Illustration by Kris Mukai

Over the past decade, Kaiser Permanente has spent more than $4 billion building the world’s largest private-sector collection of electronic health-care records. The data have become the cornerstone of a new scientific resource: a biobank that links the health records of more than 210,000 Kaiser members with samples of their DNA. The Oakland (Calif.)-based health network has teamed up with the University of California at San Francisco so scientists can use the collection to search for the genetic roots of diseases including glaucoma and prostate cancer.

Kaiser has 9.5 million enrollees in eight states and the District of Columbia, and members can see a wide variety of medical specialists without leaving the network. Every visit, lab test, prescription, and procedure is logged into a member’s electronic health record. This gives Kaiser an edge over other genomics projects, which besides collecting DNA samples must go through the expense and trouble of amassing information on subjects’ medical history. Last year biologist Craig Venter founded Human Longevity, with plans to sequence the genomes of as many as 100,000 people annually, and this summer, Google (GOOG) said it had launched its own genomics project, called Baseline Study. Both are hunting for genes associated with health and longevity.

“We recognized that a lot of the basic resources that would be needed to make a fabulous research program on genes, environment, and health—that those were attributes of Kaiser,” says Catherine Schaefer, who has served as executive director of Kaiser’s Research Program on Genes, Environment, and Health since its launch in 2005. She and her colleagues began by recruiting volunteers in Kaiser’s Northern California system, which has electronic records on patients dating to 1995. Recruits were asked to provide samples of blood or saliva—from which DNA was extracted and analyzed—and fill out behavioral surveys about their exercise habits, alcohol consumption, and sleep patterns. Researchers also compiled lists of patients’ home addresses, which could be cross-referenced with databases on air and water quality and other environmental factors.

So far researchers at Kaiser and UCSF have collected samples from 210,249 people and analyzed the DNA of more than 100,000 of them. (Most of the samples were genotyped, an analysis that catalogs the genetic variants present at specific locations along the genome, rather than sequenced in their entirety.) Researchers are beginning to comb through the data, hoping to identify genes that influence a variety of conditions, including bipolar disorder, hypertension, and cardiovascular disease. The goal is to use such findings to improve diagnostics, treatment, and prevention.

210k

Number of DNA samples Kaiser Permanente has collected—half of which have been genotyped

Neil Risch, a co-director of the Kaiser-UCSF venture, says his research using the data indicates there are genetic variants that increase the likelihood that a patient will have an adverse reaction to statins, drugs used to treat high cholesterol. Although Risch cautions that his findings are preliminary, it’s not difficult to conjure a future in which Kaiser patients would be able to take a genetic test before their doctors prescribed a medicine. That might prevent serious and costly side effects such as myopathies, muscle diseases associated with statin use.

Kaiser is also taking applications from outside researchers who want to use the banked data. Of the 75 studies that have been approved, 43 involve non-Kaiser scientists. The health network charges an administrative fee for assembling the relevant data, which are stripped of all identifying information. “What’s possible with this resource is beyond what we can do with our hands, as it were,” says Risch. “It’s almost unlimited.”

In February, Kaiser deposited information on more than 78,000 of its study subjects into the National Institutes of Health’s database on genotypes and phenotypes, a collection of genetic and health data that scientists can tap into online at no cost. Says Schaefer: “The more people who are able to use and make use of it to do good research with it, the more benefits there will be for our members and the more benefits there will be for the public at large.”

The bottom line: Kaiser Permanente is building a vast genetic database that other institutions can use for research.

Facebook CEO Mark Zuckerberg

Facebook CEO Mark Zuckerberg  Ariel Zambelich / WIRED

Facebook’s long-awaited Google AdSense competitor is finally here. It’s called Atlas, and it will allow brands to use the social network’s massive trove of data to target ads on sites across the web.1

Facebook announced the news late Sunday night to coincide with the start of Advertising Week in New York City. For other brands hoping to make headlines at Advertising Week, Facebook’s news will be a tough act to follow. Investors and the media have been waiting for an announcement like this for years.

In January, Facebook took its first steps in this direction launching a networkthat could serve up ads within mobile apps. But the launch of Atlas symbolizes a deeper commitment to controlling the web’s ads—and an even fiercer fight with Google for that control.

Atlas is not a new platform, per se. Facebook acquired the product from Microsoft last year. But according to a blog post from Erik Johnson, head of Atlas, the team has rebuilt the platform “from the ground up” in the hopes of making it easier for advertisers to follow a consumer, regardless of what type of device she’s using.

In an apparent dig at Google, Johnson writes that the method advertisers have traditionally used to track consumers—cookies—is flawed, because consumers are no longer using one device at all times. “Cookies don’t work on mobile, are becoming less accurate in demographic targeting and can’t easily or accurately measure the customer purchase funnel across browsers and devices or into the offline world,” Johnson writes. He offers “people-based marketing,” that is, marketing based on Facebook’s data, as the solution. It can not only track users between devices, but it can also connect online campaigns to offline sales to determine how effective a given campaign really was.

In the announcement, Facebook said it had already signed a contract with Omnicom to begin serving advertisements for brands like Pepsi and Intel. Instagram, which of course, is owned by Facebook, is also enabled with Atlas. The company noted in its announcement that advertisers who buy ads on Facebook, Atlas, and Instagram will be able to easily compare the results.

It’s worth noting that even Google has been interested in this people-centric strategy. That was likely the thinking behind the launch of Google+, Google’s own social network. If Google+ had been a true success the personal data it offered would have bolstered Google’s search data to perfect its ads. But, Google+ wasn’t the hit Google had hoped for, primarily because it felt like an also-ran candidate to Facebook.

Facebook is different; it’s already some hybrid of social network and advertising platform. With Atlas, Facebook stands a much better chance of beating Google at its own game.

Of course, this new advertising initiative is not likely to please any of Facebook’s already privacy conscious users. Backlash against Facebook’s existing data collection policies is what has been recently fueling the growth of Ello, a Facebook competitor that vows never to sell user data. The more partners Facebook has within its ad network, the more data it will have at its fingertips.

1. Correction: 09/29/14 1:32 PM EST This post has been updated to clarify the description of Atlas.

Umbrella manUmbrella man

IT IS a most unusual sight on Chinese soil, and most unsettling for leaders in Beijing. On September 28th and 29th tens of thousands of demonstrators surrounded government offices and filled major thoroughfares around Hong Kong, braving rounds of tear gas from riot police to call for democracy and demand the resignation of Leung Chun-ying, the territory’s Beijing-backed chief executive. One image broadcast and shared around the world, of a lone protester holding his umbrella aloft in a cloud of tear gas (pictured above), has given the non-violent protests a poetic echo of “tank man” from the crackdown at Tiananmen Square in 1989.

It also captures precisely what Communist Party leaders in Beijing fear from Hong Kong and its special status under the “one country, two systems” arrangement it has enjoyed since the territory’s handover from Britain in 1997. Not only are its people willing (and allowed by law) to challenge their government openly, but they also could become an inspiration for protests elsewhere in China. The spread of news and images of the protests has been blocked or heavily censored on the mainland, but as the protests carry on, so does the risk of contagion. In that sense it marks one of the most difficult tests of Chinese rule since Tiananmen.

Compounding the difficulty is the lack of a middle ground. The protesters’ main demand is that the people of Hong Kong be allowed to vote for any candidate of their choosing in elections for the post of chief executive in 2017 (the first in which citizens would have such a vote). President Xi Jinping has made clear he will have nothing resembling full Western democracy within China’s borders. The current election plan, put forward by the central government on August 31st, gives the central government an effective veto over nominees to ensure that Hong Kong remains firmly under its control.

Several protest movements have converged to challenge that control. Until recently the best-known movement had been Occupy Central with Love and Peace, which is modelled on Occupy Wall Street and named after an important business district at the heart of Hong Kong. But even Occupy’s leaders worried whether they could muster meaningful numbers.

The biggest driver of these protests have been university students and secondary school students, thousands of whom boycotted classes last week. On the evening of September 26th the leader of the secondary school students, 17-year-old Joshua Wong ofScholarism, was arrested; a move that, along with the use of pepper spray by police, was credited with swelling the popularity of the protests over the weekend (Mr Wong was released on Sunday). In the early hours of September 28th Benny Tai, one of the leaders of Occupy Central, announced that their protest, which had been scheduled for October 1st, China’s national day holiday, would begin immediately.

Mr Leung has shown no sign of bending. On the afternoon of September 28th, at a press conference held inside the government headquarters while thousands of protesters surrounded the building, Mr Leung repeated his endorsement of the election plan. It calls for chief executive candidates to be screened by a committee stacked with Communist Party supporters (he was elected by a similar committee in 2012, collecting 689 votes along with the derisive nickname “689”). Mr Leung acknowledged that the plan may not have been the “ideal” that some wanted, but he called it progress nonetheless. He said it had given Hong Kong citizens the “universal suffrage” they had been promised. Mr Leung said he welcomed “rational” dialogue but that the government would be “resolute” in dealing with the “unlawful” demonstrations. Asked whether the Chinese army would ever be used, Mr Leung expressed his confidence in the police. The tear gas canisters began flying shortly afterward, surprising protesters who exclaimed variations of “are you kidding?” and “shame on you”. Many donned goggles and unfurled umbrellas to protect themselves against the gas, while some raised their hands and yelled, “don’t shoot”. The protests did not become violent, but they grew and spread to other areas. The calls for Mr Leung’s resignation became louder. 

Hong Kong and central government authorities appear for now to be hoping that the protests will dissipate without an escalation of force. Riot police were pulled back on the afternoon of Septemer 29th. Censors on the mainland have worked hard to block the spread of news and images from Hong Kong. At some point during the protests Chinese authorities seem to have blocked access to Instagram, a photo-sharing site. (Facebook and Twitter have been blocked for years by China’s so-called Great Firewall.)

The expectation of the Communist Party’s supporters in Hong Kong, including the tycoons who have long run the territory, is that pragmatism will win the day over idealism. Many bankers and business executives feel there is no chance that China’s leaders will ever compromise; they view the protests as an irritant. The response from America and Britain has been almost negligible thus far (a statement from the American consulate in Hong Kong said America did not “take sides” or support “any particular individuals or groups involved”. Many of the territory’s 7m citizens are sympathetic to the demonstrations. But in most neighbourhoods people are going about their business as usual. Even near the areas of protest the city continues to function. This is partly a testament to the restraint and sense of civic responsibility of the demonstrators (who have even picked up after their own trash and, in some cases, sorted for recycling).

Without a political resolution in sight, questions remain about how much staying power the protests will have, and how much patience the government will show. The possibility looms of a more severe use of force. A two-day Hong Kong holiday this week, on October 1st and 2nd to observe national day, may bring some answers either way. Organisers expect more people to join the protests. Worryingly for the government, that could include tourists travelling from the mainland, where the holiday is also observed. The risk of Hong Kong’s unrest spilling over into mainland China may continue to rise.

What’s amazing to me is that it came from Xinhua’s Franch language newswire!!

Hint: Ils ne parlent pas le français.

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With the Centers for Disease Control now forecasting up to 1.4 million new infections from the current Ebola outbreak, what could “big data” do to help us identify the earliest warnings of future outbreaks and track the movements of the current outbreak in realtime? It turns out that monitoring the spread of Ebola can teach us a lot about what we missed — and how data mining, translation, and the non-Western world can help to provide better early warning tools.

Earlier this month, Harvard’s HealthMap service made world headlines for monitoring early mentions of the current Ebola outbreak on March 14, 2014, “nine days before the World Health Organization formally announced the epidemic,” and issuing its first alert on March 19.  Much of the coverage of HealthMap’s success has emphasized that its early warning came from using massive computing power to sift out early indicators from millions of social media posts and other informal media. 

As one blog put it: “So how did a computer algorithm pick up on the start of the outbreak before the WHO? As it turns out, some of the first health care workers to see Ebola in Guinea regularly blog about their work. As they began to write about treating patients with Ebola-like symptoms, a few people on social media mentioned the blog posts. And it didn’t take long for HealthMap to detect these mentions.” 

The U.S. government’s Intelligence Advanced Research Projects Activity (IARPA), which helps fund HealthMap, has used this success story as evidence that the approaches used in its Open Source Indicators program can indeed “beat the news” and provide the earliest warnings of impending disease outbreaks and conflict. 

It’s an inspirational story that is a common refrain in the “big data” world — sophisticated computer algorithms sift through millions of data points and divine hidden patterns indicating a previously unrecognized outbreak that was then used to alert unsuspecting health authorities and government officials.  The problem is that this story isn’t quite true: By the time HealthMap monitored its very first report, the Guinean government had actually already announced the outbreak and notified the WHO.

The first public international warning of the impending epidemic came not from data mining or social media, but through more traditional channels: a news article in Xinhua’s French-language newswire titled “Guinée: une étrange fièvre fait 8 morts à Macenta” published late in the day (eastern standard time) on March 13. The article reports that “a disease whose nature has not yet been identified has killed 8 people in the prefecture of Macenta in south-eastern Guinea … it manifests itself as a hemorrhagic fever….” In turn, this newswire article was actually simply reporting on a press conference held earlier in the day by Dr. Sakoba Keita, director of the Division of Disease Prevention in the Guinea Department of Health, broadcast nationally on state television, that announced both the outbreak of the unknown hemorrhagic fever and the departure of a team of government medical personnel to the area to investigate it in more detail. The Xinhua article further notes that the government of Guinea had already formally notified the WHO of the unknown outbreak.

Thus, contrary to the narrative that data mining led to an intelligence coup of “beating the WHO,” in fact HealthMap’s earliest signals on March 14 were actually simply detections of this official government announcement. Despite all of the attention and hype paid to social media as a sensor network over human society, mainstream media still plays a critical role as an information stream inmany areas of the world. This is not to say that there were not far earlier signals manifested in the myriad social conversations among medical workers and citizens in the region, only that it was not these indicators that HealthMap detected.

Part of the problem is that the majority of media in Guinea is not published in English, while most monitoring systems today emphasize English-language material. The GDELT Project attempts to monitor and translate a cross-section of the world’s news media each day, yet it is not capable of translating 100 percent of global news coverage. It turns out that GDELT actually monitored the initial discussion of Dr. Keita’s press conference on March 13 and detected a surge in domestic coverage beginning on March 14, the day HealthMap flagged the first media mention. The problem is that all of this media coverage was in French — and was not among the French material that GDELT was able to translate those days.

To give an idea of the importance of monitoring across languages, through a grant from Google Translate for Research, GDELT has been feeding a portion of the Portuguese edition of Google News each day through Google Translate for the past year. It turns out that upwards of 70 percent of the events recorded in Portuguese-language news do not appear in English-language news anywhere else in the world. Further, a large portion of these events relate to situations outside of Portugal and Brazil, including former colonial states in Africa, as the map below shows. Increasing our ability to process all of this material would yield tremendous gains in monitoring local media of the sort that provided the first indicators of the Ebola outbreak.

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Click to enlarge.

On a panel I served on last week, we were asked to name what we thought was the greatest challenge to better understanding the world.  A representative of a government-funded agency stated that, in his program’s view, it was a need for better computer science tools to better extract patterns from data. That’s a worthwhile goal, but not if the data set is incomplete. While there is certainly great need for better data tools, even if one could perfectly extract every piece of information from the New York Times each day, it would likely not yield a picture of the emerging Ebola outbreak any more detailed than what American government officials already have. Instead, what we truly need is better, more local data (and expanded tools that can translate and process that material) to allow us to more closely listen to and understand local communities.

There is a singular preoccupation in government today with forecasting the future. Yet, we must be careful that among investments of hundreds of millions of dollars in forecasting systems that have yet to produce useful results, we don’t miss the early warning signs of emerging pandemics that are quite literally broadcast for us on national television. Instead of trying to “beat” the international news through massive investments in computer models, we should instead be focusing on listening better.

Pascal Guyot / AFP

A look at the sizes of recent street demonstrations

PEOPLE power is increasingly on display from Cairo’s Tahrir Square to Istanbul’s Taksim Square. In recent days Hong Kong and Ukraine have come alive with public protests of their own. But how do they compare in terms of participants? Answering the question definitively is impossible. The authorities come up with one number, the organisers another, the press perhaps a third. Nevertheless, the disparities among estimates are evocative of the tensions. And the relative sizes are a useful comparison as protests start to blur together in the media din.

For instance, many people were stunned by this weekend’s images of Hong Kong awash with tear gas. But the estimated turnout of around 80,000 people was a fraction of the number who participated recently in New York for a climate-change march and for Catalonian independence in Barcelona. Egypt’s throngs in June 2013 are estimated to be around seven times larger than Brazil’s earlier that month. Though calculating crowd size is hard, one useful proxy is mobile phones. In future perhaps wireless carriers, not police nor protesters nor press, will release the data.

hard-find

 Getty

No company has a culture; every company is a culture. A startup is a team of people on a mission, and a good culture is just what that looks like on the inside. The first team that I built has become known in Silicon Valley as the “PayPal Mafia” because so many of my former colleagues, including Elon Musk, Reid Hoffman, and David Sacks, have gone on to help each other start and invest in successful tech companies.

We didn’t assemble a mafia by sorting through résumés and simply hiring the most talented people. I had seen the mixed results of that approach when I worked at a New York law firm. The relationships between lawyers I worked with were oddly thin. They spent all day together, but few of them seemed to have much to say to each other outside the office.

Why work with a group of people who don’t even like each other? Taking a merely professional view of the workplace, in which free agents check in and out on a transactional basis, is worse than cold: It’s not even rational. Since time is your most valuable asset, it’s odd to spend it working with people who don’t envision any long‑term future together.

Rule 1: The Best Startups Work a Lot Like Cults

In the most intense kind of organization, members abandon the outside world and hang out only with other members. We have a word for such organizations: cults. Cultures of total dedication look crazy from the outside. But entrepreneurs should take cultures of extreme dedication seriously.

The extreme opposite of a cult is a consulting firm like Accenture: not only does it lack a distinctive mission, but individual consultants are regularly dropping in and out of companies to which they have no long‑term connection whatsoever.

Every company culture can be plotted on a linear spectrum:
zero_to_one_graph

The best startups might be considered slightly less extreme kinds of cults. The biggest difference is that cults tend to be fanatically wrong about something important. People at a successful startup are fanatically right about something those outside it have missed.

Rule 2: Giving People a Chance to “Change the World” Is a Lousy Way to Recruit Employees

Recruiting is a core competency for any company. It should never be outsourced. Talented people don’t need to work for you; they have plenty of options. You should ask yourself: Why would someone join your company as its 20th engineer when she could go work at Google for more money and more prestige?

Here are some bad answers: “Your stock options will be worth more here than elsewhere.” “You’ll get to work with the smartest people in the world.” “You can help solve the world’s most challenging problems.” Every company makes these same claims, so they won’t help you stand out.

You’ll attract the employees you need if you can explain why your mission is compelling: not why it’s important in general, but why you’re doing something important that no one else is going to get done. However, even a great mission is not enough. The best recruit will also wonder: “Are these the kind of people I want to work with?” You should be able to explain why your company is a unique match for him personally. And if you can’t do that, he’s probably not the right match.

Rule 3: Everyone at Your Startup Should Have Just One Job

Internal peace is what enables a startup to survive at all. But most fights inside a company happen when colleagues compete for the same responsibilities. Startups face an especially high risk of this since job roles are fluid at the early stages.

The best thing I did as a manager at PayPal was to make every person in the company responsible for doing just one thing. I had started doing this just to simplify the task of managing people. But then I noticed a deeper result: Defining roles reduced conflict. Eliminating competition makes it easier for everyone to build the kinds of long‑term relationships that transcend mere professionalism.

Rule 4: Hire Employees Who Are Excited to Wear Your Logo on Their Hoodies

Startups have limited resources and small teams. They must work quickly and efficiently in order to survive, and that’s easier to do when everyone shares an understanding of the world.

It’s a cliché that tech workers don’t care about what they wear, but if you look closely at the T‑shirts people in Mountain View and Palo Alto wear to work, you’ll see the logos of their companies—and tech workers care about those very much. The startup uniform encapsulates a simple but essential principle: Everyone at your company should be different in the same way—a tribe of like‑minded people fiercely devoted to the company’s mission.

Above all, don’t fight the perk war. Anybody who would be powerfully swayed by free laundry pickup or pet day care would be a bad addition to your team. Just cover the basics and then promise what no others can: the opportunity to do irreplaceable work on a unique problem alongside great people.

Excerpted with permission from ZERO TO ONE: Notes on Startups, or How to Build the Future by Peter Thiel with Blake Masters. Copyright 2014 by Peter Thiel. Published by Crown Business, an imprint of the Crown Publishing Group, a division of Random House LLC, a Penguin Random House Company.

The founder of PayPal has written a lucid treatise on capitalism and entrepreneurship

Lucas Jackson/Reuters

A few years ago, when I lived in Washington, D.C., an editor at the The Atlanticand I used to play a game: Who could come up with the best idea for a terrible business self-help book? The competition was inspired by the book jackets that occasionally fell on our desks, which managed to express bad economic principles with even worse metaphors. I don’t recall the titles today—even if I did, it would be rude to blame individuals for the collective depravity of their genre—but our imitations would go something like this:

  • Turn the Other Tweet: Lessons from Christianity for Social Media
  • Hey, You, Get ~Onto~ My Cloud: How to Rock and Roll With the New Economy
  • Baa Baa BlackBerry: Nursery Rhymes for the Hyper-Connected Baby

Into this fog of fuzzy-headed nonsense, Peter Thiel’s new book, Zero to One,shines like a laser beam. Yes, this is a self-help book for entrepreneurs, bursting with bromides and sunny confidence about the future that only start-ups can build. But much more than that, it’s also a lucid and profound articulation of capitalism and success in the 21st century economy.

Thiel, a founder of PayPal and the data analytics firm Palantir, might be best known for his idiosyncrasies, which helped inspire the character of Peter Gregory in the HBO series Silicon Valley. Indeed, the recipients of Thiel’s donations seem torn from the pages of a Philip K. Dick novel: an anti-aging biotech firm, an organization dedicated to building ocean communities underwater, and a foundation that pays teenagers to drop out of college and start new companies. Say what you want about the Thielian future of cyborg teenagers living for 200 years in pressurized cabins under the Caribbean; this is not a man to be faulted for thinking too small.

So it’s surprising in a wonderful way just how simple Zero to One feels. Barely 200 pages long, and well lit by clear prose and pithy aphorisms, Thiel’s has written a perfectly tweetable treatise and a relentlessly thought-provoking handbook.

His most provocative thesis, excerpted in a popular WSJ column, declares that “competition is for losers” and entrepreneurs should embrace monopolies. This is an ingenious framing device—just controversial enough to arouse debate, but commonsense enough to make an incrementalist acknowledge its virtue. Thiel is not suggesting that capitalism is bad. He’s saying that, precisely because capitalism is wonderful for consumers, it’s hell for companies. Truly competitive industries, like Manhattan restaurants, see their profits gobbled by rivals and fickle eaters. Every start-up must begin small before getting big. Entrepreneurs should at first seek to dominate a small market. In other words: They should try to build a mini-monopoly.

"The perfect target market for a start-up is a small group of particular people concentrated in a group but served by few or no competitors," Thiel writes. Lots of tech hits, like Facebook and PayPal, were launched in small communities of power users. These early adopters tested the product, identified early bugs, and helped to spread the word when the company expanded. An online yearbook for Harvard students might not strike you as a $100 billion idea. But today Facebook is a $200 billion company, because Zuckerberg established monopolistic fiefdoms at colleges before expanding to take over the world.

Thiel arrived in Silicon Valley in 1985. After two tours of duty at Stanford (which did little to dissuade him of the notion that college is a waste of time) he founded PayPal (then “Confinity”) with a group of friends in 1998. Two years later, at the pinnacle of the dot-com bubble, he merged his business with Elon Musk, perhaps the Valley’s most celebrated polymath, who happened to starting a similar company, X.com, just blocks away.

The crash left an intellectual hangover in the technology space, Thiel says. The founders who survived the deluge clung to four principles: 1) Be humble and make incremental advances; 2) Stay lean and experiment agnostically; 3) Don’t try to create new markets all of a sudden; 4) Focus on product, not sales. But those who misremember history are doomed to repeat it. “The opposite principles are probably more correct,” Thiel says. Start-ups should be bold, have a clear plan, try to build a small monopoly, and appreciate that sales matter as much as product.

It’s refreshing to hear a techie extol the virtue of sales, and Thiel is good at explaining both why nerds hate marketers, and why the nerds are wrong. “Nerds are skeptical of advertising, marketing, and sales, because they seem superficial,” he writes. “They know their own jobs are hard, so when they look at salespeople laughing on the phone with a customer or going to two-hour lunches, they suspect that no real work is being done. If anything, people overestimate the relative difficulty of science and engineering, because the challenges of those fields are obvious. What nerds don’t realize is that it also takes hard work to make sales look easy … If you’ve invented something new but you haven’t invented an effective way to sell it, you have a bad business—no matter how good the product.” There is more sneakily simple wisdom in Thiel’s chapters on sales and distribution than in several perfectly suitable business books.

Thiel is brilliant at addressing his audience, entrepreneurs on the road to success. His shortcomings are concentrated in moments where he has to grapple with the limits of his boundless optimism. There is a long skippable portion of the book where Thiel haphazardly blames America’s growth of transfer spending on the federal government’s sudden allergy to planning for the future. But the programs that make up most of the spending he criticizes, including Social Security and Medicare, were passed between the 1930s and 1960s, a period that Thiel hails as the apogee of American technological daring. Perhaps Washington has severely altered the way it thinks about technology since the 1970s. The more significant explanation is that America, like every rich democracy in the world, is just getting old.

Zero to One slips into the worn-out grooves of its unfortunate genre by building a theory of success without studying failure with equal rigor. Thiel’s chapter on fortune, “You Are Not a Lottery Ticket,” is a impassioned defense of the idea that skill outweighs luck in the market place. But in the next chapter, “Follow the Money,” he acknowledges that most of the bets that venture capitalist make are, indeed, failures.

"The biggest secret in venture capital is that the best investment in a successful fund equals or outperforms the entire rest of the fund combined," he writes. This power law distribution of VC investments means that a few bets will get fabulously unequal returns and it’s almost impossible to predict which ones those will be. In a winner-take-all world where even the experts running VC firms don’t know which company will win, commanding entrepreneurs to transcend the vicissitudes of luck is asking a generation of young men and women to defy gravity.

Thiel repeatedly rebuts the argument that success is the result of built-in privilege. He doesn’t point out that Silicon Valley, which is overrun by educated white dudes, is America’s petri dish of cumulative advantage.

As one of the Valley’s stars, Thiel is preaching the gospel of success in an industry where failure is the law of the land. There is not much here about what happens when your business runs into the ground. I would have liked to read more about how PayPal, which was founded to create an an alternative currency to the dollar, succeeded, not as a crypto-currency, but rather an a convenient online payment system. A book about home runs needs to address that question:What do you do in the batters box after the first swing-and-miss?

When Thiel is interviewing for a new position, he says one of his favoritequestions to ask is: “What important truth do very few people agree with you on?” With Zero to One, he has written a book that answers his own question many times over. But some of Thiel’s best thinking feels like refreshinglyhumanist advice: Remember that your founders are your family, give great employees limited tasks, start with ambitious yet small products that dominate a narrow market, stop hating on salespeople, and focus on a corporate thesis statement, or “secret,” that distinguishes you from your rivals.

This is a treatise meant to inspire entrepreneurs, but it is also serves as an inspiration for its genre. Zero to One has entered an uncompetitive market and proved its own thesis. Among its rival business books, it has built a small monopoly.

Chess

A moth evolves ears that can hear the sonar of bats, and bats adapt by hushing their calls to whispers. A newt evolves powerful poisons that can kill would-be predators, and a snake evolves immunity to those poisons. A gazelle becomes faster to outrun its hunter, and a cheetah becomes faster still. The natural world is full of these evolutionary arms races—endless battles where one party’s adaptations are met by counter-adaptations from its opponent. Both sides move in and out of check, changing all the time but locked in a perpetual stalemate.

The human genome is engaged in a similar evolutionary arms race… against itself.

The opponents are jumping genes called retrotransposons that can hop around the genome. They increase in number by copying themselves and pasting the duplicates into new locations. This mobile lifestyle is so successful that retrotransposons make up more than 40 percent of the human genome. Some have settled down, and are now static shadows of their once-active selves. Others are still on the move.

If the copies land in the right place, they could act as clay for building new adaptations. If they land in the wrong place, which is perhaps more likely, they could cause diseases by disrupting important genes. So genomes have ways of keeping these wandering sequences under control. One involves a gene called KAP1. It’s a kind of tranquiliser—it sticks to retrotransposons and stops them from activating.

KAP1 works differently in different species, targeting those retrotransposons that are active in that owner’s genome. Our KAP1 won’t keep a mouse’s jumping genes in line, and vice versa. Some scientists believe that this specificity is caused by another group of genes called KZNFs. They tell KAP1 where to go by searching for, and sticking to, specific retrotransposons. They’re like beat cops that patrol a neighbourhood, look for crime, and radio for back-up. Each KZNF targets a different type of retrotransposon and different species have their own set.

At least, that’s what happens in theory. In reality, we know that many KZNFs exist, but no one had matched any one of them to a specific target. Partly, that’s because these cops do such a good job that it’s hard to see jumping genes in action.

Frank Jacobs and David Greenberg from the University of California, Santa Cruz solved this problem by sticking the retrotransposons in mouse cells—a less policed environment. They filled the mouse stem cells with a single human chromosome. Mice are adapted to control their own retrotransposons, so they’re oblivious to ours. The jumping genes on the human chromosome, freed from their usual restraints, started spreading, much like an invasive species running amok on an island with no native predators. Now, the team could pit different human KZNFs against these restless genes to see if any could bring them to heel.

They found two that could—ZNF91 and ZNF93. Each of these represses a major class of retrotransposons—SVAs and L1s, respectively—that are still jumping about in the human genome today.

ZNF91 and ZNF93 are only found in primates, but they have changed a lot even without our narrow lineage. For example, the human version of ZNF91 has deluxe features that are shared by gorillas but not by monkeys. To understand the value of these changes, Ngan Nguyen and Benedict Paten took the modern genes and worked backwards, reconstructing their ancestral versions at different stages of their evolution.

They found that between 8 and 12 million years ago, ZNF91 gained features that dramatically improved its ability to keep retrotransposons in line. That’s the point in primate evolution before humans diverged from gorillas and chimps. ZNF93 went through similarly dramatic changes between 12 and 18 million years ago, before the we (and the other great apes) diverged from orang-utans.

These results suggest that ape KZNFs have rapidly evolved to keep jumping genes in check. Indeed, the KZNFs are one of the fastest growing families of primate genes. We have around 400 of them, and some 170 of these are primate-only innovations. This expanded police force reflects our ongoing genomic arms race.

And the jumping genes are starting to fight back. For example, the team found that ZNF93 represses L1 genes by recognising a short signature sequence that most of them have. But some L1s, especially the most recently evolved ones, have lost this signature entirely. They can jump unnoticed.

The missing sequence would normally makes the jumping genes better at jumping. But this booster rocket ended up as a wheel clamp, since ZNF93 evolved to recognise it. So some of the L1s lost the rocket. They jumped less effectively, but at least they could still jump.

anchorman-well-that-escalated-quicklyThis is a classic evolutionary arms race. The hosts thrusts, the parasite parries, and the duel continues. But unlike more familiar battles between snakes and toads, or hosts and viruses, this is a case where we’re waging war against our own DNA.

There’s a sense of futility about this. Much of our genome seems to be engaged in an ultimately pointless duel whether neither side can give or gain any ground. But these battles aren’t quite as fruitless as they might seem.

The team found that KZNFs partly suppress the genes around a retrotransposon too. When the cops finds their target, they tell all the bystanders to the lie on the ground too. This is important because it seriously affects the activity of many human genes, beyond retrotransposons. It means that KZNFs can eventually be used to control the activity of genes that jumping genes land next to. (“Excuse me, officer, but while you’re manhandling your suspect, would you mind also rescuing my cat?”) This arms race could have given rise to more complicated networks of genes, and perhaps more complicated bodies or behaviours.

Reference: Jacobs, Greenberg, Nguyen, Haeussler, Ewing, Katzman, Paten, Salama & Haussler. 2014. An evolutionary arms race betweenKRAB zinc-finger genes ZNF91/93 and SVA/L1 retrotransposons. Naturehttp://dx.doi.org/10.1038/nature13760

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