These stray dogs that were caught for experiments eventually saved countless diabetics

April 24th of each year is Laboratory Animal Day .

In the history of biomedicine, almost every achievement that saved humanity was made possible by the efforts of experimental animals. However, due to the limitations of the times, some experimental animals in the past could not be treated in a scientific and standardized manner.

For example, the insulin experiment conducted on dogs . Although this research completely changed the treatment of diabetes and won the researchers a Nobel Prize, it also caused great controversy because of the treatment of experimental animals.

No. 33 without a name

On November 18, 1921, after being injected with anesthesia, a female shepherd dog numbered "No. 33" was put on the operating table. Under the scalpel of surgeon Frederick Banting, her entire pancreas was removed , which was artificially causing her to suffer from diabetes , a disease that was considered a terminal illness at the time.

Number 33, 1921. The man next to him may be Banting | Thomas Fisher Rare Book Library, University of Toronto

At that time, Banting believed that a hormone produced by the pancreas might be able to inhibit diabetes. As an experiment, he injected pancreatic extract into "No. 33" who had his pancreas removed, and then drew blood regularly to analyze the composition of blood and urine. Two months later, the once energetic and vibrant "No. 33" gradually became very weak and could hardly stand. Only after the injection of pancreatic extract could it recover its spirit - Banting was very happy, which fully demonstrated the effectiveness of the extract.

However, the pancreatic extract was very limited, and the remaining had been reserved for testing on diabetic patients and could no longer be used to sustain the life of "No. 33". Moreover, after the effectiveness of pancreatic extract was proven, "No. 33" seemed to be no longer valuable; after repeated acupuncture to draw blood, its body was covered with abscesses.

Finally, more than 70 days after the pancreas was removed, on January 27, 1922, "No. 33" was euthanized , and its life was transformed into two data charts produced by Banting.

Banting's two graphs showing blood sugar and urine sugar levels for No. 33 | Thomas Fisher Rare Book Library, University of Toronto

However, being able to live for more than 70 days after the pancreas was removed, "No. 33" is already the luckiest dog in this experiment. Previously, due to the unsuccessful application of the extract, most dogs died within a few days after the pancreas was removed .

Due to lack of experience, Banting's surgical operation was not mature, and he needed a large number of dogs to "practice"; at the time when animal experiment standards were not perfect, the dogs used for experiments were all stray dogs outside the laboratory. Moreover, Banting did not track the postoperative conditions of each dog, nor did he keep a complete record of all experimental dogs - because of this, we don't even know how many dogs participated in this cruel experiment .

Banting, Best and the dog "No. 408", who died four days after having his pancreas removed｜Thomas Fisher Rare Book Library, University of Toronto

We also don’t know what kind of environment these experimental dogs lived in. But Banting and his colleague Charles Best once complained about the small and hot laboratory space. The experimental dogs may have undergone surgery in such an environment, and ended their lives in crowds and fear.

After controversy, "No. 33" has a name

The lives of experimental dogs have brought about great progress in diabetes treatment.

In early 1922, Elliott Joslin, a diabetes doctor, used insulin to treat a patient for the first time. The patient's blood sugar level dropped significantly, and he was stunned on the spot, as if he saw a mountain of dead bones standing up, regaining flesh and blood, and regaining vitality.

Leonard Thompson, the first patient saved by insulin｜Insulin Collection, University of Toronto

Honor and fame came quickly - two years later, Banting won the Nobel Prize for his discovery of insulin . At the age of 32, he became the youngest Nobel Prize winner in Physiology or Medicine. He received a letter from the then Prime Minister of Canada and was even invited to Buckingham Palace to meet the public with King George V.

After winning the Nobel Prize, Banting appeared on the cover of Time Magazine.

But behind the honor, controversies related to experimental dogs have gradually surfaced.

Many people accused Banting of not caring about the welfare of experimental animals. The Abolitionist, a Canadian anti-vivisection magazine, accused Banting and his colleagues of being a "dog stealing gang" and included an illustration of a doctor holding a scalpel in one hand and a shivering puppy in the other, pointing the scalpel at its belly: "You are such a healthy puppy, now I will remove your pancreas and give you diabetes."

Illustration of the Anti-Vivisection Magazine accusing Banting | Thomas Fisher Rare Book Library, University of Toronto

Thanks to the efforts of animal protectors, people learned about the existence of "No. 33". People believed that "No. 33" was a hero who sacrificed for the advancement of medicine and should not have only a cold code name. So, the dead "No. 33" finally had a name - Marjorie.

However, Banting refuted the accusation of animal abuse. He took out a photo of himself and a laboratory dog, saying that he had a good relationship with the dog. He used an anthropomorphic description to describe the dog in the experiment: "One dog looked very smart, as if it knew its mission in this experiment."

Banting with a lab dog, with surgical instruments on the operating table. Thomas Fisher Rare Book Library, University of Toronto

These controversies related to experimental animals have caused tension in the scientific community. In order to avoid arousing sympathy and losing control, biomedical journals have deleted the names of experimental animals, and their images have become a series of data charts . Editors also require authors to use objective medical terms, and all statements that imply animal suffering cannot appear in journals.

We need experimental animals, but we also need legal protection

On the one hand, these controversies and changes have made people begin to pay attention to animal welfare and standardize experimental procedures. On the other hand, they have also made the animals that died in the experiments "invisible" in the results.

In fact, for hundreds of years, these nameless experimental animals have saved countless human lives . Insulin discovered by dogs has saved 9 million patients with type 1 diabetes; the polio vaccine developed by rhesus monkeys has enabled more than 20 million people to walk and avoid paralysis; the leprosy treatment method developed by armadillos has also cured millions of people...

Nine-banded armadillo | birdphotos / Wikimedia Commons

It is estimated that about 100 million vertebrates are used in experiments every year worldwide, and this does not include invertebrates such as fruit flies and nematodes, which are used in larger quantities. Under existing technical conditions, the use of experimental animals is still unavoidable ; but fortunately, with the strengthening of animal protection awareness, more and more countries and people have realized that the rights of experimental animals should also be protected.

At present, each country has formulated relevant regulations and review procedures for the use of experimental animals. Although the regulations are slightly different, they are all based on the internationally recognized 3R principle - minimizing the number of animals sacrificed for experiments and minimizing the pain that animals need to endure before sacrifice.

3R Principles

Replacement

Use other methods to replace the use of animals, such as using cell and tissue culture, using mathematical and computer models, etc. If absolute substitution (completely eliminating experimental animals) is not feasible, relative substitution can also be considered, such as using invertebrates instead of vertebrates.

Reduction

Reduce the number of animals used in each experiment. Researchers can obtain sufficient information from fewer animals by improving experimental methods; data and resources should be shared between research organizations and researchers, so as to minimize the consumption of animals due to repeated experiments.

Refinement

Minimize the pain that animals may experience and improve animal welfare. This can be applied to almost every aspect, such as: improving their food; providing them with suitable housing and as many enrichment facilities as possible; providing them with appropriate anesthetics and analgesics to relieve the pain they suffer; training animals to cooperate with experimental procedures such as blood collection to avoid stress for them.

Every drug or vaccine that ultimately saves millions of people is not the result of just one or a few people. Every animal that suffers and dies as a result is a great collaborator —human researchers have devoted their time and energy, but they have devoted their lives.

Rats used in experiments | Janet Stephens / Wikimedia Commons

In 2014, Jen Jacobs, a diabetic patient, painted a picture of Marjorie.

Marjorie in this picture has the same pose as in the 1921 photo, with her head raised and her eyes looking expectantly, and a vial of insulin dangling around her neck - but this time, there is no experimenter beside her to perform experimental operations. Next to this picture, the editor wrote: "Remember, heroes don't always wear capes, sometimes they wear furry coats."

Marjorie by Jacobs | Jen Jacobs

References

[1]https://www.journals.uchicago.edu/doi/full/10.1093/envhis/emx134

[2] https://theconversation.com/the-discovery-of-insulin-a-story-of-monstrous-egos-and-toxic-rivalries-172820

[3] https://www.thediabetescouncil.com/from-death-to-life-the-discovery-of-insulin/

[4] https://researchanimaltraining.com/articles/3rs-and-humane-killing-of-animals/

[5] https://pubmed.ncbi.nlm.nih.gov/8785959/

[6] https://en.wikipedia.org/wiki/Leprosy

[7] https://pubmed.ncbi.nlm.nih.gov/10816969/

[8] https://www.who.int/zh/news-room/fact-sheets/detail/poliomyelitis

Author: Cat Tun

Editor: Mai Mai

Image source: Thomas Fisher Rare Book Library, University of Toronto