"I'm Addicted to Playing Chess Against God": Aaron Ciechanover Wants to Make Cancer a Chronic Illness | Israel today

Aharon Ciechanover is

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Aaron Ciechanover, when you were a 9-year-old child orphaned by your mother who had cancer, and 6 years later by your father who died of heart disease.

Not simple events for a young child.

What do you remember about them, what did you learn from them?

"I grew up in the Hadar HaCarmel neighborhood of Haifa, in a middle-class house, but our walls were always covered with books, and we attended concerts of the Philharmonic. My mother was an English teacher, my father was a lawyer who started studying at age 50 with my older brother.

My study walls are empty of documents in drawers, but his diploma hangs on the wall in front of me.

"My parents taught me to be curious, to solve problems and to look for answers to questions. I learned from them not to leave details behind, to be careful about language, to be accurate. It's a way of life. "The groundbreaking achievements in biology are related to the character I described, to the parents, to the environment, to good teachers and perhaps to talent - which I do not know how to define precisely."

Is the decision to become a doctor and researcher related to the death of your parents?

"I may have never thought of it that way. As a child I did not know what biology was, but I met doctors as a child and had little idea about their occupation. The pressure at home was to study law, but for some reason - I fell in love with medicine. "At the end of the disease process or when it is deep inside, and I wanted to understand why diseases start in the first place. I was naive and did not understand that I would not investigate all possible diseases, not even one in depth, but only the 'kettle chopstick'."

When your mother died understanding what is death, what is cancer?

"I did not know then what cancer was, what is more the knowledge on the subject was then very little. She came in and out of hospitals. Emotionally, we were a bit religious and I knew the prayer 18 which says' and you are faithful to raise the dead, blessed are you the 'resurrection of the dead'. "The vision of Ezekiel's dry bones, those bones that wear skin, flesh and tendons. So my impression was that it was temporary, that she would return. It was self-comfort."

Part of your reaction to death after your father's death was to degenerate into the street.

"It was like a step between me and crime, juvenile delinquency. To my delight, my brother quickly understood the situation and with his help and the help of my aunt, my mother's sister, who took me to her house - I reset. After two and a half years I successfully completed my matriculation. "Alone, I'm not sure I would have been able to do that."

"After winning, I came to the cemetery to visit my parents. I imagined them sitting upstairs and watching."

Ciechanover at the Nobel Prize Ceremony, 2004,

Was there anger there too?

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Can you say that you even experienced a certain sense of relief?

"Ostensibly, yes."

After winning the Nobel you visited them in the cemetery.

"The cemetery is a place I love. As a biologist there is nothing there, but there is nostalgia there. In the cemetery, to which we immediately went with the announcement of the win, I imagined them sitting upstairs and watching, and talking to them. I told them I hope they are happy with me on this important day. "I wanted them to see where I got to. Everything is in my imagination, unfortunately."

Is this closing a circle that you felt you owed to yourself?

"Yes. It was very important to me."

You mentioned earlier your certificates that are in the drawers.

Why actually?

"The important thing is the work, not the certificates on the wall. I will add and say that just recently I decided to award the medal and the Nobel Certificate as well as my doctoral dissertation at the Technion - describing the discovery we won, my supervisor Prof. Avraham Hershko and I, the prize - to the Haifa Science Museum. "Youth will enjoy and learn from the story behind these items, and also to donate money to a museum where the research, certificate and medal work will reside. It is a combination of philanthropy, science and education. I thought it was useless to reside with me to no avail."

"Priority scale went wrong"

Let's talk about current affairs, at your disposal.

The issue of education has made headlines again in recent days.

In the last five years, about 30,000 teaching staff have resigned from the education system due to wages and conditions, and the wage crisis is now threatening the system once again.

Can I stop this snowball?

"The education system is a reflection of society, and unfortunately we are down. You ask about teachers' salaries - which are only part of the matter. If you add another NIS 2,000-1,000 to teachers then there will be a computer for each student? Will there be labs? Schools will be less outdated? , But improving wages will not help solve core problems.

"For example, it is about teachers' salaries in secular education. What about ultra-Orthodox education? What about education in the Arab sector? As a child, I received a better education from very dedicated teachers. They walked with me hand in hand. Maybe there was a different mentality then, maybe Israel's small size influenced "

"What about computers and innovation?"

Demonstration on teachers' salaries, Photo: Coco

Are you talking about the educational environment?

"For example. The atmosphere, culture, verbal and physical violence in the daily discourse that unfortunately exists in government institutions, and radiates downward on parents and students. As a student I looked at Murray at school in reverence. Who would dare to be rude? This is a whole ecosystem, not a single pay slip." .

If you were the Minister of Education, what approach would you take?

"We have a deep problem in education, and there are no magic solutions here. A revolution is needed. The educational atmosphere is being built in kindergarten. The education system is a supportive society in the most fundamental sense, because there is no state without education. All Israel's achievements - Everything comes from education, and this is a food chain: what you nurtured and built in kindergarten, will go to elementary school, high school and university.

"We are talking about education, but the deterioration is in other areas. The health system for example - there are excellent people, but they are few. There is a shortage of beds and many professionals. Why does a mother living in a Galilee moshav have to wait months for a psychologist to see her son? Wait a year to get an appointment for prostate surgery? The health care system is dry. The interns' conflict is a reflection of the number and quality of doctors in the State of Israel. Most of our doctors come from abroad.

About 60 percent of our doctors did not study here.

But in medicine, professionals are needed who speak the language we speak now, understand the public about its cultural diversity. "

You do not sound particularly optimistic.

"Unfortunately, the State of Israel has largely abandoned the citizen. We are a rich country whose systems support society - education, health, and also welfare and social work - have dropped to an unbearable level of priority. Something has gone wrong with our priority scale. .

Choose a partner according to the genes

Next weekend (June 9-8) you are expected to attend the Future Medicine Conference, MEDICINE 2042, which will be held in Tel Aviv, where treatment methods and groundbreaking research and cancer, AIDS, diabetes, obesity, etc. will be presented and analyzed. .

"It is amazing to think that until a few decades ago medicine was relatively primitive, observing the disease with almost no interest in the patient. And decipher the DNA, RNA and proteins that make us up - you can create a personal medical profile, and understand what is going on in it.

Problematic discourse.

Knesset of Israel, Photo: Noam Moskowitz / Knesset Spokeswoman

"So today, medicine turns the gaze away from the disease, to the disease in the context of the patient. Instead of attacking the patient, first characterize him. Breast cancer, for example, can result from different mutations, but mutation A is not mutation B, and treatment is different from one. .

"Take for example a car that does not light up in the morning. This is the disease. The reasons for not lighting up can be varied: an empty battery, a lack of oil or fuel. The disease is visible - the car does not light up, but the reasons are completely different. "The cause of his disease. The goal of personalized medicine, by and large, is to locate the cause of the disease at the molecular level and adapt a drug to the cause itself. It will be much more gentle and effective, with far fewer side effects."

This revolution is already taking place, and it seems that we are only at the bottom scratching stage.

"True, but we produce a road map and better understand Anna leading the way. Of course things get complicated given diseases caused by some mutations - when we do not know who the driver is, who the co-driver is and who the hitchhiker is."

I guess the price of the drugs that will be developed with the technologies is also an issue.

"Unfortunately, very advanced medicine is very expensive, and therefore not as widely accessible as medicine should be. This is also the case in countries where the public medical systems on paper are excellent, such as Israel. Prices are high, and more will rise, For example, enjoying 2-3 drugs, the expansion of knowledge will lead to one cancer being divided into about 20 types.

"It means for pharmaceutical companies to develop dozens of new drugs with an investment of billions of dollars each. Of course they are not economically viable. The cost will be passed on to health insurance systems, which are inherently limited."

These limitations will lead to a problem in the accessibility of drugs, and here comes a problematic, moral aspect.

Medicine should be accessible because diseases do not differentiate between the rich and the poor.

"What you are describing is a serious moral issue. Accessibility is committed to reality and companies and countries will have to consider it. But it does not end there. Think about access to genetic information. Our DNA contains information that we do not necessarily want to be exposed to others - mental illness or any Another serious future illness.

Imagine a situation where hackers may extort money from you for the information, insurance companies may charge you the policy depending on your medical condition, and employers may even want to recruit better and healthier people into their ranks.

"This is worrying, because already in the womb a person may have a medical identity card, at least in part."

This is an ethical issue in itself - we can determine what our descendants will look like.

We are entering areas of tremendous sensitivity here.

"That's right. Medicine relies on three thresholds - the patient, the disease and the treatment. All the thresholds are being undermined before our eyes. The patient can be a sperm or an egg; the disease can be theoretical. Is considered blue? And how do you distinguish between mutations that cause disease and 'innocent' mutations, which only indicate differences? And most of them by the way.

More beds are needed.

Hospital Corridor, Photo: Illustration: Oren Ben Hakon

"If a person undergoes a general examination that detects in the blood markers of cancer or Alzheimer's disease that could develop in 15 years, what does it mean? Am I sick today? What will be the reaction of the insurance company, and will our employer choose to part with us?"

It seems that our gardens will become almost a commodity in the market.

"In this matter, in vitro fertilization, for example, is just the beginning. We are increasingly separating the second generation issue from the family issue, from interpersonal relationships. When my mother was pregnant she did not even know if it was male or female. Today you can direct sex, and diagnose Diseases of the fetus while in the womb, so the ethical dilemmas are great. Where will we stop? And where did the love and emotion go? Already today we choose a partner by color, perhaps religion, education, economic status, appearance. Now another parameter is added - genetic profile. "Your children, and maybe you will choose to change things along the way. If I had told these things to my father - he would have thought I was crazy."

In the future can we pre-select eye color, height and character traits of our descendants?

"It is possible. Eye color is multigenic, but theoretically - definitely. We will start with physical traits, but also character traits will come. Scientists are starting to get their hands on genes that cause the autism spectrum, ie genes responsible for behavioral diseases, including psychiatric diseases. Many layers of behavior - expressive, comprehension, perception. From the abnormal we will understand the normal. I am a big believer in chemistry, and my practice is biochemistry. In the end - everything is chemistry. When we pass from the world - we leave behind only spiritual real estate, what we have written and created, the spirit is lost with us.

And when we understand the chemistry - we will have access to things we did not dare to imagine. "

How will technology change the role of doctors?

"The doctor will increasingly become a professional consultant, and the knowledge that will be available to him will be vast - sequences of DNA, RNA, proteins, small molecules. He will also be more knowledgeable. Degree programs are already opening in medical schools - medicine combining computer science and engineering Electricity, for example. People ask me if in custom medicine the doctor would be more humane? So no, he would sit behind a bigger screen, and it would be colder and more technical, but much more accurate. "Human. It will probably not be possible to replace it. We will have to think carefully about how to produce a doctor who knows how to balance the technological language with humanity and compassion."

"The word 'cancer' is misleading"

More than 40 years after discovering with Prof. Avraham Hershko and Prof. Irwin Rose the protein ubiquitin, also known as the "death tag" and responsible for breaking down body proteins we do not need - do you anticipate that in the foreseeable future the system will be even more sophisticated to deal with With cancer?

Maybe even maneuver it in our favor to some degree?

(Disclosure: Ciechanover is one of a group of international and Israeli researchers receiving a competitive research grant from the Adelson Medical Research Foundation).

"The answer to your question is a categorical yes, because ubiquitin-based drugs have already been developed that are very effective against certain cancers, and yes - there will be more drugs later. There is great progress in understanding the disease. Today, patients are cured with the help of antibodies that activate the immune system to reject the disease.

Choose a character too?

fertilization,

"On the basis of our system, a drug was discovered that completely changed the clinical face of one of the more aggressive cancers - multiple myeloma, a type of leukemia that previously led to the death of patients in about a year and a half. "A dramatic change in the clinical landscape of the disease. But unfortunately there are still malignancies that remain as they were 40 years ago - pancreas, liver, brain. There has been almost no progress on the subject."

How do you explain that?

"Because the word 'cancer' is misleading, there is no such disease as is commonly thought. It is a collection of diseases with common external characteristics, but each one is individual in its mechanism, and therefore also aggressively, in the ability to send metastases, at the time of detection. The word cancer contains hundreds if not thousands "Various diseases - some mild and some severe."

100 years ago, when people died at the age of 50 from infectious diseases, we discovered the antibiotic - which caused them to prolong life, and then came the cancer.

Are we approaching the day when we can live with good quality cancer as a chronic disease?

"It is very possible. I think the ambition of medicine is that we can live with the chronic diseases side by side, make them chronic - for example HIV, diabetes, hypertension, high cholesterol. The goal is first to prolong life and give quality of life."

What excites you today in the field of cancer research?

"I have an active laboratory where I am moved by discoveries of nature, the complexity of nature. I feel like someone who plays chess with the Creator of the world. There are those who are addicted to drugs, I am addicted to playing chess with God. That is what excites me. "In the beauty of nature, in its complexity, in the way it was created. The way evolution progresses is an amazing thing. We are such complex creatures, and there is nothing wonderful about it."

Is there a chance to win the game of chess against the Creator of the world?

"The knowledge is infinite, so I do not think we will ever know all the possible things. But the game itself is exciting and fascinating, and we are definitely advancing in understanding its norths."

The extreme in diseases

We opened this conversation by talking about death.

Do you find yourself thinking about it more recently, certainly after the corona plague?

"Death is inevitable. I also feel the age. My prayer is for a quick and sharp death, without suffering along the way, without losing the spirit. Blessed is He who created two extreme diseases - and in the middle threw away all the rest. The mind leaves the body. There remains a body, a shell, and the same person is unaware of himself or his environment. He is absent. On the other side we have the ALS disease in which the body leaves the mind. The body goes silent, nothing remains of it, but the patients remain In full intellectual power, in human beings composed of body and mind, these two diseases symbolize extremism.

"So on the one hand - I'm not afraid and sleep well at night. But alongside these there is the fear of losing my mind, my intellect - my ability to talk to you, to think, to think, to create new ideas, to contribute, to discover the secrets of nature. "The fear is to lose the spirit, the chemistry that builds what we call spirit." 

For suggestions and comments: Ranp@israelhayom.co.il

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