Perhaps owing to its ethical and religious ramifications, few scientific questions have transcended the academic world to capture people's attention the way stem cell research has. As an example, there are few, if any, precedents to California's Proposition 71, which successfully asked taxpayers for hefty financial support to advance stem cell research in a heavily politicized atmosphere.

It was therefore timely that the meeting Days of Molecular Medicine 2005, sponsored by Nature Medicine, the Institute of Molecular Medicine (University of California, San Diego) and The Salk Institute, focused on stem cell biology and human disease. The meeting aimed to encompass all areas of stem cell research, and included sessions on stem cell lineages and niches, stem cell engineering, tissue engineering and translational studies. This organization provided a useful framework to examine the questions that currently occupy the field and to identify the areas in which more needs to be done before successful therapies can be developed.

One of the basic, largely unanswered questions about stem cell biology is what defines a stem cell. In other words, what inherent characteristics of a cell define its 'stemness'? Much of the study of this problem has centered on the analysis of the transcription factors that are relevant to stem cell biology, as well as in the identification of markers to isolate and study stem cells more efficiently, and might eventually offer us new insights on their intrinsic properties. At the meeting, the talks of Stuart Orkin, Sean Morrison and others exemplified recent advances in this line of research.

The other side of the same coin is the effect of extracellular cues on stem cell maintenance and differentiation. This is arguably the issue around which most efforts have recently revolved, and many of the presentations at the conference highlighted progress in this area. The talks ranged from organisms such as Drosophila (Allan Spradling, Margaret Fuller) to the mammalian lung (Brigid Hogan) and skin (Fiona Watt).

Ultimately, the results from these two lines of inquiry will enable us to manipulate and differentiate stem cells as a first step to realizing their therapeutic potential. Recognizing this issue, several speakers focused on stem cell engineering. Some of them (such as George Daley and Ron McKay) discussed how our understanding of stem cells is enabling us to nudge them to differentiate into a phenotype of interest. Others (such as Peter Schultz) acknowledged that many factors relevant to stem cell differentiation still elude us, and discussed the feasibility of using chemical biology and high-throughput screening approaches to identify pharmacological modulators of stem cell fate.

But knowing how to turn a stem cell into a neuron or a hepatocyte is only the beginning of the road from biology to therapy. The next part is succeeding in integrating these differentiated cells into their target organs. It is therefore important to understand how organs form and how we can artificially form organs from differentiated cells. At the meeting, the presentations of Gerard Karsenty on bone and Sangheeta Bhatia on liver illustrated some of the problems that need to be addressed before stem cell biology can be translated into therapy.

The last session of the meeting focused precisely on translational studies. Not surprisingly, these are early days for the use of stem cells to cure disease, and most of the successes have been documented in animal models, as exemplified by the presentations of Markus Grompe and Georg Beilhack. But the possibility that insights from stem cell research make their way to the clinic may not be as remote as some think. As discussed at the meeting by David Scadden, the finding that parathyroid hormone affects hematopoietic stem cell development could give rise to a successful therapy against a variety of liquid tumors.

As every year, Days of Molecular Medicine included a forum to highlight emerging issues with implications beyond the immediate experimental sphere. In 2005, the forum focused on regulatory and ethical issues on the use of stem cells. But in addition to the ethical questions, the forum highlighted a different point. Although for some critics the key arguments against stem cell research continue to be moral, many people are now turning their attention toward the issues of transparency regarding the way resources are used in support of stem cell therapy. This sentiment is particularly evident in California, where the meeting took place, as there are growing public concerns about the way the funds allocated by Proposition 71 will be disbursed and whether there are any hidden agendas being pushed by its most enthusiastic supporters. These issues deserve to be analyzed on their own at another opportunity.

The general atmosphere at the meeting was of optimism about the future of stem cell research: optimism about progress in the field and about the determination of the community to overcome the political barriers to this research. But attendees were also aware of the challenge they face, not only intellectually, but in terms of their accountability to society and on the high expectations the public has on stem cell therapy.

In 2006, Days of Molecular Medicine will travel to Sweden. Together with the Institute of Molecular Medicine and the Karolinska Institute, we will collaborate on a meeting devoted to inflammation in chronic disease, another field that has seen explosive growth and that, coincidentally, has also received a lot of public attention after the withdrawal of several anti-inflammatory drugs from the market. We hope you have the opportunity to join us next year in Stockholm.