A COVID-19 vaccine was ready January 13, 2020 – long before the pandemic began.

Margaret Keenan, a 90-year old Irish-English grandmother, was the world’s first to receive a coronavirus vaccination.

While the world is crowing about Margaret Keenan, a 90-year old Irish-British grandmother of four, being the first in the world to receive a coronavirus vaccine yesterday, on Tuesday, December 8, 2020, around 0630 local time (GMT) – she received the version collaboratively developed by the American company Pfizer and German company BioNTech – the American biotechnology company Moderna, in Massachusetts, had long had a vaccine developed.

Moderna had already designed a COVID-19 vaccine – mRNA-1273 – by January 13.

It was only recently, on  November 16, that they reported a 94.5% efficacy rate.

Moderna developed their vaccine only two days after the genetic sequence had been publicized internationally by Chinese researcher Professor Dr. Yong-Zhen Zhangm Ph.D. His humanitarian act of scientific generosity resulted in him being temporarily forced out of his lab.

Professor Dr. Zhang believes science holds the key to predicting viral outbreaks with similar accuracy as with which we now anticipate typhoons and tornadoes. He said, “If we don’t learn lessons from this disease, humankind will suffer another.”

Moderna’s vaccine design only took one weekend to develop at their Massachusetts facilities.

In fact, Moderna had completed development of their COVID-19 vaccine mRNA-1273 before the Chinese government had acknowledged the disease was transmitted by human-to-human means, and more than a week before the first confirmed coronavirus case in the United States – January 21.

And by the time the first American coronavirus death was reported a month later, on February 29, Moderna’s mRNA-1273 coronavirus vaccine had already been manufactured and shipped to the National Institutes of Health to begin its Phase I clinical trial.

All of that was long before the President had made any announcement about his “Operation Warp Speed,” the public-private partnership to develop a coronavirus vaccine, and yet even 2 months before Bloomberg News reported on April 29 that such a plan was in the works.

Regarding the announcement of the first known coronavirus-related death, it should be noted that, following autopsy results in mid-to-late April, the Santa Clara County California Medical Examiner’s office reported on April 21 that the first known COVID-19 related death occurred in United States on February 6. The first death was previously thought to have occurred in Kirkland, Washington on February 29. The New York Times reported that, “The virus has an incubation period of 14 days and people who die of it are often sick for at least three weeks, so the individual who died on February 6 could have been infected — and transmitting the infection to others — in early January, experts said.”

In essence, what that means, is that for the entire time the COVID-19 coronavirus pandemic has infected well over 15 million – and counting – in the United States, we had the tools we needed to prevent it, as well as the death of over 250,000 Americans… and counting.

So, that begs the question: If Moderna had a vaccine ready in January, why has it taken until now – December, very nearly a year later – to have a vaccine readily available?

Moderna, a publicly-traded company (stock symbol: MRNA) with operations and headquarters in Massachusetts, is a biotechnology firm focused exclusively upon development of vaccines using mRNA – messenger RNA. Their vaccine is the first in the history of vaccine development to use mRNA.

Drs. Emmanuelle Charpentier-L & Jennifer A Doudna-R, are 2020 Nobel laureates, and creators of the CRISPR/Cas9 gene editing tool

Vaccines made using mRNA are fundamentally different from any other vaccine ever made. The history of vaccination began on May 14, 1796, when a country doctor from Gloucestershire, England, Dr. Edward Jenner, MD, first took some fluid from a cowpox blister and scratched it into the skin of James Phipps, an 8-year-old boy.

Dr. Jenner developed his vaccine while he was still a medical student, after noticing that milkmaids who had contracted a disease called cowpox, which caused blistering on a cow’s udders, did not catch smallpox. However, unlike smallpox, which caused severe skin eruptions and dangerous fevers in humans which often led to death, cowpox led to few ill symptoms in those women.

Science has come a very long way since then. While traditionally, vaccines were first made using active, live, then attenuated, then inactivated, or dead cells from the organism or virus. Throughout the history, the process of making vaccines used chickens’ eggs for the protein they contained, and were literally injected into the shell of an egg. Some are still made that way.

Most recently, two women have forever changed health, medicine, and many other life sciences, which gives hope to millions, and holds untold promises. Dr. Emmanuelle Charpentier, Ph.D., Director of Infection Biology at the Max Planck Institute, and Professor Dr. Jennifer A. Doudna, MD, Ph.D., Professor of Chemistry, Biochemistry & Molecular Biology, Li Ka Shing Chancellor’s Professor in Biomedical and Health at the University of California Berkeley, in October 2020 won the Nobel prize in chemistry for the development of the revolutionary CRISPR/Cas9 gene editing tool which has been described as enabling “rewriting the code of life.”

Drs. Emmanuelle Charpentier-L & Jennifer Doudna-R, are the 2020 Nobel laureates in chemistry, and creators of the CRISPR/Cas9 gene editing tool.

Cas9 is a type of modified protein and acts like a pair of scissors that can cut parts of DNA strands. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, in essence, a repeating mirrored DNA sequence in genomes that repeats. The technology has worked in most every organism that it has been used on, including plants, animals, microbes and humans.

By using the gene editing platform CRISPR, which could be thought of as cut-and-paste, the idea is to remove parts of a genome using RNA as a means of guiding to a particular place within a genome, genes can then be modified to eliminate mutated, or harmful parts.

The ability to use such sophisticated gene splicing technology holds enormous promise.

As it relates to the coronavirus, the gene splicing technology uses a very small portion of messenger RNA (mRNA) from the coronavirus genome, and produces a gene that codes for the spike protein – the characteristic protruding part seen on images.

The coronavirus has 4 proteins, the spike is 1, and is the part that enables the virus to invade cells. By using only that part of the virus, it causes the body to produce antibodies that neutralize that spike protein. RNA vaccines cause the body to make only that spike protein. Then, encased in a fat molecule mRNA then enters cells, and sends a coded message to the body to make the protein, which in turn causes an immune response.

RNA vaccines have many advantages, which, unlike other vaccines produced other ways, they stimulate the production of killer T-cells which stop the coronavirus from replicating. And because mRNA vaccines are produced in test tubes or tanks, rather than being cultivated in cells (such as in eggs), they should be relatively quick and easy to produce.

The use of mRNA to treat disease, even genetic-based disease, such as cystic fibrosis, is brand new, but holds exciting possibilities. Moderna is perhaps one of the most promising mRNA therapeutics research firms in the world. And under the leadership and direction of Chief Science Officer Dr. Melissa Moore, Ph.D., Moderna has developed, and publicized, the scientific blueprint for a unique form of cancer therapy using mRNA which when used used, ensures its mRNA is made only inside cancer cells. Ryan Cross reported in Chemical and Engineering News on September 3, 2018 in “Can mRNA disrupt the drug industry? Messenger RNA technology promises to turn our bodies into medicine-making factories. But first Moderna—and a long list of old and new competitors—needs to overcome some major scientific challenges.” and wrote in part that, “Moderna scientist Ruchi Jain designed an mRNA that causes cancer cells to self-destruct but is recognized by, and destroyed in, healthy cells.”

Dr. Moore has a distinguished scientific pedigree, and since being brought on board in late 2016 as Chief Science Officer, has brought a new spirit, and ethic to the firm, and their work. She was a postdoctoral fellow in geneticist Dr. Phillip Sharp Ph.D.’s lab at MIT when he won the Nobel Prize in Physiology or Medicine in 1993 for his work on RNA. She then went on to study RNA as a Howard Hughes Medical Institute investigator for nearly 20 years, and was a founding co-director of the RNA Therapeutics Institute at the University of Massachusetts Medical School.

One significant way in which mRNA therapy is different from tradition therapies is that while doses of traditional medicines are carefully measured before being dosed, the amount of protein that a single mRNA makes can vary widely. Cells can reuse a single mRNA to make on the order of 1,000 to 10,000 proteins. Controlling that number will help mRNA work more like traditional therapies.

Moderna’s company profile by Business Insider states in part that the company “engages in the development of transformative medicines based on messenger ribonucleic acid (mRNA). Its product pipeline includes the following modalities: prophylactic vaccines, cancer vaccines, intratumoral immuno-oncology, localized regenerative therapeutics, systemic secreted therapeutics, and systemic intracellular therapeutics.” The company itself states this about their mission: “Every cell in the body uses mRNA to provide real-time instructions to make the proteins necessary to drive all aspects of biology, including in human health and disease. Given its essential role, we believe mRNA could be used to create a new category of medicines with significant potential to improve the lives of patients. We are pioneering a new class of medicines made of messenger RNA, or mRNA. The potential implications of using mRNA as a drug are significant and far-reaching and could meaningfully improve how medicines are discovered, developed and manufactured.”

Moderna’s founding has a fascinating history, and one that starkly contrasts with, and exposes the flaws in the current administration’s immigration policy and strategy, and in part, the nation’s immigration laws. On August 11, 2020 Stuart Anderson, Senior Contributor to Forbes, featured Moderna in his article “Immigrant-Founded Moderna Leading The Way In Covid-19 Response.” Mr. Anderson was Executive Director of the National Foundation for American Policy, an Arlington, Virginia-based non-partisan public policy research organization focusing on trade, immigration and related issues. And from August 2001 to January 2003, he served as Executive Associate Commissioner for Policy and Planning and Counselor to the Commissioner at the Immigration and Naturalization Service.

“Moderna is the first company to have shipped a vaccine for testing against the novel coronavirus, and was founded by an immigrant. Not only did an immigrant found Moderna but many of its key leadership positions, including its CEO, are immigrants. The story of how Moderna rose to its position in helping to lead the fight against Covid-19 and other medical threats is uniquely American, a story of welcoming talent from all over the world.

“Noubar Afeyan, co-founder and chairman of Moderna, is a two-time immigrant. He was born to Armenian parents in Lebanon and immigrated with his family in his early teens to Canada. After attending college, Afeyan came to the United States and earned a Ph.D. in biochemical engineering at the Massachusetts Institute of Technology (MIT). He started his first company at age 24 and ran it for 10 years, during which time he founded or co-founded five additional companies.

“In 1999 he founded Flagship Ventures to develop new companies through its in-house division VentureLabs. In addition to investing in startups the idea was to be more systematic in developing companies. VentureLabs conducted its own research and formed new companies if the research proved promising.

“The U.S. immigration system has no startup visa for founding a company, which is often is an obstacle for foreign nationals with good ideas. However, Afeyan gained permanent residence through another route and is credited as a founder or co-founder of 38 companies. He also has over 100 patents. In 2009, he co-founded Cambridge, Massachusetts-based Moderna, Inc.

“Moderna’s CEO is Stéphane Bancel, who immigrated to America from France. He earned a master of engineering degree from École Centrale Paris (ECP), and came to the United States as an international student, receiving a master of science in chemical engineering from the University of Minnesota and an M.B.A. from Harvard Business School.

“Other immigrants in key leadership positions at Moderna include Chief Medical Officer Tal Zaks, in charge of clinical development at the company. Zaks earned an M.D. and Ph.D. from the Ben Gurion University in Israel before coming to the United States for post-doctoral research at the National Institutes of Health, as well as clinical training in internal medicine at Temple University Hospital. Chief Digital and Operational Excellence Officer Marcello Damiani immigrated from France. Moderna’s Chief Technical Operations and Quality Officer Juan Andres immigrated from Spain. Both Damiani and Andres have extensive international business experience.

“Today, the company has approximately 820 full-time employees and a market capitalization of about $28 billion. The company is publicly traded on Nasdaq.

“On February 24, 2020, the company made worldwide news when it announced the release of “the first batch of mRNA-1273, the Company’s vaccine against the novel coronavirus, for human use.” Vials were shipped to the National Institutes of Health (NIH) for a Phase 1 study.

“Noubar Afeyan explained in an interview that the promise of messenger RNA. He said changes to DNA can be essentially permanent, like hardware. By contrast, messenger RNA is more like software: it can be used to perform a task and then can be programmed to disappear.

““Instead of making protein medicines in factories very far away, what we are trying to do is to inject you with messenger RNA so that your own body will make the protein,” said Stéphane Bancel in a 2015 interview with CNBC.

““RNA vaccines are great if a vaccine has to be built as fast as possible,” according to Dr. Ivan Martinez, associate professor at West Virginia University, in an interview with USA Today. “It’s a technology that could potentially give us a vaccine within a year from now.”

““The new approach I’m most excited about is known as an RNA vaccine,” wrote Bill Gates in the Washington Post. “Unlike a flu shot, which contains fragments of the influenza virus so your immune system can learn to attack them, an RNA vaccine gives your body the genetic code needed to produce viral fragments on its own. When the immune system sees these fragments, it learns how to attack them. An RNA vaccine essentially turns your body into its own vaccine manufacturing unit.”

“In late April, Moderna requested permission from the Food and Drug Administration to move to a second phase of testing. In June, Reuters reported,“A series of studies in mice of Moderna Inc’s Covid-19 lent some assurance that it may not increase the risk of more severe disease, and that one dose may provide protection against the novel coronavirus, according to preliminary data.”

Steps in the rules of life from DNA through mRNA to protein.
Diagrammatic representation of Monod’s discovery of the transcription of the genetic code from DNA to messenger RNA, Jacob’s finding that each transcribed code is translated in the ribosome as a specific amino acid, Holley’s description of transfer-RNA and its role in transporting specific amino acids to the ribosome and, the formation of a peptide bond between a growing peptide and a specified amino acid.
It also shows the cracking of the genetic code by Nirenberg and synthesis of DNA and RNA by Khorana. Red octagons identify Monod, Jacob, Holley and Khorana as NSF-supported researchers who were awarded the Nobel Prize in Physiology or Medicine. Credit: Paul Lartey, AAAS-STPF/NSF

“On July 27, 2020, the National Institutes of Health announced, “A Phase 3 clinical trial designed to evaluate if an investigational vaccine can prevent symptomatic coronavirus disease 2019 (COVID-19) in adults has begun. The vaccine, known as mRNA-1273, was co-developed by the Cambridge, Massachusetts-based biotechnology company Moderna, Inc., and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The trial, which will be conducted at U.S. clinical research sites, is expected to enroll approximately 30,000 adult volunteers who do not have COVID-19.””

The design, prototype, manufacture, and testing of new automobiles takes at least a year, and new models are awaited with bated breath by automobile industry experts and news reporters. New fashions are shown at least half a year in advance. Even “instant potatoes” take time – more time to prepare them for packaging, sale, and distribution, than it does to make them for a meal. Similarly, vaccine development takes time. And because it involves human life, the scrutiny is even more stringent, thereby increasing time.

This is literally the fastest development time for any vaccine in the history of vaccines, and the United States and the world are justifiably celebrating that fact.

To answer that question of time to development, Dr. Nicholas A. Christakis, MD, PhD, MPH, Director of Yale’s Human Nature Lab, said, “That would be like saying ‘We put a man on the moon,’ and then asking the very same day, ‘What about going to Mars?’”

As well as being a physician, Christakis is a sociologist and has authored a new book entitled Apollo’s Arrow which examines the the way in which COVID-19 may shape our near-term future. He said that while the speed of development of Moderna’s vaccine mRNA-1273 was genuinely “astonishing,” the design of other vaccines by AstraZeneca, BioNTech with Pfizer, and Johnson & Johnson was almost nearly as fast.

But, could things have moved faster from design to deployment?

That’s the question David Wallace-Wells, Deputy Editor and columnist for New York magazine, recently asked in The Intelligencer section.

In his December 7, 2020 article “We Had the Vaccine the Whole Time,” he also pointed out what Dr. Peter J. Hotez, M.D., Ph.D. said to him, which was that “Operation Warp Speed” fundamentally changed how vaccine development occurred; conducting clinical trials simultaneously rather than sequentially, while simultaneously manufacturing a vaccine, and authorizing its use under the FDA’s “emergency use” provisions in December, and basing everything exclusively upon preliminary data – which in no way tracks the vaccine’s long-term protection – or even if it has any effect upon transmissibility, only that it protects against COVID-19.

Dr. Hotez is Dean of the National School of Tropical Medicine and Professor of Pediatrics and Molecular Virology & Microbiology at Baylor College of Medicine, where he is also the Director of the Texas Children’s Center for Vaccine Development (CVD), and Texas Children’s Hospital Endowed Chair of Tropical Pediatrics.

Perhaps the greater related question which many want answered is:
Does the COVID-19 vaccine prevent someone from being infected asymptomatically as a carrier?

As renown Georgetown University virologist Dr. Angela Rasmussen, Ph.D., M.A. told David Wallace-Wells, the very name “Operation Warp Speed” may have unnecessarily risked the trust of Americans who were already concerned about the safety of the prospective coronavirus vaccine, or of any vaccine.

Dr. Rasmussen is Associate Research Scientist at Columbia Center for Infection and Immunity in the Columbia Mailman School of Public Health.

In fact, in May, it would have been difficult to find any credentialed health science professional, epidemiologist, vaccine researcher, or public health official who would have recommended a rapid rollout of a coronavirus vaccine.

Dr. George Church, PhD, is Professor of Genetics at Harvard Medical School and Professor of Health Sciences and Technology at Harvard University. Pictured outside his home, he worked on the Human Genome Project to decipher humanity’s genetic code, establish the Personal Genome Project, which integrates genomes with other data and makes that information openly available worldwide. As a young boy and early adult, he struggled in the classroom to the extent that he had to repeat 9th grade and his first year of graduate school. Those struggles, however, were offset by his voracious appetite for science, an ability to work independently, and a passion for laboratory work that has sometimes blotted out all else.
In a 2016 interview, he said in part, “Follow your dreams, even if it does mean taking a risk. If you’re not failing, you’re probably not trying as hard as you could be. And being petrified of failure means you’re going to be probably a very extreme underachiever. One of the things we recruit people for in my lab is being nice. That’s the ethos we try to encourage. “Nice guys finish last” — isn’t that a terrible message to be sending to the next generation? I think what goes around comes around. You have to really want all the teams to succeed, all the boats to float. You want your competitors to not fail. It’s hard enough to get progress in the world if everybody’s succeeding.”
Stephanie Mitchell/Harvard Staff Photographer

However, in July the MIT Technology Review reported that a group of 70 Harvard and MIT scientists – renown geneticist Dr. George Church, Ph.D. among them – were self-administering an intra-nasal COVID-19 vaccine developed by Dr. Preston W. “Pete” Estep, Ph.D., Director of Genome Sequencing, and part of the senior management team of the Personal Genome Project at Harvard Medical School, which was made from “a simple formula that you could make with readily available materials.” Their efforts were outside the scope of regulation in a somewhat “grey regulatory area,” because no money was involved, no testing was proposed, and they were not proposing public use. It was literally a “made-in-the-kitchen sink” type of operation using off-the-shelf, publicly available materials.

Dr. Church is Professor of Genetics at Harvard Medical School and Professor of Health Sciences and Technology at Harvard and the Massachusetts Institute of Technology (MIT), Director of the U.S. Department of Energy Technology Center and Director of the National Institutes of Health Center of Excellence in Genomic Science.

In June this year, the Chinese military began inoculating their military.

In August, Russia approved their version of a coronavirus vaccine.

While many Americans may express concern about the rapidness of those, or other initial vaccination offerings, the way in which we have approached the problems wrought by the pandemic raises significant questions about the almost arcane way in which vaccination development is conducted. To many, the requirements are strange, the entire ordeal is unnecessarily complicated, frequently contradictory, the problems surrounding the matter of risk are uncertain, of course, and yet, they all point to the now-unspoken question: How do we do things differently when there is a next time?

To some, the fact that a vaccine was readily available at the outset of the pandemic, but not used, is angering, because it could have saved so many, many, many lives, and untold suffering of all types, including economic. To future researchers who study the history of this pandemic, the question they may have is, “why didn’t they use it sooner?”

Historically, cures for infectious diseases and vaccines – if they have appeared – were found only toward the natural end stage of the disease progression in public health. By that time, most of the damage had already been done, and the death rate was already declining. Examples of such events are found in outbreaks of measles, scarlet fever, tuberculosis, typhoid fever, and others. The primary difference between this time and historical developments, is that previously, the treatments and vaccines stopped the diseases permanently. There’s no promise that will happen this time.

The persistent echo in this process of the coronavirus pandemic and vaccine development, and others, is the McKeown thesis, so named for Dr. Thomas McKeown, MD, an Irish-born Rhodes scholar physician who later practiced in England, performed consultancy work for the World Health Organization, Commonwealth Fund, Josiah Macy Foundation, and Rockefeller Foundation, and was the first Chair of Social Medicine at the University of Birmingham, England, where he remained until his death in 1988. His work continues to spark debate, though some have summarily dismissed it.

The essential question Dr. McKeown’s work sought to answer was:
Are public health ends better served by targeted interventions, or by broad-based efforts to redistribute the social, political, and economic resources that determine the health of populations?

Throughout his research from the 1950s to the 1980s, he hypothesized that, from the late 1700s to the modern era, the population increase in industrialized nations was not due to advancements in medicine or public health – however life-saving they might have been – but were instead due to significant improvements in standards of living, including nutrition, all which resulted from improved economic conditions. In his historical analyses, he questioned some very sacred cows in health and medical practice, such as sanitary reforms, quarantine, and vaccination, though he remained a proponent of vaccination, citing the example of small pox. Controversy over his work continues to this day.

The questions central to McKeown’s thesis – What are the most important determining factors of a society’s patterns of morbidity and mortality? and, How should public health practitioners most effectively focus their efforts? – are as relevant today as when he first proposed them.

CDC Director Dr. Robert Redfield, MD has predicted this will be “the most difficult time in the public-health history of this nation,” with over 200,000 additional deaths in America.

The FDA has taken unprecedented actions by issuing Emergency Use Authorizations for medications such as hydroxychloroquine on March 28, for remdesevir on May 1, and for convalescent plasma on August 28. Their efforts, while well intentioned, and without solid evidence, were useless for all those medicines. The only one to have been found effective was dexamethasone, an inflammation-reducing medicine in the cortiosteroid family. And yet, all of those medicines have lethal risks.

These were all speculative authorizations — gambles, without concrete evidence, that existing treatments which scientists and doctors had some reason to suspect might help with the treatment of COVID-19 would be both safe and effective. All of these bets were lost. None of them, in the end, proved effective. Hydroxychloroquine, famously, proved dangerous, too, increasing risk of death in patients receiving it. Just one drug, the steroid dexamethasone, has proven to be a worthwhile treatment for COVID-19 in a randomized control trial — though given too early, it too can be dangerous.

Thus, the development of the mRNA-based vaccine is the most promising, because it contains neither an active, live, attenuated, nor killed virus – not even a portion of it – only a minuscule segment of its genetic makeup which is non-viral material, which makes it impossible for the virus to be transmitted.

The matters of public behavior, including social distancing and mask-wearing, continue to be important. And yet many feel justifiably frustrated at what they perceive to be ever-changing stances by public health officials and other health-related regulatory agencies. None of that has been helped by the current administration – the President in particular – which by its actions have openly undermined levels of public confidence in their traditional roles to preserve the safety of the public by behavior modification, and other measures, such as vaccination.

This again, crosses lines of public expectation, and undermines scientific efforts, especially given that Moderna’s vaccination was safe to begin with.

The lessons we should learn in this midst of this pandemic tragedy is perhaps not how to do things when the next one comes around.

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EDITOR’S NOTE: This article has been rewritten, edited for clarity and abbreviated. The article “We Had the Vaccine the Whole Time,” published December 7, 2020 in its original form by David Wallace-Wells, Deputy Editor and columnist for New York magazine, may be found in The Intelligencer section of the New Yorker website. David Wallace-Wells has been a national fellow at the New America Foundation and was previously the deputy editor of The Paris Review. He resides in New York City.