In winter of the year 1925 the City of Nome, Alaska was stricken by a diphtheria epidemic. Late in January Dr. Curtis Welch and Nome mayor George Maynard realised, after the deaths of several children, that the small arctic city was in the grip not of an epidemic of tonsillitis as they had thought, but rather of the dreaded child killer diphtheria. Dr. Welch had only a small supply of badly outdated antitoxin which proved ineffective. On the 22d January Welch radiogrammed the governor in Juneau and the U. S. Public Health Service in Washington, D.C., asking for help. At first it was thought that the nearest supplies of fresh antitoxin were in Seattle, Washington, but on the 26th January 300,000 units were discovered in Anchorage Railroad Hospital. The latter were delivered to the town of Nenana, as far as they could be taken by rail; that was not until the 27th. Delivery of the antiserum to Nome by airplane was discussed, but the only aircraft available were WWI J1 biplanes with water-cooled engines, not able to cope with extreme winter temperatures. Air delivery in midwinter temperatures was virtually impossible. The Nome Board of Health decided that the serum must be delivered by dogteam, a controversial decision that attracted much scorn and indignation in the local press.

Leonhard Seppala, universally acclaimed as the best dog driver in Nome, was sent out on the 27th on what he thought was a solo run to meet the train at Nenana, or at best to meet a second dog team at Nulato if the serum had been sent on from Nenana. After he and his dogs were on the trail it was decided to send out other mushers in a relay. Seppala ran over 170 miles across some of the most dangerous and treacherous parts of the run. He met the serum runner unexpectedly shortly after crossing the treacherous sea ice on Norton Sound, took the hand off and returned back another 91 miles, re-crossing the Sound and having run over 261 miles in total. He then handed the serum off to Charlie Olson. Charlie carried it 25 miles to Bluff where he turned it over to Gunnar Kaasen. Kaasen was supposed to hand-off the serum to Rohn at Port Safety, but Rohn had gone to sleep and Kaasen decided to keep going to Nome. In all, Kaasen and Balto ran a total of 53 miles and many thought his decision to not wake Rohn was motivated by a desire to grab the glory for himself and Balto.

The black sleddog Balto in particular, who led the team that covered the final stretch into Nome, became the most famous canine celebrity of the era after Rin Tin Tin, and his statue is still one of the most popular tourist attractions in New York City's Central Park. The publicity also helped spur an inoculation campaign in the U.S. that dramatically reduced the threat of the disease. There is much controversy surrounding Balto's role in this race and the statue in Central Park. According to Leonhard Seppala, he was a scrub freight dog that was left behind when he set out on the trip. Many consider Seppala's lead dog Togo to be the real hero of the run. The actual statue of Balto was modeled after Balto, but displayed him wearing Togo's colors (awards). In the last years of his life Seppala still was heartbroken by the way the credit had gone to Balto, in his mind Togo was the real hero of the serum race.