A look into the future of genetic medicine

The ability to manipulate the human genome – the collection of 30,000 or so genes that uniquely combine and interact to produce each human being – is indisputably compelling. Among other things, it promises a future when genetic diseases ranging from cystic fibrosis to schizophrenia might not just be cured, but prevented altogether.

In recent years, scientists in San Diego and around the world have made major, even monumental, progress toward teasing out the power and potential of genetic medicine. But in almost every case, the research remains fundamental and basic. Techniques like whole genome sequencing, which identifies the specific genetic sequence of an individual, have been touted as a road map to personalized medicine. Stem cells may ultimately be used to create restorative tissues and even whole organs for patients in need.

We asked two scientists at the University of California San Diego School of Medicine to assess recent developments: Bing Ren, a professor of cellular and molecular medicine who specializes in epigenetics, the study of how genes are changed by mechanisms beyond DNA, and colleague Kun Zhang, an assistant professor of bioengineering who focuses on stem cell research.

Q: Currently, is there therapeutic value in doing whole genome sequencing? What is the likelihood that the process can or will lead to actual therapies for individuals who are sequenced? How much does the value of this knowledge depend upon sheer numbers (doing lots of sequences, having a big database) and conducting extensive, subsequent analysis?

A: Ren: No, I think it too preliminary to say this is the case. The main bottleneck is that we do not know how to interpret the functional relevance of sequence variations except for a small number of them. The scientific value lies in generating a large database and the possibility to identify causal links between sequence variations and genetic diseases.

Q: Where does genomic sequencing fit into the larger “omics” picture, which includes proteomics (proteins), lipidomics (fats) and metabolomics, among others? Is it possible to assess the relative values of these endeavors?

A: Ren: We have genome sequence maps for many species. These maps serve as a foundation to understand the biological processes, and enable the development of other “omics” technologies. Each of these “omics” techniques provides complementary views of the cellular processes and they are all valuable.

Q: A new study out of the University of Melbourne reports that many of 138 diverse human embryonic stem cell lines allowed to replicate over time showed evidence of mutations, which might mean the introduction of unwanted effects, such as cancer. You’ve also conducted research indicating a mutation risk in human embryonic stem cells (HESCs). Broadly speaking, how concerning is this kind of news?

A: Zhang: This is just another cautionary note to the community that cells might adapt to long-term in vitro culture by acquiring changes in their genome. Since roughly 20 percent of the cell lines acquired such abnormalities, I believe that, as long as all the HESC lines are routinely screened, and the abnormal ones are eliminated, the therapeutic potential for HESCs is not diminished.


