A lot happens in the first month of human embryo development as a single cell morphs into multitudes. Yet despite its significance, this period is basically a “black box” to researchers, says stem cell biologist Jacob Hanna.
He and his team at the Weizmann Institute of Science in Israel have taken steps toward probing that puzzle. Last year, they announced they had grown a synthetic human embryo, equivalent to a 14-day-old human embryo, in the lab without the aid of a human sperm or egg cell.
The discovery may serve as a model for better understanding the earliest days of human development, potentially helping scientists to grow organs and tissues for transplant down the line. Hanna, who was named to the 2024 STATUS List as one of 50 people shaping the future of health and life sciences, sat down with STAT to discuss his career path, the promise of his research, and navigating the ethics of stem cell research on embryo development.
Tell me about yourself, Jacob, and what has inspired you to get to where you are now?
When I was a medical trainee, as a Palestinian minority and being gay here, I always wanted to immigrate to the U.S. I thought, if I emigrate, how am I going to compete with the U.S. medical residents? I should have a Ph.D.! That’s how I got into science.
I did my Ph.D. in immunology. I happened to interview in a stem cell lab just for the fun of it. It’s serendipity, which is the fun part of science. Five years ago, I would have never predicted exactly what I’m doing today.
What is it you do now as a scientist?
I work on embryonic stem cells that are at the earliest phases of development. We have been studying, “What are they? What are their characteristics? What is their metabolism?” [They’re] very fascinating creatures. It turns out they are the first building blocks of an embryo. They can make an entire embryo on their own. Basically, we unveiled that encoded within them is a self-propagating reaction or domino effect. They start making not only the embryo parts, but also the extra embryonic tissues like the placenta and the yolk sac, which are also very critical not only for feeding the embryo, but also for giving it shape.
What did you and your colleagues do in 2023, and why was it so important?
We showed that if you take human and mouse stem cells, and you grow them under the right conditions, they can self-organize into an embryo-like entity that has organs, or early organ progenitors, that are very, very, very similar to the real embryo. The potential of this is yet to be shown.
In humans we showed that we can get to day 14, which is just about when the organs start forming. It’s more than a proof of a principle — 2023 is the year when science fiction turned into science.
What is important about the first four weeks of embryo development?
I call it the drama period. This is where all the drama happens. The first four weeks of human embryo development is when the embryo makes all of its organs. The rest is just growth.
During this period it’s just impossible to obtain samples. It’s too early. It’s unethical. Women usually don’t know they’re pregnant. Even if you get sent one sample here, one sample there, this is very good for building an atlas or a reference, but for biology, as we know from mice, you need millions of samples. We’re never going to have that. And we shouldn’t have that. But this becomes an alternative. Even though it’s not identical — that’s why we call it a model — it might allow us an easy way to see how organs form from stem cells outside the uterus without using an egg and sperm. When we start from stem cells, in this day and age with CRISPR technologies, we can engineer the cells, we can label them, we can track them. Which is really exciting for us.
What are your future goals with this? What do you see on the horizon for this technology?
What I see on the horizon is that we can recapitulate the first 40 to 50 days of human development with stem cells. Let’s say that you can make high-efficiency entities that look like an embryo of day 40. That would be an incredible platform. For example, pharma wants to do drug testing, but you can’t do drug testing on pregnant women, it’s just impossible. But envision that maybe with this, you can use this for testing.
And think about how much we’ve learned from using mouse knockouts. This is like the equivalent of human knockouts. We start from stem cells. We don’t need to take donated embryos or donated eggs. We don’t need the uterus. We do it in a Petri dish, but we can still learn about what each gene influences in organ development.
For the everyday Jane or Joe on the street here, how could this technology change their lives in the future?
Let’s imagine a woman who for some reason doesn’t have eggs, maybe she could be a cancer survivor because of chemotherapy, or she decided to have babies a bit too late in her career or things like that, or it could be Joe who developed leukemia, and he cannot find a suitable blood donor. They would give a drop of blood or a skin cell. We will make stem cells from them. We will take them to this naive condition that is very early on. Then we will move forward in these unique conditions and devices. Then make an embryo model of about day 50 or day 40. And then from there, just take the blood cells and give a bone marrow to Joe, or take the gonad and after one month give Jane eggs that she can go and do IVF with a sperm donor or her husband or whoever she chooses.
When you’re expressing your science to the public, how do you take into consideration the ethical perspectives? And how do you make sure your work isn’t being over-sensationalized or scaring people?
I’m a gay Palestinian doing this kind of research in Israel. You almost don’t have to speak, you already sound suspicious to a lot of people.
We love science fiction. I’m a big science fiction fan, but it’s not about science fiction. There is a need here for cells and organs for transplantation. There’s a need to understand human development. And we explain to the public there is no other way than doing it. I’m not saying that it has no ethical price at all, but I do think it does alleviate the difficulties of dealing with aborted embryos and donated embryos and so forth.
We want to explain to the public why we are trying to do this and what is the benefit. These are very complex issues. I think the most important thing is to bring them under the light and also to make sure that the public knows that they are under the light — that nobody’s doing anything in the shadows.
I think there’s a lot of benefit in this. I also think that with every field of research you can think of a downside. You don’t ban nuclear physics because somebody can make a nuclear bomb. You don’t ban virus research because somebody can make a biological weapon. The same thing here. Organ transplantation, cell therapy, there’s a huge need as one of the biggest challenges in modern society, and we can’t just go and stick our head in the sand when we are seeing this phenomenon. I do believe in regulation. I do believe in legislation, and the good thing is that we have time.
We also have to accept that different countries, different societies, different religions also have different boundaries and definitions of these things. I think it comes down to emphasizing to people that this is not about making an embryo-like entity for the fun of it. We are in 2023 and our knowledge of the most critical period of pregnancy is really a black box. This is not a cliche. It’s kind of mind-blowing how much we don’t know about it.
You were saying how as a gay Palestinian scientist in Israel, you’re already met with suspicion doing this work in stem cell research. But I want to ask you, how are you doing? How have the past couple of months in particular been for you?
It’s been very, very, [hard]. On the one hand, the atrocities that happened October 7 and the killing of innocent civilians — there’s absolutely no justification for that. And on the other hand, seeing the war … the human suffering and thinking about hunger. I’ve been very, very depressed in the last [several] months. My productivity went down a lot and we’re piecing ourselves together. I have to, you know, do it for my students … My lab is a very mixed group. I have a student from Gaza whose brother was killed by the bombardment.
I’m sorry to hear that.
Thank you. A former student, just like five days ago, his brother was shot. That’s very high statistics, you know? And thinking of the famine. These are my people. It’s just this frustration. I mean, we’re sitting here discussing how we’re going to save human lives, and BOOM! You kill a thousand people here, and 20,000 people there. You realize, “Really? Then why am I trying so hard?”
We’ve also had foreign student postdocs who decided not to stay in Israel. One of them is Ukrainian and he was like, I can deal with one war, I can’t deal with two wars. I understand him. It’s a big hit as well in that respect, you lose talent, you lose projects. But this is secondary.
This is a big problem, this injustice that’s been going on for the Palestinians for many, many years. And this needs to be resolved with peace, and that’s what’s giving me hope.
Thank you, Jacob. You light up when you speak about your students and training this next generation of brilliant scientists. Is it also your students who are giving you hope during this dark time?
Oh, definitely. Definitely. I think that’s very much so. We rise together. I don’t have my own biological kids. I would say my trainees are my kids. These people who come and are so passionate about the science. They dedicate four, five, seven years of their life in my lab. I really want to make sure that nobody leaves and says, training under Jacob was a mistake and I didn’t fulfill my maximal potential. This thought scares me to death. I really care about them and I think we should do all that we can so they succeed.