There are many choices we make over the course of our lives. Some are fairly insignificant, like the clothes we put on in the morning; others, such as the vocations we settle on, have life-changing consequences. But there’s one critical decision we don’t get to make: the choice of being born into a human body—and all the arbitrary ailments and inevitable biological breakdowns that follow.

This is what sets health care apart from other industries. The ¬business of medicine is quite literally one of life and death. And throughout much of the world, it remains a messy, inefficient, ¬expensive sector in need of radical reform.

Just consider some of the heart-wrenching numbers. Nearly one in four non-elderly American adults had past-due medical debt in 2015. That’s actually an improvement from 2012, when the figure was closer to 30% (insurance coverage gains under the Affordable Care Act are one likely reason for the decline). In Mississippi, more than 37% of the population owed money to care providers in 2015. Medical expenses are the top driver of personal bankruptcies. And last year the federal government projected that the nation’s health care bill would top $10,000 per person for the first time in history.

So what do we get for these extravagant private and public costs? A system where it takes weeks to see a doctor face-to-face, where more than 6,500 locales are officially deemed to have too few medical professionals to meet patients’ needs, and where U.S. health outcomes are consistently mediocre compared with those of many of our developed-nation peers (and even some of the less developed ones).

This status quo is ripe for disruption. And while true reform will require all the relevant parties—government, industry, and health care consumers themselves—to make major adjustments, an insurgent group of digital health companies is doing its best to drag American medicine into the 21st century kicking and screaming.

That means superseding physical constraints like having an actual hospital by harnessing the power of mobile technology, making the act of taking your medicine less of a hassle, and peering into our very biological building blocks to wage war on the most intractable maladies.

To offer a preview of what this tech-optimized future might look like, we identified 21 innovative companies in five categories—each of which is challenging the conventional approach to medicine.

Welcome to the digital health revolution.

人们一生中要做很多选择。有些选择微不足道，例如早晨穿什么衣服；另一些则可能改变整个人生，例如选择从事的职业。但有一项非常重要的决策不由任何人定，即来到这个世界成为人类一员，以及天生的疾病和缺陷。

这便是医疗行业明显有别于其他行业之处。医药行业经常可以决定生死。而在世界上绝大多数地方，医药行业都很混乱、低效且昂贵，急需大力改革。

先看些让人揪心的数字。2015年美国近四分之一非老年成人出现医药费逾期。比起2012年这还是进步，当时逾期比例接近30%（比例降低的原因之一可能是平价医疗法案下医保覆盖面增加）。2015年的密西西比州，37%人口欠医疗机构钱。医疗支出是个人破产最主要原因。去年联邦政府预计每人医疗支出将超过1万美元，为史上第一次。

公共和私人医疗系统如此昂贵，实际运作如何呢？现实是想面对面看医生得等好几个星期，超过6500的地方医疗专业人士没法满足病患需要，而且美国医院的治疗结果比起很多发达国家都很一般（甚至比不上一些欠发达国家）。

现状不妙，说明是时候颠覆了。要来一场真正的改革需要各方参与，从政府、行业到医疗消费者自身都要调整，目前来看，拖着美国医疗行业不情不愿走进21世纪的倒是一群数字医疗公司。

数字医疗的好处在于摈弃了实体局限，例如以前非得建起医院，现在则是充分发挥移动技术的力量，通过潜心研究人类自身寻找复杂疾病的治疗之道。

为了一窥科技引领的未来有哪些可能，我们先来看看21家创新公司在忙什么，这些公司分为五类，每一类都在挑战各自领域的传统治疗方式。

欢迎参观数字医疗革命。

图片提供：molistudio

Telemedicine

How health care is transcending physical walls.

At the turn of the 20th century, getting a checkup in America frequently meant your doctor came to you. Armed with a modest black bag of tools and old-fashioned medical know-how, physicians of yore would often take care of you right at your bedside.

As quaint as that image may seem today, it’s in some ways a vision of the future. New technologies are bringing back the house call—or a digital version of it, anyway.

The Companies

A slew of telehealth companies, from the Boston-based ¬American Well to San Francisco startup ¬Doctor On Demand, are again bringing health care to your doorstep—or more commonly, to your workplace. The National Business Group on Health last year surveyed 133 large companies employing 15 million Americans about their benefit practices: An astounding 90% said they expect to make at least some telemedicine services available to their workers this year. By 2019, nearly all of them will.

So what does that brave new world look like? Say you’ve been working after hours and suddenly feel feverish and woozy. You would walk down the hall to your company’s on-site digital health station—that’s a fancy word for “kiosk” (which, in turn, is a fancy word for “booth”)—where you would consult with a physician immediately by phone or video. That same doctor can take your vital signs—temperature, pulse, blood pressure—and if needed, send a prescription to the nearest pharmacy. Or maybe just tell you to go home and get some rest.

In December, American Well partnered with Concentra, which has more than 300 medical centers in 40 states, to provide some of those on-call physicians.

One obvious advantage of telemedicine is that the doctor can be anywhere—which is not the case for our traditional health care system. At hospitals across the country, in fact, there is an entrenched doctor shortage, which has grown only more acute as millions of Americans have gained health coverage in recent years.

New digital platforms are helping to solve that problem too. One New York startup, Nomad Health, pairs doctors with hospitals in need of physicians in three specialties—internal medicine, emergency medicine, and psychiatry. Nomad cofounder and CEO Dr. Alexi Nazem, in an interview with Fortune, likens the system to an Airbnb model for medical staffing. The professional matchmaking process lets health systems find doctors with specific credentials (say, an internal medicine specialist with five years’ experience who is free to work at a New York–area hospital in July) and vice-versa. The platform then automatically takes care of tasks like providing malpractice insurance if the hospital and doctor strike a contract.

This isn’t just convenient from a medical resource perspective; it also plays into a nascent “gig economy” in health care that’s become increasingly popular among younger, tech-savvy physicians. “With very little effort we’ve been able to tap into a huge flow of doctors who want to do short-term, freelance, flexible work,” says Nazem. “And I think that trend will continue [among millennials] not only because of the attitudinal shift [on freelance medical work] but also because the existence of technology actually makes it possible to do this kind of work.” Last summer the company raised $4 million in an early funding round led by First Round Capital and RRE Ventures.

And it’s not just medical startups driving this mobile health surge. Ride-sharing giants Uber and Lyft have started new programs to provide non-emergency medical transport for patients who struggle to get to a hospital. One platform that launched last fall, called Circulation, integrates medical records into Uber’s API so that nurses, caregivers, and hospital transportation coordinators can more easily schedule rides for patients and accommodate their needs (such as if they have a wheelchair or trouble seeing).

The Future

These technologies may one day fundamentally shift the way that health care is delivered and consumed. But before that transformation takes hold, some other changes will have to happen—including new reimbursement rules from insurance companies and policy shifts that make it easier for physicians to practice across state lines without gaining extra licenses or accreditation. There’s also the matter of whether mobile medical care will ultimately reduce national health spending: At least one recent report suggests that the technology may well cause people to pursue care they don’t need precisely because it makes it so convenient to get.

Still, don’t bet against the trend. For consumers, after all, convenience has always been king—and convenient and cheap? Well, there’s no beating that.

远程医疗

如何让医疗服务穿过实体围墙。

20世纪初那些年，在美国看病通常意味着医生来找你。过去的医生带着黑色药箱，里面装满治疗工具，治疗手段也都是旧式的，看病经常就在床前。

现在看起来这一幕有些怪异，但未来可能会变回这样。新技术让医生出诊更方便，只是变成了数字方式。

相关公司

现在有很多远程医疗公司，从波士顿的“美国健康”（American Well）到旧金山创业公司Doctor On Demand都在把医疗服务送到门口，更普遍的是送到办公室。全美企业员工健康组织去年调研了133家大型企业，共计1500万美国员工的福利待遇，竟然有90%的企业表示预计今年至少会向员工提供部分远程医疗服务。到2019年，所有企业都会提供。

未来世界到底会是什么样呢？想象下你工作好几个小时突然感觉有点想发烧头晕，可以走到公司里的数字医疗服务站，其实就是个信息亭（更直白点说就是个电话亭一样的地方），然后可以立刻通过电话或视频咨询医生。医生可以即时提供检测，例如体温、脉搏和血压，如果有必要会将处方发送到最近的药房。或许只会叮嘱你回家休息一下。

去年12月，“美国健康”公司与康森特拉公司（Concentra）达成合作，确保了部分值班医生供给。康森特拉在40个州拥有超过300家医疗中心。

远程医疗一个明显优势在于医生可以身处任何地方，传统医疗系统可做不到。全国各地都很缺医生，随着近年来上成百上千万美国人加入医保系统，医生紧缺越发严重。

新型数字医疗平台可以顺道解决缺医生的问题。一家名叫Nomad Health的纽约创业公司可以匹配医生和缺医生的医院，主要在三个领域：内科、急诊和精神科。Nomad公司联合创始人阿雷西·纳泽姆博士（Alexi Nazem）接受《财富》杂志采访时表示，其匹配医疗行业人才的方式类似民宿行业的爱彼迎（Airbnb）。通过专业匹配流程，医疗系统可以寻找具备特定资质的医生（例如7月能在纽约地区医院工作，具有五年从医经验的内科医生），帮医生找医院也是同样道理。如果医院和医生签订合同，平台还自动提供医疗事故保险。

从医疗资源匹配角度来看，这简直太方便了。而且形成了医疗行业的“零工经济”（gig economy），年轻一代对科技较敏感的医生非常热爱。“我们很容易就找到一大群愿意短期、自由且灵活执业的医生，”纳泽姆表示。“而且我相信趋势会延续下去（尤其在千禧一代中），不仅因为（针对医疗领域自由职业）态度在转变，而且随着科技进步，很多工作确实可以远程完成。”去年夏天该公司早期融资获得400万美元，领投方包括首轮资本公司（First Round Capital）和科技创业投资公司（RRE Ventures）。

投身移动医疗的还不只医疗创业公司。优步和Lyft等网约车巨头也启动新项目，向去医院就医有困难的病人提供非急救医疗转运服务。去年新成立名叫Circulation的平台将医疗病例接入优步的应用接口，护士、护理人员和医院运输协调员可以更好地安排接病人的次序，而且可以满足病人个性化需要（例如病人需要轮椅或是眼睛看不清）。

未来

总有一天各式新技术可能完全改变医疗服务提供和接受的方式。但那一天来临之前，还需要一些必要的铺垫——包括保险公司新的偿付规则，以及政策调整允许医生跨州执业，不必额外申请执照或许可。还有个问题就是移动医疗究竟能不能降低医疗消费，最近一项报告称新科技可能导致过度医疗，因为太便利。

不过，还是要顺势而为。毕竟对消费者来说，方便一定是最重要的，如果既方便又便宜呢？那就谁也没法拒绝了。

图片提供：molistudio

Algorithmic Medicine

Big data and AI push learning.

The term “big data” gets tossed around so casually that it’s easy to forget just how big “big” really is. Consider that 2.5 quintillion bytes of data are created every day, according to IBM (ibm, -1.79%). In health care, this amounts to an hourly avalanche of new research papers, clinical trials, scientific studies, and patient health information. And it’s impossible for doctors and medical researchers to keep up with even a tiny fraction of it.

Enter machine learning and artificial intelligence. Shorn of human weaknesses like the need to eat or sleep, computers are now speed-¬reading through not only the vast academic literature but also CT scans, electronic medical records, and mountains of data from clinical trials and genomic studies. AI is also giving drugmakers critical insights into who benefits most from their treatments and changing the way hospitals manage their administrative operations.

The Companies

With IBM, the metamorphosis seems to have happened overnight: The starched-shirt centenarian went from a stolid mainframe and consulting giant to an upstart digital health pioneer—all in the blink of an AI. Big Blue can thank Watson—its Jeopardy!-winning, cognitive computing superstar—for that. And the company’s ravenous dealmaking business unit, IBM Watson Health, seems to be redefining daily what AI applications can be used for.

In the two years since Watson Health launched, it has struck partnerships with an impressive array of academic institutions, such as the Memorial Sloan Kettering Cancer Center and prominent biopharma companies like Pfizer (pfe, -1.14%), Medtronic (mdt, -1.52%), and Johnson & Johnson (jnj, -0.86%). In each case, Watson is given roughly the same task: Feast on reams of data and find hidden patterns—and hopefully new knowledge—within them. Watson can do this with electronic medical records as well as with so-called unstructured data (like that found in the image of an X-ray or brain scan).

And as with telemedicine, its insights can be made mobile. Earlier this year, for instance, Watson’s oncology-focused unit struck its first deal with a community hospital, a 327-bed outfit in Jupiter, Fla., that can now harness the supercomputer’s power to match cancer patients with the treatments most likely to help them (thanks to a clinical data set expertly reviewed by Memorial Sloan Kettering).

But what if AI and deep learning could help doctors figure out a patient’s disease simply by analyzing a face—no scans or testing required? That’s precisely what Boston-based startup FDNA is trying achieve with its Face2Gene platform. The firm has put together a photo database of people with more than 2,000 rare genetic diseases. Doctors can snap pictures of their patients and upload them to FDNA’s mobile app, which then spits out a list of disorders they might have by analyzing telltale facial features associated with those conditions (the tech is not a diagnostic tool, but rather a way to narrow down the list of possible genetic suspects). And the company hopes the system can drastically improve the “diagnostic journeys” that those with rare diseases typically face: Such patients, on average, are seen by seven doctors before the correct diagnosis is made.

Cutting costs and catching on to illnesses as early as possible are major goals for this type of tech. But it can also be used to combat administrative headaches like long hospital wait times. Last October, GE Healthcare and the Johns Hopkins Hospital launched a fully digital hub to better manage everyday operations. The Judy Reitz Capacity Command Center gets a constant influx of data about important events at the hospital; it receives about 500 messages every minute from more than a dozen different Hopkins IT systems and with the help of predictive analytics turns this swamp of data into suggestions for action that prevent bottlenecks and get patients both into and out of the hospital faster.

And, according to Johns Hopkins at least, it’s showing impressive early results. The hospital says the command center has shaved more than an hour off the time it takes to dispatch an ambulance to another facility and that emergency room patients are assigned a bed 30% faster than before.

The Future

Now for a sobering fact: All the whiz-bang computing power in the world can’t find knowledge in the data if the data isn’t shared to begin with. And surprising as it may seem, says Greg Simon, former executive director of the White House Cancer Moonshot, we “still live in an information-scarce medical world.”

The federal government and private organizations have tried to encourage sharing in recent years through initiatives like the Genomic Data Commons, a “unified data repository” intended to hasten cancer cures by making research public. But real progress on this front will take more than a handful of public-private initiatives: It will require a change in mind-set—a radical new willingness to share and share alike.

算法医药

大数据和人工智能推动学习。

近来“大数据”谈得太多，人们已经很难想起大数据的“大”到底怎么回事。据IBM统计，每天新增数据达2.5百亿亿字节。医疗行业里，每小时新增的研究报告、临床试验、科学研究和病人医疗信息不计其数。医生和医疗研究人员得顾及每个细节。

机器学习和人工智能要参与。计算机没有人类的弱点，例如要吃要睡，所以可以帮助人类迅速遍览学术文献，还可以查看CT扫描，电子病历，以及海量临床试验和基因研究数据。人工智能可以告诉医药厂商哪些病人疗效最好，还能改变医院的管理方式。

相关公司

蓝色巨人IBM的蜕变仿佛一夜之间，向来西装笔挺示人的百年老店从呆板的大型机生产商和咨询行业巨头变成了数字医疗行业的领头羊——而且全靠一款人工智能产品。IBM应该好好感谢超级计算机“沃森”（Watson），这款赢下美国智力游戏Jeopardy!的认知机器明星。如今IBM旗下沃森医疗部门业务十分繁忙，而且似乎每天都在拓展人工智能的应用领域。

沃森医疗成立两年来，迅速与不少知名学术机构达成合作，例如史隆凯特琳癌症研究中心、注明生物医药公司辉瑞、美敦力和强生公司等。每起合作中沃森的角色基本一致：处理大量数据寻找暗含的规律，最好能得出新观点。沃森不仅能解读电子病历，还能处理所谓的非结构化数据（例如X光片或脑补扫描片提供的数据）。

跟远程医疗一样，沃森的处理结果也可实现移动化。例如今年早些时候，沃森负责肿瘤的部门首次与佛罗里达朱庇特一家327床位的社区医院合作，利用超级计算机为癌症病人寻找最可能奇效的疗法（也要多亏史隆凯特琳癌症研究中心精心审查过的临床数据支持）。

要是人工智能和深度学习能帮医生分析一下病人的脸，不用扫描或测试就可以诊断该多好？波士顿创业公司FDNA就在努力通过Face2Gene平台实现。该公司收集了罹患2000种罕见基因病的病人照片建立数据库。医生可以拍下病人的照片，上传到FDNA应用里，程序可以通过面部特征对比分析出可能存在的病症（这项技术并非诊断工具，但能缩小可能的基因病范围。）FDNA的目标是大为缩短罕见病的“诊断历程”，目前罕见病病人平均要就诊七次才能确诊。

这类技术的主要目标是降低成本，尽可能及早开始治疗，也可以用来解决一些医院的管理流程痼疾，例如等待时间过长。去年10月，通用医疗(GE Healthcare)和约翰·霍普金斯医院(Johns Hopkins Hospital)联合成立了全数字中心，以提高日常运营效率。该中心名叫朱迪赖茨指挥中心（Judy Reitz Capacity Command Center），每分钟会从十多个霍普金斯医院信息系统获取约500条信息，通过预测分析将大量数据转化为行动建议，避免流程不畅，帮助病人要么尽快入院治疗或要么迅速出院。

从约翰霍普金斯医院的案例来看，初步效果非常不错。该医院表示，指挥中心指派救护车前往别处的时间减少了超过一小时，急诊室病人安排床位的时间减少了30%。

未来

来看看严峻的现实吧：就算计算机能力再强，如果数据不共享也无法根据数据作出判断。可能听起来不可思议，但白宫抗癌登月计划特别小组前执行主任格雷格·西蒙（Greg Simon）表示，“在医疗世界里信息还十分匮乏。”

近年来，联邦政府和私营机构一直鼓励数据共享，举办了类似基因组数据共享之类的“统一数据储存库”活动，鼓励公开研究结果以加快癌症治疗。但若想取得实质进展只靠一些公共私营领域的活动还不够，要改变的是整个思路，要变得愿意积极共享，而且切实做到才行。

图片提供：molistudio

Next-Generation Capsules

The evolution of drug delivery.

The hypodermic needle made a splash on the medical stage in the 1850s by combining two key inventions: the conventional syringe (eventually converted from metal to glass so that users could better measure doses) and sharp, hollow needles. While the innovation was initially used for ¬purposes such as injecting pain sufferers with powerful opioids, it became a true game changer once insulin came on the scene in 1921. Unlike painkillers, insulin can’t be ingested—it has to be administered via an injection or a pump in order for the body to absorb it and control blood sugar.

The way that we take our drugs has continued to evolve in the decades since then—syringes became disposable, for example—and the progress is far from over.

The Companies

In the past few years companies like Braeburn Pharmaceuticals, Intarcia Therapeutics, and Proteus Digital Health have set out to create better medical mousetraps through devices that make existing drugs more effective. That means peace of mind for diabetes patients, who no longer have to constantly prick their fingers to measure blood sugar and manually adjust insulin doses, and hope for recovering opioid addicts, who might face a relapse if they don’t adhere to a strict treatment protocol.

Last May, Braeburn and partner Titan Pharmaceuticals became the first companies to win Food and Drug Administration (FDA) approval for an implant to treat opioid addiction. Their product, Probuphine, is made up of matchstick-size implants placed into patients’ upper arms in a simple outpatient procedure. These devices dispense a drug called buprenorphine—itself an opioid, but one that doesn’t produce the sort of euphoric and addictive high that more powerful painkillers such as OxyContin and morphine do.

But rather than have patients take buprenorphine manually, Probuphine dispenses small amounts of the drug continually into the bloodstream, ensuring that people actually stick to their prescribed regimen. The device can be used for up to six months.

This type of automated, long-term delivery system could make it easier to treat everything from brain diseases to diabetes. Indeed, diabetes is one affliction that Intarcia has in its crosshairs. The Boston company is seeking FDA approval for an under-the-skin pump system that it says can dispense a steady stream of diabetes drugs for a period of six months or longer. But ¬notably—even before it has won marketing approval—some think the technology could be an effective weapon against another deadly scourge: HIV. The Bill & Melinda Gates Foundation said it will invest up to $140 million in Intarcia, in the hopes that its device can deliver prophylactic medicine—and help shield patients at high risk of infection from HIV.

The common theme of these innovations is that medicine itself is necessary but not sufficient: Patients actually have to take it as directed for it to work. Nonadherence to prescribed regimens is also costly, resulting in nearly $300 billion a year in wasted spending, according to some studies.

Automating the process is one way to tackle this problem; Proteus Digital Health, however, is taking a different approach. The Silicon Valley startup’s “smart pill” platform, Discover, helps doctors track patients’ biometrics—and whether or not they’re sticking to a drug protocol—with the help of ingestible (and on-the-body) sensors that communicate with a smartphone app. This way, patients with chronic diseases like hypertension and diabetes (and their physicians) can figure out the most effective dosing regimens.

The Future

Improving the way we take drugs could save those in the developed world many billions of dollars in annual health care expenses. It could also transform how the world’s poorest nations prevent and treat disease—whether through patches that administer vaccines or through long-acting implants that dispense HIV/AIDS drugs. Even in medicine, it seems, the delivery business is in the throes of revolution.

新一代药物

输药革命.

19世纪50年代，皮下注射针头正式踏上医药历史舞台，这项技术结合了两项关键创新：将传统的注射器（由金属改为玻璃，方便观测剂量）与锋利中空的针头结合起来。一开始这项创新主要用来给受病痛折磨的病人注射强效阿片类止疼药，但随着1921年胰岛素发明，该技术立刻成为关键。因为跟止疼药不一样，胰岛素不可口服，只能通过针头注射或注射泵输入，人体才能吸收并控制血糖。

从那之后人类利用药物的方式持续改进，如今注射方式也可以淘汰了，各种革新还在进行中。

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过去几年里，Braeburn制药公司、 Intarcia 医药公司, 以及Proteus数字医疗公司都在努力研发新设备提升现有药物效力，从而实现更好的疗效。如果真能实现，糖尿病人终于可以放下心来，每次测血糖之前不用再惴惴不安，也不用再费劲调整胰岛素剂量。止疼药上瘾戒断者也能看到希望，不用担心因未能严格遵守治疗流程出现复发。

去年5月，Braeburn制药与合作方泰坦制药成为首批获得美国食品药品管理局（FDA）批准，通过植入治疗止疼药上瘾。其产品名为Probuphine，是火柴大小的植入剂，通过简单的门诊处理就能植入病人上臂。该设备可以释放丁丙诺啡，本身也是一种止疼药，但不会像奥施康定和吗啡等强力止疼药一样产生精神愉悦和上瘾的快感。

植入Probuphine后，上瘾病人不用再特地服用丁丙诺啡，而是由植入剂持续向血液释放小剂量药物，确保病人按照处方服用。每个植入剂可以使用长达六个月。

长期自动的药物输送系统可以简化很多疾病的治疗，从脑部疾病到糖尿病都可采用。事实上，总部位于波士顿的Intarcia目标之一就是糖尿病。该公司正向FDA申请一套皮下注射系统，据称可以稳定释放治疗糖尿病的药物，持续时间可达六个月或更久。特别值得注意的一点是，哪怕还没获得市场推广许可，已经有人认为这项技术可以用来对付另一种致命瘟疫：艾滋病。比尔及梅林达·盖茨基金会表示将向Intarcia投资近1.4亿美元，希望其开发的设备可以输送预防药物，帮助艾滋病高危人群预防。

此类创新的目标都是解决必需药物不够有效的问题，也就是说病人还是要遵医嘱服药。不遵照医嘱成本巨大，一些研究显示每年因不遵医嘱浪费金额近3000亿美元。

将服药过程自动化是解决方法之一。不过硅谷创业公司Proteus数字医疗选择另辟蹊径。该公司开创了“小药丸”平台，帮助医生根据病人的生物特征检测是否遵照医嘱服药，病人口服（和贴身携带）传感器后，可向智能手机传输数据供医生查看。这样，患有高血压和糖尿病的慢性病人（跟医生一起）就能算出最合适的药物剂量。

未来

通过改进服药方式，发达国家每年可以节省数十亿美元的医疗支出。最贫穷的国家也可以借此预防和治疗疾病，可以通过皮肤贴片管理疫苗，也可以通过长期有效的植入剂注射预防艾滋病的药物。看来小到医药行业的药物输送领域，也处在变革的阵痛之中。

图片提供：molistudio

Genomic Revolution

Precision-editing the code of life.

Adenine. Thymine. Guanine. Cytosine. These four tiny compounds provide the basis of life. They are the “letters” that make up DNA’s code, and their various permutations can determine everything from our physical appearances to our risk of being born with a devastating disease.

So it’s not surprising that being able to manipulate these chemical building blocks is one of the most exciting prospects in medicine. And thanks to a gene-editing technology known as Crispr-Cas9, it’s become a whole lot easier to do just that.

The Companies

Crispr has been widely celebrated as one of the most (if not the most) groundbreaking biotech discoveries of the 21st century. That’s not to say gene editing is new (it isn’t), but Crispr simplifies the process by using molecular scissors that can be precisely targeted to snip out aberrant regions of genetic code, which can then be replaced with the correct sequences.

The technology’s possibilities are staggering—in theory, allowing medical scientists to do everything from cure genetic disorders like sickle cell disease to identify gene targets for combating HIV. Silicon Valley billionaire and cancer immunotherapy patron Sean Parker is funding the first U.S. Crispr trials in humans, which are expected to begin this year at the University of Pennsylvania and allied institutions; in March, pharma giant Allergan (agn, -1.80%) struck a $90 million deal with Crispr specialist Editas Medicine (edit, -3.06%) for access to the biotech’s experimental therapies to treat rare and serious eye diseases.

And Crispr-Cas9 isn’t even the only type of Crispr out there: On April 12, researchers at the University of Texas Southwestern Medical Center announced they had successfully paired the gene-editing tool with a different kind of enzyme, called Cpf1, to correct mutations associated with the devastating muscle-wasting disorder Duchenne muscular dystrophy. Crispr-Cpf1 could potentially prove even more promising than the Cas9 variety because the Cpf1 enzyme is smaller and can target certain genomic regions that Cas9 can’t reach.

What makes Crispr so exciting is that, thanks to its precision, the tool has opened up a world of innovation to research facilities that previously wouldn’t have been able to handle the expenses or complexities of genome editing. The possibility that different Crispr-associated enzymes may be more effective than others is fueling the scientific competition. So is the fact that Chinese scientists at Sichuan University in Chengdu launched the first-ever human Crispr trial, in a lung cancer patient last October—a milestone that American scientist Dr. Carl June predicted would “trigger Sputnik 2.0” and a “biomedical duel” in the field between China and the U.S.

The genomic revolution isn’t just a scientific one, though. It’s also regulatory. Gene-related tech has a way of putting the fear of God—or the fear of man playing God—in people. And regulators have been cautious when it comes to the field.

That’s partly what makes 23andMe’s landmark FDA victory in early April so notable. The Alphabet-backed Silicon Valley startup, valued at $1.1 billion, became the first company allowed to sell genetic tests (and accompanying health-risk reports) for 10 different diseases directly to consumers without a prescription. That includes conditions like Parkinson’s, Alzheimer’s, and celiac disease.

Victory wasn’t always assured. In November 2013, the FDA sent 23andMe cofounder and CEO Anne Wojcicki a stern warning saying that the company’s tests and health reports, which it was already selling straight to customers, were unapproved medical devices that hadn’t been cleared by the agency. The firm had to shelve many of its services as it worked to convince regulators that its genetic tests were accurate and the accompanying medical risk reports clear enough that they wouldn’t confuse or harm customers.

Now 23andMe has pulled off the kind of comeback that’s rare to see in biopharma. “The FDA has embraced innovation and has empowered people by authorizing direct access to this information,” said Wojcicki in a statement following the clearance.

The Future

Genomic technology has evolved from the stuff of science fiction to a tangible reality, with massive medical and financial implications. Just how high are the stakes? Enough that the brilliant minds behind Crispr-Cas9—University of California at Berkeley’s Jennifer Doudna, her academic partner Emmanuelle Charpentier of the Max Planck Institute for Infection Biology in Germany, and rival Broad Institute of MIT and Harvard scientist Feng Zhang—and the various biotechs affiliated with them are embroiled in an ugly, global patent spat over the rights to the tech. (Zhang and the Broad won a key intellectual-property ruling in the U.S. earlier this year, but the matter is far from settled in markets like Europe and Asia.)

And ethical concerns will continue to dog this space. The technology isn’t quite advanced enough to birth a world of “designer babies.” But even in the case of 23andMe’s home DNA kits, some question the morality of telling a customer he is at high risk for Alzheimer’s when there’s little the person can currently do about it.

No one said revolution was easy.

基因革命

精准编辑生命的密码

腺嘌呤、胸腺嘧啶、鸟嘌呤、胞嘧啶，这四种极小的化合物构成了生命的基础。这些物质仿佛“字母”组成了遗传密码，根据不同的排列方式可以决定人类从长相到患有致命遗传疾病等。

所以精准掌控遗传化学物质无疑是医药领域最诱人的一块。而随着Crispr-Cas9基因编辑技术出现，如今掌握遗传密码越发容易了。

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Crispr基因编辑技术堪称21世纪最具突破意义的生物科技进步。其实基因编辑并非新鲜事（以前就有），Crispr基因编辑技术进步之处在于简化了流程，可以利用分子剪刀精准切除基因代码中异常部分，替换为正常序列。

这项技术带来的可能性极为惊人。理论上医疗科学家可以做任何事，从治疗镰刀性贫血等遗传疾病，到确认基因靶治疗艾滋病。硅谷亿万富翁兼癌症免疫疗法自助者肖恩·帕克（Sean Parker）正协助首次人体Crispr基因编辑临床试验，今年将由宾夕法尼亚大学等机构联合尝试。今年3月，医药巨头艾尔建与Crispr基因编辑专业公司Editas Medicine达成900亿美元的合作协议，为治疗罕见又严重的眼科疾病进行生物科学试验。

Crispr-Cas9并非唯一一种Crispr基因编辑技术。4月12日，德克萨斯大学新安医疗中心宣布，已经成功将基因编辑工具与另一种酶配对，名叫Cpf1，可以用来纠正绝症肌肉疾病杜兴氏肌营养不良。Crispr-Cpf1可能会比Cas9技术更有前景，因为Cpf1酶体积更小，可以处理Cas9技术无法实现的部分。

Crispr技术最让人兴奋之处在于，由于可以精准控制，研究机构可以大胆创新，而以前由于费用过高或基因编辑技术难度太大不可能做到。由于与Crispr相关的某些酶可能更有效，也引发了科技竞赛。去年10月在中国成都，四川大学的科学家就首次尝试了人体Crispr基因编辑试验，对象是一位肺癌病人。这是了不起的进展，美国科学家卡尔·琼恩博士（Dr. Carl June）预测今后会出现类似“冷战军备竞赛2.0”，中美之间可能发生“生物医药大决战”。

基因技术革命已经不再只是科学领域。如今也引发监管革命。与基因相关的技术总是容易让人对上帝，或是对扮演上帝的人产生畏惧之情。因此监管者对该领域慎之又慎。

这也正是为何23andMe公司今年4月初获得FDA许可极为难得。23andMe是一家由谷歌母公司Alphabet投资的创业企业，估值11亿美元，今年成为首家获准不用处方即可向消费者出售基因检测结果的公司，涉及10种疾病，包括帕金森、阿兹海默症，以及腹腔疾病等。

但一时的胜利并不可靠。2013年11月，FDA曾向23andMe公司联合创始人兼首席执行官安妮·伍吉西奇下发严厉警告，称该公司直接向客户出售的基因检测结果和医疗报告皆属于未经批准的医疗服务。后来23andMe只得搁置多项服务，一边努力向监管者证明其基因检测结果很准确，提供的医疗风险报告也非常明确，不会让客户困惑或受到伤害。

如今23andMe终于实现了生物医药领域难得一见的胜利。“FDA鼓励创新，通过准许直接了解基因检测信息提高了人们的自主权。”伍吉西奇在公司获准后的声明中表示。

未来

基因技术已经从科幻小说变为触手可及的现实，牵扯到大量医药和金融行业。问题是风险到底多大？Crispr-Cas9背后的亿万富翁先不提，光是科学界就已闹腾不堪，加州大学博客利分校的珍妮弗·杜德纳（Jennifer Doudna），合作伙伴德国马克斯-普朗克传染生物学研究所的艾曼纽·夏庞蒂埃（Emmanuelle Charpentier）跟竞争对手麻省理工-哈佛大学研究所科学家张锋，还有各种相关生物科学界人士就该项技术卷入了一场丑陋的全球专利争夺战。（张锋和麻省理工-哈佛今年初赢得了关键的专利判决，但在欧洲和亚洲等市场硝烟尚未平息。）

此外，伦理方面的争论一直不曾远离。虽然目前的技术还达不到“定制婴儿”的世界，但哪怕只是23andMe简单的家庭基因检测设备都引发热议，有人质疑告诉客户有很高几率罹患阿兹海默症是否道德，因为知晓可能性也无能为力。

谁说革命会一帆风顺呢。

图片提供：molistudio

Pharma's New Frontier

The radical new models for drug discovery.

The lines between Big Pharma and small biotech are eroding. Traditional drug giants have caught on to the not-so-dirty little secret that outsourcing drug research (and in-licensing) may be a more effective strategy than trying to create groundbreaking new molecules within the confines of a single lab.

“No one company can corner in or create a monopoly on the best thinking that’s out there. And so if we’ve built the lab and we invested a billion dollars in discovering medicines, we can only do what we could in the four walls of our village,” as Allergan CEO Brent Saunders, a licensing-and-acquisition maven, put it during an interview with Fortune earlier this year. “But if we walk outside of that, we’re fishing in an ocean vs. a pond for innovation.”

But shifting collaborative models aren’t the only forces changing the face of drug development. Some companies are thinking not just outside the box but outside the planet when it comes to improving medicine.

The Companies

Elon Musk’s groundbreaking private space outfit, SpaceX, flew its 10th mission under a NASA commercial resupply contract in February. The Dragon spacecraft delivered payloads to the International Space Station (ISS), including some high-profile biopharma cargo from Merck (mrk, -1.24%) and others.

Merck has been collaborating with the Center for the Advancement of Science in Space (CASIS), which has been tasked by NASA to oversee the ISS’s U.S. National Lab since 2012. CASIS’s mission is to encourage “use of this unparalleled platform for innovation”—and Merck is taking this to heart by experimenting with drug development in the realm of microgravity.

Such an environment, it turns out, presents all sorts of opportunities that aren’t available down here on Earth, as Merck structural chemistry scientist Paul Reichert explained to Fortune in an interview.

For instance, you don’t get the kind of gravity-driven diffusion that makes molecules scatter to a specific destination based on their density (think of excess sugar falling to the bottom of an oversaturated glass). One of Merck’s main interests involves growing protein crystals, which form as larger and more organized structures in microgravity.

On the ISS, Merck has been doing experiments on its next-gen cancer medicine Keytruda. The mission, says Reichert, is “to understand the impact of the microgravity environment on the structure, delivery method, and purification” of these types of compounds. The lack of gravity-induced molecular changes on the U.S. National Lab could help Merck researchers improve drug delivery and manufacturing methods on Earth.

The Future

From tech incubators to world-class research facilities, from tweaks to biological machinery to computers that can unlock its secrets, and from research conducted on our pale blue dot to the cosmos themselves, the health care revolution is within our grasp. But ultimately realizing it will require collective changes in policy and scientific culture—and recognizing that technology, like humans, has its own limits.

制药新前沿

新药研发全新模式

大型跟小型制药公司的界限逐渐模糊。传统制药巨头发现一个灰色小秘密，比起单独弄个实验室研究突破性的新分子，外包医药研究（和引入式授权）可能效率更高。

“很明显，当今世界没有哪家公司能独占资源垄断市场。即便我们成立实验室投资数十亿美元研发新药，最终也只能局限在自己的小天地里思考，”授权收购行家艾尔建首席执行官布伦特·桑德斯（Brent Saunders）今年初接受《财富》杂志时表示。“但如果走出去，就不用在自家小池塘垂钓，可以在创新的海洋里捕捞。”

不过转换合作方式不是改变制药行业发展的唯一动力。有些企业转换思路的脑洞非常大，不仅跳出以往的局限，改进医药的创意甚至飞到外太空去了。

相关公司

今年2月，埃隆·马斯克旗下开创性的私人航天公司SpaceX根据与美国航空航天局（NASA）签署的合同，执行了第十次国际空间站补给任务。龙飞船向国际空间站运送的货物中就包括一些知名生物制药公司的产品，例如默克公司等。

默克公司一直与太空科学促进中心保持合作，自2012年起就由NASA监督国际空间站美国国家实验室进行相关实验。太空科学促进中心的使命是鼓励“使用前所未有的平台实施创新”，默克公司选择在微重力环境下研发药物，这一点执行得很得力。

默克公司结构化学家保罗·莱克特（Reichert）接受《财富》采访时表示，结果发现微重力环境下可以提供很多地球上不可能实现的机会。

举个例子，太空中不会出现重力导致的扩散，地球上分子会根据自身密度向固定方向散开（想象地球上一杯过饱和的糖水，多出的糖会聚集在杯底）。默克公司研究的主要对象包括养成蛋白质晶体，微重力环境下蛋白质晶体可以更大，结构也更有序。

默克公司一直在国际空间站测试下一代抗癌药Keytruda。莱克特表示，测试目标是“了解微重力环境对此类化合物结构、输送方式以及提纯的影响”。通过观察美国国家实验室里微重力环境下导致的分子变化，地球上默克公司的研究人员可以进一步改善药物输送和制造方式。

未来

从技术孵化器到世界级研究机构，从灵机一动发展到生物机械再到能解重大奥秘的计算机，实验也从地球做到太空，现在医疗革命越发触手可及。但要真正实现尚需政策和科学文化协同变革，而且要认识到技术如同人类一样都是有边界的。（财富中文网）

本文另一版本刊登于2017年5月1日《财富》杂志，为《医疗行业的未来》专题节选。

译者：Pessy

审稿：夏林