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A simple blood test to predict premature births could save babies’ lives

https://www.technologyreview.com/s/612931/a-simple-blood-test-to-predict-premature-births-could-save-babies-lives/

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Fifteen million babies are born pre­maturely each year. Stephen Quake’s daughter, Zoe, was one of them: she arrived via emergency C-section after Quake and his wife, Athina, made a middle-of-the-night dash to the emergency room, a month before Zoe was due. She spent her first night in an incubator, and her father, a bioengineer then at Caltech, wondered why birth couldn’t be more predictable. 

That question lingered in Quake’s mind. Months before Zoe began her junior year of high school, her dad announced he had developed a maternal blood test that may be able to alert women that they are going to deliver prematurely—before 37 completed weeks of gestation. He has since launched a startup to commercialize the technology and create a cheap, easy test that women could take around the sixth month of pregnancy.

The prematurity test isn’t Quake’s first foray into prenatal health. When Athina was pregnant with Zoe, she had undergone amniocentesis, an invasive needle biopsy used to detect Down syndrome and other conditions. When it’s executed by doctors with lots of experience, the risk of miscarriage is low, but it exists—and that’s nerve-racking for expectant parents. “I thought, Oh my God, this is awful—that you have to risk losing the baby to ask a diagnostic question,” he says.

Convinced there had to be a better way, Quake got to work developing noninvasive blood tests to assess much of the same information as amniocentesis but with less risk to the pregnancy. He used bits of free-floating fetal DNA found in maternal blood to get a peek at the genetic makeup of the fetus. More than a decade later, multiple biotech companies offer a version of similar tests for Down syndrome and other conditions to pregnant women in clinics worldwide.

Likewise, blood tests, often called “liquid biopsies,” are in development for a number of applications, including detecting early-stage cancer and revealing whether a replacement heart is failing in the body of a transplant recipient. In 2014, Quake identified evidence of dying neurons in the blood circulation of Alzheimer’s patients, a step that is being used to develop tests for neurodegenerative and autoimmune diseases.

Predicting preterm birth would be another important breakthrough. Globally, more than one in 10 babies is born preterm, a public health problem that cuts across socioeconomic and geographic boundaries. Babies in poor nations like Malawi are born too soon—the country has an 18% rate of preterm birth, the highest in the world—but so are babies in the US, like Quake’s daughter in prosperous Southern California.

Complications from preterm birth are the leading cause of death worldwide in children under the age of five. Preterm babies can struggle with infection, learning disabilities, and problems with vision and hearing. In poor countries, babies born significantly preterm often don’t survive. In wealthy countries they usually do, but sometimes with long-term consequences including behavioral problems and neurological disorders such as cerebral palsy. There’s an economic factor, too: babies born preterm cost, on average, 10 times as much over the first year of life as those whose birth had no complications.

Just ask Jen Sinconis, whose twins arrived with no warning at 24 weeks’ gestation in 2006. Twin pregnancies are considered high risk, but Sinconis’s pregnancy had been uneventful until she started having what she assumed were Braxton Hicks contractions, which can occur weeks in advance of delivery as the uterus primes itself for labor. She was wrong, and her twin boys arrived within six hours.

One of the Sinconis boys in the ICU.

Courtesy of Jennifer Sinconis

Aidan weighed 1 pound, 14 ounces (850 grams) and had to spend three months in the hospital; Ethan weighed 1 pound, 6 ounces, and was worse off. He was on oxygen for most of his first year of life and barely escaped needing a tracheotomy. Sinconis received a shot of surfactant to help develop her sons’ lungs as soon as she reached the hospital, but if a test had been able to alert her doctor that she was at risk for early labor, she could have been given the medicine sooner, when it could possibly have made a difference. “If I had known they would have been born prematurely, our entire life would be different,” says Sinconis, a creative producer at Starbucks corporate headquarters in Seattle.

The boys’ medical care cost more than $2 million and didn’t end when they left the hospital. They remained in isolation at home for the first three and a half years of their lives; Sinconis can barely keep track of the number of doctors and therapists they’ve seen through the years. She and her husband were forced to sell their home, liquidate their retirement and savings accounts, and eventually declare bankruptcy to deal with the nearly $450,000 that insurance wouldn’t cover. Now 12, the boys have mostly caught up developmentally to other children their age. But their parents are just starting to emerge from their financial struggles. “We’re way overdue for a way to predict preterm birth,” Sinconis says.

Jen Sinconis’s twins arrived at 24 weeks in 2006. Now 12, the boys are mostly healthy.

Courtesy of Jennifer Sinconis

A new test

Zoe, now 17, “is all grown up and totally healthy,” says Quake, a professor at Stanford University for the past 14 years, but figuring out how to predict preterm birth had been in the back of his mind since she was born. It “felt like the next big mountain to climb,” he says. “We had gained confidence from noninvasive prenatal testing. Preterm birth was like Mt. Everest.”

Quake knew there were no meaningful diagnostics that could identify which pregnant women would give birth too soon. The biggest tip-off is having given birth to a preterm baby before, something of little use for a first-time mom. Additionally, preterm delivery can be caused by multiple factors: infection, twins, or even maternal stress. “We don’t have any understanding about what is triggering preterm birth,” says Ronald Wapner, director of reproductive genetics at Columbia University Irving Medical Center. “We have been shotgunning it.”

Quake also knew that direct DNA measurements wouldn’t help. Analyzing a baby’s DNA, inherited from his or her parents, is fundamental to testing for Down syndrome because it can reveal the presence of an extra chromosome. “It’s a genetic question,” says Quake. But research has shown that the baby’s genetic profile makes a minimal contribution to prematurity. So instead, Quake focused on DNA’s molecular cousin, RNA. These molecules are harder to spot in blood (they’re short-lived) but would provide a more relevant readout, Quake believed, because their levels go up and down according to what’s going on in a person’s body. Could it be that a pregnancy headed for trouble was sounding early alarm signals?

Quake and his team, including Mira Moufarrej, a grad student in his lab, scrutinized blood samples from 38 African-American women considered at risk for preterm birth, in some cases because they’d previously had a premature baby. Overall, black children in the US are born prematurely about 50% more often than whites. Thirteen of the women ended up delivering early. By analyzing RNA molecules in their blood, the researchers found seven genes whose changing activity signals, taken together, seemed to predict which babies had arrived prematurely.

Quake told me he was surprised by the result. “Holy shit, might we have figured out a way to determine preterm birth?” he recalls thinking. “We’re still trying to understand the biology behind these seven genes,” he adds; it’s not yet clear whether the signals are emanating from the mother, the placenta, or the baby. Quake suspects they are “reflecting the mom’s response to the pregnancy going off track.” In other words, he says, “the whole thing is derailing and the mom is responding to that.”

“The beauty of this approach is that it allows us to see a conversation going on between the mother, the fetus, and the placenta,” says David Stevenson, co-director of Stanford’s Maternal and Child Health Research Institute and principal investigator at its prematurity research center. “It’s like eavesdropping. Now we can access this as it’s being communicated, which helps us understand what’s going on throughout pregnancy.”

Treatment Hope

Five hundred years ago, fascinated by his anatomical dissection of the womb of a pregnant women who had died, Leonardo da Vinci wrote about his intention to unravel the secrets behind conception and preterm birth. He never did, and even today, there are relatively few answers. Perhaps because so little is known, pharmaceutical companies haven’t seen preterm birth as a promising area for investment. Indeed, it is “one of the most neglected issues,” says Sindura Ganapathi, co-leader of the Maternal, Newborn & Child Health Discovery & Tools portfolio at the Gates Foundation, which along with the March of Dimes and the CZ Biohub, a medical initiative funded by Mark Zuckerberg and his wife Priscilla Chan, has funded Quake’s work.

“We need many more interventions,” says Ganapathi. “We are pretty limited in our armamentarium.”

A test could be a first step toward new drugs or treatments. Knowing who is at risk would let women prepare—say, by picking a hospital with a neonatal intensive care unit or working with an obstetrician who could prescribe progesterone, a drug sometimes given to try to extend pregnancy. “It goes back to personalized treatment,” says Wapner. “We still haven’t been able to identify how progesterone works and who it works for better. RNA could help us better understand who should get these medications.”

The new window on pregnancy could lead to applications beyond preterm birth. “From the standpoint of where this could go, you could look at placental development, fetal development, and fetal-maternal interaction,” says Wapner. “RNA has been the stepsister of DNA until very recently. It’s a damn good clue about how to differentiate who’s at risk of preterm birth, and it could give us a better way of evaluating what’s going on during pregnancy.”

In line with that, Quake has formed a startup, called Akna Dx, with lofty goals. It’s raised more than $10 million from investors including Khosla Ventures of Menlo Park, California. “Our idea is to do blood-based tests to give key insights,” says CEO and cofounder Maneesh Jain. “What is a fetus’s gestational age? Are you at risk for preterm birth, or severe postpartum depression? Pregnancy tends to still be a big black box. We want to give you insights into what is happening internally so you can take action.”

Other experts say more evidence is needed that RNA can provide those insights. That’s because so many different factors can contribute to prematurity, and it’s not clear how well Quake’s biomarkers will do in a broader population. “The difficulty is that preterm delivery is not caused by one thing,” says Diana Bianchi, director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and an expert in noninvasive prenatal testing. Infection, a compromised placenta, maternal stress, a twin pregnancy—all of these and more can trigger preterm birth. “In really small numbers, Steve was accurately able to distinguish women at risk of delivering preterm,” says Bianchi. “But the numbers were really small.”

Quake readily agrees that his initial findings need to be validated through a large clinical trial before any test would be ready for commercial use. Quake’s team is working to confirm that the results from the African-American women hold up in other groups as well. Collaborators, including some of Akna’s cofounders, are now collecting blood samples from 1,000 pregnant women.

“We hope this is going to save a lot of lives,” says Quake. “That’s really what we’re aiming for. But this is just the beginning of the story … It’s a very fertile area, no pun intended.”

Bonnie Rochman is a health and science writer based in Seattle and the author of The Gene Machine.

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These ten enterprise M&A deals totaled over $40B in 2019

It would be hard to top the 2018 enterprise M&A total of a whopping $87 billion, and predictably this year didn’t come close. In fact, the top 10 enterprise M&A deals in 2019 were less than half last year’s, totaling $40.6 billion. This year’s biggest purchase was Salesforce buying Tableau for $15.7 billion, which would…

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These ten enterprise M&A deals totaled over $40B in 2019

It would be hard to top the 2018 enterprise M&A total of a whopping $87 billion, and predictably this year didn’t come close. In fact, the top 10 enterprise M&A deals in 2019 were less than half last year’s, totaling $40.6 billion.

This year’s biggest purchase was Salesforce buying Tableau for $15.7 billion, which would have been good for third place last year behind IBM’s mega deal plucking Red Hat for $34 billion and Broadcom grabbing CA Technologies for $18.8 billion.

Contributing to this year’s quieter activity was the fact that several typically acquisitive companies — Adobe, Oracle and IBM — stayed mostly on the sidelines after big investments last year. It’s not unusual for companies to take a go-slow approach after a big expenditure year. Adobe and Oracle bought just two companies each with neither revealing the prices. IBM didn’t buy any.

Microsoft didn’t show up on this year’s list either, but still managed to pick up eight new companies. It was just that none was large enough to make the list (or even for them to publicly reveal the prices). When a publicly traded company doesn’t reveal the price, it usually means that it didn’t reach the threshold of being material to the company’s results.

As always, just because you buy it doesn’t mean it’s always going to integrate smoothly or well, and we won’t know about the success or failure of these transactions for some years to come. For now, we can only look at the deals themselves.

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Jumia, DHL, and Alibaba will face off in African ecommerce 2.0

The business of selling consumer goods and services online is a relatively young endeavor across Africa, but ecommerce is set to boom. Over the last eight years, the sector has seen its first phase of big VC fundings, startup duels and attrition. To date, scaling e-commerce in Africa has straddled the line of challenge and…

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Jumia, DHL, and Alibaba will face off in African ecommerce 2.0

The business of selling consumer goods and services online is a relatively young endeavor across Africa, but ecommerce is set to boom.

Over the last eight years, the sector has seen its first phase of big VC fundings, startup duels and attrition.

To date, scaling e-commerce in Africa has straddled the line of challenge and opportunity, perhaps more than any other market in the world. Across major African economies, many of the requisites for online retail — internet access, digital payment adoption, and 3PL delivery options — have been severely lacking.

Still, startups jumped into this market for the chance to digitize a share of Africa’s fast growing consumer spending, expected to top $2 billion by 2025.

African e-commerce 2.0 will include some old and new players, play out across more countries, place more priority on internet services, and see the entry of China.

But before highlighting several things to look out for in the future of digital-retail on the continent, a look back is beneficial.

Jumia vs. Konga

The early years for development of African online shopping largely played out in Nigeria (and to some extent South Africa). Anyone who visited Nigeria from 2012 to 2016 likely saw evidence of one of the continent’s early e-commerce showdowns. Nigeria had its own Coke vs. Pepsi-like duel — a race between ventures Konga and Jumia to out-advertise and out-discount each other in a quest to scale online shopping in Africa’s largest economy and most populous nation.

Traveling in Lagos traffic, large billboards for each startup faced off across the skyline, as their delivery motorcycles buzzed between stopped cars.

Covering each company early on, it appeared a battle of VC attrition. The challenge: who could continue to raise enough capital to absorb the losses of simultaneously capturing and creating an e-commerce market in notoriously difficult conditions.

In addition to the aforementioned challenges, Nigeria also had (and continues to have) shoddy electricity.

Both Konga — founded by Nigerian Sim Shagaya — and Jumia — originally founded by two Nigerians and two Frenchman — were forced to burn capital building fulfillment operations most e-commerce startups source to third parties.

That included their own delivery and payment services (KongaPay and JumiaPay). In addition to sales of goods from mobile-phones to diapers, both startups also began experimenting with verticals for internet based services, such as food-delivery and classifieds.

While Jumia and Konga were competing in Nigeria, there was another VC driven race for e-commerce playing out in South Africa — the continent’s second largest and most advanced economy.

E-tailers Takealot and Kalahari had been jockeying for market share since 2011 after raising capital in the hundreds of millions of dollars from investors Naspers and U.S. fund Tiger Global Management.

So how did things turn out in West and Southern Africa? In 2014, the lead investor of a flailing Kalahari — Naspers — facilitated a merger with Takealot (that was more of an acquisition). They nixed the Kalahari brand in 2016 and bought out Takelot’s largest investor, Tiger Global, in 2018. Takealot is now South Africa’s leading e-commerce site by market share, but only operates in one country.

In Nigeria, by 2016 Jumia had outpaced its rival Konga in Alexa ratings (6 vs 14), while out-raising Konga (with backing of Goldman Sachs) to become Africa’s first VC backed, startup unicorn. By early 2018, Konga was purchased in a distressed acquisition and faded away as a competitor to Jumia.

Jumia went on to expand online goods and services verticals into 14 Africa countries (though it recently exited a few) and in April 2019 raised over $200 million in an NYSE IPO — the first on a major exchange for a VC-backed startup operating in Africa.

Jumia’s had bumpy road since going public — losing significant share-value after a short-sell attack earlier in 2019 — but the continent’s leading e-commerce company still has heap of capital and generates $100 million in revenues (even with losses).

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Airbnb’s New Year’s Eve guest volume shows its falling growth rate

Hello and welcome back to our regular morning look at private companies, public markets and the gray space in between. It’s finally 2020, the year that should bring us a direct listing from home-sharing giant Airbnb, a technology company valued at tens of billions of dollars. The company’s flotation will be a key event in…

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Airbnb’s New Year’s Eve guest volume shows its falling growth rate

Hello and welcome back to our regular morning look at private companies, public markets and the gray space in between.

It’s finally 2020, the year that should bring us a direct listing from home-sharing giant Airbnb, a technology company valued at tens of billions of dollars. The company’s flotation will be a key event in this coming year’s technology exit market. Expect the NYSE and Nasdaq to compete for the listing, bankers to queue to take part, and endless media coverage.

Given that that’s ahead, we’re going to take periodic looks at Airbnb as we tick closer to its eventual public market debut. And that means that this morning we’re looking back through time to see how fast the company has grown by using a quirky data point.

Airbnb releases a regular tally of its expected “guest stays” for New Year’s Eve each year, including 2019. We can therefore look back in time, tracking how quickly (or not) Airbnb’s New Year Eve guest tally has risen. This exercise will provide a loose, but fun proxy for the company’s growth as a whole.

The numbers

Before we look into the figures themselves, keep in mind that we are looking at a guest figure which is at best a proxy for revenue. We don’t know the revenue mix of the guest stays, for example, meaning that Airbnb could have seen a 10% drop in per-guest revenue this New Year’s Eve — even with more guest stays — and we’d have no idea.

So, the cliche about grains of salt and taking, please.

But as more guests tends to mean more rentals which points towards more revenue, the New Year’s Eve figures are useful as we work to understand how quickly Airbnb is growing now compared to how fast it grew in the past. The faster the company is expanding today, the more it’s worth. And given recent news that the company has ditched profitability in favor of boosting its sales and marketing spend (leading to sharp, regular deficits in its quarterly results), how fast Airbnb can grow through higher spend is a key question for the highly-backed, San Francisco-based private company.

Here’s the tally of guest stays in Airbnb’s during New Years Eve (data via CNBC, Jon Erlichman, Airbnb), and their resulting year-over-year growth rates:

  • 2009: 1,400
  • 2010: 6,000 (+329%)
  • 2011: 3,1000 (+417%)
  • 2012: 108,000 (248%)
  • 2013: 250,000 (+131%)
  • 2014: 540,000 (+116%)
  • 2015: 1,100,000 (+104%)
  • 2016: 2,000,000 (+82%)
  • 2017: 3,000,000 (+50%)
  • 2018: 3,700,000 (+23%)
  • 2019: 4,500,000 (+22%)

In chart form, that looks like this:

Let’s talk about a few things that stand out. First is that the company’s growth rate managed to stay over 100% for as long as it did. In case you’re a SaaS fan, what Airbnb pulled off in its early years (again, using this fun proxy for revenue growth) was far better than a triple-triple-double-double-double.

Next, the company’s growth rate in percentage terms has slowed dramatically, including in 2019. At the same time the firm managed to re-accelerate its gross guest growth in 2019. In numerical terms, Airbnb added 1,000,000 New Year’s Eve guest stays in 2017, 700,000 in 2018, and 800,000 in 2019. So 2019’s gross adds was not a record, but it was a better result than its year-ago tally.

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