Nobel Laureate David Julius on Science: Persistence Pays Off

“Any country that wants to have strong research needs funding from its people and government,” says David Julius, a co-winner this year’s Nobel Prize in Physiology or Medicine.

Julius, a professor and chair of the Department of Physiology at the University of California, San Francisco, was awarded the prize along with Ardem Patapoutian, a Beirut-born neuroscientist and professor at the Scripps Research Institute, in San Diego, California. (See a related article, “Nobel Laureate Ardem Patapoutian’s Path to the Prize Started in Beirut.”)

David Julius and colleagues in his laboratory at UCSF have focused on a series of proteins called TRP ion channels that are key players in transmitting sensations of heat, cold, and pain to the brain. One of these proteins, TRPV1, responds to capsaicin, the chemical compound that gives chili peppers their heat. Another, TRPM8, detects the coolness of menthol. A third, TRPA1, the so-called “wasabi receptor,” is involved in inflammatory pain.

Julius’s team’s work has led to new insights about the fundamental nature of pain and potential targets for pharmaceutical companies to work on new, nonopoid painkillers.

In an interview with Al-Fanar Media, Julius talked about his lab’s discoveries and shared with young investigators some tips on how to succeed.

Why are senses of temperature and pain so crucial to human and living beings?

The main reason is that pain sensation is a very important protective function. If you cannot sense things that can cause pain, then you are at great risk of injuring yourself. Knowing that something is very hot or very cold is critical to protecting your body. Moreover, knowing that things are hot or cold helps us readjust our core body temperature and adapt to our environment. But most importantly is to let us know when we come in contact with something that can harm us.

Were the TRPV1 and TRPM8 receptors that you discovered previously unknown?

That’s a good question. We have discovered TRPV1. As for TRPM8, it had been identified as a gene whose expressions are somehow altering cells that form tumors. But the meaning of that was unknown. … We figured out that the protein is a receptor for menthol and cold.

Tell us about your work. When did you start and how long did it take?

It is hard to know for sure. Perhaps in 1995, we started working on this. It took us two to three years to make our first discovery identifying TRPV1 and two or three years later to identify TRPM8. Then, we continued our studying of these protein channels and others, questioning their effect on mice, what kind of drugs they like, and how they look on the atomic level. It took us 20 to 25 years, studying many questions about them and testing hypotheses about what we think they can do. They are like my children.

Such a long time, do you think persistence, determination and being passionate about your work is necessary for any scientist?

Absolutely, I keep telling people in my life when they have troubles that persistence pays off.

The insights of your work could have great practical applications, like potential new painkillers. Could you tell us about this?

If there is a practical goal, then it is to develop nonopioid drugs, to treat pain without the potential addictive side effects of opioid drugs. We do not do that translation work [of turning research into practical applications]. There are lots of drug companies that are screening drugs, compounds, different molecules, and how they work on the TRPV1 and TRPA1 receptors.

What about the temperature-sensitive receptors?

First of all, we worked on natural products, like chili peppers and mint leaves that we use a lot in our kitchen. But from a clinical point of view, especially TRPV1 and TRPA1, those enhance pain during inflammation. So, they are not only involved in sensing temperature or chemical irritants, but they contribute to pain hypersensitivity when you have an injury, like arthritis. Therefore, many companies are interested in having drugs that modulate these receptors.

What about TRPM8, the menthol receptor?

Menthol mimics the sensation of cold, which activates TRPM8 receptors, also known as cold receptors. We use a lot of those products every day, like in toothpaste, for example. There are injuries that make you hypersensitive to cold, like an injury to nerve fibers. There could be medical applications to treat this cold hypersensitivity after nerve injuries.

In the Arab world, scholars face huge hurdles to fund their research. Have you faced similar problems?

At times, we all get worried about that. I cannot complain as most of my work was funded by the National Institutes of Health, the nation’s medical research agency. … However, I keep my labs small so I do not have to worry about writing grants all the time. I like smaller labs to talk to everybody. Nevertheless, there are times that I was worried about funding. Still, it is an issue for everybody, particularly for younger investigators, and a constant issue in science.

What is your advice to scholars in the Arab region who face difficulties to fund their work?

In the United States, what really makes medical research possible is that there is public funding of research, like the NIH and the National Science Foundation. Without such support from society, it is very difficult to have a sustained research program. Philanthropy is very helpful for individuals, but it is often not enough to have that without government funding. Any country that wants to have strong research, needs funding from its people and government. Yet, it is not always possible to put money aside for basic biomedical research.

To achieve their goals with limited resources, what would you tell young Arab scholars?

Maybe they have to do part of their studies abroad, to see if they can learn some science abroad. It does not solve the problem, but you can later on come back and do science in your home country. In the long run, that is what people would do, to build scientific enterprise in one’s country. Many people try to work in France, Germany, the United States and countries with established science. Young  people who would come back would be the leaders to build science back home.

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Have you visited the Arab world or worked with scholars from the region?

I have not travelled much in the Middle East. … I have interacted with Arab scientists who come to work here at UCSF. I have colleagues from Iran and Saudi Arabia. Scientists generally do not care about what nationality or religion you are, we see ourselves as members of an international community.

How do you see teamwork, being fond of working in small labs? 

When students and postgraduates come to my lab, they usually pick something they are interested in to work on. They are their own little projects that may lead to connections to other projects. It is really a day-to-day work with meetings once a week when people talk about their findings and everybody else giving them suggestions. People are free to ask one another and help each other. I am lucky to work with people who are very open and generous with their time to help people. They have the freedom to speak to people in other labs and start collaborations.

“Scientists generally do not care about what nationality or religion you are. We see ourselves as members of an international community.‘‘

To whom do you feel grateful for this achievement? 

I feel grateful for the people I worked with at the labs, all the students and fellows, who really are the ones doing the work. I was fortunate to have a wonderful group of excellent collaborators in the United States and abroad. I would thank all the funding agencies that make it possible; my family put up with my obsession to do this work; my wife, who is also a scientist; and my parents who let me to do what I wanted and never tried to tell me, Well that is not a good thing to do to get more money. They did not care about that. They were excited for my excitement, and supported me with no interventions.

This interview has been edited for brevity and clarity.

David Julius: The Science of Pain and Touch