Tag: Cancer Research

Southern Research at 75: ‘Boss Kettering’ provides key early support

Charles Kettering, the genius engineer behind many of General Motors’ breakthrough innovations, racked up 186 patents and earned a reputation as a great inventor in his day.

Southern Research Skipper Kettering
Southern Research’s Howard Skipper, left, talks with famed inventor Charles Kettering, a strong supporter of Skipper’s cancer research.

He also became a high-profile supporter of Southern Research in its early days, thanks to a relationship with the new research organization’s chairman, Thomas Martin.

Though the dynamic founder of Southern Research and the inventor of the automobile starter motor had exchanged letters since 1934, they didn’t actually meet until both attended a nutrition conference in New York in 1945. Martin told Kettering about the work getting under way in Birmingham.

Intrigued, Kettering contributed advice, expertise and funding to help accelerate growth at Southern Research, particularly the cancer program headed by Howard Skipper, Ph.D.

“I do remember very well that a lot of the early money when I joined Skipper’s group came from Kettering, and it was pretty soon after that we also got money from the Alfred P. Sloan Foundation,” recalled John Montgomery, Ph.D., a key member of Southern Research cancer team from 1952 until 1990.

“Sloan was the money man at General Motors when Ket was the inventor, and they tossed some money in the pot, too. And so we had enough money to begin to do something,” Montgomery added.

In 1945, around the time that Southern Research was launching its first projects, Kettering joined his GM colleague to open the Sloan-Kettering Institute for Cancer Research (SKI) in New York. SKI’s director was Cornelius Rhoads, who had served with Skipper in the Army’s chemical warfare section during World War II.

SR 75th_Logo_Horz_RGBThese connections would drive growth in Skipper’s labs.

‘BOSS KET’ COMES TO TOWN

Kettering made frequent visits to check on Southern Research’s progress. The first came on Nov. 12, 1947, dedication day for the organization’s first new building – Laboratory No. 5.

At the time, Southern Research had about 50 scientists, working on early projects such as heat pump technology, extending food uses of peanuts, new paints from coal by-products, and chemical detectors for the Army. Kettering talked to the scientists, toured the facilities, and spoke that night at the Chairman’s Dinner.

Charles Kettering Southern Research
Charles Kettering speaks at Southern Research during his first visit in 1947.

“Set up your laboratories, equip them,” he told the researchers. “You cannot tell what is going to come out of them now, or 10 or 15 years hence. Your achievements will be different from what you now think, but they will be wonderful.”

He was keenly interested in Skipper’s cancer program, which was started the year before thanks to a $25,000 gift from Mobile businessman Ben May.

“One of my favorite memories is of Boss Kettering, as we called him, and his visits to our group,” Montgomery recalled in an oral history of Southern Research published in 1991. “He came to see us three or four times a year, to talk to the boys and see how things were getting along on cancer research.”

He did more than just offer encouragement to Southern Research’s scientists. He made possible the organization’s first permanent labs for biomedical research — the Kettering-Meyer Laboratory.

The Charles F. Kettering Foundation contributed $200,000, and Birmingham’s Robert Meyer Foundation donated $100,000 for the lab. Kettering attended the groundbreaking on June 26, 1953, and Sloan was on hand to turn the first shovel.

Significantly, Sloan agreed to provide substantial funding to advance the cancer work being done at Southern Research under partnership with SKI.

Just five years later, K-M Laboratory II opened on Southern Research’s campus, a project spurred by the cancer program’s rapid growth.

Kettering was among Southern Research’s many important early benefactors. Besides May and the Meyer family, these include Robert I. Ingalls, Harry Frueauff Jr., Daniel Construction Co. and the Daniel Foundation.

 

This is Part Four of a series looking at the history of Southern Research.

Southern Research at 75: Ben May’s gift launches a cancer program

Southern Research Howard Skipper
Dr. Howard Skipper led Southern Research’s cancer program to many advances in chemotherapy.

Mobile lumber magnate Ben May wanted Southern Research to do something special with his $25,000 gift in early 1946.

The non-profit research organization’s original charter spelled out a mission to support the growth of Southern industry, but May demanded that his donation focus on improving human welfare in the region.

May’s seed money launched Southern Research’s cancer program, which over several decades has contributed to significant advances in cancer treatment and drug discovery.

Southern Research’s work in the 1950s and 1960s defined the fundamentals of effective cancer chemotherapy at a time when there was widespread skepticism about the practice. Led by Dr. Howard Skipper, the team demonstrated the principles of combination chemotherapy to counter resistance to a single drug.

Skipper’s strategy was straightforward. He would harness all of Southern Research’s resources to develop “concepts, hypotheses, theories, rules, laws, principles, mathematical models,” anything that would speed progress in the battle against cancer.

“Trial and error is a slow business,” Skipper recalled later. “But we have helped in forming a number of hypotheses that have withstood the test of time and proved helpful in providing guidance to many of our clinical associates in this country and abroad.”

IMPORTANT BONDS

Early on, Southern Research’s cancer program developed close ties to the Sloan-Kettering Institute for Cancer Research in New York, whose director, Dr. Cornelius Rhoads, had worked with Skipper in the Army Chemical Warfare Section during World War II. The Sloan-Kettering connection acted as a springboard.

SR 75th_Logo_Horz_RGBIn the 1950s, major funding for Southern Research’s cancer work began flowing in from the National Cancer Institute, a relationship still intact today, and the American Cancer Society, among others. Many individuals followed May’s lead with significant gifts.

Skipper’s cancer research program quickly grew in prominence.

Southern Research’s budget for health-related research in 1950 totaled less than $73,000. Ten years later, the figure was $1.7 million, more than half the entire budget.

Medical research remains a key focus for the organization.

“WHAT HE STARTED HERE”

Ben May
Ben May

May’s involvement with Southern Research didn’t stop with that game-changing $25,000 gift. He joined its board of directors in 1951 and remained a trustee for more than two decades. He also sponsored several research projects and contributed to the capital fund.

May and Skipper remained close over the years, often exchanging letters.

On Feb. 18, 1972, May replied to a letter he had just received from Skipper.

“Dear Howard:

“Thanks a lot for your letter of February 16. I note that you feel that my seed money was not wasted at the time of the Southern Research decisions. If there was success, I figure it was due to your ability and fine work,” May wrote.

In early November that year, May and Dr. Martin Perlman of Mobile traveled to Birmingham to visit Skipper at Southern Research. May sent a letter of thanks to Skipper on Nov. 9. “It was a real pleasure to be with you again,” he wrote, “and I felt fortunate that I could make the trip and see you as I did.”

A few days later, May was dead.

Soon after, Skipper wrote Perlman:

“I loved Mr. May. You may know it. I know that he knew it. I shall always be grateful to you for bringing him to the SRI Dinner not long ago, and for allowing us to have lunch and visit with you just a week before his passing.

“I sensed that he was happy with what he started here and that he was proud, almost as a father would be proud, or what we have been able to do and are trying to do,” Skipper wrote. “This is what I wanted so much for him to feel, but one can never repay the sort of help and inspiration he gave so unselfishly.”

 

This is Part Three of a series looking at the history of Southern Research.

How Southern Research cancer advances changed a life

Allen Tucker, left, poses with his brother Alex, a member of Auburn's track team. As a child, Allen was treated for leukemia with drugs Southern Research helped develop.
Allen Tucker, left, poses with his brother Alex, a member of Auburn’s track team, at a recent meet. As a child, Allen was treated for leukemia with drugs Southern Research helped develop.

Southern Research physicist Jim Tucker has spent most of his career tackling the challenges that must be overcome to make space flight possible, so he knows all about the organization’s important contributions to the Space Shuttle and other programs.

Tucker has also seen first-hand the impact of Southern Research’s breakthrough work in a completely different field – cancer research.

His 23-year-old son, Allen, is alive today thanks to the pioneering work of Southern Research scientists who discovered the fundamentals of chemotherapy and helped developed the drugs used in his treatment.

“It has always been cemented in my mind that Southern Research is one of those bastions of research that changes your life,” Tucker said. “That was never in doubt, but this has been reaffirming for me in a powerful way.”

The story begins in August 1996, when Allen was just 3. Though he was born with Down Syndrome, Allen was a healthy child until Acute Lymphatic Leukemia (ALL) struck. At first, he was lethargic and increasingly withdrawn. Then the pain started.

The pain was so severe that Allen let out a scream when the family car hit a speed bump on the way to Children’s Hospital. By this time, Allen was running a fever and had completely stopped moving.

Tucker and his wife, Pam, were terrified when the doctor diagnosed ALL. The chemotherapy, though, restored hope.

“It was a virtual resurrection. If you’ve ever seen a child with leukemia about to start the treatment, it’s frightening,” Tucker said. “Allen was motionless and had a morphine drip. Then they started treatment, and within two or three days, he was back. It was amazing.”

TREATMENT ADVANCES

Tucker said Allen’s treatment included doses of methotrexate, 6-Mercaptopurine (6-MP), and Leucoveron — three medicines that Southern Research played a prominent role in developing.

Southern Research scientists discovered a superior method for producing methotrexate, a drug that is used against a range of autoimmune disorders, and the organization held a patent on Leucoveron’s method of production. In addition, Southern Research scientists performed the fundamental biochemistry work on 6-MP, an important chemotherapy drug.

“That was quite remarkable to me,” Tucker said.

Later, Tucker began to understand that Southern Research’s groundbreaking work on chemotherapy had played an even more significant underlying role in Allen’s treatment. That’s because Southern Research scientists led by Howard Skipper decades earlier had established many of the principles that paved the way for effective chemotherapy.

Skipper and his team showed that every malignant cell has to be eradicated to ensure patient survival and that chemotherapy drugs given in combination can overcome resistance. Skipper also introduced the concept that a dose of chemotherapy kills a specific percentage of cancer cells rather than a specific number – an important treatment insight.

“The work Howard Skipper did here essentially led to the cure for leukemia,” said Tucker, who heads Southern Research’s materials research group. “I’m a physicist, so statistics are big to me, and it was his statistical revelations that cured my son’s cancer. He made a huge impact on a lot of lives, including mine.”

17 YEARS LATER

After Allen left Children’s, he still faced a grueling 2.5 years of chemotherapy to make sure every last cancer cell was gone. Once the treatment was complete, Tucker had a message for his Southern Research co-workers.

“We want to remind people here that without their work, our son would still be in tremendous pain, battling a disease that could have taken his life,” he said in a 1999 interview for SRItems, the internal publication.

Back then, Tucker wouldn’t use the word “cure” because he feared a recurrence. Today, Allen attends an adult special-needs program three times a week, where he can enjoy art and music. He remains cancer-free.

“The concept of a cure is something I can talk about 17 years later. He was 6 when he came off chemotherapy; now he’s 23,” Tucker said. “That’s where Southern Research comes in.”

Learn more about Southern Research’s current cancer research.

Cancer researcher Wallace Brockman to be remembered at service

Wallace Brockman,standing, confers with Glynn Wheeler about the cross-linking of DNA by the nitrosoureas.
Wallace Brockman, standing, confers with Glynn Wheeler about the cross-linking of DNA by the nitrosoureas.

The late Wallace Brockman, a key member of Southern Research’s pioneering cancer research team, will be remembered at a special service in Birmingham on Saturday.

A memorial service for Brockman, who died in Virginia in April at age 91, is set for 3 p.m. at First Presbyterian Church at 2100 Fourth Ave. North in downtown Birmingham.

In the early 1950s, Brockman, who received a doctorate in organic chemistry from Vanderbilt University, joined the group of Southern Research scientists assembled by Howard Skipper who developed the initial principles of cancer chemotherapy.

Brockman was one of the first researchers to tackle the problem of why some cancer cells are able to resist chemotherapy drugs. He reasoned that biochemical differences in resistant cells act as a shield for the cancer, and he devoted years to identifying these differences.

In 1963, Brockman, then head of the Drug Resistance Section at Southern Research, published a book chapter that outlined the mechanisms of resistance recognized at that time. Cancer researchers have praised the work as “an elegant biochemical framework for resistance” and “a highly prescient synopsis of resistance mechanisms.”

With these molecular-level mechanisms in mind, the team at Southern Research began experimenting with combinations of anticancer drugs. They showed that cancer resistant to one class of drugs could be killed by another. Today, cancer is generally treated with combination chemotherapy.

Brockman continued to contribute to the scientific community’s understanding of the biochemical action of antitumor and antiviral drugs until he retired from Southern Research in 1990.

“Dr. Brockman’s scientific work at Southern Research significantly advanced our knowledge of how to effectively target cancer cells resistant to treatment,” said Art Tipton, Ph.D., president and CEO. “His insights into the mechanisms of resistance laid a foundation for life-saving therapeutic approaches.”

Brockman is survived by his wife of 67 years, Jean Early Brockman; two daughters, Alison Brockman Booth and Anne Brockman Hoos; and two granddaughters, Liza and Meredith Hoos. Read an obituary.

In lieu of flowers, donations may be made in his name to The American Cancer Society.

 

Wallace Brockman's work at Southern Research over nearly four decades contributed to the understanding of cancer cell resistance.
Wallace Brockman’s work at Southern Research over nearly four decades contributed to the understanding of cancer cell resistance.

E.A. Dulmadge: Pursuing a research dream and attacking cancer

Elizabeth Ann Dulmadge – E.A., as she was known to her friends — arrived at Southern Research Institute in 1956 with more than a decade of experience in a clinical microbiology laboratory. She soon became involved in a significant new area of inquiry for the institute: cancer research.

Over several decades, Dulmadge’s work in Southern Research’s anticancer drug screening program helped the Birmingham-based organization make important strides in the battle against a disease doctors still struggle to understand.

To mark Women’s History Month, Southern Research is highlighting the careers of some of the female scientists and technicians who have made meaningful contributions to the institute over its 75 years of scientific investigation.

“E.A. Dulmadge should be an inspiration to many young people today, particularly girls interested in science,” said Art Tipton, Ph.D., president and CEO of Southern Research. “E.A. pursued her dream of conducting research that could help save lives, and her valuable work over many years accomplished that.”

Dulmadge came to the institute after earning a bachelor’s degree in biology from Birmingham-Southern College and working for 11 years as supervisor of the clinical microbiology lab at University Hospital, now UAB.

“I wanted more of a challenge to see what I could do,” she recalled in a 1981 interview to mark her 25th anniversary at Southern Research.

CELL CULTURE WORK

Her sense of timing in 1956 was ideal. After arriving at Southern Research, she spent six months testing antiviral agents for pharmaceutical company Parke-Davis, then transferred to the institute’s fledgling anticancer drug screening program.

She worked alongside Dr. Frank Schabel, whose groundbreaking research with Dr. Howard Skipper and others at Southern Research advanced the role of chemotherapy as an effective cancer treatment and expanded the understanding of how to better counter the disease.

“Dr. Schabel put me in charge of the cell culture work since my background in microbiology was an excellent prerequisite for this type of work,” she recalled.

In those days, pharmaceutical companies were developing large numbers of synthetic drugs, and it was up to Southern Research to test them for the National Cancer Institute. Dulmadge and the team annually screened 5,000 to 7,000 compounds in cell cultures – cells grown under controlled conditions, perfect for experimental studies.

Over the years, she continued her work with cell cultures, investigating the effects of antitumor agents on laboratory-grown tumors and studying cells resistant to anticancer agents. Her inquiries included an extensive look into tumor stem cells, or those cells that give rise to cancer. She also developed effective methods of growing tumor colonies for the screening tests.

ANTICANCER ADVANCES

Dulmadge, who contributed to at least two dozen scientific papers with her Southern Research colleagues, felt a deep sense of accomplishment in the institute’s chemotherapy research.

“I think of how much more we know about cancer chemotherapy now that we did in the beginning of the program,” she said in the 1981 interview. “It’s been a privilege to work here.”

Dulmadge retired in 1992, after 36 years at Southern Research. At her death, she left a majority of her estate to Birmingham-Southern, which created the Elizabeth A. Dulmadge Scholarship Fund in 2004 for students majoring in biology or music.

Southern Research’s anticancer drug expertise has led to the discovery of six FDA-approved medicines that treat the disease. The organization remains a key player in cancer research, having received more than $90 million in funding from the National Institutes of Health over the past two decades.

Mary Trader: Unraveling leukemia’s mysteries in a Southern Research lab

Mary Trader
Mary Trader

When Mary Trader joined Southern Research in 1966, she had a bachelor’s degree in chemistry from St. Mary’s Dominican College in her hometown of New Orleans and plans to stick around for one year.

Trader’s one year blossomed into a long career at Southern Research that saw her rise to head the Experimental Leukemia Section, where she played a significant role in the institute’s pioneering chemotherapy work.

“You can’t help but feel you have made some contribution to eradicating a dread disease,” Trader recalled in a 1981 interview marking her 25th year at Southern Research.

Because March is Women’s History Month, Southern Research is highlighting the contributions of several of the organization’s prominent female scientists over its 75 years of operation.

“Southern Research has been fortunate to have employed many great women scientists like Mary Trader in its history,” said Art Tipton, Ph.D., president and CEO. “Their careful and thoughtful work in our labs has deepened the scientific community’s understanding of cancer and other diseases.”

Trader’s career at Southern Research began as the search for new cancer-fighting drugs accelerated in its Birmingham labs, thanks to a steady stream of funding from the National Cancer Institute. For Trader, the first few years were spent in a crowded lab in the Ingalls West building.

“At the beginning of the screening program, there was already a backlog of drugs that had never been tested against cancer,” she recalled. “We had a field day testing everything the government had to send us.”

IN THE LAB

In 1973, Trader was appointed head of the Experimental Leukemia Section. Her lab conducted work in mouse leukemia that contributed to improved cancer treatments, particularly of acute lymphocytic leukemia, or ALL.

In those days, ALL spread rapidly and often fatally in children, but because of advances coming from Southern Research and other organizations, survival rates began to rise sharply.

The work performed by Trader’s team contributed to these advances in several ways. For one thing, her lab developed at least 20 lines of drug-resistant leukemias that proved useful in testing drug treatments. These resistant forms of leukemia were utilized in biochemistry and cell culture studies to expose the mechanism of drug resistance.

“We want to know why a drug does not work in a person’s body and what happens to it,” Trader said in 1980.

In addition, extensive testing carried out in Trader’s lab demonstrated the validity of famed Southern Research cancer researcher Dr. Howard Skipper’s theory that just one cancer cell can trigger the fatal disease. Skipper introduced the concept that every single cancer cell must be eliminated to ensure the survival of the patient.

“This added some basic knowledge to understanding the magnitude of the disease of cancer,” Trader recalled.

Her lab also conducted studies on combination chemotherapy that explored how new and existing drugs could be used together or in sequence as an effective treatment regimen for leukemia and many different forms of cancer.

“Everything we have learned — proper scheduling of drugs, problems of drug resistance and demonstration of one cancer cell’s impact — has tied in with increasingly successful treatment of children with leukemia,” Trader said in 1980.

‘INSTANT RECALL’

Soon after marking 30 years at Southern Research, Trader died from a heart attack in 1987. She was 64 years old.

Dr. Russell Laster, then head of the institute’s Cancer Screening Division, noted her immense contribution to the organization’s work. “She was like a computer with 30 years of storage and instant recall, and you can’t replace that.”

During her career as an experimental cancer chemotherapist, Trader contributed to at least 30 scientific papers, including several with Skipper and another prominent figure in cancer research, Dr. Frank Schabel. She also presented her leukemia findings at national meetings held by the American Association for Cancer Research and others.