Jacob Hanna, biologist: ‘If a human fetus model is controversial, I will make it without a heart or brain’

Biologist Jacob Hanna, 44, is one of the best scientists on the planet. In his laboratory at the Weizmann Institute of Science, in the Israeli city of Rehovot, his team takes skin cells from people and reprograms them in such a way that they are able to self-organize and form a structure very similar to a human embryo. Just a year ago, Hanna announced to the world that he had managed to recreate a 14-day-old embryo, but he won’t stop there. The researcher, born in a Palestinian Christian family in Rameh, wants to create a living structure that is as similar as possible to a human fetus, with little arms and legs, from which, according to his prediction, cells could be obtained for personalized transplants. If a person has leukemia, a fetus could be created from their own cells in order to create the organ needed.

Hanna recounted his scientific progress on May 10 at a conference in Madrid, at the National Cancer Research Center. Three days later, he answered questions from EL PAÍS in one of the temples of world medicine: the classroom in which Santiago Ramón y Cajal — the father of neuroscience — taught for three decades at the Illustrious Official College of Physicians of Madrid. Hanna is devastated by the “genocide” being committed by the Israeli army in Gaza following the Hamas terrorist attacks on October 7, but he still has the strength to joke. “Being a Palestinian in Israel, and also gay, my way of surviving is dark humor,” he explains.

Question. Last year you grew a living structure, similar to a 14-day-old human embryo, in the laboratory, without needing sperm, eggs, or womb. Where is the limit?

Answer. In mice, we can reach day 13 of development, which is 1.3 centimeters, according to the results that we will publish this year. The gestation period of a mouse is 20 days. If you take the analogy of that state based on size, in humans it will be day 70 to 75, because human growth is much slower. This is great, because on day 60 all the organs have formed. We have a system with special incubators, in which the real embryo or the embryo model is fed by diffusion, because the nutrients are in the medium. It is an artificial system and when it grows too much, the deeper tissues do not receive nutrients, so we can only go so far.

Q. You don’t work with real embryos, but it could be creepy if you get a 70-day human embryo model with arms, legs, fingers....

A. I wouldn’t use the word creepy. One of the biggest discussions is whether an embryo model, or a synthetic embryo, should be considered an embryo or not. I think that, at the moment, they are not identical, there are big differences between them, but in ethics you have to take into account extreme scenarios. Let’s assume that one day they will be identical. Is it a person or not? Is it life? Stem cells are also a form of life. In many countries, such as Spain, you’re allowed to work with blastocysts [the stage five or six days after fertilization] and that’s an embryo too. There is fear of the word embryo. I think the most important thing is if there is cognition, if there is a sense of pain. We are far from that, that doesn’t happen until halfway through the pregnancy. Whether it’s creepy or not, the question is not about reducing it to whether it’s ethical or not. I think the way to look at it is: What are the pros and cons?

Q. What are they?

A. There is an ethical price to pay, of course. It is an uncomfortable investigation, but it is our duty to explain to people why we are doing this. We don’t know much about human development. We don’t even know where the cells go. When you explain it to someone, the first thing is to clarify that you cannot make a complete human pregnancy [in the laboratory] and we’re not trying to. This is not a replacement for pregnancy. I’m a big fan of the Matrix movie, but that’s not what we’re doing. It’s about understanding. We don’t know which genes are important for forming your liver. I want society to make decisions after having all the information, not with unjustified concerns. When we talk to people, one of their concerns is what would happen if someone took one of these embryo models and implanted it in a uterus. How are you going to force a woman to put an embryo inside herself?

Q. Maybe you can find a female volunteer.

A. It is an extreme scenario, but even if you find one, you can’t do it, because a natural embryo can only be implanted in the womb until the blastocyst stage. One day after the blastocyst, it can no longer implant, it is too late. And all the stages we work with are post that. Even if someone wanted to break the law, they couldn’t. I think there is too much fear of embryo research. It’s like it’s the only research that raises ethical concerns, but I can’t think of any scientific field that’s free of them. Artificial intelligence is a risk. In virology research it is very easy to create a dangerous virus, which is much more dangerous than if we make 10 Frankensteins. We have to be realistic. You don’t ban nuclear physics because of nuclear bombs, even though they are much more dangerous.

Q. American chemist Jennifer Doudna, the mother of the CRISPR technique for modifying DNA, said she had nightmares in which Adolf Hitler arrived with a pig mask and asked her for more information about her technology. Do you have nightmares about a terrifying scenario?

A. My only nightmare is when I imagine my daughter being killed in Gaza.

Q. You have nightmares with more substance.

A. One of my students, Shadi Tarazi, is from Gaza and half of his family has been killed. He was the first author of the first artificial mouse embryo. This is unusual, because Israel does not allow the people of Gaza to leave that cage. I had to use a Jewish friend connected to the Israeli Mossad to get the permits. We must stop the fear of the Palestinians. I am Palestinian and that does not mean that I want to destroy Israel or that I want to destroy the Jews, even though I am very critical and say that Israel is committing genocide. I feel like a Palestinian scientist inside Israel. My real connection with the country will come when it accepts peace. In my opinion, the one-state solution is the best way.

Q. Living together?

A. Yes, like in Belgium [a country made up of two regions: Dutch-speaking Flanders and French-speaking Wallonia]. The first love of my life was a Jewish Israeli. Most of my friends are Jewish Israelis. However, the Israeli authorities not only fail to promote integration, but instead engage in active segregation. The first time I interacted with Jewish people was in university.

We want to imitate the embryo because it is like a 3D printer: it makes organs

Q. Let’s talk about the positive aspects of your research, the best scenario, not the worst. You imagine a future where you can take a skin cell from a person, reprogram it by going back in time, make a pseudo-embryo from that person, and grow it for up to 50, 60, or 75 days.

A. Up to the minimum number of days needed to answer the question we are asking ourselves.

Q. Or to cure a disease of the cell donor.

A. True. We want to imitate the embryo because it is like a 3D printer: it makes organs. We discovered the phenomenon that stem cells are self-organizing, and we discovered the conditions that allow the process to be unleashed. If you make sure they don’t stick together, suffocate or starve, this domino effect begins. They do it alone. We may never be able to recapitulate this complexity, but we have been lucky and have figured out that this happens and how to trigger it. Perhaps some of the resulting cells could be useful for transplants.

Q. What cells?

A. For example, blood cells, which are normally in the bone marrow, but in the embryo they are also in the liver. There are studies in mice and in abortions that show that blood stem cells in the liver are the best cells for blood transplants. If I am a leukemia patient, it is very difficult to find a donor. With this technology you take the patient’s skin cells, you reprogram them so that they are induced pluripotent stem cells and you can grow them for the minimum number of days, which is 35 or 40, to obtain liver cells. If you want eggs, it’s more like 60 or 70 days. You can take those cells and save that person’s life. The question is not whether this is ethical or unethical, the question is to live or not live. Let’s imagine that we have a person with leukemia who is about to die and cannot find a donor. Do they have the right to give their own cells to make an embryo model? Let’s even assume that the embryo model is identical to a real embryo — even though it isn’t right now — and that it saves their life. Let’s now think about a woman who has received chemotherapy for cancer, she is already cured, but she no longer has eggs. Does she have the right to give her skin cells, reprogram them, make it to day 60, get an early ovary, grow it 30 more days, and make the eggs?

Q. Right now can you grow a human embryo model until day 70?

A. No. Our goal is to make the embryo models more like the natural human embryo and we are trying to grow them for more days, but at the same time we are saying: what makes something a person? Let’s eliminate that characteristic to ensure that it will never be a person. We use stem cells with restricted development. Now, when I start with stem cells, I can remove one gene and there are no frontal lobes of the brain. That thing can never have cognition or sense pain. To reach day 40, 50 or 60, you don’t need to do this, but if the public feels more comfortable this way, we want to give scientific options to circumvent ethical problems. To make ovaries or blood cells in the liver, you don’t need the frontal lobes of the brain, or even the heart. A clump of organs is enough. Then there are people, like the journalist Antonio Regalado, who says that we are making headless people. We cannot allow ourselves to be carried away by extravagant Frankenstein-style fears. It’s not right, we are a modern society.

What makes something a person? Let's eliminate that characteristic to make sure it will never be a person

Q. You are referring to Antonio Regalado, journalist for the magazine MIT Technology Review. In 2022, he wrote an article about a company you founded, Renewal Bio, and the headline was: “This startup wants to copy you into an embryo for organ harvesting.”

A. I didn’t like that approach at all. I told him, I was very disappointed. This day-40 thing is not you, especially if it doesn’t have frontal brain.

Q. The magazine called these structures “mini-mes.”

A. I deplored that. For us it is very important that donors know exactly what we are going to do with their cells. Some have been donated to us by other Weizmann professors and others are mine. Then they said, “Jacob Hanna is making mini-mes.” I’ve gotten induced pluripotent stem cells from myself, from my skin cells, but they’re terrible.

Q. How many embryo models of yourself do you have?

A. Very few have reached day 14. My cells grow very slowly, so my students use others that do grow at a good speed. Mine aren’t good enough, but I tried. [Laughs]

Q. What do you feel when you see those structures with their cells growing? Do you have philosophical or religious questions?

A. They are cells, a clump of organs. I am a very existentialist person, I love dark humor and I don’t philosophize too much. They are just cells. If we were trying to get to day 150, I might have questions, but if you use these developmentally restricted stem cells, they are not a human being, they are not a person.

Q. Is it possible, from a theoretical point of view, to grow a six-month-old human fetus model in the laboratory?

A. No, I don’t think so.

Q. But, theoretically, over the next half century...

A. If it works in mice until day 13, we can extrapolate and say that, theoretically, it can reach day 70.

Q. On day 70 it is already a fetus.

A. It’s a fetus, but not six months old. Six months is still science fiction. To get to that I think a great technological leap would be necessary, which is not even on the horizon.

Q. But it is theoretically possible to obtain a 70-day human fetus model.

A. Yes.

Q. It is no longer an embryo, it is a fetus, and that word is more controversial.

A. It is.

Q. People may think: what is this guy doing in Israel with models of human fetuses?

A. Yeah, what is this gay Palestinian guy working in Israel doing? All controversies in the one individual. But that’s what we have regulations for. I want to reach the minimum number of days necessary. To obtain blood cells from the liver I do not need to reach the fetal stage. Maybe for the ovaries it is necessary. If a fetus is controversial and I want to reach day 70, I will make no heart or frontal brain. And then it’s not a fetus, it’s a clump of organs. Could that be a person? No, it could never live on its own. Never forget the potential benefits. Don’t only look at the potential pitfalls.

Q. You were born in Rameh, a Palestinian Arab town in Israel, into a Palestinian Christian family. You know Christianity, Judaism and Islam well. How do each of these religions see your experiments?

A. In Judaism and Islam, until day 40 there is no controversy: it is not life until the heartbeat is formed or even after. The historical reason is that the pregnant mother is more important than the baby. Some rabbis talk about day 160, since before they do not consider it a person because it does not have cognition or feel pain, it is just a body of organs. Regarding Christianity, I am also Protestant, we don’t even have a church. My mother is Greek Orthodox and my father is Protestant, but we are not a religious family. I’m not anti-religion either, I respect that. A childhood neighbor is now at the helm of the Greek Orthodox church, and every time I publish a study, he calls me and congratulates me. The second time he did it, I asked him, “Your Holiness, are you sure you understand?” And he had completely understood it. He told me: “I don’t see any danger, because God created stem cells, God created the blastocyst, God created the ability to make stem cells and you use them to save lives.”

Sign up for our weekly newsletter to get more English-language news coverage from EL PAÍS USA Edition