Prof. Nabieh Ayoub. Ilya Melnikov

The Israeli-Arab Special Ed Student Who Became a Highly Praised Cancer Researcher

Prof. Nabieh Ayoub on being an Arab in Israeli academia, excelling against the odds and the future of cancer science.



Here’s a legend for the modern era:

Until the age of 12, Nabieh Ayoub could neither read nor write. Officially, he attended school in the Upper Galilee village of Fassuta, but mostly he helped his family till the land and herd the sheep. Today he is a biology professor at the Technion-Israel Institute of Technology, in Haifa, and a highly praised cancer researcher. In 2014, an article he published in the prestigious PNAS (Proceedings of the National Academy of Science) was selected by the journal as being among the top 5 percent of the articles appearing in its pages that year.

His is a riveting, thought-provoking and also somewhat ironic story about excellence, prejudice and education. But above all, about science. That’s what’s most important to Ayoub, and that’s what he wanted to talk about most, when I met with him at his Technion office.

Prof. Ayoub, who’s in his forties, is married to Samahar Najjar, an educational consultant by profession. The couple live in Haifa with their three children, aged 8, 12 and 14. “Nabieh” means “cautious” in Arabic, and that definitely suits his personality. He’s very cordial and sociable, unpretentious and candid, but cautious.

How is it that you couldn’t read or write until such a late age?

“That’s a good question. I think schooling didn’t mean much to me then. I would go to school, warm the bench and return home. I preferred helping my father, who was a fellah, working in the fields or tending the goats. I couldn’t even write my name. I was diagnosed as having special needs and placed in a special-ed class. The teachers were amazed that I was so dumb, because my four siblings were all very good in school. Things weren’t easy socially, either, because the good students tended to stay away from me. Who wants to be around an imbecile? When you’re categorized as weak, you have to make an effort to carve out a path to be accepted by those who are strong.”

When did the change occur?

“I had a homeroom teacher, Ayoub Shahla, who took me to the teachers’ room during recess and taught me. He proceeded gradually, little by little, until I knew the letters, and then I learned how to read and write. A decisive event for me was a speech delivered by the principal at the start of the school year, when I was in the eighth grade. He said that those who are weak can improve, and cited me as an example. All he did was mention my name, but that generated a huge self-transformation. You have to understand: All in all, I had progressed from marks of 20-30 to 50, but the fact that he made reference to it had a tremendous influence on me. That was the beginning of the spurt.”

The attention? The nice word about you?

“Yes, it was a great thing. The teachers and the principal were held in awe then, and that kind of remark by him was like winning the lottery. Generally speaking, I think a teacher can have a huge influence on the direction in which a person takes his life. If you read biographies of successful people, you’ll find that many of them had a teacher or mentor who believed in them, and were it not for him they would not have achieved what they did. That principal, the late Jeries Khoury, became my life-teacher, and I also owe a great deal to my biology teacher, Assad Endrawes, thanks to whom I fell in love with that subject.

“A teacher must accommodate the pupil. That’s the most important thing he can do for him. He has to make the pupil feel that they are on the same side, not one against the other. We pressure our children needlessly. After all, it’s not the marks that count. There is no connection between the psychometric examination [a standardized test for university admission in Israel] and a student’s achievements. In some cases, students with excellent grades ask me to be their Ph.D. adviser, and afterward it turns out that they don’t know how to work. And the opposite, too: Students with average grades can turn out to be excellent researchers.”

DNA under attack

For the past decade, Ayoub has been researching the structure of DNA and the mechanisms that repair it when it’s damaged. The fact is that DNA – the molecule that carries our genes and is responsible for our traits, abilities, functioning and health – is under constant attack. Every day, the DNA in a cell that is dividing is vulnerable to some 70,000 different types of damage – and that’s before we factor in smoking, exposure to solar radiation, food preservatives and other nasty items that exacerbate the damage. The basic harm is caused by by-products of regular life processes, which attack the cell’s DNA. These include the notorious free radicals, which we’re meant to neutralize through the consumption of antioxidants.

If so, Prof. Ayoub, the damage is unavoidable.

“It is unavoidable, because it occurs as a result of the cell’s routine activity. DNA is the only molecule that is not replaced by the body. In contrast to proteins, which break down and are therefore replaced naturally, DNA molecules are created once, and if they are flawed, the cell must repair them. In the conventional analogy, according to which the information stored in DNA is like a text whose meaning is determined by the letters and words of which it is comprised, then, obviously, damage to the identity or the order of those letters is liable to disrupt the text and distort its meaning. In biological language, distorted meaning means flawed functioning and perhaps even cancer – which is why cells developed repair mechanisms.”

There are different types of damage – pursuing the text analogy, we can say there are specific spelling mistakes, words omitted or sentences added – and accordingly, there are different types of repair.

“I like to compare the cell nucleus to a hospital with many departments, each of which has different specialist physicians. Each is responsible for diagnosing and treating a different disease, but if necessary, a physician from one field can do the work of a physician from a different field. The analogy: the existence of different families of enzymes, each of which is responsible for repairing a specific type of damage. Still, overlap sometimes occurs – you’ll have an enzyme that can do more than one thing and can take the place of another enzyme.”

What do all these repairing enzymes do?

“First, the cell has to sense that something is wrong. That’s far from simple, because DNA is not a dedicated, easily accessed molecule. It’s a very dense molecule about two meters in length – about the height of LeBron James, the basketball player – but packed so tightly in a cell that its physical length is only 10 to 15 microns [10-15 millionths of a meter]. That density is made possible thanks to special proteins around which the DNA is wrapped. The question, then is: If the DNA is so dense and coiled up, how is it possible to discover that it has been damaged?

“So, the first stage is to identify the damage. Then the DNA has to be unraveled slightly at the appropriate place to enable access to it, after which the repairing enzymes are signaled to arrive. The repair itself is the last stage. At every stage, specific enzymes are involved, and the whole process occurs rapidly, seconds after the damage takes place.”

What happens if there is no repair?

“There are two possible scenarios. In one, the cumulative damage indicates to the cell that the situation is critical, and then the cell enters a course that leads it to a type of suicide.”

Suicide?

“The biological term is ‘programmed cell death,’ because it is not simply death as a result of processes gone awry. It is an orderly, foreknown sequence of stages, at the end of which the cell dies. This is one of the mechanisms by which the body copes with DNA damage, because the moment a cell dies it is gone.”

What is the second scenario?

“In the second scenario, the cell remains alive, and it develops cancer. In many cancerous growths we find mutations in the genes that are involved in DNA repair. If the repair mechanisms are defective, protection of the DNA slackens and the damage begins to mount. A case in point is hereditary breast cancer type 2. This is the type that got a lot of publicity thanks to its famous carrier, Angelina Jolie. This particular cancer is caused by a mutation in the gene that is responsible for repairing DNA breaks. It turns out that damage to different genes of the repair mechanisms leads to different types of cancer. We are trying to identify all these genes in order to develop anti-cancer therapies.”

Can you be more specific?

“First, we are trying to identify all the elements that are involved in the repair of DNA, in all its stages, from the time the damage is identified until the final repair. To that end, we damage the DNA, our working assumption being that the agents responsible for repair will move rapidly to the site of the damage. If we follow the course of the proteins, we will be able to see which ones arrive on the scene. Because the cell contains many hundreds of enzymes, we focus on particular suspects. We fuse the suspect enzyme to a molecule that emits a green light, so that when it goes through the cell it leaves a green trail. Afterward, a laser ray is beamed into the cell to break the DNA at a certain place, and then we follow the movement of the marked enzyme. A few years ago, using this method, we discovered a new enzyme that was hastening to the site. To prove that it was indeed a repair enzyme, we damaged the gene that is responsible for its creation, and the cell became very sensitive to radiation. We therefore inferred that the enzyme we found does in fact protect the cell from radiation damage.”

Why did you single out this specific enzyme? Why did you suspect it from the outset?

“It was due to theoretical considerations, which took into account what we knew about enzymes. In the scientific literature, enzymes are described as removing certain chemical groups from DNA, and it’s known that this action ‘re-formats’ the DNA. In a similar manner, we discovered quite a few more repairing enzymes of this sort.”

How can identifying a repair enzyme help in developing a cancer treatment? After all, you don’t anticipate introducing it into the cancerous growth in order to repair the DNA and restore the cell to its previous condition.

“Quite the opposite: The idea is to aggravate the damage to the DNA. By increasing the damage to the DNA and heightening the cancer cell’s genomic instability, we hope to turn the cell in the direction of suicide.”

In other words: The worse things are, the better they will be.

“That’s basically what regular chemotherapy does. The chemo materials act by way of arresting the division of cancer cells, and/or inducing DNA damage. The excess of DNA damage and prolonged cell-cycle arrest can trigger programmed cell death.”

In what way is the treatment you’re proposing better than regular chemotherapy?

“At present, chemotherapy attacks genes randomly. It does its work in both cancer cells and the body’s healthy cells. We want to aim the damage at the genes that are involved in DNA repair. If we succeed in striking at them specifically, the cell’s condition will deteriorate and it will embark on the course of planned death.”

You said earlier that the repair mechanism is already damaged in a large percentage of cancerous growths. Effectively, then, you said that this is the cause of such cancers.

“That’s correct, but we also said, when using the image of repairing enzymes acting like physicians, that sometimes their activity overlaps. One can do the work of the other, so that if one such enzyme is damaged, another can cover for it, at least for some functions. That’s the reason the cancerous cell is still alive and kicking and continues to divide rapidly. It’s only if both repair proteins are damaged that the cell will collapse. We can now diagnose patients’ tumors on an individual basis, such as by doing a biopsy from a woman’s breast cancer, and thus identify the flawed protein that led to that particular cancer. If we become highly knowledgeable about the repairing enzymes and their modes of cooperation, we will be able to develop material that will attack specifically the enzyme that is cooperating with the flawed enzyme, and thus we will cause the whole repair system to collapse.”

You mean customized medicine.

“Exactly. That’s medicine of greater precision, which reduces the harm to healthy cells. The ability to choose our targets intelligently and to intervene in them in a focused manner, will allow us to target only one of the constituents of the repair mechanism. The second constituent will remain in the healthy cells and take the place of the first one until the storm blows over.”

How many repairing enzymes do we know about?

“Given the fact that there are thousands of types of damage, we expect that there will be many dozens, even hundreds, of enzymes.”

How did such sophisticated mechanisms develop in the course of evolution?

“To begin with, you have to remember that these mechanisms are not 100-percent effective. That very ineffectiveness is the driving force of evolution: Natural selection operates by variance, which stems from the changes that occur in the DNA. So a delicate balance exists between the need to streamline the repair mechanisms intensely, and the need to leave a few errors in the DNA. In any event, repair mechanisms developed in all animals by degrees. A repair process exists even in bacteria, whose DNA is far simpler, and it is almost identical to one of our types.”

Yaron Kaminsky

‘Lesson for life’

When he was in ninth grade, Ayoub transferred to an Arab high school in Ma’alot-Tarshiha, a mixed Arab-Jewish town in northern Israel. “There I really began to excel,” he notes with a smile. “It was a new institution and free of prejudice. The teachers and students attached no stigmas to me, and I was able to turn over a new leaf.”

Subsequently, he enrolled as a biology student at the Hebrew University of Jerusalem, though that too turned out to be a difficult process. “Fassuta is a small, isolated village by the border,” Ayoub notes. “Until university, my only encounters with Jews had been when I went to the hospital in Nahariya for care. The only Jew I ‘knew’ was [television news anchor] Haim Yavin When I entered university, I started to watch more television and read the papers a little, to discover whether I was capable at all of understanding the [Hebrew] language.”

However, in university, he recalls, “I couldn’t understand what the lecturers were saying, much less take notes. Fortunately, there was a beautiful student, a religiously observant woman name Ruthie – I still remember her name. I don’t understand why she always agreed to give me her notes, but that’s what saved me.”

And now comes the de rigueur bit about how you, the gentle and educated Arab, fell in love with the captivating settler woman

“I don’t think I allowed myself to fall in love with her,” he laughs. “By the way, she knew I was an Arab, of course, if only because of my accent. Still, after two weeks, I called my (late) father and told him I didn’t feel as though I belonged, and so I was coming home. That was the end of the world for him. He said, ‘Under no circumstances are you coming back! Did you think you were going to a health spa?’”

So you stayed on because of your father’s demand?

“Yes. I owe my father a great deal. He was tough but also emotionally sensitive and smart. He understood that there was no future for us, his children, in working the land, especially not in Fassuta, where it’s hilly and the soil is crusty. He had a mobile flour mill with which he made the rounds of the villages, and he took me with him just to show me how difficult and unprofitable it was. He wanted me to see how tedious it was and to get schooling instead. It was a lesson for life.

“He encouraged me in my studies and never let me off easily. In high school, for example, when I was already a good student, I told him one day that I wouldn’t be coming to work because I had an exam the next day. He dismissed it, saying, ‘That’s your problem, not mine. You knew you had an exam and you knew you had work, too, so you should have planned your time to manage both.’ In today’s lingo, it’s called ‘time management.’ It was really a downer when I was a boy, but today I have a very high regard for the values he instilled in me. Regrettably, he did not live long enough to see how far I got.”

What kind of father are you to your three children?

“My dream is to be like my father, but unfortunately I’m not. I am very demanding with the children, I want my children to be the best, maybe to spare them what I went through. I am less flattering to them than my wife.”

So you do resemble your father, after all.

“Hmmm You’re right,” he exclaims in surprise. “I really am like him.”

What you said about school – about the weak and the strong and about not encountering stigmas in the new high school – inevitably raises questions about your situation as an Arab in a Jewish society.

“Personally, I have been very fortunate. I do not represent anyone here other than myself, but I have always been treated excellently by everyone with whom I’ve had occasion to interact. I met people who did a great deal by way of cultivating me. I did my master’s degree at the Hebrew University during the first intifada under the tutelage of Prof. Jacob Wahrman, who was an amazing individual. For my birthday one year, he bought me the novel ‘Arabesques,’ by Anton Shammas, whom I’d never heard of until then, even though he was from my village! Wahrman cut out items about Fassuta from the papers, a habit I learned from him.

“I met many more good people – Prof. Amikam Cohen, who was my Ph.D. adviser, Prof. Haim Cedar, who was a member of my examining committee – and many colleagues, religious and nonreligious alike. If I was privileged to get different treatment, maybe it was for the good.”

Maybe it was because you were especially good.

“Maybe others were good, too.”

Do you want to tell me that you never encountered racism here?

“Not in academe. On the street, certainly. At the airport, always. I say to the airport security people: ‘Check the passengers’ identity before they get to the airport. Why do you humiliate people in this way?’ Luckily, I spend 99 percent of my time at the Technion, so my interaction with the street is very limited.”

And your family, the children?

“My children attend the [Carmelite Sisters] Italian School, in Haifa, a private institution of the Catholic Church, so they don’t encounter Jews very much. We also hardly use public transportation.”

Life in a bubble

It sounds like you’ve created a bubble for yourselves.

“Academe is definitely a bubble in that regard, which is why I am against foreign calls to boycott it. It’s the sanest institution in the country, and therefore should be supported and also strengthened. I think that higher education, and in my case the Technion, where the number of Arab students is increasing amazingly from year to year, could be a model for equal opportunity and life together in this country.”

You don’t sound in the least bitter, not even divided. Is the solution to live in a bubble?

“If you’re asking me how I would describe my existence here, I would say [in the words of a popular Hebrew song], ‘both of us together and each separately.’”

Meaning?

“I am very much together with my colleagues. We have close interaction and common fields of interest. I am very much together with my Jewish friends. But there are things in which I am separate, because I am an Arab. That’s expressed in the holidays, for example, and in the music I listen to, in the way we host guests and in a few other practices of daily life. That basis remains mine, and it’s separate from that of Jewish society.”

Ilya Melnikov

Does your being an Arab have an influence on the identity of the students who come to your lab?

“Most of my students are Arabs, possibly because they feel more comfortable coming to me. Sometimes they come only to seek my advice, and if I see that they’re really good, I will try to tempt them to work with me. So I take good advantage of my status You could say that in regard to the good Arab students, I have an advantage over other [potential] advisers. But I have Jewish students, too, though only women, because to date no Jewish male students have approached me.”

How do you explain that?

“I have no idea. Maybe it’s because there are more women than men in biology in general.”

A few years ago, Ayoub and 12 other Arab faculty members from all of Israel’s universities founded an organization they call Al-Maram [meaning “peak,” “high up”]. The association’s members visit Arab high schools in order to serve as inspiration and role models for the students. They encourage outstanding students to study the sciences at university – biology, chemistry, physics and mathematics.

So you and Education Minister Naftali Bennett see eye to eye on that.

“In regard to the importance of the sciences, definitely. Science needs the most brilliant minds, and we want the best to come to us and not only to medicine.”

Do the top Arab students in Israel go into medicine?

“Yes. Many are opting for medicine today, and for all kinds of reasons. In the past, Arabs went into the nursing professions, and the ratio was 80 percent Arabs and 20 percent Jews. The wave of immigrants from Russia [in the early 1990s] pushed out the Arabs, and the proportion was almost reversed: Today there are only 30 percent Arabs in those professions, while almost 70 percent are from the new-immigrant population. Jewish students today prefer high-tech to medicine, because the earnings there are higher, and that makes more room for Arabs. There’s also the matter of a minority that wants to excel and acquire a profession – like the Jews in the past. For all those reasons, there are many Arab physicians in the hospitals. But we want to cultivate the sciences.

“In fact, I myself went into biology only in order to go on to medicine afterward. But when we started to learn about DNA and how it multiplies, how the double helix opens and how that wonder occurs, I fell in love. It was definitely love at first sight, and I understood immediately that this was my home. I think that’s the secret of my success, and that’s also one of the messages we try to convey to the high-school students: that the way to excellence is to do what you love.”

You use words like “home” and “belonging” in the context of science, and not for a particular physical place.

“If I have a connection to any one place, it’s to Fassuta, my small village in Upper Galilee. I love the view and the goats and the smells. When we lived in England, when I was doing a postdoc, which was followed by a research position there, we went on trips, and whenever we saw sheep – and they have plenty – the children would look at me and say: ‘Now Daddy is happy!’ Other than that, I’m in the world of science, which has no geographical venue.”

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