"There's an app for that." Get ready for a cutting-edge twist on this common phrase. In the life sciences, researchers in the field of synthetic biology are engineering microbes to execute specific tasks, like diagnosing gut inflammation, purifying dirty water, and cleaning up oil spills. Here are five academic and commercial projects underway now that will make you want to add the term "designer bacteria" to your vocab.
1) Bacteria that can sense, diagnose and treat disorders of the gut.
Dr. Pamela Silver at Harvard Medical School has engineered non-pathenogenic strains of E. Coli bacteria, which she calls "living diagnostics and therapeutics," to accurately sense whether an animal has been exposed to antibiotics and whether inflammation is present in its intestines.
Imagine a "living FitBit" that could report on your gut health in real time.
So how does it work? "The bacteria have a genetic switch like a light switch," she explains, "and when they are exposed to an antibiotic or an inflammatory response, the light switch flips to on and the bacteria turn color." In a study that Silver and her colleagues published earlier this year, the bacteria in mouse guts turned blue when exposed to the chemical tetrathionate, which is produced during inflammation. Then, when the animal excreted waste, its feces were also blue. For safety reasons, the excreted bacteria can additionally be programmed to self-destruct so as not to contaminate the environment.
The implications for human health go way beyond a non-invasive alternative to colonoscopies. Imagine "a living FitBit," Silver says with a laugh – a probiotic your doctor could prescribe that could colonize your gut to report on your intestinal health and your diet—and even treat pathogens at the same time. Another potential application is to deploy this new tool in the skin as a living sensor. "Your skin has a defined population of bacteria and those could be engineered to sense a lot," she says, such as pathological changes and toxic environmental exposures.
But one big social question in this emerging research remains how open the public and regulators will be to genetically modified organisms as drugs. Silver says that acceptance will require "patient advocacy, education, and showing these actually work. We have shown in an animal that it can work. So far, in humans, it's unclear."
"Live biotherapeutic products" is a whole new category of drug.
2) Bacteria that can treat a rare metabolic disease.
The startup company Synlogic, based in Cambridge, Mass., has designed an experimental pill containing a strain of E. Coli bacteria that can soak up excess ammonia in a person's stomach, treating those who suffer from toxic elevated blood ammonia levels. This condition, called hyperammonemia, can occur in those with chronic liver disease or genetic urea cycle disorders. The pill is genetically engineered to convert ammonia into a beneficial amino acid instead.
Just a few weeks ago, the company announced positive data from its Phase 1 trial, in which the pill was tested on a group of 52 healthy volunteers for the first time. The study was randomized, double-blind and placebo-controlled, which means that neither the researchers nor the subjects knew who was getting the active pill vs. a sham one. This design is the gold standard in clinical research because it overcomes bias and produces objective results. So far, the pill appears to be safe and well-tolerated, and the company plans to continue the next phase of testing in 2018. Synlogic's treatment stands to be the first of this category of therapy—called "live biotherapeutic products"—that will be scrutinized by the FDA when the time comes for possible market approval.
3) Bacteria that can be sprayed on land to clean up an oil spill.
"This is science fiction, but it's become a lot less science fiction in the last couple of years," says Floyd E. Romesberg, a professor of chemistry whose lab at the Scripps Research Institute in California is on the forefront of synthetic biology.
"We have literally increased the biology that cells can write stories with."
His lab has added two new letters to the code of life. At the most fundamental level, all life on Earth, including human, animal, and bacteria, relies on the four "letters" or chemical building blocks of A, T, C, and G to store biological information inside a cell and then retrieve it in the form of proteins that perform essential tasks. For the first time in history, Romesberg and his team have now developed an unnatural base pair—an X and a Y—capable of storing increased information.
"We have literally increased the biology that cells can write stories with," he says. "With new letters, you can write new words, new sentences, and you can tell new stories, as opposed to taking the limited vocabulary you have and trying to rearrange it."
The implications of his research are immense; applications range from developing therapeutic proteins as drugs, to bestowing cells with new properties, such as oxidizing oil after a spill. He imagines a future scenario in which, for example, specially engineered bacteria are sprayed on a beach, eat the oil for three generations of their life—less than a day—and then die off, since they will be unable to replicate their own DNA. Afterwards, the beach is clean.
"What we are struggling with now is the first steps toward doing that – the cell relying on unnatural information to survive, rather than doing something new yet," he says, "but that's where we are headed."
4) Bacteria that can deliver cancer-killing drugs inside tumors.
Researcher Jeff Hasty at UCSD has engineered a strain of Salmonella bacteria to penetrate cancer tumors and deliver drugs that stop their growth. His approach is especially clever because it solves a major problem in cancer drug delivery: chemotherapy relies on blood vessels for transit, but blood vessels don't exist deep inside tumors. Using this fact to his advantage, Hasty and his team designed bacteria that can sneak drugs all the way into a tumor and then self-destruct, taking the tumor down in the process.
So far, the treatment in mice has been successful; their tumors stopped growing after they were given the bacteria, and along with the use of chemotherapy, their life expectancy increased by half.
Many questions remain in terms of applicability to tumors in human beings, but the notion of a bacterial therapy remains a promising clinical approach for treating cancer in the future.
Craft beer experts couldn't tell the difference between beer brewed with regular vs. recycled water.
5) Bacteria that can convert wastewater into drinkable water.
Boston-based company Cambrian Innovation has a patented product called the EcoVolt MINI that uses microbes to generate energy through contact with electrodes. The company has collaborated with breweries across the country, taking their waste water and converting it to clean water and clean energy. Through the company's bioelectrochemical system, microbes eat the contaminants in the wastewater, and as a byproduct they produce methane, which can be converted to heat and power; in some cases, the process generates enough energy to send some back to the brewery.
"The main goal of the system is to produce cleaner water; the energy is an added product," explains Claire Aviles, Cambrian's marketing and communications manager.
The wastewater treatment is so effective that the water can be made suitable for reuse. One brewery client, for example, recently experimented with using the recycled water to brew a beer at a festival in California. They used the same recipe for two beers—one with typical city water and one with recycled water from Cambrian's system—and offered a side-by-side taste test to consumers and craft beer experts alike.
"Most people couldn't tell which was which," Aviles says.
In fact, most of the tasters preferred the beer brewed with the recycled water.
Turns out bacteria aren't always dirty after all.
When David M. Kurtz was doing his clinical fellowship at Stanford University Medical Center in 2009, specializing in lymphoma treatments, he found himself grappling with a question no one could answer. A typical regimen for these blood cancers prescribed six cycles of chemotherapy, but no one knew why. "The number seemed to be drawn out of a hat," Kurtz says. Some patients felt much better after just two doses, but had to endure the toxic effects of the entire course. For some elderly patients, the side effects of chemo are so harsh, they alone can kill. Others appeared to be cancer-free on the CT scans after the requisite six but then succumbed to it months later.
"Anecdotally, one patient decided to stop therapy after one dose because he felt it was so toxic that he opted for hospice instead," says Kurtz, now an oncologist at the center. "Five years down the road, he was alive and well. For him, just one dose was enough." Others would return for their one-year check up and find that their tumors grew back. Kurtz felt that while CT scans and MRIs were powerful tools, they weren't perfect ones. They couldn't tell him if there were any cancer cells left, stealthily waiting to germinate again. The scans only showed the tumor once it was back.
Blood cancers claim about 68,000 people a year, with a new diagnosis made about every three minutes, according to the Leukemia Research Foundation. For patients with B-cell lymphoma, which Kurtz focuses on, the survival chances are better than for some others. About 60 percent are cured, but the remaining 40 percent will relapse—possibly because they will have a negative CT scan, but still harbor malignant cells. "You can't see this on imaging," says Michael Green, who also treats blood cancers at University of Texas MD Anderson Medical Center.
The new blood test is sensitive enough to spot one cancerous perpetrator amongst one million other DNA molecules.
Kurtz wanted a better diagnostic tool, so he started working on a blood test that could capture the circulating tumor DNA or ctDNA. For that, he needed to identify the specific mutations typical for B-cell lymphomas. Working together with another fellow PhD student Jake Chabon, Kurtz finally zeroed-in on the tumor's genetic "appearance" in 2017—a pair of specific mutations sitting in close proximity to each other—a rare and telling sign. The human genome contains about 3 billion base pairs of nucleotides—molecules that compose genes—and in case of the B-cell lymphoma cells these two mutations were only a few base pairs apart. "That was the moment when the light bulb went on," Kurtz says.
The duo formed a company named Foresight Diagnostics, focusing on taking the blood test to the clinic. But knowing the tumor's mutational signature was only half the process. The other was fishing the tumor's DNA out of patients' bloodstream that contains millions of other DNA molecules, explains Chabon, now Foresight's CEO. It would be like looking for an escaped criminal in a large crowd. Kurtz and Chabon solved the problem by taking the tumor's "mug shot" first. Doctors would take the biopsy pre-treatment and sequence the tumor, as if taking the criminal's photo. After treatments, they would match the "mug shot" to all DNA molecules derived from the patient's blood sample to see if any molecular criminals managed to escape the chemo.
Foresight isn't the only company working on blood-based tumor detection tests, which are dubbed liquid biopsies—other companies such as Natera or ArcherDx developed their own. But in a recent study, the Foresight team showed that their method is significantly more sensitive in "fishing out" the cancer molecules than existing tests. Chabon says that this test can detect circulating tumor DNA in concentrations that are nearly 100 times lower than other methods. Put another way, it's sensitive enough to spot one cancerous perpetrator amongst one million other DNA molecules.
"It increases the sensitivity of detection and really catches most patients who are going to progress," says Green, the University of Texas oncologist who wasn't involved in the study, but is familiar with the method. It would also allow monitoring patients during treatment and making better-informed decisions about which therapy regimens would be most effective. "It's a minimally invasive test," Green says, and "it gives you a very high confidence about what's going on."
Having shown that the test works well, Kurtz and Chabon are planning a new trial in which oncologists would rely on their method to decide when to stop or continue chemo. They also aim to extend their test to detect other malignancies such as lung, breast or colorectal cancers. The latest genome sequencing technologies have sequenced and catalogued over 2,500 different tumor types, says Chabon, which gives the team the opportunity to create more molecular "mug shots."
The team hopes that that their blood cancer test will become available to patients within about five years, making doctors' job easier, and not only at the biological level. "When I tell patients, "good news, your cancer is in remission', they ask me, 'does it mean I'm cured?'" Kurtz says. "Right now I can't answer this question because I don't know—but I would like to." His company's test, he hopes, will enable him to reply with certainty. He'd very much like to have the power of that foresight.
The white two-seater car that rolls down the street in the Sorrento Valley of San Diego looks like a futuristic batmobile, with its long aerodynamic tail and curved underbelly. Called 'Sol' (Spanish for "sun"), it runs solely on solar and could be the future of green cars. Its maker, the California startup Aptera, has announced the production of Sol, the world's first mass-produced solar vehicle, by the end of this year. Aptera co-founder Chris Anthony points to the sky as he says, "On this sunny California day, there is ample fuel. You never need to charge the car."
If you live in a sunny state like California or Florida, you might never need to plug in the streamlined Sol because the solar panels recharge while driving and parked. Its 60-mile range is more than the average commuter needs. For cloudy weather, battery packs can be recharged electronically for a range of up to 1,000 miles. The ultra-aerodynamic shape made of lightweight materials such as carbon, Kevlar, and hemp makes the Sol four times more energy-efficient than a Tesla, according to Aptera. "The material is seven times stronger than steel and even survives hail or an angry ex-girlfriend," Anthony promises.
Co-founder Steve Fambro opens the Sol's white doors that fly upwards like wings and I get inside for a test drive. Two dozen square solar panels, each the size of a large square coaster, on the roof, front, and tail power the car. The white interior is spartan; monitors have replaced mirrors and the dashboard. An engineer sits in the driver's seat, hits the pedal, and the low-drag two-seater zooms from 0 to 60 in 3.5 seconds.
It feels like sitting in a race car because the two-seater is so low to the ground but the car is built to go no faster than 100 or 110 mph. The finished car will weigh less than 1,800 pounds, about half of the smallest Tesla. The average car, by comparison, weighs more than double that. "We've built it primarily for energy efficiency," Steve Fambro says, explaining why the Sol has only three wheels. It's technically an "auto-cycle," a hybrid between a motorcycle and a car, but Aptera's designers are also working to design a four-seater.
There has never been a lack of grand visions for the future of the automobile, but until these solar cars actually hit the streets, nobody knows how the promises will hold up.
Transportation is currently the biggest source of greenhouse gases. Developing an efficient solar car that does not burden the grid has been the dream of innovators for decades. Every other year, dozens of innovators race their self-built solar cars 2,000 miles through the Australian desert.
More effective solar panels are finally making the dream mass-compatible, but just like other innovative car ideas, Aptera's vision has been plagued with money problems. Anthony and Fambro were part of the original crew that founded Aptera in 2006 and worked on the first prototype around the same time Tesla built its first roadster, but Aptera went bankrupt in 2011. Anthony and Fambro left a year before the bankruptcy and went on to start other companies. Among other projects, Fambro developed the first USDA organic vertical farm in the United Arab Emirates, and Anthony built a lithium battery company, before the two decided to buy Aptera back. Without a billionaire such as Elon Musk bankrolling the risky process of establishing a whole new car production system from scratch, the huge production costs are almost insurmountable.
But Aptera's founders believe they have found solutions for the entire production process as well as the car design. Most parts of the Sol's body can be made by 3D printers and assembled like a Lego kit. If this makes you think of a toy car, Anthony assures potential buyers that the car aced stress tests and claims it's safer than any vehicle on the market, "because the interior is shaped like an egg and if there is an impact, the pressure gets distributed equally." However, Aptera has yet to release crash test safety data so outside experts cannot evaluate their claims.
Instead of building a huge production facility, Anthony and Fambro envision "micro-factories," each less than 10,000 square feet, where a small crew can assemble cars on demand wherever the orders are highest, be it in California, Canada, or China.
If a part of the Sol breaks, Aptera promises to send replacement parts to any corner of the world within 24 hours, with instructions. So a mechanic in a rural corner in Arkansas or China who never worked on a solar car before simply needs to download the instructions and replace the broken part. At least that's the idea. "The material does not rust nor fatigue," Fambro promises. "You can pass the car onto your grandchildren. When more efficient solar panels hit the market, we simply replace them."
More than 11,000 potential buyers have already signed up; the cheapest model costs around $26,000 USD and Aptera expects the first cars to ship by the end of the year.
Two other solar carmakers are vying for the pole position in the race to be the first to market: The German startup Sono has also announced it will also produce its first solar car by the end of this year. The price tag for the basic model is also around $26,000, but its concept is very different. From the outside, the Sion looks like a conservative minivan for a family; only a closer look reveals that the dark exterior is made of solar panels. Sono, too, nearly went bankrupt a few years ago and was saved through a crowdfunding campaign by enthusiastic fans.
Meanwhile, Norwegian company Lightyear wants to produce a sleek solar-powered luxury sedan by the end of the year, but its price of around $180,000 makes it unaffordable for most buyers.
There has never been a lack of grand visions for the future of the automobile, but until these solar cars actually hit the streets, nobody knows how the promises will hold up. How often will the cars need to be repaired? What happens when snow and ice cover the solar panels? Also, you can't park the car in a garage if you need the sun to charge it.
Critics, including students at the Solar Car team at the University of Michigan, say that mounting solar panels on a moving vehicle will never yield the most efficient results compared to static panels. Also, they are quick to point out that no company has managed to overcome the production hurdles yet. Others in the field also wonder how well the solar panels will actually work.
"It's important to realize that the solar mileage claims by these companies are likely the theoretical best case scenario but in the real world, solar range will be significantly less when you factor in shading, parking in garages, and geographies with lower solar irradiance," says Evan Stumpges, the team coordinator for the American Solar Challenge, a competition in which enthusiasts build and race solar-powered cars. "The encouraging thing is that I have seen videos of real working prototypes for each of these vehicles which is a key accomplishment. That said, I believe the biggest hurdle these companies have yet to face is successfully ramping up to volume production and understanding what their profitability point will be for selling the vehicles once production has stabilized."
Professor Daniel M. Kammen, the founding director of the Renewable and Appropriate Energy Laboratory at the University of California, Berkeley, and one of the world's foremost experts on renewable energy, believes that the technical challenges have been solved, and that solar cars have real advantages over electric vehicles.
"This is the right time to be bullish. Cutting out the charging is a natural solution for long rides," he says. "These vehicles are essentially solar panels and batteries on wheels. These are now record low-cost and can be built from sustainable materials." Apart from Aptera's no-charge technology, he appreciates the move toward no-conflict materials. "Not only is the time ripe but the youth movement is pushing toward conflict-free material and reducing resource waste....A low-cost solar fleet could be really interesting in relieving burden on the grid, or you could easily imagine a city buying a bunch of them and connecting them with mass transit." While he has followed all three new solar companies with interest, he has already ordered an Aptera car for himself, "because it's American and it looks the most different."
After taking a spin in the Sol, it is startling to switch back into a regular four-seater. Rolling out of Aptera's parking lot onto the freeway next to all the oversized gas guzzlers that need to stop every couple of hundreds of miles to fill up, one can't help but think: We've just taken a trip into the future.