Nome.
Driver Gunnar Kaasen apparently moved Balto into the lead harness after two more experienced dogs balked at running into the wind, i.e. semi-blind, forced to rely on their noses to find the trail.
The Kaasen team was not even supposed to be out that day, but a downed telegraph line kept Kaasen and the previous driver, Charlie Olson, from finding out that they had been ordered to wait out the storm.
Blinded himself by wind and snow, early into what was supposed to have been the next-to-last rather than the final leg of the relay, Kaasen had little choice but to depend on Balto to get them there.
“Damn fine dog!”
Balto made mistakes, running them into a drift at one point and flipping the sled at another, after he and Kaasen ran past their intended rest stop at Solomon. Yet Balto made up for inexperience as a lead dog with rare ability to find the trail beneath the drifts and determination to get the job done.
Reaching Port Safety at three in the morning, Kaasen found final leg driver Ed Rohn and team asleep. Rather than lose an hour waking Rohn up and harnessing his team, Kaasen and his dogs kept going.
When they reached Nome, wrote the Salisbury cousins, Laney and Gay, in their 2003 history of the serum run The Cruelest Miles, “Witnesses to this drama said they saw Kaasen stagger off the sled and stumble up to Balto, where he collapsed, muttering ‘Damn fine dog!’”
Sleepy Ed Rohn & team were heroes too
As matters developed, it was fortunate for Nome that Kaasen had left the sleeping Rohn behind, because that left Rohn and his team right where they needed to be to become the heroes of the second serum run a few days later.
The second run was urgently needed to resupply Nome after the first serum stock was exhausted.
The longevity of the serum run participants, including the dogs, became legendary in itself. Togo survived to age 16, Balto to age 14, and Sye, the last of his serum run teammates, to 17.
Leonhard Seppala lived to age 90. The last of the human mushers, Edgar Nollner, died in 1999 at 94.