Yale Bulletin and Calendar

November 17, 2006|Volume 35, Number 11|Two-Week Issue

Haifan Lin, pictured with Hua Li, research associate and laboratory manager, will work to galvanize stem cell research at Yale.

Lin: Great care needed in
studying 'finicky' stem cells

Haifan Lin, the newly appointed director of the School of Medicine's stem cell program, has two immediate goals: to galvanize Yale's stem cell community and to hire new recruits to help advance the program.

After an international search in which he emerged as the top candidate, Lin comes to Yale from Duke University, where he was founder and co-director of the stem cell program. His undergraduate training was in biochemistry at Fudan University in Shanghai, China. He earned a Ph.D. in developmental biology from Cornell University and conducted four years of postdoctoral work at the Carnegie Institution in Washington, D.C.

The eldest of four children, Lin is a native of Dongtou, a tiny island off the coast of mainland China. He and his wife, Edna Hu, recently moved to a home in the East Rock section of New Haven.

Lin spoke recently about his move to Yale and his plans for the program, which will be based in the Amistad Building. Construction is to be completed in May 2007.

When did you first become interested in stem cell research?

The interest started at Cornell, where I did my graduate work in how embryonic cell division leads to the development of a whole individual. From those studies I realized that stem cells played an important role. I first worked on stem cells at the Carnegie Institution from 1990 to 1994, when stem cells were only studied in humans and in mice. I thought it would be more effective to look at stem cells in smaller organisms, specifically the fruit fly. Fruit flies have been a genetic powerhouse for a century. Many of the important genes and genetic principles for human development were first discovered in fruit flies. I thought it should be relatively easy to identify stem cells in flies, see how they divide, and look for genes that control the process. An added advantage is that fruit flies have a very small number of genes so you effectively have the use of hundreds of millions of years of evolution that pre-selected the most important genes for stem cells.

As School of Medicine Dean Robert Alpern has said, you were appointed to work on basic research on the cellular and molecular biology of stem cells. What is your approach?

Stem cell research can be done in two ways. The first is what I call the "lead by science approach," which is to try to understand the inner working principles of stem cells and then take this knowledge and move on to manipulate and harness these cells with a logical purpose and expectation.

The other approach is to isolate these cells and directly culture them into the damaged tissue and then try out different "cocktails" to see which will make stem cells become the type of cells we need to cure a particular type of disease. This is the disease-oriented approach. Each has its advantages and disadvantages. Ideally a program will have a combination of both, but that requires a huge investment. I believe that in the long term, the lead by science approach is going to prevail as the way to understand cells and manipulate them for medical applications.

What do you see as the limitations of the disease-oriented approach?

It's empirical. It largely depends on luck and chance and the results are difficult to reproduce. In addition, even if it works, you don't know how it works.

In the long term this could be dangerous because you don't have a rational understanding of what these transplanted cells are likely to do in your body for years to come. For example, we don't know if these cells are more carcinogenic. I understand the public's enthusiasm and support for the disease-oriented approach. Everyone hopes stem cells will cure many diseases quickly, but stem cells are not easy to harness, although they may be the most important cells in our body. In the next few years I don't expect stem cells to cure major diseases, but I am confident that we will be much closer to understanding the fundamental mechanisms of stem cells.

What attracted you to the Yale School of Medicine?

I was extremely attracted to Yale because of its visionary leadership, its outstanding faculty and students, and its collegiality. Yale wants to do the right kind of research. [Its leaders] realize that stem cells are a deep and important part of the future of medicine and biology and that stem cell research is a long-range effort. We cannot expect to use stem cell research to cure neurodegenerative diseases or cancer in a few years, but it is a very important investment both intellectually and financially for the continued and future success of the medical research enterprise at Yale. This vision echoes what I think about stem cell research, so this is the right place for me to do it.

There is a perception by some that Yale has a limited stem cell program. Is that an accurate evaluation?

No. Yale actually has a much larger stem cell research community than people realize. We have at least 43 different stem cell researchers in 18 different university departments, including four basic science and 11 clinical science departments in the medical school. Their work spans from human embryonic stem cells to various types of adult tissue stem cells in humans and experimental model organisms.

One of my tasks is to develop collaborative research efforts. I have started one-on-one meetings with stem cell researchers at Yale to get to know them and to get their input. We have already written several collaborative research grants for the state of Connecticut and are in the process of putting together a few more for the federal government. We will organize activities such as joint lab meetings and retreats to bring stem cell researchers at Yale together to share their latest research results and ideas, and to promote synergistic interactions. We also will build core facilities to help accelerate stem cell research at Yale.

What will Yale's stem cell program look like?

Yale's stem cell program will have a two-layered structure. There will be a core group of stem cell researchers fully devoted to fundamental stem cell research in one interactive setting in the new Amistad building. This group will also advise and collaborate with other Yale researchers interested in stem cell research. Together they will form an interactive stem cell program at Yale. We will organize programmatic activities, as mentioned earlier in the interview, to support our stem cell researchers.

We also will build three core facilities. The first core is the human embryonic stem cell facility, which should be a very valuable resource. Human embryonic stem cells are very difficult to culture. The second core will be a cell-sorting facility to sort stem cells away from other cells. The third core will be a microscopic imaging facility to examine and image the proliferation and differentiation of stem cells. By establishing such facilities, a lab interested in working on these cells can bypass the hurdles of learning each technology and can receive assistance from the facility. Together, these core facilities should significantly strengthen the infrastructure for stem cell research at Yale.

What are the challenges of working with human embryonic stem cells?

These cells are very finicky. They have very long cycle times. They can easily lose their self-renewing ability and are very easily contaminated by other cells or microorganisms. You need experts and special clean room conditions to culture these cells. There are not too many people who know how to culture human embryonic stem cells properly. A challenge for me is to hire one of the best experts in producing and culturing human embryonic stem cells to be in charge of this facility.

What are your views on the controversy surrounding human embryonic stem cell research?

To me it is a question of benefit versus risk, or life versus only potential for life. A common misconception is that when you use stem cells from embryos you destroy life, but when you have an embryo that is only several cells it only has the potential to become life. It is not life itself. Also, for most purposes, one can use embryos that are to be discarded in fertility clinics.

Now, if someone argues in the most extreme sense that every fertilized egg is a life, I would still respect his or her belief. However, I hope that this person will then agree that in vitro fertilization (IVF) destroys life, since about 70% of the embryos produced in vitro do not survive. Yet I know that a lot of people who do not support stem cell research support IVF. To push this biologically fact-based argument even further, I would say that sex is the biggest destroyer of life because the chance that any fertilized egg will develop into a fetus is much lower than the likelihood that something will go wrong and the egg will be wasted. So sexual activity constantly destroys new "lives" if one defines life that way. Yet, even according to this definition, embryonic stem cell research does not destroy new lives because it uses already wasted early embryos from the assisted reproductive processes.

You've mentioned that one of Yale's strengths is that it has a stem cell research committee in place. Why is that valuable?

Stem cell researchers should be very conscientious about the ethical implications of their research. They should not work alone. Their research should be watched and supervised by a panel of stem cell researchers, ethicists, legal workers, non-stem cell researchers and representatives of the public. Yale already has such an oversight committee in place called the ESCRO (Embryonic Stem Cell Research Oversight) committee, which has the ultimate power to approve or disapprove a stem cell research project at Yale.

Were you attracted to science as a child?

Yes. As a child I was always curious about the things that surrounded me and I asked many questions. Science could often provide definitive answers to my questions and taught me how to find answers by myself. This attracted me to science. My father was an accountant. He described everything by numbers. He gave me a sense of precision and quantification. My mother was a primary school teacher who enjoyed her job a lot, so she gave me a great sense of teaching as a very fulfilling profession. I aspired to become both a scientist and a teacher. As a professor you have the opportunity to pass down your knowledge to other people and to inspire other people. Meanwhile, you constantly learn new things from the people you teach. I like this kind of lifestyle.

What else inspired you to become a scientist?

The island where I grew up, Dongtou, is three to four miles wide and 10 miles long. There is a town of 7,000 people in the middle and the town is surrounded by fishing villages. My family lived in the town near a construction company. I used to watch the men using tools and I began making my own models. When I was in fourth grade I built an electric fan and an electric crane. I thought I would become a ship engineer or a physicist, but eventually the complexity of biology intrigued me even more, so I became a molecular biologist.

-- By Jacqueline Weaver

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