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December 13, 2020

Why Were Fetal Cells Used to Make Certain Vaccines?

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Sometimes people are surprised to find out that a subset of vaccines are made using human fetal cells. Typical questions related to the use of these cells include which vaccines use them, whether it is amoral or against one’s religion, and whether the DNA from these cells could cause cancer or other diseases in vaccine recipients. We and others have addressed each of these questions (see resources below); however, at the root of these concerns is “why?” Why would scientists choose to use cells from an aborted human fetus? We address this briefly on our fetal cells webpage, but a recent book by Meredith Wadman, The Vaccine Race (2017, Viking, Penguin Random House, LLC), provides a detailed, well-written account of this part of vaccine history.

The Vaccine Race focuses on researchers at the Wistar Institute of Anatomy and Biology during the late 1950s and 1960s under the direction of Dr. Hilary Koprowski. The story closely follows efforts by Dr. Leonard Hayflick (known for defining the “Hayflick Limit” thereby opening the door for a new field of research into cellular aging) and Dr. Stanley Plotkin (co-inventor of several vaccines including rubella, rotavirus and rabies).

While there is much to learn about vaccine history from this book, the story provides a great opportunity to understand how fetal cells came to be used for making vaccines including rubella, chickenpox, shingles, hepatitis A and one version of rabies vaccine.

In the beginning . . . before vaccines were even a thought

As part of the Wistar Institute rebirth under Dr. Koprowski, Leonard Hayflick was invited to join the team based on his expertise in cell culture. Koprowski was a polio researcher. The polio virus had been successfully grown in cell culture by Frederick Robbins, Thomas Weller and John Enders in the late 1940s, so Koprowski wanted a scientist who could provide cells not only to his own lab, but to other researchers as well.

But Hayflick would not be satisfied to simply supply cells to other labs. He had questions he wanted to answer, too. In 1958 after settling into his new lab at the Wistar Institute, Hayflick focused on creating cell lines that would grow continuously in the lab. The famous and versatile HeLa cells could grow repeatedly in the lab, but they were cancerous cells. So, at that time, when researchers wanted to use non-cancerous cells, their choices were limited. Some researchers were using monkey kidney cells and others would use cells from freshly isolated rodent tissues. These cells did not grow well in the lab, so they had to be prepared fresh each time they were needed by sacrificing lab animals. In addition to being cumbersome, costly, and requiring large numbers of animals, this method made it difficult to consistently assure the same quality of starting material.

Hayflick was aware that researchers at UCal Berkley, Jorgen Fogh and colleagues, had used cells from human placentas to create two cell lines, so when his wife gave birth to their daughter Susan, Hayflick took the cells to try growing them in the lab. Today, it appears that these cells, called WISH cells, were contaminated sometime later by the HeLa cell line. Either way, this effort was Hayflick’s first attempt to isolate cells from a human source, and the goal was to establish a continuously growing cell line.

Can viruses cause cancer?

At the time, another question that researchers were trying to understand related to whether viruses could cause cancer. Although we now know that some viruses cause cancer, it had not been proven at the time. Hayflick collaborated with a surgeon at the University of Pennsylvania, Robert Ravdin, to obtain several hundred tumor samples in a series of experiments designed to answer this question. His goal was to isolate the broth used to grow the tumor cells in the lab, incubate it with non-cancerous cells, and see if the non-cancerous cells were infected and, subsequently, transformed.

However, Hayflick was worried that cells obtained from people or monkeys might inadvertently contain cancer-causing viruses that would confound his results. He reasoned that because a fetus in the womb is protected from most outside pathogens, aborted fetuses would offer the “cleanest” source of cells for the latter part of his experiment. Although Hayflick was not the first to use fetal cells, the use of these cells was not widespread, and according to federal and state law at the time was illegal. However, in the medical community, abortions deemed necessary were referred to as “therapeutic abortions” and were legal in limited situations. As with the tumor samples, the aborted fetuses would be discarded as medical waste, so Hayflick was able to obtain some fetuses and successfully isolate and grow cells. But, his new cells would do much more than help him address viruses as a cause of cancer.

Cells and aging — the Hayflick Limit

Through a series of elegant experiments, Hayflick and colleagues were able to prove that normal, noncancerous cells, such as his fetal cell lines, reproduced a limited number of times. They went on to show that these limits were based on events in the nucleus (not the cytoplasm) and were not based on the age of the person from whom the cells were isolated.

And now to vaccines . . .

Following the success of the polio vaccine program, researchers were excited at the possibility of preventing other diseases caused by viruses. In some cases the viruses themselves had not yet been isolated. In other cases the viruses had been isolated, so the path to developing a vaccine would be shorter. Unfortunately, as this work was progressing, it was discovered that the monkey kidney cells in which the Salk and Sabin polio vaccines had been grown contained a cancer-causing virus of monkeys, called SV40, which stood for Simian Virus-40. As it turned out, the virus did not cause cancer in people, but that was not known at the time.

Wistar researchers Hayflick, Koprowski and Plotkin realized that as long as viral vaccines were being grown in animal cells, the potential existed for contamination by viruses that had yet to be identified. For this reason, and since Hayflick had fetal cells which were much less likely to have been exposed to viruses, they started researching the use of fetal cells as growth factories for vaccine viruses.

First, they had to determine whether viruses identified as vaccine candidates would grow in fetal cells. Plotkin, who had been studying rubella for years, realized that the rubella virus could grow in fetal cells since the disease was most devastating to developing fetuses when their moms were infected during pregnancy. Koprowski also started working on a version of the polio vaccine grown in fetal cells, performing a series of experiments to determine “safety” of this version of the polio vaccine before giving it to babies.

However, not all scientists agreed with this approach. Indeed, a panel convened by the NIH determined that fetal cells could also have undetected viruses and that the cells needed to be better characterized. In other parts of the world, reception to the use of fetal cells enjoyed more support including that of the World Health Organization. As more information and experience accumulated, successful vaccines were made in human fetal cells that were well-characterized. However, none of the vaccines were made using fetal cells that Hayflick was working with at the time.

The source of human fetal cells used in vaccines

As it goes in the lab, sometimes the end result of an experiment or project is determined by something completely out of the scientist’s control. And, this was the case for Hayflick when his first 20-some strains of fetal cells were lost due to a freezer failure. Fortunately, he had published the experiments he completed on them, and he was quite adept at the process of culturing them. So, he saw this as an opportunity to create a strain for vaccine manufacturing that could be considered a gold standard. To this end, he sought an aborted fetus that came from a relatively healthy woman; that is, one who did not have cancers or genetically-based diseases that could theoretically be transmitted to future vaccine recipients. To his way of thinking, the necessary criteria was a cell line free of viruses and cancer and that would be available in such large quantities that manufacturers would never run out of the supply.

So, how could the supply be limitless? The beauty of cell culture is that the cells grow to confluence in the container to which they are seeded. Once they reach confluence, they can be “split” into a series of additional containers which can then be “split” when they reach confluence and so on. In this way the cell quantities expand exponentially. A single set of lungs from a fetus that was aborted between 3 and 4 months of gestation was large enough to dissect and create many ampules of low passage cells. Hayflick calculated that with a single small bottle that would hold about 10 million cells, he could produce up to 10 sextillion cells (1022 cells) or 87,000 times more cells than a company would need to make enough of one vaccine to ship to more than 40 countries in one year (p.89).

By the time Hayflick set out to replace his fetal cell supply following the freezer incident, he was collaborating with a Swedish scientist, Sven Gard, who was more readily able to supply the fetal tissue for him. The cell line that was ultimately used for some vaccine production was named WI-38. The fetus was from a woman who had several young children and a husband who was often out of town for his job. She indicated that when he was home, he drank and had been in prison; otherwise, she was a healthy woman with an unremarkable health history. 

WI-38 cells from that single abortion were shared with researchers around the world and used to develop vaccines against polio, rubella and rabies. They were also used in public health labs in England and Wales, as well as sent to WHO labs on four continents, for use in detecting diseases in hospitalized patients.

Eventually, researchers at the British Medical Council in the UK prepared cells from a second aborted fetus. This second cell line was named MRC-5. Ultimately, the rubella vaccine and one rabies vaccine were made using WI-38 cells, but due to concerns around legal and supply issues during the 1970s when other vaccines were being developed, the vaccines against hepatitis A, chickenpox and the original shingles vaccine were made using the MRC-5 cells. Both cell lines have been extensively characterized and continue to be used to produce the aforementioned vaccines.

For more details related to this story, read The Vaccine Race by Meredith Wadman (Barnes and Noble, Amazon.com)

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