In this interview, we discuss his unique background, the rise of extracellular vesicles (EVs) and exosomes as diagnostic tools, advantages of saliva over other bodily fluids, and current and future applications for saliva-derived EVs and exosomes.
Cade Hildreth: What is your background and how did you become involved with extracellular vesicles (EVs)?
Dr. Paul Slowey: My background is in Synthetic Organic Chemistry. After completing my PhD at the University of Newcastle-Upon-Tyne in the UK, I spent three wonderful years as a Post-Doctoral Fellow in Canada, the first two at the University of Victoria, in Victoria, British Columbia, and the third at the Memorial University of Newfoundland in St John’s, Newfoundland. They were two extremes in terms of geography and also terrain.
While in St John’s, I was offered a job in my native UK at Sterling Drug, Inc. in Alnwick, Northumberland, accepted the position, and spent five years there as a Group Leader in Medicinal Chemistry, leading a group of PhDs and support staff involved in Drug Discovery. After moving back to Canada in 1989, I made the transition to sales and marketing and spent 6 years with INCSTAR Corporation [now Diasorin] first in Vancouver, Canada, then in Stillwater, Minnesota.
Cade Hildreth: Wow, you did a lot of globetrotting during that time. I am from the Twin Cities in Minnesota and grew up minutes from Stillwater, Minnesota.
Dr. Paul Slowey: How interesting, and yes, at INCSTAR I was responsible for all International Sales and Marketing, which included managing 110 distributors in 79 countries as well as several subsidiaries of INCSTAR Corporation and its affiliate Sorin Biomedica [Saluggia, Italy].
In 1996 I was head-hunted by a small startup Company, Saliva Diagnostic Systems [SDS] and so began my 22 years in the oral fluid diagnostics business. I started at SDS as Vice President of Sales and Marketing and soon graduated to Chief Operating Officer (COO).
I was at SDS for three years before moving on to work at Epitope, Inc., which became OraSure Technologies, the market leader in Oral Fluid Diagnostics during my tenure there. I spent 2 years at the Company during which time I licensed the peptides used in the OraQuick HIV 1 / 2 Rapid Oral Fluid HIV test for the Company. I also sold the very first order of 250,000 Units of Product to the Centers for Disease Control (CDC) for distribution to 15 sub-Saharan African countries.
With the knowledge and experience gained at these two “pioneers” in the salivary diagnostics world, I set off on my own with a business partner in 2002 and began to develop the portfolio of products that we now have. In 2006 I bought out my business partner so have ran the Company since that time.
A few years ago the liquid biopsy market was just beginning to develop, and concurrently with that, the interest in collection of samples non-invasively for nucleic acid testing [DNA, RNA, proteins] was gaining momentum. The mammoth success of consumer based genomics through companies like 23andMe, Ancestry.com, and others exemplifies this trend.
A little bit ahead of this time, we had begun a collaboration with Dr. David Wong, a “guru” in the field of salivary diagnostics. Dr Wong is the Felix and Mildred Yip Endowed Professor at UCLA and Associate Dean in the School of Dentistry and his objectives are to investigate clinical applications of saliva, notably gastric cancer, lung cancer, oral cancer, and Sjogren’s Syndrome, among others, as well as to be able to offer suitable diagnostic alternatives using either laboratory based methods or point-of-care tests based upon non-invasive saliva sampling.
Our collaboration resulted in the development of two tools that are able to effectively remove cells and large interfering DNA from saliva, providing a sample that is rich in cell free DNA, cell free RNA, proteins and exosomes. We published the results of our work and at the time it created a few “waves” in the saliva world, but not in the rest of the IVD [in vitro diagnostics] arena.
I believe this is changing as more and more applications appear using saliva looking for salivary miRNAs, cfDNA from saliva and exosomes.
Cade Hildreth: How and when did you found Oasis Diagnostics?
Dr. Paul Slowey: I founded Oasis as a subsidiary Company called Bamburgh Marrsh LLC. We operated as Bamburgh Marrsh until 2006, after which my business partner left the Company. At that time I changed the name of the Company to Oasis Diagnostics® Corporation, which is a registered trademark.
Cade Hildreth: What are the core technologies utilized by Oasis Diagnostics?
Dr. Paul Slowey: The core technologies utilized by Oasis Diagnostics® can be broken down into two groups:
1) Salivary Diagnostics
2) Genomics
Our “core competency” is in the design, development and manufacture of tools for standardized saliva collection and testing, so over the course of the last 15 years [almost 16], we have developed a series of tools to harvest DNA, RNA, proteins, drugs of abuse, hormones and almost anything else from saliva.
In addition we have developed “population-specific” devices for neonates, small children, geriatrics, as well as for small and large animals for veterinary applications. Lastly we have developed a unique point-of-care technology LIAM™ that allows full quantification of multiple biomarkers from a saliva specimen in 20 minutes with full reporting capability to a SmartPhone or laptop computer.
LIAM™ and the associated quantitative lateral flow test strip format [VerOFy®] were developed under National Institutes of Health [NIH] Small Business Innovation Research [SBIR] grants from the Federal Government. On the genomic side, we work with several European companies to provide a series of high quality PCR and real time PCR assays to our US and Canadian customers.
Our relationships with ViennaLab Diagnostics [Vienna, Austria], Molzym [Bremen, Germany], Operon [Zaragoza, Spain] and Blackhills Diagnostic Resources [Zaragoza, Spain] are key to this strategy as our main collaborators and we try to tie the two technologies [saliva and genomics] together by offering non-invasive genetic options for our customers, by validating, where possible, as many of the assays to a saliva specimen so that we can offer validated protocols to them.
Cade Hildreth: I am impressed with your extensive expertise in the areas of salivary diagnostics and non-invasive genomic testing. What is your patent position in this area and in what regions have they been issued?
Dr. Paul Slowey: We have 17 or 18 issued patents at the present time with another 8 or 9 in the application phase going through the system. These patents pertain to the saliva collection and testing tools we have developed, as well as some very interesting technologies we have licensed on an exclusive basis for the potential diagnosis of Alzheimer’s disease, Parkinson’s disease and sleep disorders.
These patents cover the application of multiple biomarkers in saliva to detect and potentially diagnose patients in the mild, moderate and severe forms of the diseases. A few years ago we received a small grant from the Michael J Fox Foundation with collaborators from the Mayo Clinic in Scottsdale, AZ, to look at saliva specimens in Parkinson’s disease.
In the future we hope to be able to develop lab-based and point-of-care tests using saliva for each of these diseases and conditions.
Cade Hildreth: How are saliva-derived extracellular vesicles (EVs) and exosomes currently being used? How do you predict they will be used in 5-10 years?
I firmly believe that as more and more data is published on the application of salivary EVs and exosomes, we will see an “explosion” in the development of research AND clinical tools, similar to the rapid growth seen in the consumer genetics market.
In 5-10 years there will undoubtedly be a number of clinical tools available to assess multiple diseases, including cancers, diabetes, neurodegenerative diseases, traumatic brain disorders and others. Although not immediately focused on saliva, the example of Exosome Diagnostics’ foray into the world of exosome based diagnostics is a positive sign for diagnostics based upon EVs and exosomes.
The large funds invested into the Company shows a strong interest from the investment community and a trust to deliver positive results. GRAIL, Invitae and Sema4 may be other good examples.
Cade Hildreth: In your opinion, what are the advantages of using saliva as a source of EVs / miRNA / mRNA / exosomes for use in diagnostic tools?
Dr. Paul Slowey: Current methods for isolation of EVs / miRNA / mRNA / exosomes from bodily fluids are labor intensive, require a significant number of reagents in a kit format to isolate the EVs, are costly and take several hours to achieve a product which can be used in downstream applications.
In the case of blood, serum, tissue and others the sample is invasive for the patient, so the ability to use saliva eliminates the invasive nature of the sampling and cuts down on sample prep time. Our work in this area is by no means extensive, but our preliminary work has also shown that in some cases the saliva sample provided does not need immediate stabilization, as is typically the case for nucleic acid components such as miRNAs / mRNAs.
A couple of other factors that apply to all saliva specimens is that they are easy to transport and do not require special shipping conditions. In some cases dry ice or cold packs are required, but no special biohazardous waste regulations need to be adhered to.
There are also certain populations that are unwilling to donate a blood sample and saliva has advantages there. Examples include Jehovah Witnesses and certain populations in Africa who believe blood to be “part of their body or soul” and are unwilling to part with blood, but are happy to provide a saliva sample.
Lastly when comparing apples with apples, the true cost of saliva collection is more cost effective than blood. This is because a blood draw requires a trained phlebotomist to collect the sample whereas a saliva sample can be collected by untrained individuals with minimal training.
Cade Hildreth: I have been heavily involved with the sport of rugby, representing the USA National Team for years, training at the Olympic Training Center, playing overseas in New Zealand, being named the “International Athlete of the Year,” and playing with Superclubs around the globe.
I understand that you are working with a group that is targeting salivary miRNAs for concussions. Could you tell me more about this?
Dr. Paul Slowey: Coming from England, rugby is one of my favorite spectator sports and at schoolboy level I did play a little rugby myself, so I can appreciate why concussion has rapidly become a “hot topic” in the world of rugby and contact sports in general. You are correct that as a tool or sample prep provider we are in discussions with a number of key opinion leaders and companies looking at salivary miRNAs for concussion and our goal is to be able to provide simple and effective tools for ready isolation of salivary miRNAs in just a few short minutes.
Being able to detect and react to a concussion at field side is fundamental to the safety of the player and saliva offers the most attractive option for rapidly and non-invasively providing an assessment of the athlete’s concussion status.
While some of this work remains the subject of confidentiality agreements, which I am not at liberty to discuss, what I can say is that there have been some very important studies recently published by some of the key opinion leaders in this area, particularly Dr. Steven Hicks [Penn State University], Dr. Anthony Belli [University of Birmingham, UK], Dr. Kendall Van Keuren-Jensen [TGEN, Phoenix], Dr Balwant Rai [JBR Research Group, Denmark] and several others.
As you are probably aware, this field is developing rapidly! In the case of each of these academics, and others out there, I see opportunities for them, through collaborations with the commercial sector, to develop their respective technologies from interesting research tools to useful screening and clinical tools for the accurate and effective detection of concussions on the sports field.
Cade Hildreth: That would be a very exciting advance for the field, as well as for the sport of rugby. What is the North American Saliva Symposium (NASS) and what is your invovlement?
Dr. Paul Slowey: For the last few years, I have organized the North American Saliva Symposium, known as NASS. I co-Founded this meeting in 2014 with Dr. Jill Maron from Tufts Medical Center. This year I am organizing our Fifth NASS to be held in Houston from October 12th – 14th 2018.
The meeting brings together key opinion leaders from both academia and the commercial sector for three days of oral presentations, roundtables, networking and posters on novel applications for saliva. I am currently in the middle of putting the line up together for this year’s meeting, but it’s events like this and spin-off meetings held in Australia and China that are putting saliva on the world map.
Cade Hildreth: Thank you for the honor of doing this interview on the topic of EVs, exosomes, and the future of non-invasive diagnostics. It is an honor to talk with an expert from the industry and I appreciate your valuable insights.
To learn more about this rapidly growing industry, view the “Market for Stem Cell Exosomes.”
