Dr. Rob Philibert, CEO of Behavioral Diagnostics, uses a multichannel pipette to prepare samples of bisulfite-converted DNA for pre-amplification, as Cardio Diagnostics CEO Meesha Dogan explains the process. PHOTO DAVE DEWITTE
By Dave DeWitte
Say a law firm wants to prove that a client who got in trouble due to behavior associated with alcoholism has given up the drink over the last five months in order to help him regain custody of his children. Or an insurance company, asked to underwrite a $10 million life insurance policy on a corporate CEO, wants to know if she’s really given up smoking before deciding how to price the premiums.
Such high-stakes determinations could soon be made more reliably thanks to new tests introduced last week by Behavioral Diagnostics LLC of Coralville. The startup at the University of Iowa BioVentures Center has developed epigenetic testing technology that eliminates many of the limitations and vulnerabilities associated with existing tests for alcohol and tobacco use.
Smoke Signature and Alcohol Signature are the names of the tests unveiled at the Iowa Association for Justice Conference, held April 19-20 at the Coralville Marriott. They can be ordered online, performed using a single drop of blood and mailed in for processing at the company’s headquarters.
The patented tests make use of the fact that alcohol and tobacco use can significantly modify DNA methylation – the modification of a gene in response to environmental stimuli such as substance intake without changing the DNA sequence (see sidebar at bottom for more).
Behavioral Diagnostics CEO Dr. Rob Philibert says that while other tests indicate short-term changes in behavior, the biosignatures measured by his company’s tests register average intake over time and are virtually impossible to fake.
“The beauty of the test is, we give the results to your lawyers,” Dr. Philibert said. “If it looks good, you show it to the judge. If not … you talk to the judge.”
The Smoke Signature and Alcohol Signature tests could replace technologies such as alcohol-monitoring ankle bracelets that can be tricked, and expensive ignition interlock devices on vehicles that are used in adjudicating the roughly 1.4 million DUI cases in the United States each year, Dr. Philibert said.
The cost of an Alcohol Signature test will be $475 for the initial test while the Smoke Signature tests will cost $149. Optional genotyping can be conducted in connection with the tests to ensure the identity of the client.
“It’s genetically based, so we know who you are,” Dr. Philibert said. He is not concerned about potential challenges to the validity of the science behind the tests, saying they’re backed up by more than 50 peer-reviewed studies.
While the launch of Alcohol Signature and Smoke Signature is a big event for Behavioral Diagnostics, Dr. Philibert sees even greater potential in the work of Cardio Diagnostics LLC, a related venture at an earlier stage.
Cardio Diagnostics is combining epigenetic testing technology with analysis of genetic traits in subjects to more accurately predict their risk of coronary heart disease.
“The test can tell what someone’s risk is before there is an event that requires an intervention,” said Cardio Diagnostics CEO Meesha Dogan.
Ms. Dogan was lead author of a study published in January that demonstrated the strong potential of genetic-epigenetic algorithms for predicting the future onset of heart disease, the leading cause of death in the United States.
The technology uses epigenetic tests to track environmental factors such as smoking and the consumption of trans fats that contribute to heart disease and adds them to genetic factors. The analysis includes the way the subject’s underlying genetics can reduce or amplify the effects of the environmental factors, known as confounding effects.
“In other words, we are determining risk for an outcome such as a heart attack by summating an individual’s unique genetic and environmental risk factors,” Ms. Dogan explained.
Conventional methods of predicting coronary artery disease aren’t very accurate, Dr. Philibert said, and one reason is the human factor. Patients asked by health surveys to report how much they drink, smoke, sleep or eat usually don’t provide accurate responses, he said. Many patients are so anxious to avoid the hospital that they even alter their daily intake of food, tobacco or alcohol in advance of appointments to test blood for things like cholesterol and triglycerides.
Cardio Diagnostics could essentially automate the prediction of heart disease, Dr. Philibert said, enabling users to have a blood sample drawn at a local pharmacy and quickly know their risk of heart disease. With the rapid changes in health care, including the move to a vertical service delivery model involving players like CVS, Walmart and Amazon, he sees Cardio Diagnostics providing convenient, cost-saving solutions that could save lives and money on a large scale.
“We [Behavioral Diagnostics] can absolutely tell you how much you’re smoking and drinking, and her [Ms. Dogan’s] cardio tests are just an extension of that,” he said.
Founded in 2017, Cardio Diagnostics is attempting to raise about $1.5 million from angel investors for upcoming validation studies and the development of laboratory tests for coronary heart disease, which is expected to take place between June 2018 and March 2019.
Longer-term, the company plans to raise $5 million to expand and develop congestive heart failure and stroke tests.
Dr. Philibert a University of Iowa professor of psychiatry, co-founded Behavioral Diagnostics in 2009 with former UI faculty member Anup Madan, and has helped the company secure some $3.5 million in funding from the National Institutes of Health. Co-owners of the company include Dr. Philibert, Mr. Madan, Mike Levin and Terry Osborn.
Ms. Dogan, who has a Ph.D. in biomedical engineering from the UI, brings a strong background in machine learning to the team. Although the companies could likely find a buyer for the promising technologies they’ve been developing, Ms. Dogan and Dr. Philibert plan to commercialize their discoveries here if possible.
At a time when health care is eating up 21 percent of gross domestic product, Dr. Philibert said Cardio Diagnostics is developing disruptive technology that could yield tremendous savings both in life and health care dollars. Much of the intellectual property for the companies was developed at the University of Iowa, and he’d like to see Iowa reap the benefits.
“This can happen here,” Dr. Philibert said. “It just a question of getting the financing and keeping the team together.”
How it works
Behavioral Diagnostics’ tests are based on the concept of DNA methylation, or the modification of a gene without changing its DNA sequence.
When smoking tobacco, for instance, the body ingests polyaromatic hydrocarbons, which are absorbed into the bloodstream. The body’s white blood cells sense the toxins and activate key enzymes that can destroy them by removing the methyl groups that serve as “off switches” for the genes that metabolize them.
Behavioral Diagnostics’ Smoking Test measures the amount of methylation at the site controlling the release of enzymes. The more the test subject smokes, the more demethylated the site becomes.
The company uses polymerase chain reaction technology to count the number of demethylated genes, providing evidence of how much the subject smokes. And as that subject stops drinking or smoking, the “biosignature” reverts back to normal.