Slowly but surely, cyber security is evolving from the days of castles and moats into the modern era of software driven business. In the 1990s, after several failed attempts to build secure operating systems, the predominant security model became the network-perimeter security model enforced by firewalls. The way it works is clear: Machines on the inside of the firewall were trusted, and anything on the outside was untrusted. This castle-and-moat approach failed almost as quickly as it began, because holes in the wall had to be created to allow emerging internet services like mNews, email and web traffic through.
Artificial intelligence will replace large teams of tier-1 SOC analysts who today stare at endless streams of threat alerts.
With a security wall that quickly became like Swiss cheese, machines on both sides were still vulnerable to infection and the antivirus industry emerged to protect them. The model for antivirus then and now is to capture an infection, create a signature, and then distribute it widely to “immunize” other machines from getting infected by the same malware. This worked for vaccines, so why not try for cyber security?
Fast-forward to 2016, and the security industry hasn’t changed much. The large security companies still pitch the castle-and-moat model of security — firewalls and signature-based detection — even though employees work outside the perimeter as much as inside. And in spite of the fact that most attacks today use one-and-done exploit kits, never reusing the same malware again. In other words, the modern work force coupled with modern threats has rendered traditional security techniques obsolete.
Software is eating security
While most enterprises today still employ these dated security techniques, a new model of security based on artificial intelligence (AI) is beginning to take root in organizations with advanced security programs. Necessity is the mother of invention, and the necessity for AI in security became obvious when three phenomena emerged: (1) The failure of signature-based techniques to stop current threats; (2) the voluminous amounts of security threat data; and (3) the scalability challenges in addressing security threat data with people.
“Software is eating the world,” the noted venture capitalist Marc Andreessen famously said in 2011 about such obvious examples as Amazon, Uber and Airbnb disrupting traditional retail and consumer businesses. The security industry is ripe for the same kind of disruption in the enterprise space, and ultimately in the consumer product space. Artificial intelligence will replace large teams of tier-1 SOC analysts who today stare at endless streams of threat alerts. Machines are far better than humans at processing vast amounts of data and finding the proverbial needle in the haystack.
Artificial Intelligence is experiencing a resurgence in commercial interest because of breakthroughs with deep learning neural networks solving practical problems. We’ve all heard about IBM’s Watson winning at “Jeopardy,” or making difficult medical diagnoses by leveraging artificial intelligence. What is less well known is that Watson has recently undergone a major deep learning upgrade, as well, allowing it to translate to and from many languages, as well as perform text to speech and speech to text operations flawlessly.
Many of us interact with deep learning algorithms unwittingly when we see TV show and movie recommendations on Netflix based on what we’ve viewed previously or when your Mac properly identifies everyone in a picture uploaded from your phone. Or when we ask Alexa a question and Amazon Echo gives an intelligent response — likewise for Cortana and Siri. And one of the most hotly debated topics in machine learning these days is self-driving cars, like Tesla’s amazing Model S.
Deep learning allows a machine to think more like a human. For instance, a child can easily distinguish a dog from a cat. But to a machine, a dog is just a set of pixels and so is a cat, which makes the process of distinguishing them very hard for a machine. Deep learning algorithms can train on millions of pictures of cats and dogs so that when your in-house security camera sees the dog in your house, it will know that it was Rover, not Garfield, who knocked over the vase.
With deep learning, today’s next-generation security products can identify and kill malware as fast as the bad guys can create it.
The power of deep learning becomes clear when you consider the vast speed and processing power of modern computers. For instance, it takes a child a few years to learn the difference between a house cat and a dog. And if that child grew up to be a cat “expert,” it would take Gladwell’s 10,000 hours to become a feline whisperer. The amount of time it takes to expose a human to all of the training data necessary to classify animals with near perfection is long. In contrast, a deep learning algorithm paired with elastic cloud computing resources can consume hundreds of millions of samples of training data in hours, to create a neural network classifier so accurate and so fast that it would outperform even the most highly trained human experts.
What’s more fascinating than this new technology allowing machines to think like a human, is allowing machines to act like a human. Since the 1950s, we’ve been fascinated with the notion that robots might one day be able to think, act and interact with us as our equals. With advances in deep learning, we’re one giant step closer to that reality. Take the Google Brain Team’s DeepDream research, for instance, which shows that machines trained in deep learning can create beautiful pieces of art, in a bizarre form of psychedelic machine “dreaming.” For the first time, we see incredible creativity from machines because of deep learning, as well as the ability to make decisions with incredible accuracy.
Because of this ability to make classification decisions with incredible accuracy, deep learning is leading a renaissance in security technologies by using the technology to identify unknown malware from benign programs. Like the examples above, this is being done by training the deep learning neural networks on tens of millions of variants of malware, as well as on a representative sample of known benign programs.
The results are industry-changing, because unlike legacy security products that provided protection either through prior knowledge of a threat (signature-based) or via segmentation and separation, today’s next-generation security products can identify and kill malware as fast as the bad guys can create it. Imagine a world where security technologies actually enable more sharing rather than less, and allow a more open approach to data access rather than restrictive. This is the direction deep learning is allowing us to go.
Are you ready?
Disruption is clearly coming to the security space. The market has been waiting for better technology that can keep pace with the fast-evolving adversarial threat. Breakthroughs in deep learning artificial neural networks are now stopping attacks previously unseen in real time before they even have a chance to run. It’s time to get on-board with a new generation of technology that is disrupting traditional castle-and-moat security models.
Tata Communications launched the 2016 F1 Connectivity Innovation Prize, focusing on how virtual reality (VR) or augmented reality (AR) technologies could be used to make the sport more immersive for fans, and help the teams work more effectively together in the run-up to and during each Grand Prix.
The aim of the $50,000 prize is to inspire fans worldwide to harness their technical know-how and passion for F1 racing to drive innovation in the sport through two technology challenges.
Tata Communications is the Official Connectivity Provider of Formula 1, enabling the sport to seamlessly reach its tens of millions of fans across the globe.
The first challenge, set by Formula One Management, calls on technology enthusiasts to develop a solution that uses VR and AR to enable fans at home to experience a Grand Prix virtually.
The solution should allow fans who are not at the live event to immerse themselves into the exhilarating world of F1 racing – from the pit lane and the Formula One Paddock Club, to the drivers’ parade and the starting grid formation.
“We want to give as many fans as possible the opportunity to experience first-hand the thrill of a Grand Prix – and VR or AR could enable us to do just that,” said John Morrison, CTO of Formula One Management and one of the judges.
“These technologies represent the next big innovation opportunity for the sport. In the not-too-distant future, they could enable fans to get virtually transported to a Grand Prix, complementing and enriching the race experience,” said Morrison.
Julie Woods-Moss, Tata Communications’ CMO and CEO of its NextGen Business, said that in the last two years, the F1 Connectivity Innovation Prize has grown into a major platform for showcasing the huge potential of data and superfast connectivity in boosting F1 teams’ competitiveness, and in bringing fans closer to the sport
“We now invite fans from all over the world to share their ideas for how VR and AR could take fan engagement to the next level,” she said.
The market for augmented and virtual reality technology continues to heat up, and now one of the more promising startups making both AR hardware and software has raised a $50 million round to keep up the pace.
Meta, which makes an AR headset/glasses of the same name, as well as software to run on it, has raised $50 million in a Series B round of funding. The company plans to use the money to continue building out its technology, developing apps, expanding into new markets like China, and working on the next generation of its headset, the Meta 3 — according to a short statement announcing the round. The news comes just ahead of the E3 gaming conference kicking off this week, where we may see yet more AR and VR news emerge.
This latest round includes investments from Horizons Ventures Limited (which led its $23 million Series A round), as well as a list that includes several strategic backers with several specifically out of China: Lenovo, Tencent, Banyan Capital, Comcast Ventures, and GQY.
Meta is not disclosing its valuation, but filing documents provided to us by VC Expertspoints to a valuation of up to $307 million post-money for this latest round (the actual valuation depends on how many of the authorized preferred as well as common shares were issued). The Series B originally started as a $40 million round and then expanded before it closed.
Meta was founded in 2012 and is based out of Redwood City, but also has an R&D operation in Israel, where its founders hail from originally.
Many VR and AR companies tend to focus on the software end of the spectrum, developing content and technology to produce more engaging and realistic (and potentially less nauseating) experiences not just for smartphones and other screens but newer products like the Oculus Rift, Samsung VR and HTC Vive — devices that appear to be taking a lead in this still-nascent market to tap into more immersive games and other consumer media, as well as more practical enterprise applications.
Some of the most interesting of that group of software startups are getting snapped up by companies that want to make a mark in this area.
Meta is taking a different route: a vertically integrated approach in which it is using its own software development (which is heavy on computer vision, machine learning, and AI based on neuroscience) that works on hardware of its own design, which lets you immerse yourself in virtual situations that are embedded in real environments, giving you the ability to manipulate the virtual elements with gestures and other hand movements.
Taking the vertical route a road less travelled, but not entirely unpopulated. In addition to the likes of Facebook-owned Oculus, apparently Magic Leap — which is still in stealth but nonetheless valued at $4.5 billion after its last round — is also building its AR approach end-to-end, and from the ground up.
Interestingly, the investors think that Meta, despite its far more modest fundraising, could give Magic Leap a run for its money.
“In our view, Meta has built a world-class team,” said Bin Yue, Founding Partner of Banyan Capital, in a statement. “Meta is probably the only startup which has the capabilities to compete with giant companies’ projects like Microsoft Hololens and Magic Leap.”
Back when Meta was more of an idea than a publicly available product, I met Meron Gribetz, Meta’s CEO, for a demo of its prototypes and saw that he had an incredibly focused and singular vision of how he wanted to develop the company. The headset they were working on, he said at the time, was something they wanted to be easy enough to use that it could be attainable by the mass market. That was years ago, and so it’s great to see them coming along so far.
“It is incredibly gratifying to have the support of big thinkers and investors who understand the importance of creating a new human-computer interface, anchored in science. Our… investors really get what we’re doing and why Meta is different from the other players in AR,” he said in a statement today. “They understand that the combination of our advanced optical engines along with our neuroscience-based interface design approach are what will create a computing experience that is 100 times easier to use and more powerful than traditional form factors.”
Meta’s funding is a sign of how investors are keen to get in early in what is still far from a mainstream industry, but also a mark of how no one is quite sure which way it will develop.
“Augmented reality represents a transformational platform for communication, collaboration and how individuals will work in the future,” said Michael Yang, Managing Director at Comcast Ventures, in a statement. “Meta’s platform enables a host of new ways to conduct business across a wide array of industries. We look forward to supporting Meta as our first investment in the AR market.”
While several of the investors in this round are based out of China, the GQY involvement in particular will see Meta making some significant inroads to China.
“Through the investment in Meta, GQY is looking to bring the best-in-class Augmented Reality applications to China,” said Jier Yuan, VP, North America, GQY, in a statement. “This goal will be achieved by leveraging Meta’s leading-edge AR hardware, software and GQY’s in-depth knowledge and relationships in industrial training, public transportation and education sectors in China.”
The health care industry is turning to high tech to help consumers think healthy.
Even with hacking threats and privacy breaches everywhere, technology and health companies are using connected health — an emerging field that links patients and doctors remotely — to boost health care analysis and diagnoses.
With that in mind, the AT&T Foundry for Connected Health opened last week, with a goal to use the internet of things, another hot technology field, to innovate the health care space.
AT&T’s Foundry which resides inside Texas Medical Center’s Innovation Institute in Houston, is currently developing technology like a connected wheelchair to monitor patients in real-time. The company is also working on an electroencephalogram headband, a vital signs monitoring device, to detect patient discomfort.
Chris Penrose, senior vice president of AT&T’s Internet of Things division, said that by connecting things that haven’t been connected before, caregivers and doctors will have the ability to better monitor patients. They can also improve overall patient life, both at home and at health care facilities.
“This is a real way we can bridge together what you’re doing in your home with the health care ecosystem to provide a better experience for that patient,” Penrose told CNBC’s “Closing Bell“.
The overall connected health market is expected to see huge growth in the coming years. A 2015 report by MarketResearch.com, estimated the health care internet of things is poised to hit $117 billion within the next several years.
Robert Graboyes, senior research fellow at the Mercatus Center at George Mason University, predicts connected health care will be a dominate form of medicine in a few years — especially when looking at millennials who are comfortable dealing with electronic devices, he said.
“There is a convergence of technology that is opening up — big data, artificial intelligence — and it’s allowing doctors to identify patterns in health that wouldn’t have been available to intuitive practitioners,” Graboyes said.
Although connected health is a growing industry, with things like artificial intelligence and robotics entering the realm and building excitement, the overall idea is not a new phenomenon.
Analyst Tom Carroll, managing director at Stifel, said that health information technology has been through many cycles. Those precursors have spurred developments like electronic data and record keeping that are hallmarks of the health industry.
Carroll added that recent advancements in technology makes today feel like another revolution in the health care space.
Dr. Steven C. Garner, chairman of radiology at New York Methodist Hospital, told CNBC that connected health innovations are not only beneficial for collecting and reporting data, they can also be beneficial for the hospital, helping cash-strapped institutions to save money.
Garner said health tech in hospitals actually saves the hospital money, because doctors can better monitor patients and get second opinions from other medical professionals who may not be physically in the building. That ultimately can lead to quicker discharge times for patients.
The use of some robotics in surgery, Garner said, can also cut down on complications. He noted some doctors will use robots that can perform surgical tasks that result in less bleeding and fewer complications for certain surgeries.
“The accuracy of the technology can help cut down on a lot of problems,” Garner said.
In advertising, how often do we get a chance to explore something completely new, where no rules apply and where the experience needs to be imagined from start to finish? Telling a story, selling a product and leading a user inside a VRad environment was previously uncharted territory.
While exploring this new medium, we quickly realized that VR holds a huge opportunity for all types of advertisers — if they understand how to harness it.
Despite knowing what kind of experience we want to provide when designing a VR ad, we learned that doing so has its fair share of challenges. For example, we discovered that images or content placed at the bottom or top of the VR ad tend to warp, and we learned quickly to keep those areas for the background image only. Despite the challenges, especially when it came to finding the right design elements, it has been a fascinating process from Day One.
Naturally, it is still very early in the evolution of this new medium, and it may take a bit of time for it to reach the masses. But, these early VR ad experiments show that this technology could be the holy grail for marketers and brand advertising in terms of unparalleled brand engagement and a whole new level of interactivity and awareness.
Let’s dive deeper into why VR could be a huge deal for brands.
Firstly, the option to immerse a user in a brand, or a brand message, is something that we simply couldn’t do before. On TV, online or on mobile, there is still a barrier in the form of the physical device screen between the ad and the user.
With virtual reality, we have a tool that can turn into an incredibly powerful selling channel.
In virtual reality, we can engulf the user in the brand, and place them in practically any scenario that we imagine. Promoting new basketball sneakers? Put the user in the shoes of the best basketball player in the world during a game at Madison Square Garden. The sensation of true presence can only be produced in VR — and all of our senses react to it. This capability is incredibly powerful for any ad campaign.
Secondly, the ability to track, analyze and understand if and how a message made its way to the user is more in-depth and detailed in VR than in any other medium. On TV, we can get a general sense if a user saw the ad; on the web, we are able to track clicks and post-click activity; mobile allows us to track ad activity based on location and device.
With VR, we will be able to track where the user is actually looking within the ad environment we’ve built. Moreover, we’re making strides in tracking and analyzing real human emotions that are experienced inside the VR environment, adding an incredibly valuable and powerful layer to analytics and tracking.
Lastly, interactivity and user engagement inside VR goes way beyond what’s currently available on other platforms. When the user can feel as though they are a real part of an ad and actually interact, touch and play, they are able to engage with the product on a whole new level. While we have seen ad interactivity begin to emerge in online and mobile ads, they are still missing the crucial element that only VR can offer — letting the user exist within the ad itself. With virtual reality, we have a tool that can turn into an incredibly powerful selling channel.
It’s certainly not only brands and advertisers that can benefit from VR. Virtual reality and the entire VRecosystem has a lot to gain from top advertisers and brands entering the industry, bringing with them a lot of spending that can drive a VR-based “free-to-play” economy. This will allow VR publishers to create amazing, top-quality content, monetize it with gorgeous, interactive ads and distribute it for free.
Free content, and, most importantly, quality content, will be the driving force for mass consumer adoption ofVR. If all apps, games and experiences are behind a paywall, it will hinder VR adoption and deter people from testing and exploring this new medium.
With VR, we have a win-win situation. Brands will gain access to what is potentially the most powerful advertising medium in history (though it will take time to learn how to do it right), and publishers can start building incredible VR experiences without burdening themselves with paid distribution and the low download counts that go along with it.
The VR industry is still working out a few kinks — like proper distribution channels. But in the very near future, this ecosystem will have all the ingredients it needs to grow — and thrive.
Living cells are capable of performing complex computations on the environmental signals they encounter.
These computations can be continuous, or analogue, in nature — the way eyes adjust to gradual changes in the light levels. They can also be digital, involving simple on or off processes, such as a cell’s initiation of its own death.
Synthetic biological systems, in contrast, have tended to focus on either analogue or digital processing, limiting the range of applications for which they can be used.
But now a team of researchers at MIT has developed a technique to integrate both analogue and digital computation in living cells, allowing them to form gene circuits capable of carrying out complex processing operations.
The synthetic circuits, presented in a paper published today in the journal Nature Communications, are capable of measuring the level of an analogue input, such as a particular chemical relevant to a disease, and deciding whether the level is in the right range to turn on an output, such as a drug that treats the disease.
In this way they act like electronic devices known as comparators, which take analogue input signals and convert them into a digital output, according to Timothy Lu, an associate professor of electrical engineering and computer science and of biological engineering, and head of the Synthetic Biology Group at MIT’s Research Laboratory of Electronics, who led the research alongside former microbiology PhD student Jacob Rubens.
“Most of the work in synthetic biology has focused on the digital approach, because [digital systems] are much easier to program,” Lu says.
However, since digital systems are based on a simple binary output such as 0 or 1, performing complex computational operations requires the use of a large number of parts, which is difficult to achieve in synthetic biological systems.
“Digital is basically a way of computing in which you get intelligence out of very simple parts, because each part only does a very simple thing, but when you put them all together you get something that is very smart,” Lu says. “But that requires you to be able to put many of these parts together, and the challenge in biology, at least currently, is that you can’t assemble billions of transistors like you can on a piece of silicon,” he says.
The mixed signal device the researchers have developed is based on multiple elements. A threshold module consists of a sensor that detects analogue levels of a particular chemical.
This threshold module controls the expression of the second component, a recombinase gene, which can in turn switch on or off a segment of DNA by inverting it, thereby converting it into a digital output.
If the concentration of the chemical reaches a certain level, the threshold module expresses the recombinase gene, causing it to flip the DNA segment. This DNA segment itself contains a gene or gene-regulatory element that then alters the expression of a desired output.
“So this is how we take an analogue input, such as a concentration of a chemical, and convert it into a 0 or 1 signal,” Lu says. “And once that is done, and you have a piece of DNA that can be flipped upside down, then you can put together any of those pieces of DNA to perform digital computing,” he says.
The team has already built an analogue-to-digital converter circuit that implements ternary logic, a device that will only switch on in response to either a high or low concentration range of an input, and which is capable of producing two different outputs.
In the future, the circuit could be used to detect glucose levels in the blood and respond in one of three ways depending on the concentration, he says.
“If the glucose level was too high you might want your cells to produce insulin, if the glucose was too low you might want them to make glucagon, and if it was in the middle you wouldn’t want them to do anything,” he says.
Similar analogue-to-digital converter circuits could also be used to detect a variety of chemicals, simply by changing the sensor, Lu says.
The researchers are investigating the idea of using analogue-to-digital converters to detect levels of inflammation in the gut caused by inflammatory bowel disease, for example, and releasing different amounts of a drug in response.
Immune cells used in cancer treatment could also be engineered to detect different environmental inputs, such as oxygen or tumor lysis levels, and vary their therapeutic activity in response.
Other research groups are also interested in using the devices for environmental applications, such as engineering cells that detect concentrations of water pollutants, Lu says.
Ahmad Khalil, an assistant professor of biomedical engineering at Boston University, who was not involved in the work, says the researchers have expanded the repertoire of computation in cells.
“Developing these foundational tools and computational primitives is important as researchers try to build additional layers of sophistication for precisely controlling how cells interact with their environment,” Khalil says.
The research team recently created a spinout company, called Synlogic, which is now attempting to use simple versions of the circuits to engineer probiotic bacteria that can treat diseases in the gut.
The company hopes to begin clinical trials of these bacteria-based treatments within the next 12 months.
MIT chemists have devised a new way to synthesize a complex molecular structure that is shared by a group of fungal compounds with potential as anticancer agents. Known as communesins, these compounds have shown particular promise against leukemia cells but may be able to kill other cancer cells as well.
The new synthesis strategy, described in the Journal of the American Chemical Society, should enable researchers to generate large enough quantities of these compounds to run more tests of their anticancer activity. It should also allow scientists to produce designed variants of the naturally occurring communesins, which may be even more potent.
“This is just the foundation,” says Mohammad Movassaghi, an MIT professor of chemistry and the paper’s senior author. “We’ve laid the foundation for implementation of this strategy to access other variations, both natural and nonnatural.”
Communesins are a unique family of polycyclic and complex naturally occurring alkaloids. One of the major hurdles to synthesizing communesins in the lab using this new strategy is a chemical reaction in which two large, bulky molecules must be joined together in a step known as heterodimerization.
Movassaghi’s lab, which has been working on this type of synthesis for several years, was inspired by the way related compounds are produced in nature. The details of the natural synthesis are not fully known, but it is believed that it also involves a heterodimerization step. In fungi, there is evidence that an enzyme catalyzes this reaction.
Without an enzyme, the heterodimerization required to produce communesins is difficult to carry out because it requires forming a bond between two carbon atoms that are each already bonded to four other atoms, some of which have additional bulky groups attached to them. This makes it challenging to bring the two molecules close enough for them to fuse together.
To overcome this, Movassaghi’s lab developed an approach in which they transform the two carbon atoms into carbon radicals (carbon atoms with one unpaired electron). To create these radicals, the researchers first attach each of the targeted carbon atoms to a nitrogen atom, and these two nitrogen atoms bind to each other.
When the researchers shine certain wavelengths of light on the reactants, it causes the two atoms of nitrogen to break away as nitrogen gas, leaving behind two very reactive carbon radicals that join together almost immediately.
“If you break the carbon-nitrogen bond, the intermediate has a very short lifetime. We predict it to be roughly on the order of picoseconds,” Movassaghi says. “Dinitrogen pops out and now you have two radicals in very close proximity.”
Once the heterodimer is formed, three more chemical steps are required, including the transfer of a nitrogen-containing chemical group from one carbon atom to another.
“Just heterodimerizing is only half the battle,” Movassaghi says. “There were two major challenges in this successful synthesis. One was how do you get to a heterodimer, and once you fuse the two halves together, how do you guide the rearrangement to match the structure that you find in nature?”
In this study, the MIT team prepared a key precursor that was converted to the compound known as communesin F in only five steps. The critical heterodimer rearrangement step proceeded to yield 82 percent of the desired heptacyclic communesin structure.
Scott Miller, a professor of chemistry at Yale University, describes the new approach as “a masterful synthesis.”
“The strategy is incredibly ambitious and reflects a sophisticated assessment of the plausible biosynthetic precursor. This is really very clever, since these pathways are typically not known at the level of complete understanding, so outstanding intuition and creativity are required,” says Miller, who was not involved in the research.
This strategy can also be used to produce related communesins, including variants not found in nature.
“Nature has likely evolved these compounds for chemical defense or signaling between different organisms, but if we’re thinking about their potential for treatment of human disease, we may need to access nonnatural derivatives,” Movassaghi says. “Our ability to go in with pinpoint accuracy and make structural variations to these complex alkaloids is going to be helpful in enabling the thorough evaluation of these compounds and related derivatives.”
The study was conducted by graduate student Matthew Pompeo and former postdocs Stephen Lathrop and Wen-Tau Chang. The project was funded by the National Institutes of Health and the National Science Foundation.
Freenome, a year-old liquid biopsy diagnosis platform that detects the cell-free DNA sequencing of cancer, has landed $5.5 million in seed funding led by Andreessen Horowitz, with participation from Founders Fund, Data Collective, and Third Kind Venture Capital.
The deal is a bit of a coup, coming as it does from Andreessen Horowitz’s months-old, $200 million Bio Fund. The vehicle, led by longtime Stanford professor Vijay Pande, has now made a handful of investments (almost all undisclosed). But its stamp of approval for Freenome is meaningful given the number of liquid biopsy companies that Pande is seeing and not funding.
The technology is “very hot,” says Pande. The reason why, he explains, is that beyond the first challenge of catching cancer with liquid biopsies instead of by extracting tissue (which entrepreneurs are solving), and beyond the second challenge of detecting cancer from DNA (which is also being done), the biggest challenge in medical testing today is pinpointing exactly where a cancer is growing and how serious a threat it is. He calls it part of the “holy grail.”
The “cure to cancer isn’t going to look like another drug,” says Pande. “It will be our ability to predict that someone has cancer far before traditional means, then giving [those diagnosed with the disease] existing drugs. At least 80 percent or more of cancers could be treated successfully if only they were caught ahead of time.”
Apparently, Freenome has come the closest that Pande has seen to striking on the right understanding of both computer science and biology to detect the mutations that make it possible to diagnose particular cancers — and determine the best course of treatment for them based on their composition.
Freenome cofounder and CEO Gabe Otte says the “big differentiator here is that our technology allows us to answer these additional questions because we’re looking at different biologies. Other companies are capturing a small fraction of DNA fragments to determine: cancer or not cancer. . . But we realized early on that if there was going to be a successful biopsy test that could also impact treatment, we need to answer many more questions. We wanted to answer not just cancer or not cancer, but malignant or benign, and where the tissue is. So we capture all the [genetic material floating in our blood] rather than fixating on a few mutations known to be associated with cancer.”
Not that it’s a slam dunk. Even Otte admits that while the young company has validated its tests with hundreds of samples, and that it’s “likely to work on thousands and tens of thousands of samples,” what Freenome didn’t want to do is “blow $100 million” in venture capital on its platform before its technology is proven beyond a doubt. (Presumably, that “$100 million” number is a reference to companies like Guardant Health that have raisedbig-league rounds in recent years. Guardant makes a non-invasive genomic sequencing test for cancer.)
Pande doesn’t seem overly concerned that Freenome will flop. He says he has met with its five-person team “many times over the last nine months. I’ve seen their trajectory. And while there is work to do, they are moving very fast.”
MIT biological engineers have created a programming language that allows them to rapidly design complex, DNA-encoded circuits that give new functions to living cells.
Using this language, anyone can write a program for the function they want, such as detecting and responding to certain environmental conditions. They can then generate a DNA sequence that will achieve it.
“It is literally a programming language for bacteria,” says Christopher Voigt, an MIT professor of biological engineering. “You use a text-based language, just like you’re programming a computer. Then you take that text and you compile it and it turns it into a DNA sequence that you put into the cell, and the circuit runs inside the cell.”
Voigt and colleagues at Boston University and the National Institute of Standards and Technology have used this language, which they describe in the April 1 issue of Science, to build circuits that can detect up to three inputs and respond in different ways. Future applications for this kind of programming include designing bacterial cells that can produce a cancer drug when they detect a tumor, or creating yeast cells that can halt their own fermentation process if too many toxic byproducts build up.
The researchers plan to make the user design interface available on the Web.
No experience needed
Over the past 15 years, biologists and engineers have designed many genetic parts, such as sensors, memory switches, and biological clocks, that can be combined to modify existing cell functions and add new ones.
However, designing each circuit is a laborious process that requires great expertise and often a lot of trial and error. “You have to have this really intimate knowledge of how those pieces are going to work and how they’re going to come together,” Voigt says.
Users of the new programming language, however, need no special knowledge of genetic engineering.
“You could be completely naive as to how any of it works. That’s what’s really different about this,” Voigt says. “You could be a student in high school and go onto the Web-based server and type out the program you want, and it spits back the DNA sequence.”
The language is based on Verilog, which is commonly used to program computer chips. To create a version of the language that would work for cells, the researchers designed computing elements such as logic gates and sensors that can be encoded in a bacterial cell’s DNA. The sensors can detect different compounds, such as oxygen or glucose, as well as light, temperature, acidity, and other environmental conditions. Users can also add their own sensors. “It’s very customizable,” Voigt says.
The biggest challenge, he says, was designing the 14 logic gates used in the circuits so that they wouldn’t interfere with each other once placed in the complex environment of a living cell.
In the current version of the programming language, these genetic parts are optimized for E. coli, but the researchers are working on expanding the language for other strains of bacteria, including Bacteroides, commonly found in the human gut, and Pseudomonas, which often lives in plant roots, as well as the yeast Saccharomyces cerevisiae. This would allow users to write a single program and then compile it for different organisms to get the right DNA sequence for each one.
Using this language, the researchers programmed 60 circuits with different functions, and 45 of them worked correctly the first time they were tested. Many of the circuits were designed to measure one or more environmental conditions, such as oxygen level or glucose concentration, and respond accordingly. Another circuit was designed to rank three different inputs and then respond based on the priority of each one.
One of the new circuits is the largest biological circuit ever built, containing seven logic gates and about 12,000 base pairs of DNA.
Another advantage of this technique is its speed. Until now, “it would take years to build these types of circuits. Now you just hit the button and immediately get a DNA sequence to test,” Voigt says.
His team plans to work on several different applications using this approach: bacteria that can be swallowed to aid in digestion of lactose; bacteria that can live on plant roots and produce insecticide if they sense the plant is under attack; and yeast that can be engineered to shut off when they are producing too many toxic byproducts in a fermentation reactor.
The lead author of the Science paper is MIT graduate student Alec Nielsen. Other authors are former MIT postdoc Bryan Der, MIT postdoc Jonghyeon Shin, Boston University graduate student Prashant Vaidyanathan, Boston University associate professor Douglas Densmore, and National Institute of Standards and Technology researchers Vanya Paralanov, Elizabeth Strychalski, and David Ross.
An MIT spinout, Synlogic, is aiming to create a new class of medicines, by re-programming bacteria found in the gut as “living therapeutics.”
Based on research by its co-founders, MIT professors Tim Lu and Jim Collins, Synlogic creates so-called synthetic biotics, which sense and correct metabolic abnormalities that underlie some major diseases and rare genetic disorders.
Human intestines are filled with trillions of bacteria, collectively called the microbiota, that carry out vital health functions. Synlogic’s synthetic biotics — capsules, liquid suspensions, or other dosage forms that can be taken regularly — augment the microbiota with new metabolic capabilities or complement lost functionality in organs such as the liver.
“Over the past decade or so, the intricate connections between microbes and our bodies have become clearer and clearer, and it’s well known now that the bacteria that live in our gut have a major influence on human health,” says Lu, an associate professor of electrical engineering and computer science and of biological engineering, and head of MIT’s Synthetic Biology Group, who serves as scientific advisor for Synlogic. “We leverage that interface as a way of treating human disease.”
Last month, Synlogic raised an additional $40 million in venture capital and secured its first industry partnership with pharmaceutical giant AbbVie. For the partnership, Synlogic will collaborate with AbbVie to develop synthetic biotics for the potential treatment of inflammatory bowel disease, which may include probiotic microbes programmed to detect intestinal inflammation, and produce anti-inflammatory molecules or break down pro-inflammatory effectors.
Two of Synlogic’s main candidate drugs, expected to enter clinical trials during the next 12 months, treat rare genetic metabolic disorders. One drug candidate is for treating urea cycle disorder (UCD), which is caused by an enzyme deficiency that leads to a buildup of toxic ammonia in the blood. The other is for treating phenylketonuria (PKU), which involves a dangerous excess of the amino acid phenylalanine due to a mutation in another metabolic enzyme. In both cases, Synlogic’s drugs process and flush out the toxic metabolites from the body.
Think of Synlogic’s drugs like biological thermostats, says Collins, the Termeer Professor of Medical Engineering and Science in MIT’s Department of Biological Engineering and Institute for Medical Engineering and Science, who also chairs Synlogic’s scientific advisory board. Instead of identifying and regulating the temperature of a room, he says, “The synthetic biotics detect and regulate the amount of an enzyme or metabolic byproduct in a patient’s body.”
Programming E. coli
For more than a decade at Boston University and MIT, Collins and Lu (who is Collins’ former student) have been developing “genetic circuits” for bacteria, which include on/off switches made with synthetic DNA or RNA sequences that instruct the bacteria to count, store memory, and even perform logic.
Collins and Lu have used these genetic circuits to program bacteria to seek and cure infection. In 2011, this approach earned Collins funding from the Bill and Melinda Gates Foundation to engineer bacteria to detect cholera and produce targeted antimicrobial peptides to treat it.
A few years ago, Lu and Collins, along with several venture capitalists, launched Synlogic to focus on commercializing “a new class of therapeutics based on living cells,” Collins says. In 2014, Synlogic came out of stealth mode, securing $30 million in funding from venture firms and the Gates Foundation.
Since then, Synlogic has worked primarily on programming E. coliNissle, a strain of bacteria derived from the gut that is also used widely and safely as a probiotic. The programmed E. coliNissle, Lu says, provides greater precision, safety, and efficacy for disease treatment, compared with traditional methods.
For inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis, for instance, current treatments include small-molecule drugs or antibodies with anti-inflammatory properties. But the challenge is getting the right dosage, Lu says. “If you apply too little, it’s not going to work. If you apply too much, you have a chance you may immunosuppress the patient and cause side effects,” he says.
Synlogic can “program microbes to detect inflammation and make anti-inflammation molecules at the site of inflammation, as well as produce molecules that positively impact immune system function,” Collins says.
Then there’s the more rare but debilitating urea cycle disorder, which affects 2,000 to 6,000 people in the United States and impairs their ability to processes ammonia. If ammonia builds up too much and reaches the brain, it can lead to brain damage, coma, and death. The best available treatment option for people with UCD today is a liver transplant.
Synlogic aims to treat UCD with a daily biotic that functions in a surprising way: “It can decrease the ammonia in the bloodstream, without even contacting the blood,” Lu says.
Ammonia levels in the bloodstream, he explains, are dependent on ammonia production in the large intestine. Synlogic’s biotic converts intestinal ammonia into an amino acid, which is flushed out of the body through the stool, thereby dramatically reducing the flow of ammonia to the blood and reducing ammonia levels in the bloodstream.
Synlogic’s biotic for PKU, which affects 13,000 people in the United States, functions in a similar way, to regulate the processing and extraction of phenylalanine. PKU patients must adhere to a lifelong, extremely low-protein diet that can result in serious developmental disorders, because they can’t eat normal foods that contain phenylalanine — including many meat, dairy, and seafood products. “If we can degrade phenylalanine with convenient administration of this probiotic, that will change the course of this disease,” Lu says.
Collins says Synlogic has potential to treat many other rare genetic metabolic disorders. But the recent AbbVie deal, he says, also “opens up possibilities of using these microbes to produce biologics or other small molecules to treat a range of conditions.” These include cardiovascular disease and autoimmune, oncology, and central nervous system disorders, which have been linked to metabolic dysregulation.
Reaching clinical efficacy
Part of the reason that probiotic treatments are not used for serious diseases is their lack of clinically validated efficacy. Synlogic, on the other hand, aims to overcome these efficacy issues with potent and precision-programmed synthetic biotics, Lu says.
For example, in engineering the safe and easily programmable E. coliNissle, Synlogic engineers have designed the microbe to consume a massive amount of toxic metabolites. TheE. coliNissle strain that forms the basis of Synlogic’s UCD program, for instance, can consume orders of magnitude more ammonia than natural E. coli can, Lu says. “For this treatment to work for patients, you want the max performance you can squeeze out of any one of these biotics,” he says.
Based on their preclinical data, Synlogic’s treatments have the potential to reach “clinical levels” of efficacy not seen often in synthetic biology, says Collins: “Synlogic is programming these probiotic microbes to consume ammonia or phenylalanine for example, and they are reaching levels that are expected to be clinically meaningful, which is quite remarkable.”