Fast FAQs: Promises and realities in embryonic stem cell research

For all the controversies, it's still early days for the science

Whitehead Member Rudolf Jaenisch weighs in on what we can, can’t and (hopefully) will one day do with human embryonic stem cells.

What do we know for sure that embryonic stem cells can do?

Illustration: James Yang

Embryonic stem [ES] cells have in principle an enormous potential for research and therapy. We can extrapolate much from our knowledge of mouse ES cells. From these cells, we know we can generate any tissue type in the Petri dish. We also know they’re useful for therapy. We’ve used them to treat a mouse variant of the human disease severe combined immunodeficiency. We showed that one can restore the immune system using customized embryonic stem cells.

But the human system is much more complex. These cells don’t grow rapidly, they’re difficult to grow as single cells, and they suffer chromosomal aberrations quite easily. All these issues we can handle in the mouse.

We need to learn how to make the human ES cells as easy to work with as mouse ES cells. The issues are strictly technical.

Whitehead Member Rudolf Jaenisch Photo: Sam Ogden

How successful have we been in turning ES cells into specific tissues?

There are major efforts to derive neurons, heart muscle and blood cells. There have been major successes, but we’re not yet able to produce a tissue for patients.

What do ES cells offer for basic research?

These cells have enormous value as research tools. The hope would be to use somatic cell nuclear transfer [SCNT] to generate human models of complex diseases like Parkinson’s, Alzheimer’s and diabetes. [In SCNT, an egg’s DNA would be replaced with DNA from a patient, and the egg would be used to generate patient-specific ES cells.] All the genetic mutations causing the disease would be present in the ES cell.

If we could derive ES cells from a Parkinson’s patient, we would like to coax these cells into forming neurons, and as we study the process, hopefully find the defects that cause the disease. In other words, we can study a very complex disease in the Petri dish with the potential to look for compounds that treat it.

But does SCNT work in humans?

It works in mice, cows, sheep and rabbits. It will work in humans. We need to resolve the technical issues.

Why do we need to keep deriving additional lines of human ES cell?

The presidentially-approved ES lines are useful to an extent. But they were created under conditions that we no longer use.

The Harvard ES lines [not presidentially approved] are also very useful. But what’s become clear in the last few months is that the way you isolate or culture the cells determines how the cells react later. For example, all the human lines that we work with have been isolated under high oxygen concentrations. But if you grow these cells under lower oxygen, they do much better. We need to grow these cells under different conditions and decide what the best conditions are.

What about alternative means for deriving ES cells?

These other methods are driven by ethical objections. We did a proof-of-principle experiment in mice to show that one can generate embryonic stem cells without destroying a viable embryo. Generating ES cells from amniotic fluid also has gotten a lot of attention recently, but I think that approach is overblown.

The real goal of the field is to generate ES cells without using eggs. Take a skin cell and treat it in some way that redirects it back to an ES-cell-like cell. Nuclear transfer shows that the egg can do it.