Fascination of Science, page 33
No?
My life was okay. It was normal. I was loved by my parents—my grandparents. Now, of course, with DNA, it could be that I'll discover who my father is.
Are you curious?
I am, maybe because I'm a geneticist. I'm curious about where half my genes came from. I'm not obsessed with it, but I'm curious.
“I have always known I'm the boss, this is my job, and I am doing it.”
Ruth Arnon | Immunology
Professor of Immunology at the Weizmann Institute of Science, Rehovot
Robert Koch Medal 1979
Israel
Professor Arnon, in kindergarten you were already one of the best students. What motivated you?
I was curious, asking questions all the time, and I had a good memory. My older siblings saw that I was ready to absorb things and they enjoyed teaching me. So, I already knew arithmetic and how to read and write when I entered school. In fact, I was so good that I was able to jump straight to the second grade. Quite soon, I also discovered my love for science by reading the book Microbe Hunters by Paul de Kruit, which described the fascinating lives of great scientists and their discoveries. I was particularly thrilled by Marie Curie, who was so curious that she went to the lab in the middle of the night to check on her experiments. I didn't even know yet that this was called research, but it was definitely what I wanted to do! When I was 15 years old, I decided to study the life sciences, biochemistry, medicine, but I also realized I was not interested in becoming a doctor, who only treats patients.
Did your parents influence your decision to go into science?
Both my parents always taught me that education is important, as it gives additional meaning to life. My mother was a teacher, and she was constantly pushing for education. I think she was also pushing my father to study electrical engineering, by telling him: “Don't complain; just follow your wishes and your dreams.” My father was an unbelievable person and was important in my life, as he was knowledgeable about a lot of things, not just things of his profession. I think his example had an indirect effect on my life.
What kind of research do you do?
As an immunologist, I study the immune system. Our immune system is geared to recognize foreign materials and to eliminate them. Thus, it fights the diseases induced by viruses or bacteria. Normally, our immune system also recognizes our own body components and does not react against them. But if something breaks down in this mechanism of self-recognition, it can result in an autoimmune disease.
My team started researching multiple sclerosis (MS). We synthesized a polymer that is similar to the protein that induces MS, which would serve as a research tool to study the mechanism of the disease on animal models. What happened was that our polymer did not induce the disease; rather, it inhibited it. And this led to the development of a drug against multiple sclerosis, called Copaxone.
So, it was a discovery by accident?
Absolutely. We had treated guinea pigs with our synthetic polymer, and in the control group eight out of ten animals died, whereas in the treated group only two animals were sick and the others were completely cured. It was a revelation when we discovered that our synthesized material could prevent and even inhibit the disease. It was a fantastic feeling!
And then we had to continue, because you have to look for the mechanism behind the results. As a scientist, when you have a phenomenon, you are always interested: Why did this happen? So, it never ends. And tracking the mechanism is even more interesting than the discovery.
How long did the whole process take?
From the initial basic research to the FDA approval of the drug took twenty-nine years. We worked on the basic research, understanding the animal model of the disease, for approximately nine years. We tested it with different species, including primates. And then we spent about seven or eight years collaborating with clinicians who were doing the clinical trials with patients. It was only after we produced successful results in the clinical trials that a pharmaceutical company became interested and started development of the drug. It took another nine years until they got the approval of the FDA.
Can you describe how your research has made a contribution to society?
The development of Copaxone was a significant contribution. When we started our research, there was no drug at all for MS and the situation that patients faced was terrible. One year before Copaxone was approved by the FDA, the Interferon Beta drug came on the market, so unfortunately we were only second on the scene. But there had remained a great demand for a better drug against multiple sclerosis. Hundreds of thousands of patients are using our drug to this day, and they all have significantly less exacerbation. So, MS patients today can live an almost normal life. It is the highest satisfaction for me when patients tell me “Copaxone changed my life.”
Wasn't it a big disappointment to be only second?
Partly. But that's life. There was some competition, as we knew about development of the other drug, and so we were a bit disappointed when they got the approval some months before us. This was already at a stage when the drug was in the hands of the company and we didn't have any influence anymore. It took the company nine years to do the scaling up, to fulfill all the requirements of the regulatory authorities, and they had to do another phase 3 clinical trial. But it didn't really matter. Some patients are helped by our drug, and some are helped by the other drug. Both drugs are still selling today.
You are one of the pioneering scientist women in Israel. How was it for you as a woman in this field?
It took more energy because I also had a family—a husband and two children. As a woman, you have to have children while still young, but you also can't postpone your career until you have raised your kids. You have to do both at the same time. So, when my children were small, my life consisted of very, very long days. I was getting up at 4 or 5 o’clock every morning to do all my creative work of thinking and planning. This was my time of peace and quiet, until the kids got up at 7 o’clock.
We always lived close to work, so I could go home and have lunch with them. I stopped working at 4 o’clock in the afternoon, and often I went back to the lab at night, when the kids were asleep. This was my normal routine; I didn't see it as exceptional. My husband was very supportive, and when I wanted to study in Melbourne, London, or Paris, he took a leave of absence from his work to come with me on what we called our “mini-sabbaticals” for three or four months. And we both loved it. We always supported each other, and I think this is very important.
Some women prefer to work in industry because of the more regular working hours. Did you ever consider making that change?
Never. I always wanted to decide on my own what I research. And in industry, someone sets a target and you have to push in that direction. In basic research, you follow your curiosity and sometimes it will lead to something that can be applied, sometimes it will not.
So, how was your work-life balance during those years?
I love music, opera, and theatre, and I feel enjoying life is important, as well. But science and family always came first, and I invested in both the best I could. With six grandchildren and one great-grandchild, I have a full family life. I have always worked hard, but I hope I found the right balance among work, my children, and moments of pleasure with my family. Many years ago, we took a whole month off and went to the national parks of Africa. The children still remember this trip very fondly.
Why should young people study science?
They should always follow their instincts and their passions, and only study science if they love it. Because you will only do your best doing what you love to do. You can feel it in your bones if something is right for you. What fascinates me about science is that you can choose your own path. Of course, there is always the risk of being unsuccessful. Because sometimes you work on a project, and it just doesn't give any results.
I really don't say that lightly, but you also need to be lucky. I know many scientists who work very hard and simply have not been as lucky as my colleagues and I were. Sometimes you reach a dead end, and you have to make a switch in your mind and say, Well, I thought this would be the way, but it is not.
Have you experienced ups and downs in your research?
I always had doubts. That is why I constantly worked on more than one project at the same time, hoping that when one was down, there would be another that was up. So, I can still enjoy my work.
At the moment, I am also working on the development of a universal vaccine for influenza, which is now in a phase 3 clinical trial. Soon we will know the results. It may be a complete failure. It worked beautifully in animals. It worked in phase 1 and in phase 2. But there are many drugs that have failed totally in phase 3. I hope that won't be the case. It does not help if I am nervous all the time. So, I try to look on the bright side.
You have held a lot of high positions, both at the Weizmann Institute and on several scientific bodies. Did you find that women are treated differently?
I have worked with men; I have worked with women; I've had men above me and men under me; and I have never seen a problem in this. A scientist is a scientist, and the gender doesn't matter to me. I hope it doesn't matter to others, either. And even after my children were grown, I found being a woman changed nothing. I could evolve, and it was up to only me to decide what I wanted to do with my time. I never felt any discrimination, either as head of the department or as dean, or as vice president, or as president of the Academy. I have always known I am the boss, this is my job, and I am doing it.
But what can be done to get more women into science?
We have to attract girls to physics and to mathematics and chemistry, so that they will not be afraid of those subjects. And we have to improve the level of science teaching in high school. for both boys and girls. This is a development I strongly recommend and support, as science is our future.
Today, the wealth of a country is defined by its knowhow and its technology, rather than by its natural resources. So, it is important to devote more effort to educating and attracting young people to become scientists and engineers.
What characteristics does a good scientist need?
You have to be persistent and you need a strong will, in order to stick with your research and not stop working on it, even if you face failure. Not everything will happen according to what you have planned. If the results are more or less what you expected them to be, wonderful. If not, you have to be flexible and maybe even change the initial concept.
As for our discovery of Copaxone, in the beginning, for a research tool, we were synthesizing a material to induce the disease. But it didn't work; it inhibited the disease. So we switched and took a new direction. And if the experiment then succeeds in the way I thought it would succeed, this gives me the feeling of absolute satisfaction.
How was it for you to work with animals?
I didn't like the experiments, but I knew that without these experiments you cannot get anywhere. Many organizations are against doing experiments on animals. That is not only nonsense, it is also dangerous. Experiments with animals are absolutely essential if we want to develop new drugs to improve human health. Only when we get good results on animals can we try something to see if it also works on people. You can't start with experiments on people. But of course, you have to be careful not to be cruel to the animals.
As a scientist, you work in a group. Do you like this arrangement?
I always worked in a team. In the development of Copaxone, the team was Professor Michael Sela, Dr. Dvora Teitelbaum, and me. Especially in biology, working in a team is almost always necessary. You cannot be a lone wolf, because there is a lot of experimental work that has to be done simultaneously. And everyone plays his or her part so that together you solve the whole puzzle. You sit, you think, and you plan the experiment together.
Have you changed over the course of your scientific career?
I am still hungry, and I enjoy it. Maybe now I don't need it so much any longer, and I also do it for fun, as an added bonus. I was the president of the Israel Academy of Sciences for five years. And at that time, I spent three days a week in Jerusalem and only two days here in the lab. But when I retired from the Academy, I got the urge to do research again. So, when I get up in the morning, I still feel the joy of, How wonderful; I am going to my lab! And there is nothing more satisfying than planning another experiment. I will keep on doing that as long as I can.
“You mustn't be afraid to cross boundaries.”
Vittorio Gallese | Neuroscience
Professor of Psychobiology at the University of Parma
Einstein Visiting Fellow since 2016
Italy
Professor Gallese, why should young people study science?
Because it is the best thing they can do. It is the most entertaining, inspiring, exciting work—excluding art for a moment. Every day is different, you don't know what will happen when you turn the corner. It is like hiking in the mountains instead of walking at the beach. You are challenging the unknown. Choose the topic that interests you the most. And put a lot of effort in it. In science, everything has to be conquered with a lot of work and effort, and there are no set working hours. It's a mind attitude. I am flabbergasted by the dedication and enthusiasm of the people I am working with.
In 1991, you and Giacomo Rizzolatti, together with Leonardo Fogassi, Luciano Fadiga, and Giuseppe di Pellegrino, discovered the mirror neurons. Could you explain this finding?
We were already looking for visual properties in motor neurons. For that, we were recording “canonical neurons,” which have a double property—that is, they fire, as we say, to explain that they discharge every time the macaque grasps an object. But we found they also become active when the macaque is merely looking at the object.
To do a clinical test on the neurons, we picked up objects and showed them to the macaque. What we expected to see was that nothing was happening during our grasping phase but to observe a discharge of the neurons when we looked at the object in our hands. To our big surprise, we discovered that some of the neurons were already firing when we grasped the object, well earlier. That is, they started firing when the macaque was simply looking at the object.
This was an exciting moment, but we were pretty quick to temper our enthusiasm and determine whether we were mistaken. But after a couple of months, it became pretty obvious that we had made a big discovery. And it was one of the most exciting times in my scientific career. The more we were able to eliminate alternative explanations, the more we became convinced that we had uncovered a sort of a neuro go-between operating between the agent and the observer. Of course, there are always doubts. Science is a constant enterprise of verification, doubts, and confirmation; it's also marked by excitement and frustration. So, there was no such thing as the one single eureka moment.
Does this discovery mean that my thoughts are mirrored in your thoughts?
Well, the discovery was made in the macaque monkey brain, so we were not dealing with thoughts or ideas—we were dealing with overt behavior. But that was just the tip of the iceberg, as we developed further research. In 1999, with the American philosopher Alvin Goldman, we proposed the hypothesis that this mirroring mechanism could be applied not just to action but also to emotions and sensations.
Our hypothesis was that the part of the brain that enables me to experience a given sensation, like touch or pain, is also active when I see that sensation being experienced by someone else. Empirical research that was guided by this hypothesis proved it to be correct. So, the notion of empathy came into being.
So, if we see someone cry, we feel compassion?
Empathy is one of the basic elements of our humanity; it enables us to directly grasp what the other person feels. But that doesn't necessarily mean we have compassion. Even a sadist can be empathic, in that he recognizes the pain in others, but he feels no sympathy. Unfortunately, often there is no clear distinction made between empathy and sympathy.
For example, I once read in a newspaper that a man jumped down onto the rails of a subway line to save a girl who was a total stranger to him. And the newspaper report said that now we know why he did this—because we have mirror neurons! But that is rubbish. Mirror neurons merely form the ability to understand what is going on in another person, they do not cause us to help that person. But this “experimental” form of understanding might enable us to decide to act compassionately.
Did you experience rivalry or jealousy in your field after your discovery?
Well, of course, when you discover something that changes the complex scientific landscape, it has consequences, such as confrontations with other scientists who are sometimes even harsh, or articles whose main goal is to demonstrate that our interpretation of the data wasn't correct. But that is part of the business. I would call it healthy scientific dialectics. Science moves forward because we confront different points of view, and a new discovery brings with it discussions, contrapositions, rivalries, or personal issues.
