Bloomberg 长篇特写正面聚焦基因编辑，核心信息均为 Beam Therapeutics Alpha-1 项目旧数据，无新增临床或商业事实

Three years ago, at the age of 50, I found out I have dangerous genes. So in June, I went to Cambridge, Massachusetts, to see how they could be fixed. Among my 6 billion base pairs of DNA are two mutations — one inherited from my father, one from my mother — that give me Alpha-1-antitrypsin deficiency syndrome, also known as AATD or just Alpha-1. My mutation creates a misfolded protein that can’t fight off everyday lung damage, as it normally would. This protein can also pool in the liver, causing degeneration there too. The worst form of the mutation can make a carrier 10 to 20 times more likely to develop emphysema.

I went to Cambridge to visit Beam Therapeutics, which was founded to develop base-editing therapies. This is one of four techniques, three of them built on the science of Crispr, that are now available to permanently alter our DNA. One of the treatments Beam is working on seeks to repair the mutation that causes Alpha-1. In an ongoing trial, 29 volunteers have received the therapy, with encouraging outcomes and no complications so far. Before I visited Beam, David Liu — a co-founder of the company who’s also the primary inventor of base editing and a biochemist at Harvard University, the Broad Institute and the Howard Hughes Medical Institute — told me this was “the first time a pathogenic mutation in a person has ever been corrected.” In other words, it was the first time the specific DNA mutation causing a disease had been irreversibly altered. Liu also told me that an estimated 400 million people worldwide have a genetic disease. About 25 million of them are in this country.

On a high floor overlooking the Charles River, Beam engineers were optimizing toaster-size robots to move cell samples and base-editing molecules from machine to machine, traveling on tracks near the ceiling. On another floor, scientists were carefully rearranging tubes and pumps to test one of the company’s recipes for proprietary “lipid nanoparticles.” Everyone from lab employees to Beam’s chief executive officer, John Evans, were proud to already be treating patients by permanently editing their DNA.

They were also aware that, after many years of hype, investors still have pointed questions about the technology. Will base editing indeed be a permanent fix? Will it prove safe for years afterward? Can a “one and done” therapy gain enough patients in a crowded market? Will insurance companies pay for it? And can Beam advance its science for yet more diseases before commercial revenue comes in?

The company is completing or just about to begin trials for treatments for Alpha-1 and for sickle cell, glycogen storage and phenylketonuria diseases. If all goes as planned, the Alpha-1 therapy will come to market around 2029. It and comparable treatments from Beam’s competitors are being viewed as a bellwether for the entire gene-editing ecosystem. Because of how the Alpha-1 mutation works and where it’s found, it’s widely regarded as the ideal medical and business test to see if editing our DNA can cure other diseases as well.

At Beam’s headquarters, I joked with Evans that I was going to snatch a vial of the company’s Alpha-1 therapy and down it, like one of the bad kids in Charlie and the Chocolate Factory. Evans laughed and told me drinking it wouldn’t work.

I knew that. But the actual two-hour IV treatment, which could someday forever alter my DNA, wouldn’t be that much harder to take.

A week later, back home in New Orleans, I found myself in a plexiglass box, hands on my cheeks, exhaling as hard as I could for 10 seconds, certain I would pass out before this breathing test was done. It was one of a battery of tests I now undergo every six months on my doctor’s advice. Thankfully, none involves pull-ups.

The data said my lungs are still at the low end of normal functioning, which could be due to Alpha-1 or to a childhood spent warming the bench. But they were getting slightly worse.

We each inherit, by one study, about 400 potentially damaging genetic mutations from our parents, most of them with no noticeable effect on our health. These variants and others unique to us are the reason greeting cards are true — “There’s no one like you!” — and also why there’s life on Earth. Mutations and natural selection are the locomotion of evolution. For 10,000 years, people have sought mutations for plant and animal breeding. And for 50 years, since biotech company Genentech Inc. inserted genetic materials into cells to manufacture insulin for humans, we’ve used DNA, and then RNA, as tools to fight disease. Hype over the possibilities accelerated with the Human Genome Project, which got underway in 1990 to breathless headlines promising a map of our biological foundation and cures for every disease. It took until 2003 for that map to be completed. It took even longer for scientists to put it to work in earnest against the human body’s many ways to foil treatments. The first commercial gene therapy product for an inherited disease didn’t come out until 2018.

Companies pursuing gene therapy for inherited mutations can today draw on four basic methods, each with a defining mechanism that I keep straight with a mnemonic tied to NBA teams. There are scientists and companies I call the Nuggets, after the first commercial approach, gene addition, which involves adding a strand of DNA into cells, usually via an engineered, disarmed virus. There are the Clippers, gene editing efforts working with “standard” Crispr, the approach that gained prominence after the publication of a groundbreaking paper by future Nobelists Jennifer Doudna and Emmanuelle Charpentier, showing how the ancient natural immune system of bacteria could be adapted to find and cut both strands of a DNA sequence for disruption or repair. There are the Knicks, pursuing the base editing that originated in David Liu’s lab, which builds on Crispr science but eschews the double-cutting of both strands of DNA for a more subtle “nicking” of one strand. This technique then uses atomic chemistry to change one of four nitrogenous bases, such as cytosine, to another one. And then there are the Spurs, those developing “prime editing,” the least-tested approach in humans and one also developed in Liu’s lab. Prime editing also nicks one strand of DNA, but it can do more than change a single base: it synthesizes new code onto the cut end and stitches it back into the double helix.

The more you probe this science, the more awe-inspiring it is. Take base editing — that is, the Knicks. Our more than 6 billion base pairs of DNA come to us, in somewhat different form, from the 3 billion or so pairs each of our parents give us in their half of our 46 chromosomes. Base editors are “molecular machinery” with three parts: They have guide RNA to deliver the machinery to the right cells, a Crispr enzyme to cut one DNA strand, and an editing enzyme that rearranges the atoms in a molecule (in the case of Alpha-1, from adenine to guanine). I marveled to Liu that this was like sending a drone from Boston to Asia and finding a specific person. Liu said it was more than that: The drone could also “repair the person’s hat and do so in a way that’s minimally perturbative, so ideally they can keep standing in line at Disneyland.” Already, base editing is finding applications beyond Alpha-1: Last year, Liu advised a team at the Children’s Hospital of Philadelphia on how to use it to treat “Baby KJ,” a 6-month-old boy with an extremely rare genetic disorder that was causing a likely fatal buildup of ammonia in his body.

The business headlines on gene editing have been different, filled less with awe than with caution and disappointment. I spoke to Ben Auspitz, a venture capitalist with Curie.Bio in Cambridge and a former partner at F-Prime Capital, which co-led Beam’s Series A. “I tell all my associates,” he said, “that if you’re seeing a gene therapy, a cell therapy or a gene-editing proposal, and you think there is any other way to achieve a therapeutic effect that will be equivalent, do that first.”

The primary biological challenges with gene editing are threefold, Auspitz told me. First, there aren’t many illnesses for which a single change to our DNA will fix a majority of symptoms. Second, current technologies can’t effectively deliver gene-modification mechanisms broadly throughout the body, limiting applications primarily to the liver, eyes, blood stem cells and spinal motor neurons. Third, our defense systems tend to attack anything foreign, which can lead to toxic immune responses and defeated treatments.

And those three challenges don’t get into the systemic economic issues, notably the $2 million to $3 million cost per patient even for relatively routine treatments. The commercial history of the Nuggets offers a warning to potential investors and acquirers. In 2019, Roche bought Spark Therapeutics Inc., the developer of a cure for an ultra-rare type of pediatric blindness and other diseases, for $4.8 billion. By 2025, it had shelved many of Spark’s treatments, and it reported only $27 million in sales of the blindness treatment in the first half of this year. Novartis AG, after paying $8.7 billion in 2018 to buy AveXis Inc., the developer of a treatment for spinal muscular atrophy, has seen good sales but at half the initially forecast level.

Younger, Crispr-branch companies — the Clippers, Knicks and Spurs — have been both inspired by those two acquisitions and wary of the downslope of gene editing’s hype cycle. They’ve thus sought to treat diseases that aren’t so rare or affect parts of the body where delivery challenges aren’t as acute.

Thus far, the only commercial Crispr-based treatment is Casgevy, a Clippers-style medicine developed by Crispr Therapeutics AG and licensed to Vertex Pharmaceuticals Inc. It was first approved for use against sickle cell disease, a condition that can cause sudden severe pain, anemia, frequent infections and sometimes death from complications such as strokes. To learn how Casgevy helps patients, I spent some time with Ben Watkins, a pioneering hematologist at Tulane University and Manning Family Children’s, in his office at a converted hospital for sailors in New Orleans. Watkins grew up poor on a blueberry farm in the Ozarks. He’s a passionate advocate for broadening access to treatment for sickle cell, which afflicts an estimated 100,000 Americans, almost all of them Black. He has long experience with the pre-Crispr cure for sickle cell: stem cell transplants, which are highly limited by donor availability. Only a few thousand have been performed in 40 years.

In 2023, Daniel Cressy, a young truck driver who was determined to cure his sickle cell disease so he could become an airline pilot, approached Manning Family Children’s about a stem cell transplant. Lacking good donor options, the conversation shifted early the next year to treatment with Casgevy, which had just been approved. This past March, Watkins infused Cressy with stem cells edited using Casgevy, making Manning the first hospital in the Deep South to complete a commercial patient cycle of the therapy.

Casgevy works using a clever, lucky edit: It silences a gene that turns off the production of our fetal hemoglobin soon after birth, allowing the revived fetal hemoglobin to prevent sickling inside red blood cells. A patient effectively donates his own cells, edited ex vivo (out of the body) by Vertex’s technicians.

Unfortunately, the process is still, like any type of stem cell transplant, a gnarly, grueling gauntlet of powerful chemotherapy and frequent, sometimes long hospital visits. It’s also extremely expensive. The Louisiana Department of Health nonetheless approved the payment for Cressy with little drama. It made more sense, Watkins explained to me, to spend $2.4 million on a 10-milliliter vial of edited stem cells than to spend $5 million to $10 million on a lifetime of care.

In June, Louisiana’s governor and the mayor of New Orleans joined hospital brass to celebrate Cressy’s treatment, and a few months later Cressy was medically cleared to pursue his commercial pilot’s license. Watkins told me there’s now “a line out the door” of sickle cell patients seeking the Casgevy therapy — surprising him, since early adopters can be hard to find. But some 3,000 people have the disease in Louisiana alone, about half of them children.

Watkins knows he won’t be able to treat most of these prospective patients until gene-editing therapies become cheaper and easier. He hopes the chemo can become less intense or that one day new options will emerge to allow in vivo (in body) gene editing. He suspects we’re still a decade away from the latter.

As it stands, the market for Casgevy is still unproven. Crispr Therapeutics’ stock soared in early 2021, with human trials of Casgevy well underway, on hopes for broad uptake and additional future therapies as well as a general pharmaceutical market mania fueled by mRNA Covid-19 vaccines. Since then, Crispr’s stock has hovered at a quarter of its peak value. Another company, Bluebird Bio, developer of an approved gene-addition treatment for sickle cell, reached a peak market value of $10 billion but ended up being taken private last year for $29 million and renamed. Its valuation vaporized for the usual reason: too few patients for a too-expensive medicine. Beam, for its part, has a Casgevy competitor in the works that it’s hoping will get Food and Drug Administration approval next year. But the company told me the stock market has been completely indifferent to it.

From 2022 to 2025, investors basically stopped caring about the biotech sector, according to one entrepreneur I spoke with. Since then, interest in gene-editing companies has remained stagnant even as the broader biotech index is up almost 50% over the past year. For the most part, big drug companies have remained on the sidelines, likely remembering the lessons of AveXis and Spark.

Such trends are immensely frustrating to Fyodor Urnov, a genetic scientist at the University of California at Berkeley and the Innovative Genomics Institute. In addition to being a trailblazing researcher, Urnov has become a kind of poet-apostle for the field, touting its wonders — and decrying its obstacles — with Nabokovian command of his adopted English. “The only chink in Crispr’s armor that’s been discovered,” he told me, “is the failure of market capitalism as instantiated in healthcare to take this extraordinary technology, which has demonstrated definitively curative outcomes in multiple disease indications, and actually put it to the full scope of its use.”

Evans, the Beam CEO, took a strange route to biotech. An English major at Yale University, he also sang tenor for the Whiffenpoofs, the college’s best-known a cappella group. He coordinated a tour for the Whiffs after graduation before randomly finding a temp job at Bayer AG. That led him to further studies at the University of Pennsylvania, then to jobs in drug development at two small pharmaceutical companies before he was recruited by venture firms in 2017 to become Beam’s founding CEO. I heard him described as a tough competitor, but he also has a buoyant optimism and boyishly open face that wouldn’t surprise you if it broke into “Midnight Train to Georgia.”

Evans took me through the history of conventional wisdom on gene editing, from “that’s never going to happen” to “it’ll be really messy” to “it might work” to “it does work and looks pretty safe.” Now the industry faces the next step: to show people that selling these drugs can become a “functional business.”

The path will go through Alpha-1. At a clinic in Boston, Andrew Wilson, a pulmonologist and the scientific director of the Alpha-1 Foundation, explained to me why the condition is uniquely suitable for Knicks-style base editing. First discovered in Sweden in 1963, it occurs when a mutation on a single base pair in the Serpina1 gene causes the Alpha-1 antitrypsin (AAT) protein to misfold and aggregate into crystals. The aggregated protein then builds up inside the liver instead of traveling to the lungs, where AAT serves its primary known purpose: regulating elastase, a substance white blood cells release to fight microbes and other intruders. Without AAT, elastase becomes, in effect, a wayward vigilante, damaging the lungs instead of protecting them.

You wouldn’t wish the risks associated with Alpha-1 on anyone. But at the same time, Wilson said, “I tell patients when they’re newly diagnosed … this is a great disease to have if you’re going to have a genetic disease”

We all have two Serpina1 genes, one from each parent. Each gene should make the normal protein, called M. If you have only one mutated gene — the most common mutation is called Z, and an estimated 6 million Americans have the MZ genotype — you’ll likely have moderate AAT deficiency. People with two Z mutations produce little AAT, and sometimes almost none. By age 80, according to one study, two-fifths of them will have liver disease and three-fifths will have lung disease (with smokers facing much higher risk). About 200,000 people worldwide are believed to be ZZ, half of them in the US, though only about 15,000 here have actually been diagnosed. I have the Z mutation and a more obscure P variant, resulting in AAT production well below what those with the MZ genotype have but somewhat above those with ZZ.

You wouldn’t wish the risks associated with Alpha-1 on anyone. But at the same time, Wilson said, “I tell patients when they’re newly diagnosed — and I try to say this nicely because it could come off as tone-deaf — that this is a great disease to have if you’re going to have a genetic disease.” Alpha-1 is monogenic, fully attributable to the mutation on the one base pair. Diagnosis is straightforward, requiring a simple test to assess the genotype and a blood draw to monitor AAT levels. And though there are 800 identified mutations of Serpina1, more than 95% of people with severe Alpha-1 have the ZZ mutation, allowing for a therapy to be mass manufactured. The liver is also the easiest organ to target with current in vivo gene-editing medicine, enabling an IV treatment to work. And though Alpha-1 is rare enough to qualify for formal “orphan disease” regulatory benefits, the patient and research community is substantial and well-organized through the Alpha-1 Foundation. The 30-year-old group leads advocacy efforts, provides research grants, stokes excitement about prospective therapies and helps recruit trial volunteers.

For drug developers, it’s also good news that Alpha-1 doesn’t have great current treatments. Since 1988 patients have been able to get augmentation therapy, in the form of weekly hourlong infusions of AAT derived from human plasma. This doesn’t address all the problems of Alpha-1. It’s also, in my clinical assessment, too annoying.

Even though Beam was focusing on Alpha-1 from the outset, it took until June 2024 for the company to get its treatment into a human trial. To understand why, it’s helpful to realize that the drone-to-hat-wearer-in-Asia metaphor describes finding a DNA pair in only one cell. And that each of us is made up of almost 40 trillion cells. To treat Alpha-1, Beam sends a flood of two bundled molecules — mRNA, which instructs those cells to produce the Crispr-cutting and base-editing enzymes, and a guide RNA to tell the enzymes which DNA to edit — to reach as many of a patient’s 200 billion or so primary liver cells (called hepatocytes) as it can. So the complete metaphor turns out to be that base editing is like building 400 trillion rockets to send to 200 billion planets, hoping at least one rocket lands on each planet carrying separate instructions on how to build a hat-swapping drone factory and how to find that planet’s hat wearer. There’s no way this is always going to work.

The commander of Beam’s molecular space invasion is Pino Ciaramella, a wry Neapolitan who’s been president of the company since its founding. Ciaramella, the co-inventor of Moderna Inc.’s Covid vaccine, brought to Beam his expertise in lipid nanoparticles, or LNPs, which are essentially microscopic balls of fat that serve as the delivery mechanism for mRNA vaccines. These also proved ideal for delivering a base-editing payload to the liver, which exists in part to process fat. Ciaramella told me he’s been working to “industrialize what had been the original academic activity” of base editing. To improve outcomes in animal test subjects, Beam has had to build better guide RNA, better mRNA, better enzymes, better LNPs, better everything. The company failed to get what it needed from outside vendors often enough that it built its own manufacturing facility in North Carolina.

“At the very beginning,” Ciaramella recalled, “the editing rates for Alpha-1 were only about 1% to 2%. We are now at 70%.” The first human trial involving 29 subjects has gone as well as Beam could have hoped. In September, Beam reported that there had been no adverse side effects 18 months into the trial and that AAT levels had increased to normal ranges in all patients. “These drugs are not like some pills, where you have to look at a thousand people to see a slim benefit in half of them,” Evans told me. “Every single person gets a very dramatic instant effect.”

And yet, Beam’s stock is still below where it was in March 2025, when it began providing positive updates on its Alpha-1 trial. The market’s apathy in part reflects the challenges it faces from rival gene editors and other treatments.

There are currently five companies seeking to treat Alpha-1 with base editing or prime editing. In private and public, competitors cast shade on others’ patents, business models, efficacy and science. (A Knicks-Spurs rivalry between Beam and Prime Medicine Inc. has gotten particularly testy.) As a potential patient, I want the competition to be heated. “We know from the 37-year history of gene therapy that multiple groups developing multiple shots on goal for the same disease indication, even using the same technology, is the only way forward,” Urnov, the UC Berkeley geneticist, told me.

Evans professed not to be worried about “copycat competitors.” He knows he must continually press Beam’s advantages: its technological head start, its in-house manufacturing, its $1.2 billion in cash on hand from licensing deals and opportunistic capital raises, its relationships with payers, patients and doctors.

But fellow gene editors aren’t his only worry. The NBA has more than four teams, and Alpha-1 is experiencing an upsurge in other types of advances, if not yet in approved drugs. There are infusions of manufactured AAT from Sanofi SA, which has reported early results showing patients maintaining triple the level of AAT as plasma therapy, from visits one-third as frequent. There are treatments designed to intercept and edit RNA after it’s created by mutated Serpina1 genes — an approach Paul Bolno, CEO of Wave Life Sciences Inc., told me will be cheaper than weekly augmentation or a multimillion-dollar one-time treatment. (He added that it also has the advantage of being temporary, should permanently altering DNA prove to be unnecessary or dangerous.) And there are pills, including one that British company Mereo BioPharma Group Plc is developing to inhibit vigilante elastase from harming the body.

Evans isn’t shy about admitting that his company will initially need to charge “multimillion-dollar prices” for its treatments

Evans told me that gene-editing companies can’t rely solely on pitching their therapies being one-and-done if they’re to be widely adopted. The treatments must also offer better health outcomes and prove their safety and durability. Establishing all this will require more patients and data, as well as something Evans can’t accelerate: time. Beam anticipates getting FDA approval for its Alpha-1 treatment after one more study involving 50 participants over the next two years. But even if the company introduces the therapy in 2029, it won’t be possible for years to assess whether patients’ AAT levels remain permanently corrected, nor whether patients escaped liver disease or the long-term lung conditions associated with low levels of AAT.

Safety concerns could also sneak up on patients. For Beam, the theoretical worries first center on the liver’s reaction to its gene-editing payload, with cancer being the biggest fear. Everyone I spoke to was confident, based on research into how LNP delivery works and on outcomes for the billions of people who’ve received an mRNA vaccine, that these risks are very low. There’s also the possibility of bad outcomes when — as will sometimes happen when you try to edit 200 billion cells in a patient — Beam’s editors accidentally change a proximate DNA base (that is, reach the wrong hat wearer in Asia). To date, the off-target edits have proved benign.

Beam will have to start marketing to patients and doctors without comforting long-term data. And finding the largest possible set of paying early adopters will pose other challenges, too. Many of the current 15,000 or so US Alpha-1 patients won’t qualify for gene editing because they’re too old or too sick. Others might prefer to continue with augmentation therapy or choose a different new alternative. To get the volunteers and patients needed for the new trials and treatments of Beam and others, the Alpha-1 Foundation now offers free testing, targeting “the 90% of Alphas out there that have the condition but have no idea that they’re sick,” CEO Scott Santarella told me.

Everyone I spoke to in the field has been surprised by the Alpha-1 community’s enthusiasm for gene editing. But even if enthusiasm helps Beam and its peers find thousands of willing patients, it won’t pay for the medicine. Evans isn’t shy about admitting that his company will initially need to charge “multimillion-dollar prices” for its treatments. The first obligation of a biotech, he said, is to “tread water” and not depend on equity raises to stay afloat. Beam expects to spend its $1.2 billion in cash over the next three years to advance current and prospective medicines.

Supporters of gene editing have good arguments for why the healthcare system can and should pay for Beam’s Alpha-1 treatment and others like it. Monogenic diseases are rare, with any one insurer having to cover only a few patients with each known condition. David Liu pointed out to me that the US system finds money for other rare and expensive treatments, such as nearly 50,000 live organ transplants per year. The long-term math, as with Casgevy, suggests that gene editing should also save payers money.

This systemic view nonetheless ignores the challenges for individual insurers. The most discussed issue is that, even if a functionally cured Alpha-1 patient saves many companies (and Medicare) millions over her lifetime, a single insurer will bear the whole cost of the one-and-done treatment. And every insurance company today, facing intense employer outrage over rising premiums, is trying to limit new spending however possible. Michael Sherman, formerly chief medical officer of a health plan and an expert on payer dynamics, told me it would be hard right now for a $2 million one-time treatment to get insurer approval versus a $100,000-per-year good-enough therapy unless there was a “clear quality difference.” Any plan considering whether to be the first to pay for a new ultra-expensive treatment also risks being flooded by other patients seeking that treatment.

So for Beam to succeed, it will have to either raise outside capital again by 2029 or find a way to move from high, often inaccessible prices for the few to moderate prices for the many. This is a well-trodden, if not always easy, route for technology companies of all types. Sherman estimated that the no-brainer price for an insurance company to pay for Alpha-1 gene editing would be two to three times the cost of a year’s worth of augmentation therapy.

One way for Beam to get there would be a creative and well-crafted approach to initial payment terms. It would also help if patients get loud. Then, over time, the company would hope to prove the long-term efficacy and safety of its treatment, capturing market share and driving down unit costs though economies of scale.

I laid out all the hurdles to Evans and asked him how Beam would address them.

He paused before answering but kept right on being upbeat. “Honestly,” he said, “we’re at the point now, finally, where I think we’re going to make it. Those are all challenges, for sure, but they feel less existential than they have in the past.”

Even if you’d never heard of Alpha-1 before reading this article, you want Evans to be right. Ex vivo treatments, like for sickle cell, seem destined to remain bespoke, expensive medicines for lucky patients whose insurers are willing to pay.

“Jennifer Doudna politely reminds us that a $3 million cure is not a cure,” Urnov told me. “So we need a $50,000 Crispr on-demand injection. And the gap right now is not between the challenge and what the technology can do. That gap has been closed. There are 500 immune diseases that we could be treating today using existing Crispr. There are hundreds of diseases of the metabolism, lung, skin.

“Let’s go,” he urged. “Let’s go.”

I asked Urnov to handicap two scenarios. The first, I dubbed the Concorde scenario: Gene editing, technologically superior but luxury-priced, survives as a niche business, until, perhaps, an idiosyncratic safety incident (like the 2000 crash of a Concorde jet) brings down a specific drug or the category in general.

I find myself in a cohort who worry about our liver and lungs — and who are the ideal pioneers for a mind-boggling medical advance

Urnov, without missing a beat, labeled the more optimistic scenario the Dreamliner: an economically manufactured and easily delivered gene-editing platform, capable of treating a variety of organs without requiring regulatory approval for every molecular tweak. In this vision, the healthcare system would save tens of billions of dollars and giant pharma companies would get on board. Therapies would treat common monogenic diseases and then address polygenic ones. And they would regularly be quickly redesigned for individual rare conditions, such as Baby KJ’s.

Drug companies could also seek beneficial mutations to improve lifespans or fight noninherited diseases. Attempts at this have already begun: Last year, Eli Lilly & Co. acquired Verve Therapeutics to accelerate its work (using base-editing technology licensed from Beam) to lower cholesterol long term by “knocking out” a natural gene all of us have. Other companies are delivering CAR-T therapies that insert a new gene into a patient’s T-cells to help fight blood cancer.

Ever optimistic, Urnov said the Dreamliner scenario could start to emerge in as few as five years. When I spoke with Andrew Hack — a doctor, biotech investor with Bain Capital Life Sciences, and former gene-editing company executive — he agreed that it could happen, if probably on a longer timeline. He also brought the conversation back to Alpha-1: “I’d probably put something like a two-thirds probability that Alpha-1 gene correction is the breakout product that enables the field to flourish over time.”

Peter Kolchinsky of RA Capital Management LP, an investor in three different Alpha-1 therapies, outlined for me how this could happen. Many patients — he put the number in the tens of thousands — will need to be followed for a decade, across all sorts of gene-editing treatments for different diseases, without any untoward results. After that, Kolchinsky said, “there will be meta-analyses across all those patient groups, ultimately looking at how scared should we be for real or hypothetical off-target” editing, in addition to demonstrating improved health outcomes.

“Alpha-1 probably will contribute a disproportionate number of people in that dataset,” he added.

This was a strange prediction to hear three years after discovering that a mutation I didn’t want can lead to a disease I’d never heard of, with symptoms that, while now slight, are likely to worsen over time without treatment. I find myself in a cohort who worry about our liver and lungs, who might have just learned we have the condition or might have been trudging to augmentation therapy for years — and who are the ideal pioneers for a mind-boggling medical advance. I suspect many are like me, eager to put our body to the test and accept our unasked-for role in the history of gene editing. We have good luck in our bad luck. As Urnov says: Let’s go.