TUESDAY, April 28 — The COVID-19 pandemic has kicked up a flurry of creative thinking among scientists, but regulations barring academic researchers from clinical work are proving harder to shake loose, even in a pandemic that calls for all hands on deck.
In early May, an MSU research team adapted equipment they were using to study Parkinson’s disease to “MacGyver” a COVID-19 test that’s 50 times more sensitive than most of the tests now in use.
The test can pick up very small viral loads, avoiding the dreaded false negative that allows infected people to go on their merry way, spreading the virus.
The MSU researchers are already working on a follow-up test that would use saliva, not nasal-pharyngeal swabs, and could become widespread in homes and offices, enabling the country to re-open with greater confidence that the virus is not spreading while hidden from view.
But research labs like MSU’s Translational Neuroscience Department, where the new test was developed, don’t have the accreditation to do clinical work, and need an emergency go-ahead to do clinical testing.
Last week, MSU neuroscience Professor Jack Lipton made the case for academic labs to join the clinical fight against COVID-19 in an op-ed piece in The Wall Street Journal and has made the rounds of news outlets, including Fox News. Lipton chairs the Department of Translational Neuroscience, a part of MSU’s College of Human Medicine, where researchers spend much of their time looking into the genetic changes wrought by Parkinson’s and Alzheimer’s diseases.
Lipton told Fox News last week that if even one-tenth of the nation’s academic labs joined the clinical effort, “we could test an additional 500,000 to 1 million samples a day.”
Today, Lipton told City Pulse he’s still hoping for action from the state.
“We do not have anything definitive yet,” Lipton said. “But the Michigan congressional delegation is working with us to have CMS [Centers for Medicare & Medicaid Services] consider broadening the allowances for labs to let us test. Nothing official though.”
Work on the new COVID-19 test began at MSU when a light bulb went off in the brain of Joseph Patterson, a research assistant professor.
Patterson was intrigued to learn that a Chinese research team had adapted a “droplet digital PCR,” a sensitive device capable of probing genetic material in a variety of tests, to develop a more accurate test for the COVID-19 virus.
“We went, ‘Wait, this is all that it is? We do that now,’” Patterson said. Patterson was already using the machine in his research on Parkinson’s disease, to measure how genes change in the early stages of the disease, before nerve damage is evident.
“Being able to isolate RNA from human samples was no stretch for us,” Patterson said. “We were basically taking everything we already know how to do, and using it to measure this virus’s RNA as opposed to the RNA we usually measure.”
About that time, the lab went into shutdown mode, along with the rest of the university. Lipton, Patterson, their colleague Dr. Caryl Sortwell and others on the staff were able to keep the lights on because of the critical nature of their work.
Within a week, “expedited” approval came from MSU’s Institutional Review Board to work with human specimens. The test was used on volunteer faculty and staff, including one who had already tested positive for COVID-19.
It’s not uncommon for Patterson to wait months for approval for studies on animals, let alone humans.
“To get a human study through in a couple of weeks is really fast,” he said. “In about a week, we were able to transition over to everything we needed to detect the virus with our own equipment.”
The droplet digital PCR looks like a compact humidifier, and with good reason. Both devices dole out delicate droplets. According to the manufacturer’s website, a “singulator” carefully “sips” 20,000 tiny drops from a sample and sends them in single file past an optical detector. Each droplet is designated positive or negative for the presence of the target RNA — in this case, the genetic signature of COVID-19.
Patterson called the digital droplet PCR the “Cadillac” of genetic testing equipment and compared its more common counterpart, the “real time PCR,” to a Chevy Malibu.
“I’m sticking with American cars because my in-laws all work for GM,” he said. Digital droplet PCRs are used in many labs across the United States.
Car talk aside, the genetic sensitivity of the “Cadillac” makes it extra valuable when tracking a virus that doesn’t always cause symptoms. Standard tests give a false negative from 20 to 30 percent of the time, according to an MSU study.
“This technique would be good for monitoring the progression of the disease,” Patterson said. “You can actually see when the viral load is completely gone, rather than when it becomes undetectable by the less sensitive equipment.”
Another possible application for the new test is screening large groups of people at once, such as an office of 100 employees.
“It could be a potential get back to work plan, where you’d have people submitting saliva samples at the beginning of each week,” Patterson said.
Instead of running 100 tests, the workers could be divided into 20 groups of 5. If a group tested positive, each member would be tested individually.
“It would cut down on costs and expedite the process,” Patterson said.
The protocols for the new test have already been published on line.
“To get the information out so quickly is a big thing,” Patterson said.
Patterson is always scanning for new information. Only a few days ago, new studies from Rutgers and Yale suggested a technique to test for COVID-19 from saliva with more accuracy than the traditional nasal-pharyngeal swab.
Saliva tests have the exciting potential to finally get the nation on top of the massive task of tracking the COVID-19 virus, making testing easy and widespread at home and work.
“We’re already looking at a screening process using saliva,” Patterson said.
In the rush to contain the COVID-19 pandemic, the international scientific community has ramped up the unusual practice of “pre-publishing” its findings on line, where new work can be seen around the world, without waiting months to publish an official study in a journal.
“I’ve had journal articles that have sat around for months,” Patterson said. “You always have a reviewer that says, ‘Nope, we want this one more experiment. This isn’t quite this or that.’”
Outside the scientific community, however, the norms have proven a lot more rust bound.
“Our big hurdle right now is the certification to go through and offer this as a diagnostic test,” Patterson said. “Right now our hands are a bit tied. All we can do is run tests in a research project capacity because we’re not a clinical lab.”
MSU’s translational neuroscience lab isn’t the only academic lab itching to join the fight against COVID-19.
“We’re trying to do everything we can do to be up and running if we do get approved, or if something changes, but there’s a lot of labs right now that are shut down and everything’s gone cold right now,” Patterson said.
Lipton is working overtime on that logjam, making his case in national media and lobbying lawmakers.
“We do this kind of test, this PCR test, all the time,” Lipton told Fox News last week. “And there are thousands of labs across the country that could do the same thing with high rigor, reproducibility and confidence.”
Patterson hopes the pent-up energy and expertise of academic labs around the nation can be freed to do clinical tests, but he’s not sure it will happen soon. In addition to state legislation, the federal FDA would have to waive the requirement that a lab has to be accredited by the Clinical Laboratory Improvement Amendments, or CLIA, to do diagnostic clinical testing.
“Even if you have legislators behind you, you still need the executive branch to back it up, and it’s hard to tell right now what the executive branch is going to do, which is the kindest thing I can possibly say,” Patterson said. “We’ve been very good at McGyver-ing things in the past with minimal supplies. We can adapt. We can improvise. We worked out a COVID test in a week. I’m not saying we shouldn’t be regulated. I’m just saying, deputize us to do work that there aren’t enough hands for right now.”