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Questions & Answers – Michael Croft

The role of T cells has long been overshadowed by their antibody-producing brethren. The work of Michael Croft brought them into the light.

As a high school student, Michael Croft, Ph.D., Professor and Head of the Division of Immune Regulation, was interested in biology and not much else—with one exception: “Pretty much all I did was play soccer,” remembers Dr. Croft, who grew up in a small village in the Midlands of England. Ultimately, his scientific interests gained the upper hand and he pursued a bachelor’s degree in applied biology. The four-year degree required him to work several months each year in a research lab in the pharmaceutical industry to gain hands-on experience in a real world setting.

During one of these stints Dr. Croft landed in the immunology department at Glaxo Pharmaceuticals in London and he credits that experience for triggering his interest in immunology. “As part of the degree, we didn’t learn much about immunology,” he says. “Back then, there really wasn’t much immunology anywhere.” But Dr. Croft was hooked. He returned to Glaxo for a short period as a technician before starting his Ph.D. in immunology at Sussex University in Brighton, U.K. During his doctoral thesis he studied T cell factors that induced B cells to produce antibodies, laying the groundwork for his career as a pioneering T cell researcher.

Dr. Michael Croft on Mt. Palomar

WHAT HAS CHANGED SINCE YOU ENTERED THE FIELD?

We are much more precise in what we do. When I started out you would take fluid from cultured T cells that may contain 20 or 50 different proteins and you would throw the mixture onto other cells and see what happens. Now, we know most of the proteins that play a role in the immune system. We don’t necessarily have a complete picture of how and where they function but they all have been characterized to a certain degree.

WHAT IS THE ROLE OF IMMUNOLOGY FOR THE FUTURE OF MEDICINE?

Most people probably still don’t quite appreciate how many diseases are caused by the immune system or how many diseases can be prevented by the immune system. Cancer is a great example. Most of the work that has been done on cancer in the last 20 years was not immune-related. No one really believed that you could manipulate the immune system and get any strong anti-tumor effect.

ARE THERE OTHER EXAMPLES?

Cancer is probably the main one but some of the successes we’ve had with biologics, the large manufactured drugs such as antibodies that are being used more and more for treating patients, have shown that the immune system is really a major player in many types of inflammatory disease. The fact that you can manipulate the system and can get therapeutic benefits in patients is tremendous. Certainly, when I started in immunology there was little to say about how you can target the immune system and heal disease.

WHAT ARE THE BIG QUESTIONS YOUR RESEARCH FOCUSES ON?

First and foremost, I consider myself a T cell biologist. The primary question guiding my research has been how can you generate more T cells that are either protective or pathogenic and how can you manipulate those T cell responses? The focus has been on so-called co-stimulatory molecules that drive better and more effective T cell responses and that really has been my primary expertise for over 15 years.

WHAT HAS CHANGED SINCE YOU ENTERED THE FIELD?

We are much more precise in what we do. When I started out you would take fluid from cultured T cells that may contain 20 or 50 different proteins and you would throw the mixture onto other cells and see what happens. Now, we know most of the proteins that play a role in the immune system. We don’t necessarily have a complete picture of how and where they function but they all have been characterized to a certain degree.

WHAT IS THE ROLE OF IMMUNOLOGY FOR THE FUTURE OF MEDICINE?

Most people probably still don’t quite appreciate how many diseases are caused by the immune system or how many diseases can be prevented by the immune system. Cancer is a great example. Most of the work that has been done on cancer in the last 20 years was not immune-related. No one really believed that you could manipulate the immune system and get any strong anti-tumor effect.

CAN YOU EXPLAIN WHAT A CO-STIMULATORY MOLECULE IS?

Essentially, it is a molecule that stimulates a T cell to do something that it couldn’t do without it. For example, it stimulates that cell to divide and accumulate in great numbers, or to make specific proteins. I started with the concept of co-stimulation and concentrated almost exclusively on what’s known as the TNF family of proteins. There are a set of six or seven of these proteins that are really strong regulators of T cells, which means they play an important role in antiviral, inflammatory, and autoimmune responses.

ARE THERE ANY CLINICAL APPLICATIONS FOR YOUR WORK?

One of our initial discoveries has been in asthma and there are clinical trials blocking the molecules we have worked on, but there are other indications, such as inflammatory bowel disease and organ transplants. In general terms, we can suppress the immune system and there’s a potential application for anything where the immune system is overactive. On the flip side, the molecules we work on are targets for stimulatory agents in clinical studies of cancer, in this case trying to generate better anti-tumor immune responses.

WHAT’S THE BEST PART OF BEING A SCIENTIST?

The discovery part—simply the fact that you can learn new things all the time is the most attractive part of what we do. We are all experts to a certain extent but we are not truly experts because we are always learning something new.

BY THAT DEFINITION THERE’S NO SUCH THING AS AN EXPERT?

[Laughs.] There are people who know a lot about certain things.

ANY POINTERS FOR STUDENTS CONSIDERING A CAREER IN ACADEMIA?

First of all, you have to have a major passion for your area of research, whatever it may be. And then it requires a certain type of logic that not everybody has, but which I think helps tremendously. One of the toughest things is to not just understand the work you are doing, but the work everybody else is doing in the area. It is too easy to become focused on your own little universe and what you are working on. If you can see the big picture it helps push your own research further and of course, it is much more interesting if you can also understand what other people are doing. It comes back to being an expert. We are all fairly intelligent people and fairly good at what we do. But ultimately we are feeding off of each other since we learn from other people just as much as we learn from the experiments we do in our own labs. I think that’s key.

WORK-LIFE BALANCE IS IMPORTANT TO YOU. HOW DO YOU RECHARGE?

I spend a lot of time tending to my garden. I like being surrounded by things that grow. The other thing I really enjoy is riding my motorbike. I own a Yamaha FJR1300, which is a mix between comfort and speed. I don’t go slowly but I don’t race like a 20-year old either. On weekends, I like to go out into the mountains by myself and enjoy the twisties.