Talking to: Dr. Karina Yaniv, 45, chemist and biologist from the Department of Biological Regulation at the Weizmann Institute of Science, Rehovot, about her groundbreaking research in embryonic development. Where: Tel Aviv café. When: Thursday, 4 P.M.
You are studying the formation and development of embryos. When exactly is an embryo formed?
In principle, at the moment when the chromosomes from the sperm cell fuse with the chromosomes of the ovum.
That’s the moment at which we can say we have an embryo?
At that moment, we have an embryo, but we don’t have a single individuum yet. It is important to understand that at this point, it is still possible for twins or triplets to emerge from that fertilized egg. And when we talk about cloning, it’s possible to create 100 beings like that. At the moment of fusion, we don’t yet have a unique being.
At what stage do the cells become something that is unique?
Even that seemingly simple question generates a host of disputes and theories. Some say that as long as the egg can produce a number of identical people, it cannot be considered human. However, the Catholic Church, for example, views the fertilized egg as a living being in every respect.
In halakha (Jewish religious law), the embryo is considered a living being after 40 days.
Yes. Scientifically, around three or four weeks after fertilization, implantation occurs and an additional stage of development, called gastrulation, takes place. This produces what we call the “three germ layers,” from which one single embryo emerges – one being. That’s it, there can be no more dividing. The organs begin to develop; at around eight weeks, we have an embryo that has all the basic organs, which only need to mature.
Interesting that halakha addressed this timing issue.
Yes, but some will say that as long as the embryo lacks mental capabilities, there is no difference between it and any other living creature, so it cannot be called human. Mental ability arrives at a far later stage of pregnancy – at 24 or 25 weeks.
Sometimes, the initiation of life is directly related to how death is determined. In some countries, death is determined according to the cessation of brain activity – which already exists in the fetus in these weeks. In other countries, including Israel, death is determined when there is no heartbeat. At present, we have far more means for determining the existence of life than we had 300 to 400 years ago, when the embryo was determined to be alive when a mother felt its movements in her abdomen. Today we can detect a beating heart already in week 6, and say that this is a living being. This is what technology makes possible: It is perhaps not meant to change the definition of what constitutes life, but in practice it does so. In fact, our laws and system of ethics today are technology-oriented.
When do you think life can be said to begin?
I conducted research in the United States for five years and experienced first-hand how the pressure wielded by the Church, because of its conception of what life is, simply does not allow research to progress. As I see it, in this discussion we have to differentiate between what is permissible for research purposes and what is not. An aborted embryo is an amazing research tool. To object to using it as such is like saying we will not use the results of a biopsy of a cancerous tumor for research because the tumor belonged to a living person.
In the past I taught anatomy. In, Israel, someone who donates their body to science is buried after a year, and every last bit of the body must be interred. In other words, Judaism places a very high value on human tissue, but if it’s possible to save a life with it, it falls under the category of pikuah nefesh [the principle in Jewish law that preserving human life overrides virtually every other religious consideration].
Judaism shows flexibility and accepts these things. If the study of aborted embryos will help us cure diseases, we are obliged to use them. I also think that even people who object in principle to abortions and to stem-cell experimentation would not be against the creation of organs in a lab for implantation if their life or a relative’s life could depend on that. This is where the discussion should take place.
What about producing embryonic stem cells for research? It’s allowed in Israel, but not in other countries.
I think it is proper. The reason stem-cell research in Israel is so advanced is that the regulation here was introduced in a timely manner, and in an intelligent, correct way. Again, there is a difference between using stem cells for research and for cloning purposes. We normative scientists are not interested in cloning people. But to stop scientific progress because we don’t want to deal with ethical issues or because we’re afraid to run afoul of the Church and the religious establishment, is a huge loss.
Let’s go back to embryonic and fetal development. As I understand it, from the “zero moment” until the moment the fetus is viable, we go from one cell to 200 million.
Think of it, say, in terms of building an airplane. What is truly astonishing in the process of embryo-building is that everything is already there. The instructions, the raw materials and the engineers are already present in one cell – the fertilized egg. That is a genuine wonder. There is nothing else in the world that is primed to start acting as it is being created. For example, we need a heart to be formed in order to be able to pump blood to the other organs, and without that, the surrounding organs are not able to form. For that to happen, that first cell needs to undergo divisions, from which many cells emerge. During gastrulation, the cells differentiate into three large groups. One gives rise to everything related to the nervous system, and to skin, hair, everything external. The second gives rise to muscles, bones, cartilage, heart and blood vessels. And the third gives rise to all the internal organs – liver, pancreas, stomach.
Until then, theoretically at least, each cell can become everything.
Yes, until gastrulation. Afterward, each cell receives its particular identity or designation. But it’s not enough for the cell to know what it is; the organ itself has to assume a three-dimensional form. We do not know what determines organ size. Researchers in hundreds of labs around the world are working on this question alone, trying to understand how it all comes about – the shape and size of the liver, say. Because organs have to be a certain size and possess certain proportions. In addition, each one must be in the right place and also “know” where the organ next to it is. The organ acquires size and then has to be situated in its space, like in a jigsaw puzzle.
Does that happen concurrently or in sequence? Does the liver grow parallel to the heart or, say, ahead of it?
It happens concurrently. There are some organs that develop later, especially in human beings; the line of development proceeds more or less like the line of evolution.
Can you elaborate?
If you look at Darwinian theory, you can draw a parallel between the development of the embryo and the evolution of species, because more primitive species will complete their development earlier. If we look at vertebrate embryos in the early stages, we can hardly see any differences between them – human development will resemble the development of fish and mice, for instance. The initial embryo will possess minimal things: heart, blood vessels, brain, liver. Afterward, when the land creatures arrived, it was necessary to develop lungs, an organ that had not existed before. Well, in the human embryo, the development of the lungs does not take place parallel to the liver, the kidneys, etc. It begins later, and in this sense, one can see in human beings, which are the most developed creatures, all the stages of development.
All embryos also have a tail at the beginning, right?
It’s very surprising that all embryos are alike in the first stages of development. You yourself work with zebrafish embryos. It’s odd that they resemble human embryos.
By “similarity,” I am referring to genetic similarity, and at that level it is amazing. That is precisely the issue of developmental biology. The differences are in size and length of time: A human embryo is bigger than a fish embryo, and it takes longer to arrive at the same stage of development. What a fish does in 19 hours will take a human being about three weeks.
If I were to show you the embryos of a cow, a fish and a human being, would you be able to tell them apart?
I would be able to identify the fish, and possibly also a frog and a chicken, because I have worked a great deal with them. With other embryos, it will be more difficult, and anyone who is not in the field will not be able to tell the difference.
Your major discoveries in the field have to do with the lymphatic system.
Less research is being done on the lymphatic system, even though it has very important functions. It plays a crucial role in our immune system. It is also critical in regard to cancer, because cells that metastasize travel by way of the lymphatic system. For more than a century, researchers have been trying to understand where the cells that produce the lymphatic system come from. During my postdoctoral studies in the United States I discovered, contrary to what had been thought previously, that fish have a lymphatic system. We showed for the first time that the lymphatic system is formed from cells that are located in the embryo’s veins. In the past few years, at the Weizmann Institute, we discovered that these cells are a type of stem cell. In addition, we succeeded in finding substances that control the development of the lymphatic system in fish, and when we tried them on human stem cells in a culture, we were able to generate human lymphatic cells.
Actually, the applications of embryo research are a type of reverse engineering. The idea is that when it becomes possible to understand how the organs are formed and develop, we will be able not only to grow new organs in a culture but also to understand pathological processes. We know for certain that a large portion of the pathological processes that take place in the human body, particularly cancer, reactivate processes that take place during embryonic development. If we understand how an organ develops, how and at what rate the cells divide, what gave them the order to divide and what stops the division of cells – we will be able to influence pathology.
The relevance is clear: Cancer, the disease that is occupying scientific researchers, above all else, is caused by uncontrolled cell division.
True. Every phenomenon has a gene or a system of genes that controls it. If we can identify those genes, we will understand how they work and be able to inhibit or activate them more – they will serve as the “medicines” of the future. Our specific research is concerned with blood vessels. We know that cancer cannot grow without a network of blood vessels that surround it and supply it with oxygen and food, so what the tumor does at the very outset is to attract blood vessels to itself. Much research is devoted to inhibiting the increasing number of blood vessels around the tumor. In our laboratory we found, through our study of zebrafish, that high concentrations of low-density lipoproteins – LDL, the “bad cholesterol” in our blood tests – prevents the formation of blood vessels in the embryo. If the embryo has high levels of this cholesterol, its blood vessels start to disintegrate.
So we can use cholesterol to stop the growth of cancerous tumors?
We are now conducting a study, whose results will be published soon, that shows that in mice with high LDL, cancerous tumors barely grow or metastasize. We are also treating these mice with statins, drugs used to lower cholesterol, and we are seeing that as soon as we do that, their tumors grow, continue to divide and metastasize. This is something we discovered entirely by chance in our work with the fish, which might be able to influence our day-to-day life.
In principle, how much can we learn from embryonic development, given the fact that the embryo exists in a very distinctive environment? It develops within a womb and is dependent on the mother’s body and her hormones.
The embryo’s environment is indeed very isolated, but the mother’s contribution is minimal. Embryos of mothers who are drug addicts or are malnourished develop, too. Naturally, exchange of food and other materials plays a part, but our interest lies in the genes.
It is lovely that you are still enchanted by this all after so many years.
Because it is truly amazing. Some people are thrilled by the water on Mars, but I say: Forget that – this is the real thing. We can draw so much knowledge from observing how life is created! It’s like a code that was written for us that we have to learn to decipher. If we succeed, we will be able to understand how this marvel occurred, and we will be able to understand life.
To go back to the issue we began with: When does that life begin?
The scientific definitions are not always consistent with the philosophical conceptions. I think it is possible to define when it begins: As far as I am concerned, life begins the moment there is a beating heart, but our development continues throughout life even if the organs themselves stop developing. Aristotle said, “He who sees things from the beginning will have the finest view of them.” He wasn’t talking about embryos, of course, but that’s how I think of it. If we observe the earliest part of life, we can see the continuation in the clearest form, across its entire course, including adult life.
If so, how far do you think that embryonic development influences the person that embryo eventually becomes? Physically and mentally?
There is an influence, that much is clear. Metabolically, physically, and in terms of what is today perceived as mental or spiritual. I am convinced we will find the spiritual genes, too, in the end.
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