No Spring Chicken - Alexis Carrel

No spring chicken...

In the early 20th century, New York's tabloid newspapers were invited each year to celebrate chicken heart cells. The scientists who cultivated the cells even went so far as to create a special glass-walled amphitheater for the annual event, which was held on January 17. Rumor has it, they sang Happy Birthday as well...

Image source: National Institutes of Health/ Stocktrek Images/ Getty Images

In the beginning, there were cells
In 1912, French surgeon and Nobel laureate Alexis Carrel isolated and cultivated cells from the heart of a chicken while working at the Rockefeller Institute of New York. During this period, cell culture was still in its infancy stages. It was only a few years earlier in 1907 that Yale University biologist Ross Granville Harrison was the first to successfully carry out in-vitro cultivation of animal tissues. Back then, cell cultivation emerged as a rather mysterious undertaking. Carrel’s laboratory assistants were required to dress in black, the rooms were darkened and great care was taken to protect the cells from sun light to ensure their survival.

The genesis of a new dogma: cell immortality
Carrel and his coworkers experimented with several chicken cell cultures using a hanging drop method previously invented by Harrison, the cell cultivation pioneer. The cells were grown in a drop of chicken plasma diluted with water and then placed on an inverted slide, which was incubated at 39 °C. Every two to three days the cells were transferred to a fresh liquid drop.
After three months of continuous cultivation, Carrel published his first scientific paper: “On the Permanent Life of Tissues Outside of the Organism". The cells survived, constantly dividing and pulsating. Carrel and his team subsequently optimized the process by modifying the medium composition and the general cultivation methods. Although the pulsation slowed and then ceased after a few months in the summer of 1913, Carrels chicken heart tissue cultures continued to proliferate for decades.
The cells exceeded the typical life span of a chicken by a wide margin. The findings created a new scientific dogma that accepted immortality as an intrinsic property of all cells. The consensus was that cells can survive outside of the organism under optimal conditions, meaning they were capable of dividing in perpetuity. This led scientists to believe that cellular aging, as well as cell and organism death, was attributed to external factors, such as the accumulation of toxic metabolites within the body's cells.

It doesn’t fit in…
Leonard Hayflick, a young scientist active in cancer research, was maintaining several human cell cultures by the end of the 1950's. Hayflick observed that some of the cultures stopped growing after a period of time. A close look at his research notes reveals that it was always the oldest cultures that perished. Although he carried out various experiments, the results were always the same: He couldn’t keep the old cells alive.

The Hayflick phenomenon
Hayflick was aware that his findings would completely refute Carrels scientifically-accredited view on cell immortality - or the continuous proliferation of culture cells. He was thus forced to obtain support from established experts before publishing his results. This included contact with several leading researchers such as George Gey from Johns Hopkins Hospital, who had isolated the famous HeLa cells a few years before. Hayflick sent samples of his cells and asked the experts to cultivate them with their own methods.
After receiving reports that these cells were not surviving either, Hayflick was confident that human and animal cells possessed a limited capacity for replication. He finally published a report in a small scientific journal in 1965 titled “The limited in vitro lifetime of human diploid cell strains.” Using several different approaches, Hayflick determined that chicken cells divide at least 30 times before dying, while normal human connective tissue divides roughly 50 times until cell division stops. This pre-determined, limited cell division is meanwhile referred to as the Hayflick limit or Hayflick phenomenon.
With his experiments, Hayflick proved that normal cells have a finite life-span, making immortality a unique feature of malignant tumor cells.

Carrel goes astray
Alexis Carrel didn't live long enough to witness the repudiation of his hypothesis. He died in 1944 in his home country France. As an avowing National Socialist sympathizer and intellectual pioneer of eugenics and racial theory, he retired from the Rockefeller Institute at the beginning of World War II in 1939.  Then, he worked for the Vichy regime in Paris at the health ministry and served as regent of the Fondation Française pour l’Etude des Problèmes Humains, the French Foundation for the Study of Human Problems until his death.
Carrel was outsurvived by his alleged “immortal” chicken heart cells. The last batch was discarded in 1946 after 34 years of replication. The reasons for the extremely long life-span of Carrel's famous chicken cells remain a mystery.

Condemned to grow old
Despite continuous advances in anti-aging science and medicine, we are a long way from discovering a fountain of youth or a super pill that would keep us forever young. At this point, we must accept one fact: human and animal cells are not immortal. As our cells continue to age, so will we.

 

References:

1. A. Carrel: On the Permanent Life of Tissues outside of the Organism. JEM, (1912) May 1, 15 (5):516
2. B. Gifford: Jung bleiben!: Warum wir altern – und was wir wirklich dagegen tun können. Heyne Verlag, 2016
3. The Official Website of the Nobel Prize: www.nobelprize.org/nobel_prizes/medicine/laureates/1912/carrel-bio.html
4. A. Carrel (1912): On the Permanent Life of Tissues outside of the Organism. JEM, 15 (5):516
5. W. Pytlik (2011): Zellkulturtechnik: Mit Nervenfasern von Fröschen fing alles an; Dossier Gesundheitsindustrie BW; www.gesundheitsindustrie-bw.de/de/fachbeitrag/dossier/zellkulturtechnik-mit-nervenfasern-von-froeschen-fing-alles-an/
6. L. Jiang (2012): Alexis Carrel’s Immortal Chick Heart Tissue Cultures (1912 – 1949). The Embryo Project Encyclopedia; embryo.asu.edu/pages/alexis-carrels-immortal-chick-heart-tissue-cultures-1912-1946
7. Hayflick, L. (1965): The limited in vitro lifetime of human diploid cell strains. In: Exp. Cell Res. 37(3):614-636