Thomas Martin, the dynamic president of Alabama Power in 1941, saw the South’s industrial potential being held back for a simple reason – there was too little research activity to benefit businesses and drive innovation across the region.

Martin managed to make his vision come true, with the creation of what is now known as Southern Research, a Birmingham-based non-profit organization that has been committed to scientific discovery and technology development for 75 years.

From the start, Martin’s ambitions for the organization were lofty.

Its laboratories would concentrate on “discovering new products, new materials as substitutes for existing ones, improvement in existing products and their method of manufacture, use of by-products and materials now wasted, and study of potential markets for new products and new methods of manufacture,” he said.

As the 1940s began, the need for a research organization in Birmingham had actually been discussed for more than a decade, following a proposal by University of Alabama professor Stewart Lloyd.

Lloyd, the dean of the university’s School of Chemistry, Metallurgy and Ceramics, called for the creation of a research group in 1930 after preparing a report that examined the Birmingham area’s chemical assets and their industrial potential.

CALL TO ACTION

The influential Martin, president of Alabama Power since 1920, took up the cause. A pivotal moment came on Oct. 10, 1940, when he delivered a five-minute speech to the Alabama Chamber of Commerce proposing the creation of a research laboratory supported by a fund of not less than $250,000.

He declared that Alabama Power would match any pledge. Soon, momentum for the plan began to swell.

With Martin at the wheel, nearly 80 business leaders signed up as incorporators of the new research organization. On Oct. 9, 1941, in Room 236 of Birmingham’s Tutwiler Hotel, the incorporators gathered for their first meeting.

Two days later, incorporation papers for what would be called Alabama Research Institute were filed. Martin became the organization’s chairman in December 1941, but the U.S. entry into World War II after the Pearl Harbor attack put the fledgling research group on hold.

PLEDGING SUPPORT

Late in 1943, Martin made another push. He invited industrial leaders from around the South to a meeting at Alabama Power’s headquarters on Dec. 21 and kicked off a financing campaign to launch operations.

His goal was $50,000 the first year, and double that amount in subsequent years. Alabama Power pledged $15,000 per year for five years — $75,000 total.

Other businessmen responded with substantial pledges. With support for the research institute flowing in from outside Alabama, it was time for a name that reflected a regional focus.

On May 4, 1944, the Southern Research Institute was born, with the goal of becoming an economic driver for the entire region.

In August that year, Martin purchased the Morris-Cartwright House on Birmingham’s Southside for $57,500 as the organization’s base.

Before long, Southern Research’s first scientists and technicians were diving into their initial research projects.

AG129 Mouse Model:

AG129 mice were selected because they are highly susceptible to infection when challenged with the Puerto Rican strain of ZIKV, PRVABC59. As such, they serve as an ideal candidate for observing how the virus infection progresses in a living model. More specifically, the model is 100% lethal at subcutaneous challenge dose 1×10¹-1×10⁵ PFU, and AG129 exhibit pronounced clinical signs of infection, such as weight loss and neurological indications that were not otherwise exhibited in other species.

In this sense, the NHP reacted to Zika in a manner much more similar to humans.

While cynomolgus macaque models are essential for studying the safety and efficacy of candidate ZIKV vaccines,  clinical disease model such as AG129 provide a very useful tool for efficacy evaluation of ZIKV antivirals in “trigger to treat” testing.

Key Findings:

• AG129 model is 100% lethal after subcutaneous challenge dose 1×10¹-1×10⁵ PFU of the PRBABC59 strain.
• Neurological signs are detected in a majority of the animals tested.
• Presence of high serum viral load and high neutralizing antibodies (PRNT₅₀) were evident in all AG129 mice tested.
• The model is suitable for prophylactic and therapeutic antiviral drug efficacy evaluation.
• In addition to NHP model, AG129 offers an alternative model for testing candidate Zika vaccines.

In an effort to identify a vaccine for the Zika virus (ZIKV), Southern Research is running multiple animal model studies independently and through a contract with the NIAID in non-human primates (NHP).

Old-fashioned expertise in fiber spinning and a deep knowledge of polymers allowed Southern Research to become an accomplished pioneer in the game-changing drug-delivery technology called controlled release.

Today, a prescription medicine releasing its active ingredient over time is a familiar concept. Long-acting drugs work over the course of many weeks, eliminating the need for multiple daily doses. Implanted drug-delivery devices operate in the same way, often over several months or even longer.

Over many years, Southern Research scientists made significant discoveries in the field, laying a foundation for the development of products that have helped patients afflicted with cancer and other ailments.

Back in the early 1970s, though, controlled release was an emerging technology. It held promise in fields ranging from agriculture to consumer products and medicine, but technical advances were needed.

A conference at Birmingham’s Parliament House Hotel, organized by Southern Research, helped give the technology the push it needed in April 1973. “The Symposium on Controlled Release of Biologically Active Agents,” as it was called, attracted all the major figures working on the technology, including Dr. Allan Hoffman.

“This was a historical milestone in the controlled release field – this was the first ever meeting, and it was at Southern Research’s initiative to have this symposium,” recalled Danny Lewis, Ph.D., who then worked at the Birmingham non-profit organization.

“It was the kick-off meeting for controlled release as we know it today.”

The symposium was published in book format in 1974 and remained a key text for the field for many years.

Lewis was just one of several Southern Research scientists who would go on to to make major contributions to the field. He later served as president of the Controlled Release Society (CRS), an international professional organization that sprang a few years later from that symposium at the Parliament House.

Since top experts in controlled release technology gathered last week in Seattle for CRS’ 43^rd annual meeting, it’s an ideal time to examine how Southern Research emerged as a recognized authority in the field.

MICROSPHERES

Early controlled release projects at Southern Research focused on developing an anti-fouling treatment against barnacles for Navy ships and on a pesticide to kill fire ants. The organization also worked on an antibiotic powder formulation that could be used to treat wounds on the battlefield.

A pivotal early project involved a controlled-release injectable birth control product that produced the first human testing of biodegradable microspheres, absorbed in the body over a period of six months. Lewis led the testing in Mexico City.

“Southern Research pioneered a whole field called biodegradable microcapsule delivery,” Lewis said. “To me, that will always be a key project for Southern Research in controlled release because after that we gave talks, wrote papers, and we were everywhere, left and right. People found out about Southern Research.”

Another important project involved biotech company Syntex, which wanted to use a peptide — luteinizing hormone-releasing hormone, or LHRH – in a microencapsulated form. LHRH was difficult to microencapsulate, and releasing large, water-soluble molecules like a peptide from a polymer was a challenge, but Lewis and colleague Tom Tice, Ph.D., figured out how to do it.

Two years later, in 1981, a Swiss pharmaceutical firm knocked on Southern Research’s door. The company saw promise in using microencapsulated LHRH as a treatment for prostate cancer. The product, Decapeptyl SR, first went on the market in 1986 and is still in use today.

“We became dominant in the controlled release field in those early years,” Lewis said. “We were the go-to place worldwide. We had projects here from England, Switzerland, all over.”

Lewis later left Southern Research to join Medisorb Technologies, a venture that produced biodegradable polymers and was later acquired by Alkermes. He went on to become a consultant, working with pharmaceutical companies around the world.

Other Southern Research scientists also made their marks on the field. Tice drove the microencapsulation work at the organization, while Richard Dunn, Ph.D., spearheaded work on biodegradable polymers, implants and more.

Later, Dunn, one of the inventors of a novel polymeric drug-delivery technology, licensed the approach from Southern Research and joined Atrix Laboratories in Colorado. Atrix placed a number of products on the market and ultimately was acquired by QLT.

Another Southern Research veteran, Jim English, built a reactor that Medisorb used to produce biodegradable polymers. He was later involved in the founding of Birmingham Polymers, which operated another reactor of his design.

Birmingham became home to two of the four companies in the world that operated as commercial sources for biodegradable polymers, according to Art Tipton, Ph.D., president and CEO of Southern Research, Birmingham Polymers (now part of Durect), and the Alkermes polymer business (now part of Evonik). Both still operate in Birmimgham.

“Southern Research played a seminal part in the start of a very important field,” Tipton said. “The controlled release work done at Southern Research was based on strong science capabilities. It was a very vibrant group and the members were catalytic in the field.”

Other interesting Southern Research projects in controlled release included the development of a microparticle vaccine to protect soldiers against biological attacks and two Space Shuttle flights that tested the effects of microgravity on antibiotic microspheres.

SPINNING A VENTURE

Tipton, who worked at Southern Research in the early 1980s before heading off to graduate school, joined Dunn’s Atrix before returning to Birmingham to play a key role in Southern Research’s drug-delivery business.

In 2005, the non-profit organization formed Brookwood Pharmaceuticals as a commercial venture for its controlled release group, which included the manufacturing of biodegradable polymers. Tipton headed the business, which quickly attracted a suitor as revenues rose.

Brookwood was snapped up in 2007 by SurModics Inc. in a deal valued at $50 million – the largest commercial transaction in Southern Research’s history. (Germany’s Evonik later acquired the business, and Tice still works in the Birmingham operation.)

Like Lewis, Tipton has served as president of the Controlled Release Society, meaning Southern Research has produced two leaders of the worldwide professional organization.

Lewis noted that the roots of Southern Research’s work in the field actually stretch back to the 1960s and the work done in the organization’s Plastics and Fibers section. Experts there developed the ability to produce fibers that easily degraded during the spinning process.

This technique was adopted to make the first synthetic, absorbable sutures – a major advance. It also introduced Southern Research scientists to the polymers that would become the cornerstone of the organization’s controlled release work.

“Polymers were absolutely fundamental to drug delivery. We realized early on that if we were going to do all these things in drug delivery, we had to be basic in the polymers because there was nowhere to buy them,” Tipton said. “We’ve got to make them using commercial standards and with quality standards so that the FDA will approve them.

“There was just an incredible expertise here to do that.”