Of mice, men and the inner struggle of an Arab-Israeli scientist
Dr. Yaqub Hanna was the recent recipient of an award for his groundbreaking work on returning the mature stem cells of mice to an embryonic state. He discusses his research and the complexities of life in Israel.
I’d arranged to meet Dr. Yaqub Hanna at a Tel Aviv cafe near the street where he lives. We’d agreed that I would let him know when I was getting close, so as I pass by City Hall I start texting: “Be right there. I’m on Malkei Israel [Kings of Israel] Street.” I look at the message and delete the street name. Maybe it’s better to wait for a different street. I keep walking but the next street − Imber (composer of the national anthem) − also doesn’t seem quite right. When I come upon Netsach Israel [Eternal Israel] Street next, I just send: “Be right there.”
There’s this idea that when interviewing a successful woman, it’s not proper to ask her how she manages to combine work and family. Nobody would think to ask a man such a question, after all. So when meeting an Arab scientist, am I supposed to not talk about the fact that he’s an Arab, just as when interviewing a Jewish or American scientist, I never linger over the issue of their nationality? When I tell this to Hanna, he laughs. Perhaps because, to paraphrase Shalom Aleichem, “It’s hard to be an Arab.”
“I was born 33 years ago in Kafr Rama, and this definitely had a major influence on my life and what I do,” he says. “I was supposed to become a doctor, actually. My father is a doctor, my three sisters are doctors and I also studied medicine. It’s a common profession among minorities, you know...”
So you’ll have a “profession in hand”...
“Yes, to have a profession that you can take anywhere. I always knew that I needed to excel, to be the best. I thought I would study medicine, go abroad to do intership and remain there. My plan was not to return.
“In the course of my studies, I started to get interested in research. Medicine didn’t satisfy me intellectually, somehow. I was searching for something more creative. Unfortunately, I have no talent for writing or painting, and when I was 10 my piano teacher politely suggested that I quit. But when I discovered the world of research, I was enthusiastically drawn into it. Not that it went so smoothly: I made three failed attempts to begin a doctorate, at three different labs, until I came to the lab where I did my degree.”
“The first lab was very much about applied science. It bothered me because I wanted to do more basic science that would entail scientific discoveries. The second lab was too basic. In the end, I came to the lab of Prof. Ofer Mandelbaum, an amazing and happy guy, and I did my doctorate there on the immune system.”
So you’re both a doctor and a scientific researcher.
“I have a medical diploma at home, but decided not to work in medicine and to continue with scientific research instead. I’m the black sheep in the family,” he laughs.
And then you went abroad for a postdoctorate.
“To MIT, and it was fantastic. A lab that was in another league altogether: tons of room and resources, as well as lots of pressure and competitiveness. It was exciting, and my research went well, too. I didn’t have financial worries because my family supported me. That was my great good fortune. In the 19th century, scientists only came from wealthy families because they were the only ones who could afford to work in science. But even today it’s hard to travel somewhere for a postdoc without some ‘padding’ that enables you to really devote yourself fully to your research.
“I also had cousins who live in America. Basically, out of the whole extended family, my parents are the only ones who stayed in Israel. All the other relatives emigrated to the United States in different waves, before and after the Six-Day War [in 1967], so I was very comfortable there, and I was sure I wasn’t coming back to Israel.
“My choice of research subject also reflected this. The study of embryonic stem cells is very technically complex and requires vast resources. I chose a lab that’s a ‘mouse laboratory,’ a very expensive business. My thesis adviser cautioned me not to go there, because then I wouldn’t be able to come back to Israel. There’s no way, he said, that you’ll find the money to set up that kind of operation in Israel. But I didn’t care. It suited me, in fact, since I didn’t want to return.”
You were determined not to return.
“It’s not easy here for an Arab − even somebody like me who’s not called Ali, isn’t dark-skinned and doesn’t have an accent. I’m not talking about the lousy infrastructure in the villages − the electricity and sewage, etc. − but about the moment you leave the village. I remember that as kids, when we wanted to go to the swimming pool in Carmiel, my mother would tell us not to speak Arabic.
“As a university student, when I needed to rent an apartment in Jerusalem, it was a nightmare. Even now that the situation has gotten better and I live in Tel Aviv − which is a lot more open − there’s still an oppressive kind of feeling. Personally, I can’t really complain. Like I said, I don’t ‘look Arab’ and when I say my name, no one makes a big deal out of it. But still, even I have felt how stifling it can be. It’s hard for me to even imagine what a ‘stereotypical’ Muslim or Arab feels.”
And yet you still came back...
“Because in the end I felt that living in America would mean being an immigrant. I could have stayed there in terms of work and convenience, and I probably would have been quite happy to stay there, say, for another seven years or so, but not for good. I wanted to live near my friends, my family, the environment I grew up in, even with all its problems and complexity. In a certain sense, I was also refusing to be excluded from here. That wasn’t the uppermost consideration but there was still a slight feeling of, ‘If I stay there, it will be like they managed to push me out.’”
And then came the offer from the Weizmann Institute of Science...
“...who were the only ones who could provide the type of research conditions I needed. It costs millions to establish a mouse laboratory. I had a lot of talks with them, and I agonized over it privately quite a lot. When the possibility became a reality and the time was set for my return, I got very nervous, and at the last minute I canceled everything. I only came back to Israel a year later.”
You feel you returned to “your place?”
“It’s hard for me to say it’s ‘mine.’ Of course, the family is mine, and Arab society − and also Jewish society, in which I have many friends. I think it’s hard for me to use that word, ‘mine,’ about the establishment. In order to live here, I need to wrap myself in a bubble, to repress things a bit, to live in a certain degree of denial. With a lot of effort, so far I’m succeeding.
“I feel that I underwent a change at age 30, when I returned to Israel. In my twenties, when I started living among Jewish society as a medical student, I felt like I had to put a lot of energy into the area of educating young people. I’m still active in Arab schools, it’s my way of ‘bearing the burden,’ and I’m very attached to Arab society, but I don’t limit myself exclusively to this society. Basically I’m an existentialist. I exist without a need to explain. Maybe it derives from despair, or maybe it’s just the way I am.
“I’m a Palestinian who lives in Israel and is conscious of the tragedy that took place here in ‘48, and of the injustice that persists to this day, but as a human being I don’t focus on that all day long. My life is not monochromatic, and I refuse to feel like a victim. I want to live. I don’t want to throw everyone into the sea, but at the same time I don’t believe that, with just a little bit of effort, everything could be wonderful here. The situation here is very complicated. I’m a scientist, and things are good for me personally, particularly with the position at the Weizmann Institute and the prizes, but I still wonder about how Palestinians living in Ramallah and Gaza feel.”
Is it possible that you’re having guilt feelings? You seem to have some kind of “survivor’s guilt” − the disturbing feeling that, quite by chance, you’ve managed to live well while your brethren are not so fortunate.
“It’s been a lot less tough for me in life, because Israelis don’t perceive me as an Arab, and also because I’ve been very successful. I had financial support and I work at a job that’s also my passion, so my situation is as good as it could possibly be.
“When I was studying in Jerusalem, there were scholarships for outstanding students: There was a general one and one specifically for Arabs. My name was submitted for the Arab scholarship because they didn’t want me to take a spot from the Jews. I was very angry about it then, but I wouldn’t want to present it as an example of injustice because, once again, my relative situation is excellent.
“It saddens me greatly to see the injustice that is done to others. I can fight as a citizen, I can be active, but I don’t really know what I’m supposed to do about it. So I live my life. I voted for Hadash, even though I’m not crazy about them in many ways. I don’t like this term ‘coexistence.’ To say ‘coexistence’ is to declare that there are two separate entities. And who said there are only two? Anyway, I voted Hadash, as a gesture to [former Hadash MK] Tamar Gozansky at least.”
In his DNA
Hanna is gentle and, like those who are genuinely good, exudes modesty. He speaks quite articulately but sometimes haltingly, the sentences tripping on top of each other − as if wary of committing to a single assertion with a period at the end of it, when there is a counter-assertion that is also true, as if it is important to him to paint the whole picture in all its complexity and nuance. So the discussion of personal matters has a searching quality to it, an attempt to define and characterize things. But all that changes when the subject shifts to science. The words flow much more freely.
Two weeks ago you received the 2013 Rappaport Prize, a prestigious and relatively new award given for excellence and innovation in biomedical research.
“It’s a big honor. I’m the recipient of the award for a young researcher for my ‘pioneering studies on embryonic stem cells.’”
Tell me about embryonic stem cells.
“Our cells, although different from one another in form and function, do not differ in terms of their genetic content. They have exactly the same DNA − with one exception that I will talk about in a minute − but in each type of cell, it is organized differently. This organization occurs during embryonic development, in a gradual process known as ‘differentiation.’
“At the beginning, the cells are capable of anything. Each one could develop into any type of body cell: skin, liver, lung, and so on. These are the embryonic stem cells. As the DNA in a cell continues to assemble itself in a particular way, the cell’s potential is reduced. The cell becomes committed to a certain direction. It loses its ability to develop in other directions. and eventually it becomes a mature cell whose final form and function are defined.”
Two Nobel Prizes were given last year in physiology or medicine to scientists who succeeded in taking a mature cell − such as a skin cell or blood cell − and “unwinding” its DNA in a way that restored it to the state of an embryonic stem cell, which has the potential to differentiate anew.
“I like to compare it to what you do with a computer when you reset and restart it. You recalibrate it and then start all over again.”
And in the midst of the process, it’s possible to intervene in the cell’s genome and reprogram it.
“This is what I did in the lab where I did my postdoctorate. We worked with mice that had sickle-cell anemia − a disease that is caused by a genetic mutation and affects the blood cells. We took skin cells from the mouse’s tail, which are mature cells, of course, and we turned them back to the state of embryonic stem cells. Then we applied genetic engineering methods that corrected the mutation, and then we caused them to differentiate, this time to blood cells. Then we put these healthy blood cells back in the mouse’s body.”
This study made a lot of waves because it was the first time a genetic disease was cured by the reprogramming of cells.
“Yes, it was a very nice study.”
Nice!? That’s it? Everybody I talked to was saying what an incredible breakthrough this was − a first crucial step toward one day being able to transplant new fresh tissues to replace tissues that are no longer functioning, such as heart tissue or liver tissue.
“It’s definitely important work, and other people greatly admire it ... but I’m less fond of it than I am of later studies I did. It’s not really a discovery, it’s work that shows the feasibility of a process, and what I want to discover is the mechanisms. I’m dying to know what happens in a cell when it goes back in time to the starting point.”
To the point of innocence, when everything is still possible.
“Yes, something that is still a fantasy when it comes to human cells. For some reason, unlike mouse cells we haven’t been able to reset human cells back to zero. They always get to a point that’s still a little differentiated, and not beyond that. They aren’t ready to give in completely. It fascinates me to know why, and I would like to arrive at a human cell that is a total virgin, or ‘naive,’ as we call it.”
And then you’ll be accused of wanting to clone human beings.
“For sure [laughs]. I plan to restore the army of Mohammed to Palestine by means of cloning ... What interests me is the challenge of cracking the secret to the ‘fountain of youth.’ The ability to transform mature cells into embryonic stem cells is a great thing, especially since you don’t have the ethical problems that are involved in the use of real embryos. It’s the great hope for the transplant field, but it could also help in the study of diseases. For example, it may be possible to inject embryonic stem cells from a human source into a mouse embryo and to obtain a mouse that has human tissues. And if we do this with tissue taken from a diabetes or Alzheimer’s patient, we’ll obtain a mouse that is a successful model for the study of these human diseases.
“In addition, we’re doing a study that I’m especially proud of, and it is truly innovative. We’ve said that all the cells in the body contain the same DNA, but I also mentioned that there is one exception − and these are the immune cells. The immune system is capable of dealing with such a large variety of invaders because of a special characteristic of the immune cells: When they differentiate into their final form, they cut certain segments of the DNA, get rid of them and stitch the remaining segments together. Each cell does this in a slightly different way, and since this DNA is responsible for identifying the protein components of the invaders, a huge variety of immune cells results. This means that when we turn an immune cell into an embryonic stem cell, it doesn’t completely return to the starting state because it’s missing certain parts of the DNA.
“So if we turn a mouse immune cell into an embryonic stem cell and create a whole mouse from it, we’ll have a mouse that could make just one type of immune cell. It’s a sophisticated genetic tool, a cutting-edge technology, that could help us understand autoimmune diseases − diseases in which the immune system attacks the body − like diabetes and multiple sclerosis.”
How many people are in your research group?
Wow, so many!
“It is certainly one of the largest labs at the Weizmann Institute, and it’s also as much as I can handle in terms of the attention I’m able to give each person. When you have a lab, it’s a lot more complicated than when you are on your own. You have responsibility for other people, and you’re always thinking about whether you gave somebody a good project and how to advance it. Your mind is constantly occupied.
“Even now, with the position at the Weizmann and the prizes, my mother still regrets my choice to go into science because of the tremendous time investment it requires and all the pressures. Fortunately, I have three permanent, experienced researchers on my team who serve as excellent deputies to me. And I still work in the lab myself at least 50 percent of the time.”
It’s pretty unusual for the head of a lab to get his hands dirty that way.
“I really enjoy it, and it also keeps me connected to what’s happening in the field. Although, I’m not sure that my students are as keen on it as I am...”
Because you’re right there looking over their shoulder?
“And also because I’m very intense. I’m a little like the stereotypical Polish mother: ‘Did you eat? Did you put on a sweater? Did you do this? And that?’ I hope I’m not pestering them too much,” he says, and bursts out laughing.
Do you miss the time when you were a student and only had yourself to worry about?
“If there’s anything I miss, it’s the time when I was 11 or 12. In the village there was something called the Friendship Club. It was the social center for Hadash youth, and we would come there to play, to see shows, to sing in the choir. Everything was very minimalist back then. The village was in a terrible state − it wasn’t connected to the sewage system, there certainly weren’t any computers, but there was lots of activity. Today, when I go back to the village, I feel it’s become gentrified. Materially it’s been upgraded, but the activity has decreased.”
To sum up. You’re restoring to cells their lost potential, you’re reprogramming them. It would be a shame to talk about such images without also relating them to the social, human context.
“It’s impossible, of course, to reprogram the reality in which we are living, which is very complex. There is a lot of hardship here, not just for Arabs but also among Ethiopians and people from the periphery. There are different levels of misery ... I’d like to get to a situation where people understand other people’s differences and accept them. There are a lot of people here who want to change things, but the majority wants to feel good about itself and not really to change.
“It’s true that we are shaped by our sorrows and our failures and our successes and despair, but we need to think about how to enable people who have potential to realize it and to make their way up. They need guidance. I was able to realize my potential, by the way, largely thanks to people like Ilana and Pascal Mantoux, a Jewish couple who divide their time between Israel and France, who believed in me and in my research, and supported the establishment of my lab.
“I have great admiration for people who donate to research. It’s not something showy like a wing in a museum or a city plaza, even though the sums of money involved are often comparable. It says a lot about the authenticity of these people. But what about Mohammed, or the girl with the veil − not to mention the Palestinian in the territories? Are they able to fulfill their potential? Obviously not. So, unfortunately, I don’t represent anything.”