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May 2005 interview with Craig Mello, Ph.D.

Professor, Molecular Medicine, University of Massachusetts Medical School
Co-discoverer of RNA interference

Congratulations, Dr. Mello, on your election to the National Academy of Sciences. How do you envision its bearing on your work?

Thank you. I am honored by my selection and I hope my election to the academy allows me to spread the message of the good that science in general offers. If it results in more positive exposure for science, then I'll be happy. The goal of all biomedical scientists should be to seek cures for all diseases, so I don't foresee a conflict in getting that message out without sacrificing my research. I'm sure I'll have the support of the group in achieving both. I look forward to the great opportunity it presents to give something back to society in the form of advising the population on matters of science. In a way, it adds to the acknowledgement and validation of RNAi. Even though the mechanism has established a track record of progress on its own, it's always an honor to be recognized.

What do you anticipate in the future for the science of RNAi?

My commitment and involvement in RNAi obviously indicate that I want and expect good things to result from the technology; however, I can't predict its future because there are so many courses it could take, given the vast amount of applications it is employed in now, as well as the large number of outstanding researchers, including students, conducting relative scientific investigations. I do expect to see RNAi in successful therapeutic applications, but we will have to wait a while for that. I do, however, continue to be inspired by what it has accomplished thus far in laboratory environments and by how it continues to increase our knowledge in a discipline that holds so much for us to learn and benefit from. So much has been learned over the last 50 years about gene structure, expression and manipulation, beginning with the discovery of the double helix structure of DNA, right through the mapping of the human genome. Sequencing of the human genome has really enhanced the capacity of RNA interference. The two make for a very powerful tool that is now at work addressing a broad range of disease applications and enabling laboratory and clinical research that may ultimately advance corporate pipeline development

What is the biggest challenge facing the technology?

Delivery is a problem that is definitely a challenge, since there can be no in vivo therapeutic or knockout activity unless the RNAi mechanism can be effectively transported to the appropriate genes. There are a lot of qualified people working to solve that issue, and I believe when there is a breakthrough in that area, it can potentially enhance research across a wide range of applications, shutting down many disease-causing functions and pushing the discovery process with giant steps toward finding cures.

Without revealing anything too proprietary, can you tell what you are excited about in the RNAi landscape?

There is a lot of work being done to enhance the different RNAi processes in order to address some of the major problems such as delivery and stability. I am excited by the amount of progressive research here at UMMS, as well as that being conducted by colleagues elsewhere. Here at UMMS, we have so many, including Thoru Pederson, whose work in RNA traffic allows observation of fluorescent RNA molecules in living mammalian cells, or Dr. Aldo Rossini, working to incorporate RNAi into diabetes applications in order to convert the disease from a treatable one into a curable one. These are but two of many here who are advancing the science with proven and encouraging results. Fellow scientists elsewhere conducting vital research include Victor Ambrose, at Dartmouth College, the discoverer of micro RNA. It is very rewarding and uplifting to see the number of people showing confidence in RNAi to facilitate research or achieve therapeutic development.

You have corporate advisory positions in addition to your work here at UMMS, so you are familiar with both environments. Is the relationship between corporate, academia and the investment community as good as it needs to be?

Unless a better model comes along, there must be a more consistent and greater amount of investment in biomedical research in order to find more cures. That's how the process should most efficiently work; however, there has been a period recently where large-scale investment in biotechnology began to decline. Unfortunately, such dry spells adversely affect, and can even end, research projects in critical areas. After the successful genome sequencing projects were completed, there was briefly a period of uncertainty regarding what to do next with the data, even though, in retrospect, it is clear that the projects provided many research and investment opportunities. Some research efforts had to wait for the investment community to understand or gain confidence in the potential benefits to be attained from the projects. Such delays can be critical to those who are operating on the bubble.

The general stock market is not currently supportive enough of biotechnology. That may be because it is overcompensating for the beating it took for over-investing in it in the 1990s. That is regrettable, because there is lot of research that could benefit from funding, but has had to instead curtail or abandon projects. President Bush doubled the budget in his State of the Union address, but that is double-edged because it reflects a limited increase for biotechnology, when the biotech budget should be increased, say, tenfold. I acknowledge the economic considerations that must be weighed, but take into account also the fact that the potential benefit this market can offer humanity is second to none. Government funding from sources like the NIH is critical to the continual progress of the biotechnology market when there is not enough private money available.

Academia faces additional problems beyond those of the corporations, because it is more difficult to convince private funding sources to waver from their conventional trend of investing in more proven projects, such as Phase II and III, and see the value of investment in the potential of academia, even though a significant amount of what winds up in corporate pipelines has academia origins. I understand the principle of economics that seeks financial return with the least amount of resistance, but university research has a great history of discovering and advancing successful and effective projects.

We now know the story of every gene and have the data to exploit that information to our advantage, and it makes common sense to do so. The sequencing of the human genome is not, and shouldn't be, the end result. So, invest!