On a cloudy June day in Philadelphia, Dr. Leonard Hayflick leaned over the table in his research lab, wielding a pair of scalpels. His task that morning in 1962 was to process the tissue of two human lungs. After cutting the organs into small pieces, Hayflick poured them into a flask and added a chemical solution that broke the tissue down into its component parts: millions upon millions of cells. He ran the concoction through a centrifuge, then painstakingly used his mouth to suck the cells into a pipette, ultimately transferring them into several small glass bottles. Hayflick placed the bottles into the lab’s incubation room and waited. He was convinced that these cells, now quietly growing in his facility, could revolutionize the vaccine industry.
The doctor was right. His work, and the work of scientists who followed in his footsteps, led to vaccines that have saved millions of lives and spared generations of children from profound disability and disfiguring disease. But even as Dr. Hayflick took the first steps into a glorious era of public health triumphs, he tripped at the threshold. The tiny pair of lungs Hayflick cut up in his lab that day belonged to a healthy baby girl, whose life was ended in an abortion performed at 17 weeks of pregnancy. In her book The Vaccine Race: Science, Politics, and the Human Costs of Defeating Disease, Dr. Meredith Wadman reports that the Swedish obstetrician who carried out the abortion sent the baby’s body away to the research lab without getting her patient’s consent, or even telling her what was happening.
In the decades since, fetal cell lines like Hayflick’s (which he called WI-38) have become pervasive in the biotech industry. Their ubiquity belies the fact that they all trace their beginnings to a few specific abortions, all performed in the period between the 1960s and 1980s. They are used to study everything from the simplest household medications, like Tylenol, to the most advanced biologic drugs. These antique lines also continue to play a key role in the manufacture of certain vaccines, a detail that has seeped into the public consciousness slowly—and then, in the age of Covid-19, suddenly. “Religious exemption” is now a household phrase, with much of that dissent presumably arising from a newfound awareness of the cells’ tragic origins.
As we watch health officials struggle, it’s easy to feel frustrated. Sixty years after Hayflick’s breakthrough, where are the ethical vaccines that respect life—and respect the consciences of pro-life people? Public health needs to be inclusive, yet the pharmaceutical industry seems wedded to an old-fashioned industrial process that ends up excluding many of us. Although that discouragement is understandable, it’s also based on out-of-date impressions and incomplete information. Because it turns out that innovators in biotechnology are changing the game. Here’s how.
The Emergence of mRNA
Amid all the controversy over Covid-19 vaccines, it’s important to know that the technology behind some of the shots—mRNA—represents a significant breakthrough for principled vaccine development. Traditionally, to make vaccines, scientists need to use viruses. And viruses need living cells to grow in, whether those cells come from animals, like monkeys and chickens, or from people. Originally, Leonard Hayflick opted for tissue from a healthy aborted infant, because he speculated that cells straight from the pristine cloister of the womb would be “safer” than potentially contaminated animal cells. But with mRNA vaccines, like Pfizer’s and Moderna’s Covid shots, no cell line is needed at all.
In fact, after the first step of genomic sequencing is done, viruses aren’t needed either. Researchers from anywhere in the world can look at the sequence, pick a gene from the virus, and use an enzyme called RNA polymerase to create customized “messenger” RNA. In the case of Covid shots, scientists from both Pfizer and Moderna decided to make their mRNA “recipe” with the coronavirus’s spike protein gene, which it uses to attach to its victim’s healthy cells. When injected as a vaccine, the mRNA breaks down quickly, but not before helping to teach the human body to recognize the spike protein as an unsavory guest. “It’s kind of like the face on the wanted poster,” explains Dr. David Prentice, vice president and research director of the Charlotte Lozier Institute. “The immune system sees that, and it arms itself in case that face with a real virus ever shows up in our system. All done without cells.”
With the Covid-19 vaccines, though, the manufacturers didn’t let the new technology stand on its own. Instead, both Pfizer and Moderna chose to test their product with HEK-293 cells, a particularly pervasive line grown from the kidneys of a healthy baby girl who was killed in an abortion in the 1970s. “They didn’t have to do it, and they didn’t have to use these abortion-derived cells,” says Dr. Prentice, who is also professor of molecular biology at Catholic University of America and serves on the advisory board of the Center for Bioethics and Human Dignity.
“There are two tests they do. First, they vaccinate fetal cells in a dish, just to see if they will make the protein they hope our own cells will. HEK-293 is also very good at making pseudovirus particles, so they make some of that pseudovirus. Then, when they vaccinate [lab] animals to see if they make the antibodies they hoped they would, they use that pseudovirus as the target. I understand in some ways why they do that, rather than using [live] infectious virus in their lab. That makes some sense,” Dr. Prentice says. “But there are other, licitly-derived cells that they could use instead.”
Although pro-life leaders from the Vatican to the Southern Baptist Convention have approvingly spotlighted how Pfizer’s and Moderna’s vaccines avoid abortion-derived cells in the manufacturing process, the testing issue is still sensitive for millions of individual consciences. By testing their revolutionary technology with an unethical, antiquated cell line, these biotech companies created a hurdle for public health authorities and dinged their own bottom lines.
Dr. Prentice points out that there is also plenty of positive movement, with scientists choosing approaches that are modern, creative, and inclusive. For instance, the American company Novavax is in the late stages of developing a Covid-19 vaccine that doesn’t use mRNA technology, but does use cells from fall armyworm moths, a lawn-eating pest that typically torments homeowners in the Southeastern United States and other tropical regions. In 2019, the French firm Sanofi-Pasteur quietly changed the way it makes its polio vaccines, choosing to use monkey cells instead of the MRC-5 cell line, which was developed from the lungs of a little boy whose life was cut short in September 1966 during a second trimester abortion. As a result of Sanofi’s switch, millions of American preschoolers now receive ethical polio protection.
The problematic MRC-5 line was also picked by Merck to make its shingles vaccine, called Zostavax, starting in 2006. But as of November 2020, that shot is no longer available in the United States, because rival GlaxoSmithKline has introduced Shingrix, a vaccine that eats Zostavax’s lunch both ethically and clinically. Made using Chinese hamster ovary cells, it boasts an effectiveness rate up to 97 percent, compared to Zostavax’s 50-60 percent. “The Centers for Disease Control now recommends, don’t even bother with the old one that was made in the abortion-derived cells. Go for this newer one,” Dr. Prentice says. “Not only is it ethically produced, it’s better! Ethical science is better science.” In fact, the CDC even urges patients who got Merck’s vaccine to return to their doctor for Shingrix.
“‘Just as good’ works for those who are interested in the ethics,” notes Prentice. “But we really want everybody to move away from [abortion-derived cell lines]. We need something that is not just as good, but something actually better. If you’ve got something that works better, and is more efficient, that’s going to sway them.”
Agathos Bio: “Impossible” Bioethics
One group laser-focused on getting to “better” is Agathos Biologics, a startup that bills itself as “The Good Science Company.” The firm was co-founded by a trio with significant industry pedigree at Aldevron, a biotech manufacturing concern in North Dakota that was acquired in 2021 by Fortune 500 company Danaher in a deal worth more than $9 billion.
“What we saw is an opportunity to create cell lines that are both technologically superior and ethically acceptable,” says CEO and co-founder Dr. James Brown. “To some extent, you’re limited to work with what you have. These [fetal derived] cells have been around a long time. The drugs they’ve produced have helped a lot of people, and we don’t dispute that, because it’s true. We wanted to provide an alternative.”
Agathos has just started working on a replacement for those omnipresent HEK-293 cells, and takes an apolitical stance on issues both left and right, keeping a disciplined focus on its core identity as an innovating biotech company. “When we talk to other people that we might partner with, or hire employees, I don’t really care what their politics are. I’ve framed a problem, and if they’re interested in solving it, great. That’s all they need to do,” Brown told me. “We have certain parameters we are going to work with that are a little bit different from another company’s. We’re pursuing a slightly different path, but once you’ve decided the path, how you get there is the same way you do any other science.”
He compares the co-founders’ strategy to that of the celebrated Impossible Meat company, whose plant-based alternatives to beef and chicken have gone so mainstream, they’re in the Walmart freezer aisle. “These people are vegans. They’re not crazy enough to think that the whole world is going to turn vegan,” he says. “But they are crazy enough to think that if they have a better product, that people like better, that’s great, because that helps solve the problem.”
Dr. Brown describes the struggle to market ethical cell lines as a chickenand-egg conundrum. A potential HEK-293 replacement needs robust data to make it a worthy rival. But labs aren’t motivated to try new lines and generate that data when they have an off-the-shelf option they already know so well in HEK-293. Agathos is willing to step in and break that loop. “The ultimate cell line may not be one that we develop,” Brown says. “In biotech, sometimes there’s ‘Not Invented Here’ syndrome: If we didn’t invent it, it sucks. But I’ve got none of that.”
“A lot of biotech firms are formed around a technology looking for a problem. We have found a problem and we’re looking for a technology to address it. So if we need to develop something internally, or if we can get something from somebody else, that’s fine too.”
The need to effectively compare fetal cells head-to-head with a superior option led to the difficult decision to essentially use HEK-293 in order to replace HEK-293. The cell line isn’t part of day-to-day research, but Agathos does study it to understand its qualities and how they can be beat. “For us, the best outcome would be that we chart a path that others can follow, that they don’t have to use these other cell lines,” Dr. Brown says. “We want to do two things: Provide an ethical alternative, and make drugs that help people.”
JPII Medical Research Institute
At the John Paul II Medical Research Institute in Iowa, scientific director Dr. Alan Moy has been working doggedly on ethical biotechnology for almost 15 years. The Institute’s most recent innovation builds on the work of Japanese researcher Shinya Yamanaka, who won the Nobel Prize for his 2006 discovery that mature skin cells could be genetically reprogrammed to act like embryonic cells, which are “pluripotent”—meaning they have the potential to develop into any type of cell in the human body. But Yamanaka’s breakthrough had a problem. “Some of the early induced pluripotent stem cells had a safety risk. They could cause tumors,” Dr. Moy told me. “What we worked on was a way to make these iPS cells cheaper and safer. Which we’ve accomplished, and published. We’ve filed for a patent, and we anticipate it will be issued soon.”
Researchers are developing an alternative coronavirus vaccine—Dr. Moy is an emphatic skeptic of reputed mRNA miracles—but they’re also working on a substitute for HEK-293, leveraging the Institute’s legacy stem cell technology to come up with a better product. “These cell lines were produced 50 to 60 years ago, using technology that today would be considered antiquated. Viruses and radiation have been used to chemically change the cell line in important ways, with [implications for] safety and functioning of drugs,” explains Dr. Moy, noting that HEK-293 cells routinely have 64 chromosomes, which in a human being would be a lethal genetic abnormality. To make a superior replacement, the Institute is using the revolutionary gene editing tool called CRISPR to alter ethical stem cells and produce a modern cell line that avoids those drawbacks.
“Because, if we want to change the future of biotech, it has to be better than just saying ‘it’s moral.’ It has to have features that are going to be disruptive,” he says, echoing Dr. Prentice and Dr. Brown. “The goal is to [influence] the industry to use cell lines that offer scientific advantages for their bottom line, but also address the unmet consumer market.” Beyond that, Moy believes that developing a committed pro-life biotechnology sector that can scale up high volume manufacturing is indispensable. To him, coaxing an industry that doesn’t share pro-life first principles to use better, more ethical products can only go so far.
What Can We Do to Help?
Most people who care about bioethics don’t have terminal degrees in molecular biology or access to state-of-the-art labs. But we can all make a difference in dreaming toward a more ethical future. Education and encouragement are key tools. For those who respect life, there’s no need to feel sheepish about this topic: At its cutting edge, biotechnology is moving on from outdated, hidebound tradition. Dr. Prentice notes that even many researchers aren’t aware of the tragic origins of some of science’s most antiquated cell lines. In that regard, the country’s struggle over vaccine mandates and punishment for the noncompliant (who often cite the abortion-derived cells) has only served to elevate the problem’s profile. “What the government is doing is helping to accelerate that education more than I could ever do on my own,” says a rueful Dr. Moy.
When Sanofi-Pasteur switched to an ethical cell line for its polio vaccines, grateful customers launched a letter-writing campaign to thank them, though the company studiously made no comment on the reasons for its decision. “Whatever reason they picked, I think it’s incumbent on us to acknowledge that they made a good move,” Dr. Prentice told me. “Give them a little encouragement, and maybe other companies will follow. There are only nine FDA-licensed vaccines left that still use those old cell lines [for production]. [We need to offer them] as much encouragement as we can give them to use newer technology, even if it may be a little unfamiliar or cost them a bit in terms of retooling their manufacturing.
“There are opportunities, and alternatives. We need to keep pushing. We celebrate where there are successes, where there’s movement. And we keep pressing. In the end, everyone’s going to benefit.”
Margaret Brady, an associate editor at Verily Magazine, is a graduate of the E.W. Scripps School of Journalism at Ohio University. She writes from the Cleveland, Ohio area.