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Charles G. Cochrane has been a member of the Department of Immunology since its founding in 1961.
He is shown here with a figure that appeared on the cover of the journal Science,
representing some of his research on surfactant protein.

(Figure reprinted with permission from Science 254 (25 October 1991).
Copyright 1991 American Association for the Advancement of Science.)

 

Forty-One Years and Counting

rofessor Charles G. Cochrane calls himself "the Last of the Mohicans." Not because he's friends with Daniel Day Lewis or because he lives off the land with his adopted companion, Hawkeye, but because he is the last of a breed--the last active original member of the Department of Immunology at The Scripps Research Institute (TSRI).

"The department goes all the way back to the beginning of Scripps," says Professor Richard Ulevitch, who is presently chair of the department and who started his career working in Cochrane's laboratory in the early 1970s. Of course, Ulevitch adds, when it all started over 41 years ago, both the department and the institute had different names.

That year was 1961, and a group of young immunologists led by Frank Dixon--among them, Cochrane--had come from Pittsburgh to La Jolla to start the Department of Experimental Pathology at what was then called Scripps Clinic and Research Foundation (SCRF). SCRF had been formed a few years earlier from the Scripps Metabolic Clinic, established in 1924 with a gift from Ellen Browning Scripps.

"When we first came from Pittsburgh, the idea was to focus on immunology and do that so well that we would grow in strength," says Cochrane. "We were down on Prospect Street in La Jolla next to the old Scripps Hospital."

The five occupied the brand-new (and unfinished) Timken­Sturgis Research Laboratories Building, where they were shortly joined by two other departments--Microbiology and Biochemistry. For a while, all three would occupy the Timken­Sturgis building, sharing an amphitheater, a library, and other support facilities.

"In those early years," recalls Professor Thomas Edgington, who came to the department in 1965, "you knew everybody."

"We ate lunch in the lunchroom with the doctors in Scripps Clinic, and we would chat about things in the lab and clinic," says Cochrane. Things soon grew beyond that small dining room.

DEEP ROOTS AND A LASTING LEGACY

"We laid down a basic foundation in the institute that promoted maximal freedom for the scientists to pursue their individual interests unfettered by committees and regulations," says Cochrane. "Then we all went to work to put the institute on the map, through publications and presentations at national and international meetings. We were looking at a future that was undetermined--a horizon beyond our scope of imagination."

"We would meet with all the members of Scripps, Salk, and the UC School of Medicine in one room to discuss research projects and journal articles of common interest," says Cochrane. "We should have taken pictures, given all the growth that followed in the three institutions."

TSRI, of course, has grown from the original handful of researchers to almost 3,000 employees overall, with a staff of nearly 300 full-time investigators, nearly 1,000 research associates and graduate students, and a total of over 1,500 technical and support staff.

The Department of Experimental Pathology underwent many changes as well. In the early 1970s, it split into three separate departments--cellular immunology, molecular immunology, and immunopathology. Of the three, one became today's Department of Immunology. Later, the separate departments of Cell Biology and Molecular Biology were founded.

Today's Department of Immunology has 90 investigators, senior research associates, and guest scientists, along with hundreds of postdoctoral fellows and technicians, a handful of graduate students, and dozens of other support staff. The focus has broadened significantly in terms of the number of diseases that are studied and the approaches used--members of the department have always sought to put all new technologies to work as they are developed.

"But the bottom line is still the same," says Ulevitch, "understanding how the immune system functions in the setting of various diseases."

A UNIFIED DEPARTMENT OF DIVERSE INTERESTS

Today, as 41-plus years ago, TSRI's immunology department seeks to understand the major human diseases in which the immune system plays a role. These encompass all the major categories of diseases, including pathogenic viral infections, like Ebola or HIV; autoimmune diseases, like diabetes or lupus; diseases that involve the innate immune system, like bacterial-induced septic shock; and diseases where immune-based therapy can possibly make a big difference, like cancer.

Many major diseases involve the immune system either directly or indirectly. Many, in fact, result directly from some action or inaction on the part of the immune system. Our bodies depend on our immune systems to fight off common pathogenic infections on a daily basis and maintain our health. Many diseases, like diabetes and lupus, are the direct result of our immune system's autoimmune actions.

And even in diseases, like certain cancers, that are not caused by our immune system, immune cells may hold the secrets to the cure. Significantly, cells of the immune system have the ability to kill tumor cells and some investigators at TSRI are attempting to harness this ability in cancer patients through immunotherapies--drugs that help the body's immune cells target and destroy tumors.

TSRI investigators in the department seek to extend the understanding of human immunology to the molecular level so that enough information can be assembled to enable drug development and the creation of new therapeutic approaches.

"We have good interactions with our colleagues and it's a stimulating environment," says Professor Ralph Reisfeld, who arrived at TSRI in the mid-1960s. "I've received a lot of help from our colleagues. This is very important."

A TREATMENT FOR DAMAGED LUNGS

Cochrane has developed a synthetic pulmonary surfactant that has been undergoing clinical trials since 1996 and is currently in the final Phase III clinical trials for two indications. It is called KL4-Surfactant, named for the synthetic peptide, KL4, that mimics Surfactant Protein B. One of these indications is for pre-term infants who are born prior to the time their natural lung surfactant is made in the lungs.

The synthetic surfactant is administered directly into the lungs of the babies shortly after birth and within hours, their lung function approaches normalcy. Babies are being treated this way in Russia, Europe, and the Americas.

Current treatments for pre-term infants involve using surfactants derived from chopped cow or pig lungs, but these are expensive and they cannot be produced in quantities sufficient for pre-term infants world-wide, let alone for adults. "Synthetic surfactant is the only hope for infants in developing countries", says Cochrane. "It is gratifying to know that a therapeutic coming from Scripps will help millions of infants around the world who currently have no treatment."

There is a similar condition of collapsed lungs in adults known as acute lung injury, or respiratory distress syndrome, with any number of causes, such as trauma, smoke inhalation or sepsis.

"There is no approved therapy and about 30 to 40 percent of these mostly young people die from it each year in this country--about 50,000 in total," says Cochrane. "A Phase II trial is currently underway in which the injured lungs are being washed with dilute KL4-Surfactant to remove inflammatory exudate as they are being re-expanded."

Results so far are encouraging. But Cochrane believes the pulmonary inflammation requires, in addition, inhibitors of specific effectors of the injury. Current studies are directed toward this goal so that these inhibitors can be incorporated into the surfactant.

This research may also lead to an aerosol treatment for acute asthma, a possibility that Cochrane and his group are currently investigating. Clinical trials should begin this year.

ne afternoon last summer found Professor Cochrane busy at work doing part of his daily routine--entering numbers into a calculator from a page in a well-worn notebook with numbered pages. Data from the week's experiments, he says, explaining that in recent years he has reduced his laboratory from over 50 members to just four, including long-time associates Sue Revak and Zenaida Oades.

"It's like I'm a postdoc again," he says.

And while Cochrane may also call himself "the last of the Mohicans," there is at least one major difference between him and the tragic figure of Chingachook in James Fenimore Cooper's famous novel. Cochrane's tribe--in the broadest sense, his department, laboratory, and the laboratories of those whom he has mentored--has grown in the last 40-odd years. Grown and flourished.

Over the years, Cochrane, like all the investigators in the Department of Immunology, has kept one tradition alive--the training of postdoctoral fellows. Soon after it came into existence over 40 years ago, TSRI began training postdocs, and young M.D. and Ph.D. graduates have been burning the midnight oil (and burners) in the department's laboratory for several generations now. Through the years TSRI has trained thousands of postdoctoral researchers. In fact, a lot of important immunologists have trained at Scripps.

"This is a distinguished place to train in immunology," said Professor Donald Mosier in 2001 as he took a break from putting the paperwork together for the renewal proposal of the training grant he administrates.

This grant currently provides eight slots that give salary and other support for postdoctoral fellows. Established when the institute was founded in 1961, it is the oldest continuously funded postdoctoral training grant in the country and one of several training grants in the Immunology Department at TSRI.

"The institution should look upon the training of postdocs with great pride," says Cochrane, who knows whereof he speaks. He has been training them longer than any other active investigator at TSRI. "They come here and learn without limits and when they leave they have done extraordinarily well. That's always a pleasure to see."