"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.
On the morning of April 12, 1955, newsrooms across the United States inked headlines onto newsprint: the Salk Polio vaccine was "safe, effective, and potent." This was long-awaited news. Americans had limped through decades of fear, unaware of what caused polio or how to cure it, faced with the disease's terrifying, visible power to paralyze and kill, particularly children.
The announcement of the polio vaccine was celebrated with noisy jubilation: church bells rang, factory whistles sounded, people wept in the streets. Within weeks, mass inoculation began as the nation put its faith in a vaccine that would end polio.
Today, most of us are blissfully ignorant of child polio deaths, making it easier to believe that we have not personally benefited from the development of vaccines. According to Dr. Steven Pinker, cognitive psychologist and author of the bestselling book Enlightenment Now, we've become blasé to the gifts of science. "The default expectation is not that disease is part of life and science is a godsend, but that health is the default, and any disease is some outrage," he says.
The Rise and Fall of Public Trust<p>When the polio vaccine was released in 1955, "we were nearing an all-time high point in public trust," says Matt Baum, Harvard Kennedy School professor and lead author of <a href="http://www.kateto.net/covid19/COVID19%20CONSORTIUM%20REPORT%2013%20TRUST%20SEP%202020.pdf" target="_blank" rel="noopener noreferrer"><u>several</u></a> <a href="https://shorensteincenter.org/wp-content/uploads/2020/09/COVID19-CONSORTIUM-REPORT-14-MISINFO-SEP-2020.pdf" target="_blank" rel="noopener noreferrer"><u>reports</u></a> measuring public trust and vaccine confidence. Baum explains that the U.S. was experiencing a post-war boom following the Allied triumph in WWII, a popular Roosevelt presidency, and the rapid innovation that elevated the country to an international superpower.</p><p> The 1950s witnessed the emergence of nuclear technology, a space program, and unprecedented medical breakthroughs, adds Emily Brunson, Texas State University anthropologist and co-chair of the Working Group on Readying Populations for COVID-19 Vaccine. "Antibiotics were a game changer," she states. While before, people got sick with pneumonia for a month, suddenly they had access to pills that accelerated recovery. </p><p>During this period, science seemed to hold all the answers; people embraced the idea that we could "come to know the world with an absolute truth," Brunson explains. Doctors were portrayed as unquestioned gods, so Americans were primed to trust experts who told them the polio vaccine was safe. </p>
The Shift in How We Consume Information<p>In the 1950s, the media created an informational consensus. The fundamental ideas the public consumed about the state of the world were unified. "People argued about the best solutions, but didn't fundamentally disagree on the factual baseline," says Baum. Indeed, the messaging around the polio vaccine was centralized and consistent, led by President Roosevelt's successful <a href="https://files.eric.ed.gov/fulltext/EJ978264.pdf" target="_blank" rel="noopener noreferrer"><u>March of Dimes crusade</u></a>. People of lower socioeconomic status with limited access to this information were <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1551508/?page=3" target="_blank" rel="noopener noreferrer"><u>less likely to have confidence</u></a> in the vaccine, but most people consumed <a href="https://www.c-span.org/video/?506891-1/a-special-report-polio" target="_blank" rel="noopener noreferrer"><u>media that assured them</u></a> of the vaccine's safety and <a href="https://www.cbsnews.com/news/the-salk-polio-vaccine-greatest-public-health-experiment-in-history/" target="_blank" rel="noopener noreferrer"><u>mobilized them</u></a> to receive it. </p><p>Today, the information we consume is no longer centralized—in fact, just the opposite. "When you take that away, it's hard for people to know what to trust and what not to trust," Baum explains. We've witnessed an increase in polarization and the technology that makes it easier to give people what they want to hear, reinforcing the human tendencies to vilify the other side and reinforce our preexisting ideas. When information is engineered to further an agenda, each choice and risk calculation made while navigating the COVID-19 pandemic <a href="https://www.nytimes.com/2020/12/19/opinion/sunday/coronavirus-science.html?referringSource=articleShare" target="_blank" rel="noopener noreferrer"><u>is deeply politicized</u></a>. </p><p>This polarization maps onto a rise in socioeconomic inequality and economic uncertainty. These factors, associated with a sense of lost control, prime people to embrace misinformation, explains Baum, especially when the situation is difficult to comprehend. "The beauty of conspiratorial thinking is that it provides answers to all these questions," he says. Today's insidious fragmentation of news media accelerates the circulation of mis- and disinformation, reaching more people faster, regardless of veracity or motivation. In the case of vaccines, skepticism around their origin, safety, and motivation is intensified. </p><p>Alongside the rise in polarization, Pinker says "the emotional tone of the news has gone downward since the 1940s, and journalists consider it a professional responsibility to cover the negative." Relentless focus on everything that goes wrong further erodes public trust and paints a picture of the world getting worse. "Life saved is not a news story," says Pinker, but perhaps it should be, he continues. "If people were more aware of how much better life was generally, they might be more receptive to improvements that will continue to make life better. These improvements don't happen by themselves."</p>
The Future Depends on Vaccine Confidence<p>So far, the U.S. has been unable to mitigate the catastrophic effects of the pandemic through social distancing, testing, and contact tracing. President Trump has <a href="https://www.washingtonpost.com/politics/bob-woodward-rage-book-trump/2020/09/09/0368fe3c-efd2-11ea-b4bc-3a2098fc73d4_story.html" target="_blank" rel="noopener noreferrer"><u>downplayed the effects and threat of the virus</u></a>, <a href="https://www.washingtonpost.com/outlook/2020/07/14/cdc-directors-trump-politics/" target="_blank" rel="noopener noreferrer"><u>censored experts and scientists</u></a>, <a href="https://www.theatlantic.com/science/archive/2020/06/america-giving-up-on-pandemic/612796/" target="_blank" rel="noopener noreferrer"><u>given up on containing the spread</u></a>, and <a href="https://www.nytimes.com/2020/09/16/world/covid-coronavirus.html" target="_blank" rel="noopener noreferrer"><u>mobilized his base to protest masks</u></a>. The Trump Administration failed to devise a national plan, so our national plan has defaulted to hoping for the <a href="https://www.politico.com/news/2020/08/26/nation-of-miracles-pence-coronavirus-vaccine-rnc-402949" target="_blank" rel="noopener noreferrer"><u>"miracle" of a vaccine</u></a>. And they are "something of a miracle," Pinker says, describing vaccines as "the most benevolent invention in the history of our species." In record-breaking time, three vaccines have arrived. But their impact will be weakened unless we achieve mass vaccination. As Brunson notes, "The technology isn't the fix; it's people taking the technology."</p><p> Significant challenges remain, including facilitating widespread access and supporting on-the-ground efforts to allay concerns and build trust with <a href="https://www.newyorker.com/news/daily-comment/african-american-resistance-to-the-covid-19-vaccine-reflects-a-broader-problem" target="_blank" rel="noopener noreferrer"><u>specific populations with historic reasons for distrust</u></a>, says Brunson. Baum predicts continuing delays as well as deaths from other causes that will be linked to the vaccine. </p><p> Still, there's every reason for hope. The new administration "has its eyes wide open to these challenges. These are the kind of problems that are amenable to policy solutions if we have the will," Baum says. He forecasts widespread vaccination by late summer and a bounce back from the economic damage, a "Good News Story" that will bolster vaccine acceptance in the future. And Pinker reminds us that science, medicine, and public health have greatly extended our lives in the last few decades, a trend that can only continue if we're willing to roll up our sleeves. </p>
Imagine this scenario: you get an annoying cough and a bit of a fever. When you wake up the next morning you lose your sense of taste and smell. That sounds familiar, so you head to a doctor's office for a Covid test, which comes back positive.
Your next step? An anti-Covid nasal spray of course, a "trickster drug" that will clear the once-dangerous and deadly virus out of the body. The drug works by tricking the coronavirus with decoy receptors that appear to be just like those on the surface of our own cells. The virus latches onto the drug's molecules "thinking" it is breaking into human cells, but instead it flushes out of your system before it can cause any serious damage.
This may sounds like science fiction, but several research groups are already working on such trickster coronavirus drugs, with some candidates close to clinical trials and possibly even becoming available late this year. The teams began working on them when the pandemic arrived, and continued in lockdown.
Biochemist David Baker, pictured in his lab at the University of Washington.