horseshoe crab on beach
Microbial Solutions
Rachael Kerr

From the Ocean Floor to Outer Space

In the lab, with marine scientist Norman Wainwright

“How did I end up here, astrobiology and marine science, you ask? Well, both my parents completed their high school education and were both swept into supporting the war effort during WWII. My family did not have scientists or researchers in our family. I did not know how to truly describe having an interest in science. My first memory of a career was wanting to be a garbage man riding on the back of the truck; then, a desire to be a smoke jumper fighting forest fires with Smokey the Bear. This became my short-lived reality as I kicked off college in the forestry program, but quickly ended as I transferred to a science major in my second semester.”

– Norman Wainwright, PhD, Senior Director, R&D, Charles River

Norm got involved with his mentor and advisor, a cell biologist studying cells in the lens of the eye. Years of this academic progression and pathway landed him right where he wanted to be, accomplishing his postdoctoral research studies in a lab cloning genes of the eye. He even studied abroad opting to take courses in Italy where he worked on advances in techniques of injecting nucleic proteins into cells to study gene expression. Norm’s first professional experience kicked off with Roche, working in the lab cloning human interferon genes. This experience was an introduction into the developing field of biotechnology, commercializing human interferons. After several years of successful execution with the advances of interferon therapies, Norm decided to explore his eclectic interest in the sciences and expand his experience with something new. Growing up on the Jersey Shore, Norm always had an affinity and wonder for the ocean, so he decided to embark on his career journey into marine science.

Norman Wainwright, Charles River Labs, holding horseshoe crab
Norman holding a horseshoe crab at Marine Biological Laboratory around 2003.

Norm spent a brief time working with Associates of Cape Cod, Inc. before resigning to take on a role with Marine Biological Laboratory (MBL) in Woods Hole, MA. Here, in the late 1990s, is where he initiated his relationship with horseshoe crabs (HSC) and many other marine organisms. The fondness and appreciation that he developed for the HSC stimulated a connection with Dr. James Cooper, as they began corresponding and establishing a relationship that shared a common passion.

Dr. Cooper was doing his own HSC studies in Charleston, SC, and although miles apart, the Atlantic horseshoe crab was sure to keep them close. Norm was offered a position doing contract work for Charles River’s Endosafe® division while staying put at his home in Woods Hole. During this time, Norm worked on the combination of microfluidics and the Limulus amebocyte lysate (LAL) reagents that developed into Charles River Endosafe® reagent cartridges. Software and system technologies advanced simultaneously to develop a Portable Test System (PTS), using the cartridges to perform Bacterial Endotoxin Testing (BET).

“It was definitely a eureka moment in time, to have developed an understanding of the value this marine treasure, the horseshoe crab, brings, and working with a number of talented people in Charleston to achieve such technological advances. It was so rewarding to be a part of something so important and innovative. There is a lot to be said by joining at an early stage of a development process. It was truly exciting to play a part in that!”

Foster Jordan and Norm worked together very closely with the cartridge and enzymatic assay design. Foster embraced his connection with Norm and was eager for him to relocate to Charleston so they could expand future research for the company. Norm’s resistance to moving eventually waned, and in 2005 agreed to head South to join the team, building a new life in the beautiful low country of South Carolina. Once in Charleston, he started building a team of his own, developing a lab so that full focus and attention could be given to expanding the science and support for PTS technology.

Here is where his affiliation with space began. Out of an undying interest of non-culture based microbial assays, such as those required for long duration space flight, Norm started exploiting a connection with NASA. With an understanding that culturing organisms in space would be inadequate for contamination control, impossible for safe handling of microorganisms, and detrimental to the safety and health of the crew, a reasonable breakthrough technology of contained testing with handheld devices seemed to be a perfect solution for astrobiology.

“Life outside of Earth, in space, as some conjecture, may all be microbial. I knew it was going to be essential to gather information on the existing natural microbes in our solar system. The utilities that we could provide for a clean, streamlined, and portable way to gather samples and collect data while maintaining planetary protection is where I felt the Endosafe® PTS™ system would make sense.”

This partnership with NASA allowed Charles River to demonstrate Endosafe® by flying it as a

Norman Wainwright using Charles River's rapid endotoxin test system in zero gravity
Norman testing zero gravity on the NASA parabolic flight plane (KC-135) 2007.

technology demonstration on the International Space Station, using the PTS system to map the microbial contamination throughout the whole station, “Now that was a fun project!”

Norm’s ability to connect with NASA, work and train with NASA personnel, and support the studies performed paid off. Even though astrobiological microbial detection and testing was not going to be a big market, the project opportunity and success, coming at the time it did, was definitely a huge technology driver and contributing factor in the scale-up and acceptance of the PTS system and cartridge technology. The system had to go through many tests for hardware ruggedness, fire safety, electrical safety, and software robustness. The system had to prove adaptability, which contributed to the overall success in the general industry and markets that it would be sold to. Norm felt being pushed to the limit with the system’s capabilities helped in the development to move the technology forward, getting it successfully to market.

“Not everything in science is a success. Post PTS, we focused on a very challenging, yet highly sought-after goal of rapidly detecting living microbes without culturing them. In the extreme, we wanted to be able to detect a single live organism in less than an hour. We failed to meet that goal but learned a lot along the way. It is still a major focus of new product development, and I have confidence we will one day get there.”

Norm is currently working on a project that he claims, will have a much happier ending.” Over a decade ago, Norm’s lab hosted researchers from the University of Singapore to work on recombinant Factor C, a synthetic endotoxin testing reagent. After almost a full year of working on this, Norm’s team declined the offer to license this product. He felt, even then, the performance was not good enough to displace the LAL reagent. Charles River alternatively chose to focus on the new PTS technology, which in retrospect turned out to be a very good decision. Lately, the general public has become very interested in the conservation of horseshoe crabs, and that is a good thing. We believe their use for LAL has played a positive role in that regard, but coming up with a synthetic, recombinant source that performs as well as LAL has been elusive. The first enzyme in the LAL multi-enzyme cascade, Factor C, is not enough on its own. Patient safety demands a very high standard. Now, with recent improvements in modern molecular biology, Norm feels the time is right for a recombinant product. His team has started back into the deep studies and are currently working on cloning all the genes expressed during the entire enzymatic cascade in LAL. This process will more closely mimic the response when LAL, which is naturally produced by horseshoe crabs, comes in contact with a pyrogen.

“We have had success in getting the genes cloned, we are now exploring how to use these genes and develop a product that is as good as LAL and meets Charles River criteria in marketing products of better value and quality than our current products.”

Norm feels while developing new products is always exciting, it is equally important that we continue to provide data on HSC conservation efforts, partner with aquariums, and discuss and educate the public on the science and facts pertaining to the important and direct role the horseshoe crabs play in the biomedical industry and patient safety.

When asked what keeps him motivated and working at Charles River, Norm credits his constant desire to know more about biology. In general, the desire to understand the science of the biological system."

"My desire to understand, going back to choosing science vs. forestry, using experimentation to ask questions and create something new. Trial and error to learn and understand the way things really work. All the while, meeting very smart, capable people. Every step of the way… so much of our science is not a single investigator, it is very much a day-to-day battle of failures to learn from and discuss as a team to build a strategy and new direction. That’s when good things happen.”