Alfred Alberts, Unsung Father of a Cholesterol Drug, Dies at 87

Alfred. W. Alberts, a largely unknown hero behind the first cholesterol-lowering statin approved in the United States, died June 16 in Fort Collins, Colorado. He was 87.

His son Eli confirmed the death, at a rehabilitation facility. Alberts had a heart attack two weeks earlier and then bypass surgery. A resident of Wycoff, New Jersey, he had been visiting his son in Colorado at the time.

Alberts’ story was an unlikely one. He lacked the usual credentials for a medical scientist — an M.D. or a Ph.D. — and started out as a lab technician. Yet he ended up as a peer to established researchers like P. Roy Vagelos, a biochemist who became chairman of Merck, the giant pharmaceutical company.

“He was my right-hand man,” Vagelos said in a telephone interview. “We were more like brothers, like twins.”

In the late 1970s, Alberts discovered the chemical compound that led to the drug lovastatin, a leading remedy for high cholesterol. (Statins are a class of drugs that help lower cholesterol levels in the blood.)

But even fellow scientists did not always know who Alberts was.

“He never sought publicity outside Merck,” said the Nobel laureate Dr. Michael S. Brown, of the University of Texas Southwestern Medical Center in Dallas. “He never sought attention. He was basically a shy person.”

As a result, he said, Alberts “hasn’t gotten a lot of credit.” At the time of Alberts’ discovery, cardiologists and public health experts had been at a loss to help people with high cholesterol levels. Diet and exercise had modest effects, at best. Although a few drugs were available, they produced difficult side effects.

But since 1964 scientists had known that there was a path to a better drug, and that it depended on the discovery of a compound that blocked what some called the pacemaker enzyme. That enzyme, HMG-CoA reductase, is needed to synthesize cholesterol. The more of it that is around, the faster cholesterol will be made.

The challenge was to find that compound and ensure that it would be safe for humans to take as a drug. There were many claims to success, but none held up.

Vagelos, who had just begun a job as head of research at Merck, suggested that Alberts take on the task.

Almost immediately, Vagelos learned that Merck had a competitor. Dr. Akira Endo of the Japanese drug company Daiichi Sankyo had already found such a compound, and his company had tested it in the laboratory and in dogs and was starting tests in people. “I said, ‘Oh, my God, we are behind already,'” Vagelos recalled. “Then I said: ‘The hell with it. We are a lot faster than they are. Let’s go ahead.'”

Soon Alberts found a similar compound secreted by aspergillus, a fungus. The compound, he found, proved effective in the laboratory and in animal studies, so Merck began tests in people, and it did exactly what it was supposed to — reduce levels of LDL cholesterol, the dangerous kind.

Suddenly Daiichi Sankyo stopped all tests of its compound. The company would not say why, but the rumor was that it was causing tumors in dogs. That did not bode well for Merck.

“Their compound was an inhibitor of HMG-CoA reductase,” Vagelos said. “Ours was an inhibitor of the same enzyme. If the rumor was true, that it was causing tumors in dogs, the implication was that it would cause cancer in humans. We could not put humans at risk. I decided we would stop all studies.”

He continued: “Al was depressed by this. He was emotionally tied to the compound and was sure it would ultimately be found to be safe.”

With the drug, in which he had invested so much hope, yanked from clinical studies, Alberts considered leaving Merck, his wife, Helene Alberts, said in an interview. He stayed, though, while the company’s safety assessment team tested the drug. It ultimately concluded that lovastatin did not cause cancer.

Lovastatin, the first statin on the market, was approved in 1987. Alberts, whose own cholesterol was elevated, took it himself.

The drug’s success was the triumph of his life.

“Behind every drug there are heroes,” Brown said, and Alberts was “an unsung hero” of lovastatin.

When Alberts recently displayed the first signs of a heart attack, he was on vacation with his family in Steamboat Springs, Colorado. He went to a small nearby hospital, where an emergency room doctor called Alberts’ doctor in New York.

The New York doctor said, “Do you know who you have there?”

The emergency room doctor, Helene Alberts said, “ran out and Googled him.”

When the doctor was arranging for Alfred Alberts to be taken to the University of Colorado Hospital in Aurora by a medevac helicopter, he told the doctors there that Alberts had discovered lovastatin.

And when Alberts arrived in Aurora, the medical personnel there greeted him like a celebrity. “People wanted his autograph,” his wife said.

Alfred William Alberts was born in Manhattan on May 16, 1931, and grew up in Brooklyn, New York, attending Erasmus Hall High School and Brooklyn College. He was 21 when he met Helene Cuba, who was 17, on a blind date. Both were the only children of divorced parents. They married two years later.

After a stint in the Army, Alberts was accepted into a Ph.D. program at the University of Kansas, in Lawrence. But Helene Alberts, who had accompanied him, came to feel isolated in northeast Kansas, and two years later Alfred Alberts transferred to the University of Maryland to finish his doctorate in cell biology.

While there, Helene Alberts said, Alfred Alberts’ financial support from the GI Bill ran out, and he needed money to support his family.

One day, at the end of a biochemistry course, the professor, Earl Stadtman, a biochemist at the National Institutes of Health in Bethesda, Maryland, asked his students, “Does anybody need a job?” If so, he said, see him.

Alberts leapt at the opportunity. He abandoned the Ph.D. program, even though he had done all the required research and had only to write a dissertation, and took a job as a lab technician at the Institutes. He assumed he would be working with his revered professor, Stadtman. Instead, in 1959, he ended up working for Vagelos, who taught him biochemistry.

In 1966, Vagelos accepted a job as head of the biochemistry department at Washington University in St. Louis. Alberts wanted to come along, although Vagelos advised him not to, reminding him that he had a secure government job at the NIH.

“I warned him not to come because he did not have a Ph.D.,” Vagelos said.

But Alberts insisted on going, and he succeeded there. He was promoted to assistant professor and then associate professor of biochemistry with tenure.

Besides his wife and his son Eli, Alberts is survived by another son, Mitchell; a daughter, Heather Alberts; and two grandchildren. After his bypass surgery, Alberts was taken from the university hospital in Aurora to the Fort Collins rehabilitation facility to be near Eli.

In 1975, when Merck offered Vagelos a job as head of research, Alberts again wanted to join him, and again Vagelos warned him away, reminding him that he had a secure position at the university and that his future at Merck would by no means be assured.

Once again, Alberts ignored the advice and chose to accompany Vagelos, signing on with Merck at its headquarters in northern New Jersey. Although Alberts shunned publicity and did not like to write medical papers, Vagelos cited him as a co-author on many of his. But he gives Alberts full credit for lovastatin.

“That was Al’s discovery,” he said.