All new drugs that come into development are long shots, but some are longer than others. The vaccines most imminently starting trials for COVID-19 range from the promising but speculative to the highly promising but ethically fraught.
On Monday, Kaiser Permanente began soliciting volunteers to be injected with a mystery substance that will, if it works and does not cause unintended harm, release us all from quarantine purgatory when it becomes widely available in a reported 12 to 18 months. The trial is a partnership between Moderna, a Boston biotech company, and the National Institutes of Health, and it would not be an exaggeration to say that no pharmaceutical trial’s results have ever been awaited as breathlessly (if you’ll pardon the respiratory simile) as this one’s.
Moderna did not reply to a request for comment. The type of vaccine it is pursuing has never been approved by regulators, and like all experimental drugs, it could fail in many different ways.
Nearly every vaccine currently approved by the Food and Drug Administration introduces foreign proteins into a healthy but nonimmune individual. The body’s immune system finds those proteins, which are often part of a pathogen (the measles virus, say), and then quickly learns to recognize them. When the actual virus arrives, your immune system has already been introduced to the offending proteins and knows how to annihilate any living thing that bears them. The measles never stands a chance.
Moderna works on RNA vaccines—injecting not proteins but the molecules of nucleic acid that encode the instructions for building the proteins. Your cells use RNA to instruct their builders to make proteins all the time; the RNA is like the blueprints or schematics that tell the workers on the factory floor what to build. An RNA vaccine injects instructions to your cells, and hopes that your cells receive these instructions and follow them, and build the proteins that will teach your immune system to fight a virus. It is a bit like wadding up plans for a Cessna, throwing them through the ventilation shaft of a Ford factory, and hoping that someone inside finds them, and that the factory starts rolling airplanes out its doors instead of pickups.
Despite successes in animals, this strategy has never yielded a vaccine approved for human use. Moderna is a leader in this approach, and you can be sure the scientists there have considered all the ways to make it more likely to work. They throw the plans down the shaft nearest the factory manager’s office; they attach official-looking paperwork and bribes. But their approach is ambitious. If it works in humans, it will represent a huge advance in immunology and clinical medicine.
The RNA-vaccine approach has one great advantage: speed. Scientists merely need to know the virus’s genetic sequence, and they can synthesize and scale up production of an RNA vaccine in a matter of weeks. RNA is fragile. In a lab, you have to shield your face to work with it, not because it is dangerous but because you are dangerous to it. Even a gust of saliva is likely to contain enzymes that would rip RNA apart, rendering it worthless. As long as it’s formulated properly, RNA is considered nearly harmless to inject into humans, and a Phase 1 trial like this is easy to begin. Success is hardly assured, but we at least know that the RNA won’t hurt the people in the trial who are being paid $1,100 to have it injected into them. It is a clever approach—but don’t eat through your boxes of stockpiled wholesale ramen too quickly, because no one can or should guarantee that an RNA vaccine will stop the pandemic anytime soon.
There is another option, less ambitious but more likely to work, and with a calendar for deployment perhaps as short as three to four weeks, with results four weeks later. We’ll call it the human-blood-bag approach.
If you survive COVID-19—and to date, 86,025 people have done so—it’s because your body wised up to the attack and learned to fight it off. (No pharmaceutical therapy seems to do much good, so for now your body is on its own, immunologically speaking.) Congratulations: You now produce antibodies to the coronavirus. And if you are willing to share them, you are now someone’s new best friend.
The process is simple. Surrender some of your blood, and a lab will filter out the cells and keep only the amber-colored serum, with the antibodies to the virus still in there and active. This serum, further refined, is called “hyperimmune globulin.” All that remains is to infuse the serum into a healthy person (or, in much greater quantities, into a sick one). The antibodies won’t last forever, but they could last weeks or months, and either help a sick recipient heal or keep a healthy recipient from getting the virus at all.
Yesterday, a team at Johns Hopkins University led by Arturo Casadevall received FDA approval to try this technique. “This has a high probability of working, based on 100 years of experience in medicine,” he says. Indeed, it was used successfully to treat Ebola in 2014.
The approach does carry risks. Antibodies to a virus can make a viral infection worse in some cases, such as with dengue fever. We don’t know if COVID-19 will react that way. (Most viruses do not.) Despite this, Casadevall says he has already had volunteers who wish to donate their antibodies or receive the serum from others. “This is real,” he says. “In eight weeks, we may have something that’s useful.” Takeda Pharmaceuticals, a Japanese company that has developed and sold hyperimmune globulin for other conditions since 2005, has already started collecting plasma from convalescent COVID-19 patients, according to Julie Kim, an executive there. She says she hopes that Takeda’s product will become available in nine to 18 months.
A catch: Each COVID-19 survivor can support the immunity of at most a few others, and to do so, the survivor will have to be bled at regular intervals, becoming a human blood bag. Casadevall suggests that the ratio of convalescent COVID-19 patients to serum recipients might be as low as 1 to 2, or as large as 1 to 10—10 immunized recipients for every survivor who opens his veins. The next eight weeks will be devoted, among other things, to figuring out how many people a single blood bag can support. They’ll also have to figure out which convalescent patients are best endowed with antibodies, and wring as much blood plasma out of them as possible.
And if the project works, it will create ethical dilemmas. Who will be among the lucky 10 for every survivor? Will you be able to donate your antibodies to your loved ones? They’re your antibodies after all—ones you worked hard to produce—and perhaps you should have the right to choose where they should go. In free countries, we are reluctant to take away citizens’ precious bodily fluids, bleeding one another dry, without permission.
But something feels wrong about a world in which the rich can immunize themselves by buying the blood of the poor as they stagger out of the hospital. As a matter of public health, people in need should have dibs on those antibodies. Put health-care workers first in line, Casadevall suggests, and those who care for sick relatives at home. One option would be to nationalize COVID-19 antibodies: You can keep them in your own body and enjoy them all you like, but once they get sucked out of your body, they belong to humanity and might even get pooled into a massive stockpile of blood plasma, on tap for those who need it most. Another option, less restrictive, would be to treat the plasma like kidneys. You can donate your kidney to anyone but sell it to no one. This approach, it must be said, leaves us with a shortfall of 21,000 kidneys every year, and 13 people die every day on the wait list. Let survivors sell their antibodies, and more antibodies will be available.
Or we could prioritize the health of the altruistic. Want a hospital bed and a top-of-the-line ventilator? Sign a note promising that your first stop after the hospital will be your local serum bank, and you can cut to the front of the line and get intubated today. Sign a pledge even before you get sick, and you can get a human blood bag T-shirt or wristband to prove to your friends that you are civic-minded, or at least not a complete schmuck. We could develop plasma clubs, in which you and your friends—or thousands of strangers, for that matter—all pledge to donate your hyperimmune globulin if you recover, and in return, you get access to everyone else’s if you ever need it. If at some point enough members return to good health, the surplus goes to doctors and nurses.
Ideally we’d have a vaccine yesterday—one that we can mass-produce and jab into the arms and glutes of everyone on Earth. In reality, it will take a while, and short-term solutions—including social distancing—are all we know we can count on. But there is hope.
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