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Although vaccinations have saved billions of lives over the past decades, it was a cell culture breakthrough in the 1960’s - isolation of the first normal, non-cancerogenic human cell line - that made a major contribution.
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How soon we forget
Diseases such as Lassa and Ebola are frightening viral infections because they arise out of nowhere, rapidly evolve into epidemics and in most cases are fatal. We often have limited methods and medications to effectively cure these diseases or properly treat the patients.
Ebola recently broke out in the Congo, alarming the World Health Organization (WHO), its representatives and other officials, most of who still remember the last epidemic in West Africa in 2014 when more than 11,000 people died. When we think about viral infections, it's usually these types of devastating epidemics that we have in mind.
But it wasn't long ago that viral infections were an everyday threat. Many diseases that people died from as recently as 100 years ago now rarely occur or they have been eradicated.
Vaccination – a major impact
Rabies, polio and hepatitis A are examples of deadly diseases that have become much less of a threat over time. The same can be said about common childhood diseases like measles and mumps.
The key to containing viral infections is vaccination. One of the most important protagonists in the development of vaccines is a human cell line called WI-38.
Summer of 1962
In July 1962, a young and ambitious American scientist at the Wistar Institute for Anatomy and Biology in Philadelphia received an air-mail package from Sweden. The scientist was Leonard Hayflick, who ran the Wistar cell culture lab at the time. Apart from supplying the institute’s researchers with cells, Hayflick was also active in cancer research and focused on examining whether viruses could lead to human cancer.
For his research, Hayflick needed cell lines that did not exist in the early 1960’s: non-cancerogenic human cells. At that time, all established cell lines were generated from cancer tissue, such as the popular HeLa cells. Hayflick decided to work with fetal cells because they haven't been exposed to external factors and viruses that could influence cancer development. He thought they would provide the most reliable results. This was an important aspect in making them a valuable model in his cancer research.
This was easier said than done however. Because abortion was illegal in most states in the US in the 1960’s, access to fetal tissue in order to isolate the cells was difficult. In the end, he found a source in Sven Gard, the chairman of the virology department at the Karolinska Institute in Stockholm. Abortion was legal in Sweden, and that put Gard in a position to supply Hayflick with the tissues he needed to carry out his research.
Birth of an exceptional life saver
When Hayflick opened the package from Sweden, he found a set of fetal lungs on ice. A few days before, a Swedish woman had an abortion. The little fetus was transferred to the Karolinska Institute where the lungs were dissected and prepared for a shipment to Philadelphia.
Hayflick unpacked the parcel, prepared the tissue and finally isolated individual cells using an enzymatic treatment. It was his 38th attempt to isolate normal, non-cancerogenic human cells at the Wistar Institute and the result was exceptional. The WI-38 cell line was born.
He cultured the cells in small flasks at 37 °C and split the them into two flasks as soon as they covered the entire bottom. It wasn't long before he had prepared hundreds of flasks and began to fill them into glass ampoules.
Putting WI-38 on ice
Hayflick had previously observed that normal human cell cultures divide around 40 to 60 times, after which reproduction slows down until cell division stops completely - a phenomenon now called the Hayflick limit.
Together with his colleague Paul Moorhead, he also discovered that the cells interrupt their predetermined number of replications when frozen. They remain viable and start dividing after they have been thawed.
These findings were the reason why Hayflick first stored the WI-38 cells in liquid nitrogen tanks in the basement of the Wistar Institute. He wanted to preserve their ability to divide until he was able to verify that the cells would not carry any cancer disposition.
Around the globe
Hayflick received test results from Sweden one year later verifying that no close relatives of the donor fetus had contracted cancer. Now that he had the green light, he began distributing WI-38 cells around the globe. Some of the ampoules were even hand delivered to Europe and Russia, while hundreds of cultures were mailed to other scientists.
Among the recipients were several vaccine researchers. These emerging communities of vaccine producers profited the most from the WI-38 cells, a benefit eventually felt by the rest of the world.
WI-38 cells quickly evolved to become a virus identification and vaccine production tool since the cells were easily infected with a wide variety of human viruses.
In 1967, WI-38 cells became a model organism in a huge global WHO survey related to virus-based respiratory tract infections. Virologists and pharmaceutical companies also began using WI-38 cells for vaccine production. By the 1970’s, vaccinations against rubella, measles, rabies, adenovirus, polio and others were being developed.
Researchers continue to reap the benefits of Wi-38 cells to create new vaccines, such as against chickenpox.
A question of ethics
There is no question that WI-38 cells have rapidly accelerated advances in medicine. These advances are nevertheless deeply tied to ethical issues. Who owns the cells? Is donor consent required? Should permission have been obtained from the Swedish parents before isolating the cells from the aborted fetus?
In hindsight, it's easy to condemn the use of tissue without donor consent. However, this does not reflect the reality of 50 years ago. Back then, there were no laws in the US or Sweden that required permission to use fetal cells. These controversial issues are still widely discussed today. Some people are calling for stricter regulations governing the use of human cell material, while others fear such legislation will put the brakes on advances in medical research.
One thing is clear though. While mankind profited greatly from vaccines derived from WI-38 cells and pharmaceutical companies earned millions by selling them, the donor family did not benefit materially.
On the trail of life
More than a half century after Hayflick saw his WI-38 cells for the first time in one of his culture flasks, he began to trace their footsteps with the aim of understanding the impact that his "children" had, as he once called the cells.
In a recently published study, Hayflick and epidemiologist S. Jay Olshansky from the university of Illinois examined how many lives have been saved to date by the development of the WI-38 cell strain.
They estimated that in the US alone, vaccines derived from WI-38 cells prevented nearly 200 million cases of dangerous viral infections, including approximately 450,000 deaths, between 1963 and 2015. Extrapolating this figure on a global scale, that means around 4.5 billion cases of disease were prevented and more than 10 million lives were saved.
M. Wadman: Cell Division. Nature 498, 422-426 (2013)
S. J. Olshansky and L. Hayflick. The Role of the WI-38 Cell Strain in Saving Lives and Reducing Morbidity. AIMS Public Health, 4 (2): 127 (2017); DOI: 10.3934/publichealth.2017.2.127