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I’m no stranger to forced isolation. For the better part of my 20s, I served as a nuclear submarine officer running secret missions for the United States Navy. I deployed across the vast Pacific Ocean with a hundred other sailors on the USS Connecticut, a Seawolf-class ship engineered in the bygone Cold War era to be one of the fastest, quietest, and deepest-diving submersibles ever constructed. The advanced reactor was loaded with decades of enriched uranium fuel that made steam for propulsion and electrical power so we could disappear under the waves indefinitely without returning to port. My longest stint was for two months, when I traveled under the polar ice cap to the North Pole with a team of scientists studying the Arctic environment and testing high frequency sonar and acoustic communications for under-ice operations. During deployments, critical-life events occur without you: holidays with loved ones, the birth of a child, or in my case, the New York Giants 2011-2012 playoff run to beat Tom Brady’s Patriots in the Super Bowl for the second time. On the bright side, being cut off from the outside world was a great first job for an introvert.

It’s been a month since COVID-19 involuntarily drafted me into another period of isolation far away from home. I’m in Turkey, where a two-week trip with my partner to meet her family has been extended indefinitely. There were no reported cases here and only a few in California in early March when we left San Francisco, where I run a business design studio. I had a lot of anticipation about Turkey because I’d never been here. Now I’m sheltering in a coastal town outside of Izmir with my partner, her parents, their seven cats, and a new puppy.

Shuttered in a house on foreign soil where I don’t speak the language, I have found myself snapping back into submarine deployment mode. Each day I dutifully monitor online dashboards of data and report the status of the spread at the breakfast table to no one in particular. I stay in touch with friends and family all over the world who tell me they’re going stir crazy and their homes are getting claustrophobic. But if there is one thing my experience as a submarine officer taught me, it’s that you get comfortable being uncomfortable.

My training began with psychological testing, although it may not be what you think. Evaluating mental readiness for underwater isolation isn’t conducted in a laboratory by clipboard-toting, spectacled scientists. The process to select officers was created by Admiral Hyman Rickover—the engineering visionary and noted madman who put the first nuclear reactor in a submarine—to assess both technical acumen and composure under stress. For three decades as the director of the Navy’s nuclear propulsion program, Rickover tediously interviewed every officer, and the recruiting folklore is a true HR nightmare: locking candidates in closets for hours, asking obtuse questions such as “Do something to make me mad,” and sawing down chair legs to literally keep one off balance.

Rickover retired from the Navy as its longest-serving officer and his successors carried on the tradition of screening each officer candidate, but with a slightly more dignified approach. Rickover’s ghost, though, seemed to preside over my interview process when I applied to be a submariner as a junior at the U.S. Naval Academy in Annapolis, Maryland. I was warned by other midshipmen that I would fail on the spot if I initiated a handshake. So, dressed in my formal navy blue uniform and doing my best to avoid tripping into accidental human contact, I rigidly marched into the Admiral’s office, staring straight ahead while barking my resume. When I took a seat on the unaltered and perfectly level chair in front of his desk, the Admiral asked me bluntly why I took so many philosophy classes and if I thought I could handle the technical rigors of nuclear power school. My response was a rote quip from John Paul Jones’ “Qualifications of a Naval Officer.” “Admiral, an officer should be a gentleman of liberal education, refined manners, punctilious courtesy, and the nicest sense of personal honor.” My future boss looked at me, shook his head like he thought I’d be a handful, and told me I got the job.

Confinement opened something up in my psyche and I gave myself permission to let go of my anxieties.

Nuclear power training is an academic kick in the face every day for over a year. The curriculum is highly technical and the pedagogy resembles a cyborg assembly-line without even a hint of the Socratic method. Our grades were conspicuously posted on the classroom wall and a line was drawn between those who passed and those who failed. I was below the line enough to earn the distinguished dishonor of 25 additional study hours each week, which meant I was at school at 5 a.m. and every weekend. This is how the Nuclear Navy builds the appropriate level of knowledge and right temperament to deal with shipboard reactor operations.

I finally sat down for a formal psychological evaluation a few months before my first deployment. I was ushered into a room no bigger than a broom closet and instructed to click through a computer-based questionnaire with multiple-choice questions about my emotions. I never did  learn the results, so I assume my responses didn’t raise too many red flags.

During my first year onboard, I spent all my waking hours either supervising reactor operations or learning the intricacies of every inch of the 350-foot tube and the science behind how it all worked. The electrolysis machine that split water molecules to generate oxygen was almost always out of commission, so instead we burned chlorate candles that produced breathable air. Seawater was distilled each day for drinking and shower water. Our satellite communications link had less bandwidth than my dial-up modem in the 1990s and we were permitted to send text-only emails to friends and family at certain times and in certain locations so as not to risk being detected. I took tests every month to demonstrate proficiency in nuclear engineering, navigation, and the battle capabilities of the ship. When I earned my submarine warfare qualification, the Captain pinned the gold dolphins insignia on my uniform and gave me the proverbial keys to the $4 billion warship. At that point, I was responsible for coordinating missions and navigating the ship as the Officer of the Deck.

Modern submarines are hydrodynamically shaped to have the most efficient laminar flow underwater, so that’s where we operated 99 percent of the time. The rare exception to being submerged is when we’d go in and out of port. The most unfortunate times were long transits tossing about in heavy swells, which made for a particularly nauseated cruise. To this day, conjuring the memory of some such sails causes a reflux flashback. A submariner’s true comfort zone is beneath the waves so as soon as we broke ties with the pier we navigated toward water that was deep enough for us to dive.

It’s unnatural to stuff humans, torpedoes, and a nuclear reactor into a steel boat that’s intentionally meant to sink. This engineering marvel ranks among the most complex, and before we’d proceed below and subject the ship and its inhabitants to extreme sea pressures, the officers would visually inspect thousands of valves to verify the proper lineup of systems that would propel us to the surface if we started flooding uncontrollably and sinking—a no-mistakes procedure called rigging for dive. Once we’d slip beneath the waves, the entire crew would walk around to check for leaks before we’d settle into a rotation of standing watch, practicing our casualty drills, engineering training, eating, showering (sometimes), and sleeping (rarely). The full cycle was 18 hours, which meant the timing of our circadian cycles were constantly changing. Regardless of the amount of government-issued Folger’s coffee I’d pour down my throat, I’d pass out upon immediate contact with my rack (the colloquialism for a submarine bunk in which your modicum of privacy was symbolized by a cloth curtain).

As an officer, I lived luxuriously with only two other grown men in a stateroom no bigger than a walk-in closet. Most of the crew slept stacked like lumber in an 18-person bunk room and they all took turns in the rack. This alternative lifestyle is known as hot-racking, because of the sensation you get when you crawl into bedding that’s been recently occupied. The bunk rooms are sanctuaries where silence is observed with monastic intensity. Slamming the door or setting an alarm clock was a cardinal sin so wakeups were conducted by a junior sailor who gently coaxed you awake when it was time to stand watch. Lieutenant Weiner, it’s time to wake up. You’ve got the midnight watch, sir. Words that haunt my dreams.

The electrolysis machine was out of commission, so we burned chlorate candles that produced breathable air.

I maintained some semblance of sanity and physical fitness by sneaking a workout on a rowing erg in the engine room or a stationary bike squeezed between electronics cabinets. The rhythmic beating of footsteps on a treadmill was a noise offender—the sound could be detected on sonar from miles away—so we shut it off unless we were in friendly waters where we weren’t concerned with counter-detection.

Like a heavily watered-down version of a Buddhist monk taking solitary retreat in a cave, my extended submarine confinements opened something up in my psyche and I gave myself permission to let go of my anxieties. Transiting underneath a vast ocean in a vessel with a few inches of steel preventing us from drowning helps put things into perspective. Now that I’m out of the Navy, I have more appreciation for the freedoms of personal choice, a fresh piece of fruit, and 24 hours in a day. My only regrets are not keeping a journal or having the wherewithal to discover the practice of meditation under the sea.

Today, I’m learning Turkish so I can understand more about what’s happening around me. I’m doing Kundalini yoga (a moving meditation that focuses on breathwork) and running on the treadmill (since I’m no longer concerned about my footsteps being detected on sonar). On my submarine, I looked at photos to stay connected to the world I left behind, knowing that I’d return soon enough. Now our friend who is isolating in our apartment in San Francisco sends us pictures of our cat and gives us reports about how the neighborhood has changed.

It’s hard to imagine that we’ll resume our lifestyles exactly as they were. But the submariner in me is optimistic that we have it in us to adapt to whatever conditions are waiting for us when it’s safe to ascend from the depths and return to the surface.

Steve Weiner is the founder of Very Scarce, a business design studio. He used to lead portfolio companies at Expa and drive nuclear submarines in the U.S. Navy. He has an MBA from The Wharton School and a BS from the U.S. Naval Academy. Instagram: @steve Twitter: @weenpeace

Lead image: Mike H. / Shutterstock

There are many challenges to developing a vaccine that will be successful against COVID-19.eamesBot / Shutterstock

Wayne Koff is one of the world’s experts on vaccine development, the president and CEO of the Human Vaccines Project. He possesses a deep understanding of the opportunities and challenges along the road to a safe and effective vaccine against COVID-19. He has won prestigious awards, published dozens of scientific papers, held major positions in academia, government, industry, and nonprofit organizations. But Koff, 67, has never produced a successful vaccine.

“I have been an abject failure,” he says. He smiles with a charming, self-deprecating sense of humor. “That’s what the message is.”

The real reason for Koff’s lack of success is that he spent most of his career searching for a vaccine against HIV, the virus that causes AIDS. It remains, as he and many others put it, “the perfect storm” of a viral infection resistant to a vaccine development. Almost 40 years after doctors first recognized the disease in five men in Los Angeles—and 70 million people have been infected worldwide—there are no adequate animal models. Neutralizing antibodies, the backbone of many vaccines, do not stop it, and most importantly, HIV begins its assault on the body by attacking CD4 T cells, which serve as the command center of much of the immune system.

As for COVID-19, “We’re all hoping this one is going to be easier,” says Koff, a slight, bearded man with thick, curly salt-and-pepper hair. “There are research issues that still have to be addressed on a COVID vaccine. But they are a lot more straightforward than what we were dealing with in HIV.”

Let’s say we have a vaccine in 18 months. How do you make 1 billion doses or 4 billion doses or whatever it’s going to take to immunize everybody?

Koff and others started the Human Vaccines Project in 2016, modeled on the Human Genome Project. The project works with industry and academia to study the human immune system and develop vaccines, incorporating every modern-day tool, including artificial intelligence, computational biology, and big data sets. Today it is partnered with the Harvard T.H. Chan School of Public Health.

With COVID-19, Koff says, scientists “know the target is the spike protein binding site.” This is where the proteins sticking out from the virus attach to the cells in the human respiratory system. “If you can elicit antibodies against those proteins, they should be neutralizing.” He puts a strong emphasis on should. To prove antibodies will prevent infection, scientists must watch a population of people who’ve been infected for months or longer. It’s a good bet, based on similar viruses, that antibodies will appear and protect—although no one right now can predict how long and how well.

Depending on which count you use, more than 70 companies, universities, and other institutions are offering candidate vaccines. Koff says the real number of companies is lower. During the AIDS crisis, he says, “a lot of people claimed they had an experimental HIV vaccine in development. Some of those were a one-person lab who had created a paper company to attract investors.”

But even with a lower number, almost everyone involved in the search for a vaccine agrees that several different approaches from different research organizations need to proceed in parallel. The world does not have the time to bet on one horse. The race will be neither simple nor cheap.

“The probability of success, depending on whose metric is used in vaccines, is somewhere between 6 and 10 percent of candidate vaccines that make it from the animal model through licensure,” Koff says. “That process costs $1 billion or more. So you can do the math.”

Koff sees big potential problems at the outset. “In the best of all worlds, let’s say we have a vaccine in 18 months. Who knows where the epidemic is going to be then and what its impact is going to be? How do you make 1 billion doses or 4 billion doses or whatever it’s going to take to immunize everybody? Will we need one dose or two or three? These are issues people just haven’t faced before.”

COVID-19 also presents some unique dangers for vaccine safety. Based on how the virus behaves when it infects some people, there’s a chance a vaccine could dangerously overstimulate the immune system, a reaction called immune enhancement. “I’m hoping it’s more theoretical than real,” Koff says. “But that has to be addressed and it may slow down the entire process.” To ensure safety, he says, “It may mean we have to test the vaccine in a larger number of people. It’s one thing to do a 50-person trial in healthy adults as a safety signal. It’s another thing to run a trial of 4,000 or 5000 or more individuals.”

The world does not have the time to bet on one horse. The race will be neither simple nor cheap.

A virus also sometimes causes mysterious, potentially deadly blood clots. This means an experimental vaccine could hypothetically induce the same damage. “This is a bad bug,” Koff says. “We’re just starting to understand that pathogenesis.”

A big question is who should be the first volunteers for widespread vaccine testing. “Who are the high-risk groups?” asks Koff. “Is it nursing-home residents and staff, health-care workers and people on the front lines, or people someplace else like grocery stores? We must also make sure a vaccine is effective for the elderly and people in the developing world.”

Many vaccines work well in young and healthy people but not in older adults because immunity declines with age. Influenza vaccine is a prime example. Rotavirus vaccine, which protects against the deadliest killer—diarrheal disease in children—works better in the developed world. In the developing world, the virus often circulates year-round. Infants get antibodies from breast milk but not enough to prevent disease. Worse, those antibodies can make the vaccine less effective.

Another hypothetical obstacle is that a mutation in the COVID-19 virus could render a vaccine designed today less effective in the future. While the virus mutates frequently, so far there has been little change in the critical part of the spike that binds to human cells.

Of course, neither Koff nor all the others working for a COVID-19 vaccine focus solely on the potential obstacles. At one time, all vaccines against viruses either killed viruses, such as the Salk polio vaccine, or rendered them harmless, such as the Sabin polio vaccine. Now there is a multiplicity of ways to stimulate an immune response to prevent infection or reduce the consequences. These include genetically engineered protein subunits (peptides) or virus-like particles. Such approaches have led to successful vaccines against hepatitis B and human papilloma virus, which causes cervical cancer. Researchers now use “vectors”—harmless viruses attached to the protein subunits and virus particles to transmit them into the body. There are also many new adjuvants, chemicals that boost immune response to a vaccine.

Newer platforms include direct injection of messenger-RNA. M-RNA is the chemical used to translate the information in DNA into proteins in all cells. The Moderna Company, which received a $483 million grant from the U.S. government, and has begun early clinical trials, uses m-RNA to try to make the body produce proteins to protect against the COVID-19 virus. INOVIO Pharmaceuticals uses pieces of DNA called plasmids to achieve the same objective. It has also begun phase 1 studies.

“There are about eight platforms, and it would be good to see a couple vaccines in each of those advance,” Koff says. Predicting which of these most likely to succeed or fail he says would be “simply foolish.”

Many groups, including the Human Vaccines Initiative, are plotting routes to test any possible vaccine more quickly than tradition dictates with an “adaptive trial design.” Usually trials begin with a phase 1 study of some 50 healthy people to search for any immediate signs of toxicity, then moves onto about 200 people in a phase 2, still looking for hazards and a signal of immunity, and then to phase 3 in thousands of people. But the plan here is to start phases 2 and 3 even before its predecessors are finished, and keep recruiting additional volunteers so long as no danger signals arise.

Good animal models are appearing almost daily. Macaque monkeys, hamsters, and genetically engineered mice have all been infected in the laboratory and could determine whether potential vaccines exhibit various types of immunity. Members of Congress from both sides of the aisle have suggested that healthy human volunteers should be allowed to agree to be test subjects, allowing themselves to be infected. Stanley Plotkin, a vaccine researcher at the University of Pennsylvania, was among the first to suggest the idea.

Arthur Caplan, a bioethicist at New York University, says that “deliberately causing disease in humans is normally abhorrent.” But COVID-19 is anything but a normal circumstance. In this case, Caplan says, “asking volunteers to take risks without pressure or coercion is not exploitation but benefitting from altruism.” At least 1,500 people have already volunteered to be such human guinea pigs, although none of the experimental vaccines is far enough along to try such challenging experiments.

Koff says the key to a successful vaccine is a cooperative effort. “It’s going to take a whole different way of thinking to move this onto the expedited train,” he says. “The old dog-eat-dog, ‘I’m going to beat you to the end of the game,’ isn’t going to help us with this.” Seth Berkley, who worked with Koff at the International AIDS Vaccine Initiative, and now heads GAVI, an international vaccine organization, agrees that a COVID-19 vaccine needs a Manhattan Project approach. “An initiative of this scale won’t be easy,” Berkley says. “Extraordinary sharing of information and resources will be critical, including data on the virus, the various vaccine candidates, vaccine adjuvants, cell lines, and manufacturing advances.”

Koff has no regrets about spending so many years on an AIDS vaccine without results. He learned a great deal, he says, which he’s putting to work in the COVID-19 crisis. “The reason COVID-19 vaccines should be a lot easier is because most of the platforms, the novel approaches, and the clinical infrastructure for the testing of vaccines, came out of HIV.” He pauses. “We’re far better prepared.”

Robert Bazell is an adjunct professor of molecular, cellular, and developmental biology at Yale. For 38 years, he was chief science correspondent for NBC News.

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