It looks like we will be able to get vaccinated to be (somewhat) protected against Covid-19 in the near future. Or will we? There are many questions attached to the issues of vaccines: their development, their approval, their distribution, their side effects and the (un)willingness of the population to be inoculated, to name a few. I’ll try and report on some of these issues today, including the fascinating fact of people volunteering to be infected with the virus in so-called challenge trials for vaccine development that risk their deaths, given the absence of definitive treatment options for the disease when it hits you hard.

First a lightning round on what vaccines do in general: they basically fake the disease without making you sick, helping the body develop protective immune responses so when the actual crud arrives you have a shield. There are three established ways to accomplish this and one that has never been approved before but seems to be a valuable candidate in the fight against Covid-19.

For one you can take a virus, inactivate it so it can no longer multiply in your body and expose your system to it to develop a defense. Successfully done in cases of the flu, polio, hepatitis A, and rabies, for example. Secondly you can work with a viral vector that carries the immobilized virus. Loosely put, scientists use DNA as a vector (often from chimpanzee adenoviruses) that your own system copies into RNA and then acts with a protective response. It worked for Ebola, some retroviruses, and small pox among others. Third, there are protein-based vaccines, which work with viral proteins only from the spike of the virus that tries to invade your cells. These vaccines are historically very safe and effective, among others protecting against hepatitis B virus, shingles, and whooping cough. And last, there are genetic vaccines, which introduce genes directly as either DNA or messenger RNA, which is used by the cell as a template to build a protein through a process of translation, then activating the protective response. They are easier to manufacture and distribute, but we have never used them before outside cancer research, and they also will require 2 doses.

Ok, let’s say you have developed something that seems to work, like Pfizer, Moderna, Astra Seneca and various other international pharmaceutic industries claim. Now what? You need approval – usually only given for vaccines that can prove to protect for longer than a year. We have no data on that and do not know how long each vaccine will protect you. This is particularly relevant in the light of the fact that we now have cases of re-infection after 4 months.

Then you need to manufacture on a grand scale, under sterile conditions. There are shortages of the glass containers and the custom bags that line the bioreactors in which vaccines are produced. In some cases, the vaccine ingredients are so unstable that they need to be kept at insanely cold temperatures( – 94 degrees Fahrenheit!) and expire after 10 days, a problem for distribution that relies on dry ice – also in short supply, as are syringes. The vaccine must be mixed at the administration site with a sterile liquid — usually water — and given within six hours of creating the solution. Since the vaccine will be shipped in cases with a high volume of doses, rural communities may not have the population, or infrastructure, to administer a case of doses while still cold. Hospitals across the country might also not have funds available to buy the fancy freezers that can be used where there is lots of electricity. (Ref.)

Then you have to decide who gets it first, since vaccines will be in limited supply (to achieve herd immunity, we need to inoculate about 5 billion people across the world, but we, if all get approved, are only likely to have enough for 2.5 billion people, given that the vaccine needs two doses.) First responders, health professional and old people, who are the most at risk? Younger people who are the super spreaders? People in certain areas of the country, so-called hotspots? Decision vary from country to country and are based on political reasons as well as medical evaluations. Details of allocation issues can be found here.

Given that we need more vaccines, people are trying to speed up development, and one way to do so is to run studies that use far fewer than the 10thousands of participants in normal randomized trials where you wait for people to get naturally infected, a process that takes time.

These faster studies are called “challenge” trials in which half of a group of a hundred or so participants gets actively infected with the virus, with the other half being the control group after they all received the developing vaccine. No longer using your gardener’s son (as Edward Jenner did in 1796 with small pox), or prison- or developing world populations who sign up under duress or are simply forced, these trials use volunteers. The World Health Organization has established complex protocols to insure ethical proceedings, but the ethics are still a hot topic of debate.

Would you sign up to be infected by this disease when we have no known treatments that are certain to cure? Would you risk long-term impairment, even if you can avoid death under the stellar medical care these programs provide? Would you agree to isolation for months on end to be under close supervision? Well, 37.000 people have signed up for this since May alone. PBS aired a segment on the One Day Sooner website that calls for volunteers and had an insane response.

When journalists from the Radiolab Podcast asked participants for their reason they found them all over the map. From gas station attendants to Nobel Prize Winners in Physics, they calculated the gain for humanity vs. their own vulnerability, they wanted to protect their parents, or escape boredom, they felt they were dying in a short time anyhow and might as well help science, they urged a commitment to our nation and community after these years of division, they wanted to have a voice at the table for underrepresented communities, and so on. It’s an interesting short listen, if you ignore the small numbers of respondents.

In contrast to those willing to face the disease personally and help develop vaccines against it, there are the many who are not willing to be vaccinated in the first place. There are multiple reasons why they might refuse. For one, there is a large anti-vaccine and anti-science movement in this country, amplified by the partisan divide in the Covid-19 case of acknowledging the danger of the disease. If it is all a hoax, why would I allow the state to prick me with a needle and have me suffer the side-effects (by all reports getting the vaccine will make you feel sick for a bit, with fevers and aches common) or worse inject some – insert your favorite conspiracy theory here – into me. The Lancet reports: “31 million people follow anti-vaccine groups on Facebook, with 17 million people subscribing to similar accounts on YouTube. The CCDH calculated that the anti-vaccine movement could realise US$1 billion in annual revenues for social media firms.” They are also an easy target for further radicalization.

Secondly, there are understandable reason for subparts of the population to be wary of being exposed to unproven substances. The experience of poor and people of color populations in our history has been exposure to forced experimentation in combination with much reduced access to good health care and pre- existing, poverty-related vulnerabilities. A devastating summary can be found here. Suffice it to say that the Nazi defense (!) at the Nürnberg Trial used the fact of experimentation by the US Army and the University of Chicago that infected prison population with malaria in the 1940s, and many such other cases, as justification for “international practice.” Current estimates say that only 42% of the US population is willing to get vaccinated, a number too low to achieve a win in the fight against the disease (and a number much lower than comparable choices in other western nations.)

In sum, do we know if and when we will get vaccinated? Can we trust the voices that claim we’ll be well into it at the beginning of next year? I fear so many things can go wrong, so many factors will influence distribution and allocation, that there is no way to be sure. But I do know that the minute the scientific sources I trust give the green light, I will still wait a month or two to see how things unfold and also give priority to those with a more and immediate need for limited supplies. But then I will stand in line and do my part to protect the community as a whole. No worries, you’ll hear about it!

Photographs are from my local Jackson Middle School on whose fields I walk my dog. The students have decorated their buildings with totem pole-like assemblages with abundant creativity – made me think again how hard these times are on children and how much we owe them to make this a better, less dangerous and more equitable world.

And here is music from illness-induced periods of social isolation of various composers. I found the source here.

Chopin wrote this while isolated during a bout with tuberculosis.

Stravinsky wrote this while recovering from typhoid (contracted from eating oysters…) in a nursing home.

And Rachmaninoff transcribed and played this after he was stricken with the Spanish Flu upon arrival in the US in 1918.