On the morning of Dec. 29, as a historic and harrowing year was drawing to a close, Dr. Steven Pergam bared his left shoulder to receive his first dose of the COVID-19 vaccine.

An infectious disease physician-scientist at Seattles Fred Hutchinson Cancer Research Center and a cancer and kidney transplant survivor himself Pergam had plenty at stake in getting a safe and effective shot.

He described it as a moment of reflection, a time to remember those lost to the pandemic and the millions more patients and their families affected by it. The pandemic has preoccupied him for a full year, and it was crucial that the shots be safe to give to millions.

Last month Pergam sat on the U.S. Food and Drug Administrations Vaccines and Related Biological Products Advisory Committee, which reviewed results of last years massive clinical trials testing both the safety and efficacy of the Pfizer-BioNTech and Moderna vaccines. He voted to endorse their emergency use.

Now, as the U.S. grapples with the effort to distribute massive quantities of vaccine, the fundamental challenge is the more delicate task of persuading tens of millions of others it is safe to take it. A message of safety and clear benefit must overcome reasonable concerns sparked by the speed and trailblazing nature of the vaccine development effort.

That message is grounded in the results of those trials. They were structured to test the vaccines in enough people that, were some safety issue to arise, it would stand out in the data. Instead, the independent studies of both vaccines showed no significant safety concerns and found the two were more than 90% effective in preventing severe disease.

In laymans terms: amazingly good.

Some people on the fence about taking the vaccine might be convinced to get it by the shocking statistic that nearly one in every 800 Americans has already died from COVID-19 in less than a year. In comparison, the risks of an adverse reaction to a vaccine are vanishingly small.

Since the start of mass vaccinations last month, one side effect not detected in the clinical trial process emerged in small numbers of recipients a severe allergic reaction called anaphylaxis. Although it has occurred rarely, at a rate of only 11 in every 1 million shots delivered, it is a serious reaction requiring a shot of adrenaline (the ingredient found in EpiPens carried by people with severe food allergies) and hospitalization. The CDC is closely monitoring these cases to find out if an ingredient of the vaccine might be responsible.

It is not surprising that this side effect was not seen in the clinical trials, because statistically even a single case was unlikely to occur among the roughly 40,000 volunteers who received shots in each trial. More common, and not unexpected, are reports of a sore arm, headache or a slight fever the kind of discomfort sometimes experienced after flu shots or other routinely delivered vaccines.

Yet Pergam, who is also director of infection control at the Hutchs clinical care partner Seattle Cancer Care Alliance, recognizes that providing facts and figures that reassure him as a doctor may not suffice for the public at large. While convinced the two authorized vaccine are safe, he said scientists should not expect others to simply take their word for it.

To just tell someone that 40,000 people have received the vaccine in a trial and that it is going to be safe and effectivemay not translate well to the individual, Pergam said. He believes doctors must be open about side effects and not be dismissive of consumer anxiety.

Pergam and other vaccine researchers say that to win over some schooled in skepticism and conspiratorial thinking on the internet, the messenger can be just as important as the message.

One concern he often hears about is that the newly released vaccines, which contain bits of genetic material called mRNA, are so novel that scientists just dont know enough about them. But Pergam notes that the technology that made these and other coronavirus vaccines possible has been in the works for more than a decade.

Its the culmination of 10 to 15 years of investment in science, he said. We were in a race to get vaccines for Ebola, for HIV and West Nile virus. Then the time was right, and all that investment led to where we are now.

The need for vaccines is particularly acute in communities of color, which have been hard-hit by COVID-19 and have a legacy of mistreatment by medical institutions. Trust the science rings hollow to some populations lacking routine access to quality medical care, who feel disrespected by doctors, and for whom the primary access to the medical system is often the emergency room.

The legacy of distrust continues to be a pervasive concern, and some people are hesitant to jump on at this point, said Dr. Stephaun Wallace, director of external relations for the COVID-19 Prevention Network, or CoVPN, which through its operations center at Fred Hutch is coordinating five different large-scale vaccine trials.

Some people want to wait and see what happens with other people before they decide to take the vaccine. Some are waiting to see how this vaccine looks for people that they know or that look like them, he said. The videos and images of Black doctors and other health care staff getting the injection has been very helpful for many people.

Wallace honed his skills in building community support at the HIV Vaccine Trials Network, headquartered at Fred Hutch. National Institute of Allergy and Infectious Diseases Director Dr. Tony Fauci recognized the importance of that expertise when he tapped HVTN and its team of biostatisticians and virologists to operate the CoVPN vaccine trials.

Through his community outreach, Wallace has an inside track on issues that might generate hesitancy to get the vaccine, such as how thorough were the tests (as thorough as those for any vaccine in use today) and whether it was tested on people who looked like them (diversity has been a cornerstone of CoVPN trials).

One universal question asked about new vaccines is whether they can give you the coronavirus itself. The answer is no, because no virus, living or dead, is included in the ingredients of any of the vaccines under study in the U.S.

Because the two newest vaccines use a snippet of mRNA containing blueprints of the coronavirus spike, people also frequently ask if that genetic material could somehow change our own DNA. Again, the answer is no. These short-lived segments of RNA biologically cannot change our own genetic makeup.

Instead, they cause certain immune cells to post notices a bit like wanted posters of the coronavirus spikes. That information helps train other immune cells to crank out billions of antibodies that will swarm over the spikes found on real coronaviruses should they attempt to infect us, jamming their ability to do so.

What most scientists fail to understand, behavioral health experts say, is that most people do not think like scientists.

If you come at someone with a bunch of data, facts and figures, people are just not going to be able to process that, said Dr. Robert Bednarczyk, a professor at the Rollins School of Public Health at Emory University in Atlanta. Scientists rely on data. Its what we do. But living in a world of numbers is not sufficient. It can make other peoples eyes gloss over.

While scientists might be reassured by a statistical analysis that disproves a myth, Bednarcyzk who teaches classes on vaccine hesitancy to medical students says myth-busting can be counterproductive.

As a species, we dont ever like to be told were wrong, said Bardnarcyzk, who added that if you take a position that someone holds as important and wipe it away, it is important to offer a clearly understandable idea to replace it.

The politicization of mask-wearing is an example where attitudes hardened and a simple but effective prevention message went sideways, he said. In part, that was because of early mixed messages from leading health authorities about the benefits of masks, which were also in desperately short supply.

Of recent discussions about the rarity of allergic reactions to the new COVID-19 vaccines, Bednarczyk said that it would be helpful for doctors to point out that researchers are paying close attention to this issue. Public health educators should note that the discovery of these reactions is an example of vaccine safety monitoring systems working, the way they are supposed to, he said.

Fred Hutch behavioral scientist and pharmacist Dr. Parth Shah said it can be helpful to show those concerned about vaccines that, despite the highly technical development process, these are not extraordinarily complex products and that the components are disclosed.

The ingredients list in these vaccines is probably shorter than the list of ingredients in a bag of chips, he said.

Shah agree that consumers do not have a statisticians grasp of relative risk, but he said one way to put vaccine risk into perspective is to compare it the known risk of common products such as acetaminophen (Tylenol and its generic equivalents), which is marketed for its safety.

This common pain reliever generates an average of 60,000 visits to the emergency room annually, according to one study. In 2011, the rate of hospitalizations for acetaminophen poisonings was pegged at 134 per 1 million people in the U.S. That is more than 10 times higher than the rate of anaphylaxis (about 11 per 1 million does) reported so far for the new vaccine. Most of those cases appear to be among recipients who had a history of allergic reactions, and to date all have recovered.

There are things we take on a daily basis that we take for granted that have a substantially higher risks associated with them, Shah said.

When it comes to numbers, the one that Shah finds most important is the better-than-90% effectiveness rate against severe disease the vaccine trials have so far found. When it comes to protecting the public from the worst pandemic since 1918, safety appears in the form of a vaccine.

We were out looking for something at least 50% effective, and we now have something nearly twice that. Its outstanding, he said. I think there is good reason to be optimistic. We just need to be vigilant, and weve got to be a little more patient.