Dr. Andrew Brooks of RUCDR Infinite Biologics holds up a saliva sample.
The patient tilts back her head and winces as the long swab stick pushes six inches up her nose. The tip twirls around uncomfortably before it's withdrawn.
"Our saliva test can detect the virus in asymptomatic and pre-symptomatic cases."
A gloved and gowned healthcare worker wearing a face shield and mask tells the patient that she will learn whether she is positive for COVID-19 as soon as the lab can process her test.
This is the typical unpleasant scenario for getting a coronavirus test. But times are rapidly changing: Today, for the first time, the U.S. Food and Drug Administration cleared one company to sell saliva collection kits for individuals to use at home.
Scientists at the startup venture, RUCDR Infinite Biologics at Rutgers University in New Jersey, say that saliva testing offers an easier, more useful alternative to the standard nasal swab.
"Our saliva test can detect the virus in asymptomatic and pre-symptomatic cases," said Dr. Andrew Brooks, chief operating officer at RUCDR.
Another venture, Darwin BioSciences in Colorado, has separately developed an innovative method of testing saliva for the coronavirus that causes COVID-19.
Saliva testing can allow earlier detection to identify people who may not know they are contagious, say scientists at both companies. In addition, because patients spit into a tube or cup, saliva testing is safer for healthcare workers than taking swabs. This frees up scarce personal protective equipment (PPE) for use elsewhere. Nasal swabs themselves have been in scarce supply.
Saliva testing, if it becomes widespread, potentially could mean opening society sooner. The more ubiquitous testing becomes across the population, experts say, the more feasible it becomes for public health officials to trace and isolate contacts, especially of asymptomatic cases. Testing early and often will be essential to containing emerging hot spots before a vast outbreak can take root.
Darwin Biosceiences is preparing to seek an FDA Emergency Use Authorization (EUA) this month for its patented "CoVScreen" testing system, which potentially could be available to labs nationally by mid-summer.
Meanwhile, Infinite Biologics will now begin selling kits to consumers for home collection, upon order by a physician. The FDA said that the company's saliva test was as accurate as the nasal swab method used by health care professionals. An FDA summary documenting the company's data reported: "There was 100% positive and negative agreement between the results obtained from testing of saliva and those obtained from nasopharyngeal and oropharyngeal swabs."
The greatest scientific advantage, said Dr. Brooks, is that nasal and oral swabs only collect the surface area where the swab goes, which may not be the place with most viral load. In contrast, the virus occurs throughout a saliva sample, so the test is more trustworthy.
The lab at Rutgers can process 20,000 tests a day, with a 48-hour turnaround. They have 75,000 tests ready to ship now.
The Leap: Detecting Sickness Before You Feel It
"We wanted to create a device that could detect infections before symptoms appeared," explained Nicholas Meyerson, co-founder and CEO of Darwin.
For more than 300 years, he said, "the thermometer was the gold standard for detecting disease because we thought the first sign of illness was a fever. This COVID-19 pandemic has proven that not all pathogens cause a fever. You can be highly contagious without knowing it."
"The question is whether we can scale up fast enough to meet the need. I believe saliva testing can help."
Therefore, Meyerson and co-founder Sara Sawyer from the University of Colorado began to identify RNA biomarkers that can sense when a pathogen first enters a molecule and "sets off alarms." They focused on the nucleic acids concentrated in saliva as the best and easiest place to collect samples for testing.
"The isothermal reaction in saliva takes place at body or room temperature," he said, "so there's no need for complicated testing machinery. The chemical reaction can be read out on a paper strip, like a pregnancy test -- two stripes if you're sick, and one stripe if you're okay."
Before the pandemic, limited but successful human trials were already underway at CU in Boulder and at the CU Anschutz Medical Campus east of Denver. "This was our proof of concept," he said.
Darwin was founded in March and has secured enough venture capital to concentrate protype development on detecting the virus causing COVID-19. So far, said Meyerson, "Everything works."
A small double-blind test of 30 samples at CU produced 100 percent accuracy. "I'm not sure if that will hold true as we go into clinical trials," he said, "but I'm confident we will satisfy all the requirements for at least 95 percent clinical validation."
The specific "CoVStick" test strips will roll out soon, he said: "We hope before the second wave of the pandemic hits."
The broader saliva test-strip product from Darwin, "SickStick," is still one to two years away from deployment by the military and introduction into the consumer drugstore market for home use, said Meyerson. It will affordably and quickly detect a range of viral and bacterial infections.
An illustration of the "CoVStick."
(Darwin Biosciences)
A Potential Game Changer
Society needs widespread testing daily, said George Church, founding core faculty of the Wyss Institute for Biologically Inspired Engineering at Harvard University. Speaking at an online SynBioBeta webinar in April, he urged developing stockpiles of testing kits for home use.
As for any potential of false positives, Church said a much bigger risk is not having enough tests.
"Saliva testing is going to speed up the timeline for opening society a lot," said Meyerson. "People need to self-collect samples at home. A lot more people are going to be willing to spit into a tube than to push a swab six inches up their own nose."
Brooks, of Rutgers, addressed the big picture. "It's critical that we open society as soon as possible to minimize the economic impact of the pandemic. Testing is the surest and safest path. The question is whether we can scale up fast enough to meet the need. I believe saliva testing can help."
AI was integral to creating Moderna's mRNA vaccine against COVID.
But the truth is that before ChatGPT nabbed the public’s attention, AI was already here, and it was doing more important things than writing essays for lazy college students. Case in point: It was key to saving the lives of tens of millions of people.
AI-designed mRNA vaccines
As Dave Johnson, chief data and AI officer at Moderna, told MIT Technology Review‘s In Machines We Trust podcast in 2022, AI was integral to creating the company’s highly effective mRNA vaccine against COVID. Moderna and Pfizer/BioNTech’s mRNA vaccines collectively saved between 15 and 20 million lives, according to one estimate from 2022.
Johnson described how AI was hard at work at Moderna, well before COVID arose to infect billions. The pharmaceutical company focuses on finding mRNA therapies to fight off infectious disease, treat cancer, or thwart genetic illness, among other medical applications. Messenger RNA molecules are essentially molecular instructions for cells that tell them how to create specific proteins, which do everything from fighting infection, to catalyzing reactions, to relaying cellular messages.
Johnson and his team put AI and automated robots to work making lots of different mRNAs for scientists to experiment with. Moderna quickly went from making about 30 per month to more than one thousand. They then created AI algorithms to optimize mRNA to maximize protein production in the body — more bang for the biological buck.
For Johnson and his team’s next trick, they used AI to automate science, itself. Once Moderna’s scientists have an mRNA to experiment with, they do pre-clinical tests in the lab. They then pore over reams of data to see which mRNAs could progress to the next stage: animal trials. This process is long, repetitive, and soul-sucking — ill-suited to a creative scientist but great for a mindless AI algorithm. With scientists’ input, models were made to automate this tedious process.
“We don’t think about AI in the context of replacing humans,” says Dave Johnson, chief data and AI officer at Moderna. “We always think about it in terms of this human-machine collaboration, because they’re good at different things. Humans are really good at creativity and flexibility and insight, whereas machines are really good at precision and giving the exact same result every single time and doing it at scale and speed.”
All these AI systems were in put in place over the past decade. Then COVID showed up. So when the genome sequence of the coronavirus was made public in January 2020, Moderna was off to the races pumping out and testing mRNAs that would tell cells how to manufacture the coronavirus’s spike protein so that the body’s immune system would recognize and destroy it. Within 42 days, the company had an mRNA vaccine ready to be tested in humans. It eventually went into hundreds of millions of arms.
Biotech harnesses the power of AI
Moderna is now turning its attention to other ailments that could be solved with mRNA, and the company is continuing to lean on AI. Scientists are still coming to Johnson with automation requests, which he happily obliges.
“We don’t think about AI in the context of replacing humans,” he told the Me, Myself, and AI podcast. “We always think about it in terms of this human-machine collaboration, because they’re good at different things. Humans are really good at creativity and flexibility and insight, whereas machines are really good at precision and giving the exact same result every single time and doing it at scale and speed.”
Moderna, which was founded as a “digital biotech,” is undoubtedly the poster child of AI use in mRNA vaccines. Moderna recently signed a deal with IBM to use the company’s quantum computers as well as its proprietary generative AI, MoLFormer.
Moderna’s success is encouraging other companies to follow its example. In January, BioNTech, which partnered with Pfizer to make the other highly effective mRNA vaccine against COVID, acquired the company InstaDeep for $440 million to implement its machine learning AI across its mRNA medicine platform. And in May, Chinese technology giant Baidu announced an AI tool that designs super-optimized mRNA sequences in minutes. A nearly countless number of mRNA molecules can code for the same protein, but some are more stable and result in the production of more proteins. Baidu’s AI, called “LinearDesign,” finds these mRNAs. The company licensed the tool to French pharmaceutical company Sanofi.
Writing in the journal Accounts of Chemical Research in late 2021, Sebastian M. Castillo-Hair and Georg Seelig, computer engineers who focus on synthetic biology at the University of Washington, forecast that AI machine learning models will further accelerate the biotechnology research process, putting mRNA medicine into overdrive to the benefit of all.
This article originally appeared on Big Think, home of the brightest minds and biggest ideas of all time.
