Here are the facts about fetal cell lines and COVID-19 vaccines

As more people apply for religious exemptions to vaccine mandates, experts explain how and why fetal cells are used in drug development, from vaccines to common pain medications.

In the wake of federal vaccine mandates in the U.S., debate has erupted over the waves of fire fighters,police staff, and other workers who have applied for religious exemptions to getting their COVID-19 shots. The number of applications is likely to spike as the January 4 vaccination deadline nears for large private businesses and some healthcare facilities. And one common reason people give for religious exemptions is the link between vaccines and human fetal cells.

It’s true that such cells have been used either in the testing or development and production of COVID-19 vaccines. The cells are grown in a laboratory and were derived from a few elective abortions performed more than three decades ago. These same cell lines are also used to test and advance our understanding of several routine drugs, including acetaminophen, ibuprofen, and aspirin, and they continue to be used for treatment research in diseases such as Alzheimer’s and hypertension.

“So many people don’t realize how important fetal cell lines are to develop life-saving medicines and vaccines that they rely on every day,” says Amesh Adalja, an infectious disease expert at Johns Hopkins Center for Health Security. “Their use in developing COVID-19 vaccines isn’t anything different or special.”

For some religious leaders, the science is informing their recommendations. In a December 2020 statement, the U.S. Conference of Catholic Bishops referred to these cell lines as morally compromised for their connection, albeit remote, with abortions. But they reiterated the message from the Vatican justifying the use of vaccines, lacking alternatives, as an act of charity and moral responsibility in situations of serious health danger, such as the COVID-19 pandemic.

Although it’s unclear how many religious exemptions for COVID-19 shots have been granted so far, those applying are required to prove “religious sincerity” and in some cases attest that they will also avoid the routine drugs developed using fetal cells.

But doctors worry that some people’s objections may stem in part from misunderstandings of the science. Richard Zimmerman, a family medicine specialist at the University of Pittsburgh School of Medicine and a part-time physician at Pittsburgh’s East Liberty Family Health Care Center, says that some of his patients have voiced scepticism because they believe the COVID-19 vaccines contain cells from aborted fetuses. This is incorrect.

Here is the history of how fetal cells are used in drug development, where the cells come from, and why it’s been so hard to find alternatives.

Why are fetal cells necessary for drug development

Unlike bacteria, viruses need a host to survive; they can only grow and reproduce inside the host cells they infect. Vaccines typically deliver small doses of weakened or inactivated versions of the virus, or key parts of it, to give the host body a preview of the pathogen without causing illness. This enables the immune system to remember a specific virus and how to destroy it if the body ever encounters the germ in the future.

To mass produce vaccines, manufacturers need a way to make enormous quantities of the viral components.

Scientists use fertilized chicken eggs, for instance, as hosts to multiply influenza viruses and produce the annual flu vaccines. But vaccines manufacturers prefer to grow the virus in mammal cells, mainly because they help prevent the virus from mutating and help scale production. 

In the early days, scientists used animal cells. But they later realized that these cells can harbor other undesirable animal viruses, which would then contaminate the vaccine. For instance, an early version of the polio vaccine administered extensively between 1955 and 1963 was produced using monkey cells. But scientists later found out the cells were contaminated with a monkey virus called SV40.

The other issue was that some human viruses didn’t grow as well in non-human animal cells. So scientists turned to human fetal cells to produce vaccine viruses.

“They were known to rarely contain contaminating viruses,” says cell biologist Leonard Hayflick at the University of California, San Francisco. He created the oldest fetal cell strain, known as WI-38, from an elective abortion in Sweden in the early 1960s. Hayflick knew that human fetal cells, unlike adult human cells, were less likely to contain unwanted viruses.

Over the years, though, scientists have identified other animal cells that could be safely used to develop vaccines against certain viruses. African green monkey kidney cells, for instance, have been used to develop several vaccines, including certain ones for polio and smallpox.

But especially with new human viruses, “there is preference for using a human cell line,” says Alessondra Speidel, a biomaterials scientist at Sweden’s Karolinska Institute, possibly because they’re likely to infect and grow better in human than animal cells.

Where do fetal cells come from?

To create fetal cell strains, scientists must isolate millions of cells from tiny pieces of tissue collected from a dead embryo. Each cell can divide into two nearly 50 times. And these cells can be frozen—or in some cases, immortalized—so that today the cells being used come from tissue collected decades ago.

Hayflick, for instance, has frozen ten million human fetal lung cells—derived from one aborted fetus—in each of 700 glass vials after the original cell population had doubled seven times. Given their potential to continue doubling at least another 30 times, each vial can yield “tens of thousands of kilos of cells,” he says. “That’s enough cells to supply the world's vaccine manufacturers with WI-38 cells for several years.” These lung cells are currently used to produce vaccines for varicella, rubella, hepatitis A, and rabies. Other scientists have transformed fetal kidney and retinal cells so that they become immortal, dividing forever. The PER.C6 cell line, for instance, is derived from immortalized retinal cells from an 18-week-old fetus aborted in 1985.

Johnson & Johnson uses PER.C6 to produce its COVID-19 vaccine. The company used these cells to grow adenoviruses—modified so that they wouldn’t replicate or cause disease—that were then purified and used to deliver the genetic code for SARS-CoV-2’s signature spike protein. The J&J vaccine does not contain any of the fetal cells that once housed the adenovirus because they were extracted and filtered out.

Pfizer and Moderna used another immortal cell line, HEK-293, derived from the kidney of a fetus aborted in the 1970s. The cells were used during development to confirm that the genetic instructions for making the SARS-CoV-2 spike protein worked in human cells. This was like a proof-of-concept test, Speidel says, and the fetal cells were not used to produce either of these mRNA vaccines.

“The issue is whether one believes that it is ethically acceptable to develop and use life-saving medicines, vaccines, and treatments that are dependent on a cell line that was created using aborted human fetal cells a half century ago,” says Frank Graham, a molecular virology and medicine expert and emeritus professor at Canada’s McMaster University, who created the HEK-293 cell line.

Even if future vaccines can somehow avoid the use of these fetal cell lines, it’s hard to ignore their foundational role. The same applies to the widespread use of these cells in studying several common diseases like diabetes and hypertension and advancing their treatments.

And beyond the science, the message that has resonated most with several of Zimmerman’s vaccine-hesitant patients is one of altruism. “Nobody wants to be the one who triggers an infectious disease on their loved one,” he says.

Editor's Note: This story has been updated to clarify that fetal cell lines are used in research on the generic pain reliever acetaminophen.

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