The Trenches Key breakthroughs leading to the powerful mRNA against COVID-19 were forged at Penn. That triumph was almost 50 years in the making, longer on obstacles than celebration, and the COVID-19 vaccines may only be the beginning of its impact on 21st-century medicine.

By Matthew De George

atalin Kariko is most comfortable oNTech, the German pharmaceutical com- COVID-19 vaccines to hit the American at a lab bench. That’s where she’s pany she joined in 2013. (She remains an market—technology revolutionized and spent most of a career that dates to adjunct professor at the Perelman School refi ned at the Perelman lab in which the late 1970s. Even as a lead re- of Medicine.) But the diligence that served Kariko worked for decades—you don’t searcher on papers that broke new her so well in the lab still shines through get any self-adulation. Nor do you get Kground in , even as a vice as she reviews the path she’s taken any resentment at the many entities that president of an emerging biopharmaceu- through fi ve decades of science research. turned down her research funding re- tical power, she was never above doing Speaking from her home offi ce in the quests—no matter how justifi able a bit the unglamorous work in the lab: the Philadelphia suburbs in February, Kariko— of bitterness might be. repetitive cell culturing and data collec- Kate or Katy to her colleagues—strikes Instead, you get a tour through the his- tion that she easily could have delegated. a tone most remarkable for its magna- tory of all the stepwise improvements, Lately her time in the lab has been re- nimity. When you ask about the mes- from Kariko’s lab and collaborators duced by the COVID-19 pandemic, along senger RNA (mRNA) technology behind across the world, that have led us to the with a shift to a more advisory role at Bi- the fi rst two commercially available current moment, in which mRNA off ers

42 THE PENNSYLVANIA GAZETTE May| Jun 2021 ILLUSTRATION BY CHRIS GASH May| Jun 2021 THE PENNSYLVANIA GAZETTE 43 Katalin Kariko

iled her job prospects at Penn—she and her Perelman colleague , a professor of infectious diseases, battled to defend its merits. They persevered in part because of their openness to trying new things, to share their fi ndings and entertain new possibilities even when their ideas were met with skepticism. The end product is a pair of safe and eff ective vaccines, produced by and a partnership between BioNTech and Pfi zer, that have sped to market in record time. They are based on mRNA, which codes for a molecular analogue of the spike protein that lines the SARS- CoV-2 virus, and uses that analogue to teach the immune system to develop antibodies against the virus. Yet this technology isn’t just a powerful weapon against the pandemic. The underlying method represents a new frontier in biologic medicine whose vast possibili- ties encompass infectious diseases, can- cer treatments, and even repairing au- toimmune and genetic conditions. “We knew when we started with this technology that it would be very useful if a pandemic hit, because it’s so fast and so easy to make a vaccine with it,” Weiss- man says. “But we weren’t hoping for a pandemic to prove that.”

eissman’s journey to mRNA start- ed with a photocopy machine, where he used to jockey for pole position with Kariko. At least that’s what he likes to joke. Even if Wthey hadn’t spent so much time in line to run off pages from academic journals, Kariko is certain she would’ve found Weissman sooner or later. not just a chance to stanch a global pan- came before us, and people will use our The basic science of ribonucleic acid demic but also a promising new plat- data. Of course, everything was impor- (RNA) was well established by the time form to tackle all manner of diseases. tant that those people did. I would hug Kariko arrived at Penn in 1989. Discovered Though she’s not above enjoying the them if I could.” in 1961, it plays a foundational role in just acclaim she has lately received for the Kariko’s attitude is a key part of how about all forms of life, enabling cells to technology she’s long championed, she and others helped unlock the prom- synthesize proteins encoded in their ge- Kariko quickly puts her contributions to ise of a method that many dismissed as nome. In human cells, the genetic code it in perspective. a clinical dead end in the 1990s. When rests in double-stranded DNA (deoxyribo- “Science builds on science,” she says. the sector struggled to attract funding— nucleic acid). Genes are transcribed in the “We always built on the people who when Kariko’s attachment to it imper- nucleus to messenger RNA (mRNA), which

44 THE PENNSYLVANIA GAZETTE May| Jun 2021 Photograph by Candace diCarlo Drew Weissman

travels into the cell’s cytoplasm and is translated into proteins in the ribosomes. Some viruses, including SARS-CoV-2, use single-strand RNA instead of DNA as their only genetic information. Kariko arrived at Penn during what she calls “a revolution” for mRNA science. She was hired by Elliot Barnathan C’77 M’81 GM’86 GM’87, then an associate professor of medicine, to conduct basic research in his lab, which focused on blood vessels. Even in that position, Kariko was always looking for ways to incorporate mRNA, either as a remedy or part of the investigation process. Excite- ment in the fi eld was growing. In 1985, the fi rst polymerase chain reaction (PCR) machines, which allowed scientists to

Kariko and Weissman helped unlock the promise of a method that many dismissed as a clinical dead end in the 1990s.

customize strains of RNA, were patented. (Even three decades later, Kariko de- scribes that new technology as “so em- powering.”) Another key advance was the development of positively charged lipids that could encase and deliver negatively charged RNA to cells, a technology made Those fi ndings ran against the prevailing was drawn to the potential power this commercially available in the late 1980s. wisdom that because mRNA too easily class of molecules might have in medi- By 1990, the Human Genome Project degraded in the body, it wouldn’t have cine. If you could tailor mRNA to inject added attention to the fi eld of genetics, therapeutic value. into cells, you could control which pro- though it shifted funds toward DNA re- Kariko traces her interest in mRNA teins they produce, what genes they ex- search. Despite that, a proof of concept back to her fi rst day in the lab in her na- press, what metabolic pathways they fol- study of synthetic mRNA translation in tive in 1978, when her graduate low. Her zeal earned her a reputation as living mouse models was published in supervisor tasked her with collecting a “the RNA hassler,” at Penn and beyond. 1990, and the fi rst therapeutic use of RNA sample of RNA that could be shipped to “I went to meetings and if someone was in rats was reported two years later. a lab in New Jersey for sequencing. She sitting next to me, I’d ask what they were

Photograph by Candace diCarlo May| Jun 2021 THE PENNSYLVANIA GAZETTE 45 doing and I always off ered, ‘Oh I can created role as senior research investiga- Kariko. The more they chatted, sharing make an RNA for you,’” Kariko recalls. tor. When Barnathan left for the private tidbits of their research, the more “the “Kate was really just unbelievable,” says sector in 1997, she joined the neurosur- RNA hassler” made Weissman wonder Barnathan, who is now the executive di- gery lab of David Langer C’85 M’90 if mRNA could be useful in his lab. Soon rector for research and development at GM’98 for two years [“Alumni Profi les,” they were collaborating. Janssen, a pharmaceutical company un- Jan|Feb 2020]. But even as she bounced The pairing proved to be kismet, and der the Johnson & Johnson umbrella. around between increasingly tenuous while the infusion of funds from Weiss- “She was always incredibly inquisitive. perches, she continued publishing, in- man’s new lab didn’t solve all the fi nan- She read voraciously. She would always cluding a 1999 paper (based on research cial quandaries, it opened up new ave- know the latest technology or the latest done in 1996 with Barnathan) in which nues for Kariko’s explorations. They paper, even if it was in a totally diff erent she used urokinase receptor proteins to endured frustrations along the way. area, and she’d put two and two together demonstrate eff ective overexpression of Kariko had little success in getting grants and say, ‘Well why don’t we do this?’ Or, in vitro transcribed mRNA in living cells. or interest from venture capitalists. At ‘Why don’t we try this formulation?’” Weissman arrived at Penn in 1997, hav- times it seemed like the powers-that-be That enthusiasm paid off as funding ing spent seven post-doctoral years at the were rubbing her nose in it. In the early dried up in the 1990s. At that time, National Institutes of Health. In a lab run 2000s Kariko and Weissman were ap- mRNA began to fall out of favor. Since by , Weissman explored the proached by a pair of MBA students com- mRNA interventions couldn’t modify the role of dendritic cells, one of the “sentinel peting in a Wharton School entrepre- genome the way DNA therapy theoreti- cells” that detect and help defuse threats neurship competition, but the idea of a cally could, they were seen as short-term to the immune system, in HIV infection. company built around mRNA technol- aids, not the moonshot solution to At Penn, his research focused on dendrit- ogy was, according to Kariko, deemed thorny problems like hereditary dis- ic cells’ broader response to pathogens. too implausible by the contest’s board. eases that attracted much of the funding. As he dug into the literature, Weiss- “Katy and I worked on this from the Kariko was demoted from the tenure man spent countless hours xeroxing beginning,” Weissman says. “We never track in the mid-1990s, from a research pages from academic journals … which gave up. We never felt that it was bad assistant professor position to a newly meant a lot of time waiting in line with technology and we had to stop. But we

really challenged by something unexpected that you see what the Bringing the Vaccine characteristics and the culture of an organization are. Looking back at the last year, it’s really extraordinary. I feel really privileged to be to the Masses part of an organization that responded so well to this challenge.” Mace Rothenberg C’78 offers a rueful laugh when recalling his 2020 Rothenberg joined Pfi zer in 2008 and spent 10 years in its oncology calendar. As Pfi zer’s chief medical offi cer, his duties included traveling department, rising to chief development offi cer of oncology in 2016. He to the company’s many labs and research stations around the world—a became CMO on January 1, 2019, a position he held until his retirement task once done in person, no Zoom required. On his itinerary for the fi rst in January 2021. (He’ll remain with the company until the spring and will week of March: a trip to meet teams at Pfi zer’s research and development then shift to an advisory role.) Having done most of his clinical research center in … Wuhan, China, where COVID-19 was fi rst identifi ed. in cancer, he wasn’t well acquainted with mRNA vaccinology before the That trip never happened. By March, Wuhan was starting to see the pandemic. Like everyone at the company, he got a crash course as Pfi z- light at the end of a months-long tunnel of lockdowns. The United er partnered with BioNTech, the Germany-based fi rm founded by the States was staring into the abyss, with schools closed and business- husband-and-wife team of Ugur Sahin and Ozlem Tureci. es shuttered. Rothenberg’s check-ins with employees, in Wuhan and One thing Rothenberg was familiar with was Pfi zer’s potential to elsewhere, shifted from the usual to the extraordinary, emphasizing play a key role in coordinating a complex endeavor. In pulling measures to keep employees safe without disrupting a global supply together a company-wide effort, Rothenberg relied on a key standby chain of , COVID-19-related and otherwise. of his history: collaboration. One of his most signifi cant projects in By January, Pfi zer CEO decided to put Pfi zer out front oncology research was helping to create Project Data Sphere, a in the vaccine quest, marshalling resources throughout the pharma- digital “library-laboratory” that allowed scientists to share in-process ceutical giant. and pre-published cancer research. Launched in 2014, it has “It was really a test of the organization’s strength and culture,” allowed researchers to share ideas, leading to more than 100 novel Rothenberg says. “We talk about culture a lot, but it’s not until you’re datasets and more than 20 peer-reviewed papers.

46 THE PENNSYLVANIA GAZETTE May| Jun 2021 Kariko had little success getting grants had to fi ght the entire way. We spent time or interest from venture capitalists. trying to get people, biotechs, and phar- maceuticals interested in this. It took a At times the powers-that-be seemed to long time, but now we’ve achieved it.” be rubbing her nose in it. Despite those setbacks, the work con- tinued. Kariko and Weissman improved the technology by conquering one ob- Kariko dampened the unwanted immune take that information, put that together, stacle at a time. response, a process they patented in 2005 and keep iterating on how to do it.” One major issue was RNA’s inherent and have licensed to companies including The nucleoside breakthrough thrust toxicity. Free-fl oating RNA outside of cells Moderna. (BioNTech, which Kariko the technology into the fast lane. In re- is usually a sign that something is wrong, joined in 2013 as a senior vice president, cent years it has been deployed widely, like rupturing cells or viral intrusion. Its funds research at Weissman’s lab.) though most treatments remain in clin- presence triggers an infl ammatory re- From afar, Barnathan sees the totality of ical trials, which can take up to a decade sponse, and the space between cells is full Kariko’s work in this fi eld as a “patchwork” or more to complete. Moderna in 2010 of enzymes that rapidly degrade RNA. Its of little solutions, that when stitched to- used it to regenerate pluripotent stem short half-life outside of cells was a major gether produced an innovative whole. cells, and there is growing recognition impediment to overcome. “She would take those pieces of informa- that mRNA-based techniques could open By 2004, the pair had worked out which tion, put it all together, and she wanted a a new frontier in gene editing that could receptors their therapeutic mRNA pretty thing that would keep you warm complement the power of CRISPR-Cas9, tripped. Kariko noticed that a diff erent and was beautiful, and that’s what her the DNA-editing method that was hon- type of RNA, transfer RNA, rarely triggers mRNA was,” Barnathan says. “It was a ored with the 2020 in Chem- the immune system. She theorized that patchwork quilt of putting together little istry. In 2014, Kariko joined BioNTech it slipped under the radar due to modifi - scientifi c discoveries here and there— cofounders Ugur Sahin and Ozlem Tu- cations in the nucleosides that comprise some which had been discovered a long reci to author a paper hailing mRNA as it. By tinkering with the nucleosides in time ago, some that were just published “a new class of drugs.” An article by her synthetic mRNA, Weissman and in Science the day before. But she would Weissman and Kariko the next year

The same tack proved useful for COVID-19. Pfi zer was transparent zine. “As an industry, we committed to work as one team to harness with its protocols for clinical trials, releasing them to the public in our scientifi c expertise, our technical skills, and our manufacturing September. The company shared preliminary results, providing a win- capabilities to do everything in our power to get life-saving break- dow into the process and inviting feedback from colleagues. Like throughs into people’s hands as quickly as possible.” other institutions, it used pre-print servers, which publish scientifi c Like Penn mRNA researcher Drew Weissman [see main story], papers before peer review, to permit promising information (and, Rothenberg has taken a public advocacy role. Pfi zer launched a se- Rothenberg concedes, some bad data) to reach scientists faster ries of public-service announcements through the “Science Will Win” than the usual publication process. campaign, including videos of Rothenberg laying out the vaccine’s Collaboration has been vital on the distribution side, too. Pfi zer’s benefi ts in layman’s terms. His physician’s bedside manner evident, global president of vaccines is Nanette Cocero Gr’93 WG’94. In her Rothenberg says he approached it as though talking to his mother. 15 years at Pfi zer, she’s worked all over the world, formerly leading the It’s hardly conventional marketing—vaccine contracts come through emerging markets division of Pfi zer’s Innovative Health business. governments, so Pfi zer isn’t competing for consumer market share, She’s also the chair of the Vaccine CEO Steering Committee of the In- per se, but rather competing against misinformation—but then this ternational Federation of Pharmaceuticals and Manufacturers Associa- isn’t a conventional challenge. tion (IFPMA), which sets industry-wide best practices on access and af- “I think more than for most other products, there really was a need to fordability. IFPMA was an early participant in COVAX, a joint effort by educate people because this was a new platform, this was a disease the World Health Organization; the Coalition for Epidemic Prepared- that people didn’t know about, and we didn’t have long-term follow-up ness Innovations; and Gavi, the Vaccine Alliance. Against a virus that on the vaccine or even the disease,” Rothenberg says. “We’re now learn- knows no borders, global cooperation and coordination are vital. ing more about that as we go along,” and at each step “educating the “The spirit of collaboration that we have seen in this pandemic is public about the disease, about protective measures you can take, and something I hadn’t witnessed before but that I hope will continue about how the vaccine was developed—and addressing some concerns long into the future,” Cocero said in an interview with Wharton Maga- and misinformation that’s out there regarding an mRNA platform.”

May| Jun 2021 THE PENNSYLVANIA GAZETTE 47 billed mRNA as “fulfi lling the promise ples) from scientists at the beginning of While many companies are pursuing of gene therapy,” a technology coming the outbreak. “A year ago, a message COVID-19 vaccines by diff erent methods, “out of the shadows and into the spot- came over the internet and we could the fi rst two to hit the market utilize light,” as Kariko wrote. In 2017, Weiss- learn what is the sequence of the virus,” mRNA. The Pfi zer/BioNTech vaccine man and his colleague Norbert Pardi, a Kariko said during a Perry World House began its Phase 3 last July research assistant professor of medicine, panel in January. “If it had happened 20 and received emergency use authoriza- hit a signifi cant milestone in the produc- years ago, you had to have physically the tion from the US Food and Drug Admin- tion of a single-dose mRNA vaccine for sequence in your hands, the viral con- istration on December 11. A week later, Zika virus that was eff ective in mice and struct in your hands. But here, the infor- Moderna got the green light. (Three rhesus macaques. Pardi has since turned mation was suffi cient.” other vaccines in various states of devel- his attention to other pathogens, includ- The vaccines produced by Moderna opment and approval, from AstraZene- ing mRNA-based infl uenza vaccines. and BioNTech/Pfi zer have two compo- ca/Oxford, Janssen/Johnson & Johnson, “We had the platform, we just needed nents: mRNA, cased in lipid nanopar- and Novavax, utilize other technologies, to fi gure out what we wanted to do with ticles (LNPs). The latter is a delivery some of which off er advantages includ- it,” Pardi says. “It’s extremely versatile. device, an extra layer of cloaking that ing longer shelf life and less stringent We can use it for many, many purposes.” helps localize delivery without sparking storage temperature requirements.) Weissman says that when he fi rst heard an unwanted immune response. The “It was with bated breath that we of the novel coronavirus causing severe mRNA encodes a protein analogous to watched the development of this vaccine,” respiratory disease in Wuhan, China, his the spike proteins that protrude from said Paul Offi t, the Maurice R. Hilleman mind didn’t automatically jump to mRNA. the SARS-CoV-2 virus and allow it to Chair of Vaccinology at the Perelman And for all her decades of promoting the bind to and infect cells. Dendritic cells School of Medicine, at the same Perry therapeutic possibilities of mRNA, Kariko take up the mRNA, translate it to pro- World House panel. “And both the Pfi zer didn’t either. “When I heard about it in teins that are incorporated into the cell and Moderna products have been remark- February, I thought, ‘Oh, it is in China; it membrane, and present these engi- ably successful, at a level I think no scien- won’t get here,’” she recalls. “But the CEO neered products to the body to induce tist would have predicted a year ago.” of BioNTech, Ugur Sahin, he’s a visionary, an adaptive immune response. The pro- There are some limits to what we know and he immediately thought, ‘Oh, we need cess produces antibodies that remain in about these COVID-19 vaccines, mostly to do something with that.’” the bloodstream so that if a vaccinated because we’ve had a limited time to ob- individual encounters SARS-CoV-2, a serve their eff ects. The trials for both ver- hese days Weissman spends much neutralizing response can quickly be sions passed the required safety hurdles, of his time outside the lab, talking mounted. (Both vaccines encode identi- but questions remain about long-term to non-scientists about COVID-19 cal spike proteins; their proprietary eff ects for certain population subgroups, vaccines that use mRNA. In those mRNAs diff er slightly in the non-coding like pregnant women. Clinical trials on conversations, he walks a fi ne line. regions and utilize diff erent lipids.) children are also just getting off the TYes, the vaccine came together with un- mRNA vaccines have a lot going for ground. These questions can’t be an- precedented speed—less than a year them from a safety perspective. Since they swered until there’s been more time to compared to the more typical timeline don’t contain any of the pathogenic sub- study them. The same can be said of the of up to a decade. But no, the technology stance—seasonal fl u vaccines, for in- virus itself, which humans have only isn’t new. Only the application is. stance, use heat-killed or weakened virus, known for a little more than a year. “People say, ‘I’m afraid of this vaccine; which is why a small percentage of people Yet the mRNA vaccines have already it was developed 10 months ago,’” Weiss- can get sick from them—there’s no chance achieved an impressive track record, with man observes. But he is quick to answer: of contracting COVID-19 from the vaccine. more than 60 million doses dispensed by “It wasn’t. We developed modifi ed RNA The therapeutic mRNA in the vaccine can- mid-February. They are 95 percent eff ec- 15 years ago.” not penetrate the nucleus, so it can’t alter tive at blocking infection and 100 percent The mRNA technology is ideal for the the genome. The vaccines produce a rela- eff ective in blocking severe infection. challenge: quick, safe, and eff ective. It is tively robust and durable immune re- Vaccines, Offi t emphasizes, involve a risk/ produced in a cell-free system, tran- sponse. Studies as of early 2021 indicate reward calculus. The risks of a virus that scribed in vitro from enzymes and a ge- that the vaccine still protects against some has killed millions are known and dire. The netic template in a few hours. There was of the newly emerged variants of SARS- risks of the vaccine remain largely theo- nothing that physically needed to be CoV-2, though they show a “small but retical, as a full understanding of rare side- transported (i.e., cell cultures or sam- signifi cant” reduction in effi cacy. eff ects in certain populations will simply

48 THE PENNSYLVANIA GAZETTE May| Jun 2021 The technology offers a plug-and- take more time to develop. “When you look the stock symbol MRNA—be- through all the data, you can’t help but be fore its fi rst treatment had been ap- play platform compelled by the safety and effi cacy of this proved. Its market capitalization is now vaccine,” Offi t said. “The choice to get a north of $50 billion. BioNTech’s market promising drug vaccine is an easy one right now.” value has grown from $3.39 billion at its development in a initial public off ering in October 2019 to hen Weissman and Pardi pre- more than $26 billion in January 2021. fraction of the sented a paper in 2017 on an LNP- Kariko’s current research deals pri- encapsulated mRNA vaccine marily with cancer treatments, including time required by method, recent human history a partnership with the pharmaceutical was on their mind. Twice in the company Sanofi . BioNTech is also ex- traditional methods. Wprevious two decades, coronaviruses had ploring treatments for the autoimmune caused respiratory viruses that reached disease multiple sclerosis, which has pathogens that can potentially cause an epidemic status: SARS in 2002, MERS in showed promising early results. Weiss- outbreak and can potentially cause the 2012. Taking the long view, it was not a man’s lab at Penn has fi ve mRNA vac- next pandemic, and we have to be ready matter of if another pandemic would cines in trials, covering seasonal fl u, HIV, for those events. And the way to be ready happen, but when. While they were fo- and herpes. Weissman has funding from is to develop vaccines prior to those out- cused to some degree on the “renaissance the Bill and Melinda Gates Foundation breaks. And the messenger RNA technol- in the fi eld of therapeutic protein deliv- to pursue a possible single-injection ogy is really fantastic because if you de- ery” that mRNA off ered for conditions remedy for sickle cell anemia, an mRNA velop these vaccines, these prototype ranging from cancer to hereditary ge- therapy that would target bone marrow vaccines, and if you have an outbreak and netic diseases, Pardi in particular had a stem cells to rewrite the area of the ge- maybe the virus that causes the outbreak growing understanding of how the nome encoding aberrant proteins. is slightly diff erent from the vaccine mRNA technology could be mobilized in Even within the narrow lane of infec- strain, you can use the technology to very the face of an infectious disease. tious disease, the scale is mind-boggling. quickly adjust the vaccines.” Even in the midst of the COVID-19 pan- The World Health Organization has Those challenges lie in the hypothetical demic, that perspective still applies. If the identifi ed around 150 infectious zoo- future. The pathway to get there with the past is any guide, there will be another notic viruses, those that have jumped technology, if history is any guide, is to pandemic sometime in the future caused from animals to humans. Estimates of chip away at problems sequentially. For by a virus like SARS-CoV-2, maybe one the reservoir of potential zoonotic vi- now, mRNA’s potential is being showcased deadlier than the current crisis. The tech- ruses in mammals vary widely, from globally at a critical moment, even as nology that informs the COVID-19 vac- around 10,000 to half a million. Any one many additional innovations are being cines presents a powerful weapon in the of them may have the potential to mu- tested. The arduous journey from theory arsenal for when that day comes. tate and jump from animals to humans to application is a rewarding one for those “The technology really is limitless,” like SARS-CoV-2 did. who have shepherded the technology. Weissman says. “There are thousands of It’s possible that the next blockbuster “It’s very important to know that what diseases, there are hundreds of vaccines use for mRNA is a disease unknown to I’m working on is something useful,” Par- that we could make, many of which science. But the technology’s simplicity di says. “And now, we see that the work is we’re working on. A lot of it is how to and scalability off er a plug-and-play very useful … and we hope that we can pick, and we pick based on how impor- platform promising drug development come up with more RNA therapies in the tant the disease is and how doable it is.” in a fraction of the time required by tra- future and help even more people—not Economic incentives play a role—and ditional methods. just vaccines but also other kinds of med- that dynamic has now fl ipped. From a “I think governments and policymakers icines. It’s a really fantastic feeling, and technology for which Kariko once strug- also need to learn the lesson that they this is what keeps us moving forward.” gled to obtain thousands of dollars in should support basic science, and they “It’s a fantastic feeling,” Weissman adds. funding, mRNA therapy is now a multi- should support vaccine development “I’m a clinician, so my dream was always billion-dollar industry. AstraZeneca, for prior to a pandemic because it’s too late to develop something that would make instance, paid Moderna $240 million in to develop vaccines in the middle of a people better. And I think we’ve done that.” 2012 for drugs that hadn’t yet been de- pandemic,” Pardi says. “You need to de- veloped. Moderna was valued at $7 bil- velop these vaccines before a pandemic. Matthew De George is an author, newspaper ed- lion when it went public in 2018— with We know many of the viruses and other itor, and freelance writer based in Philadelphia.

May| Jun 2021 THE PENNSYLVANIA GAZETTE 49