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An Interview with Dr. Story Landis

Just before Christmas, PDF News & Review was fortunate to be granted an early morning interview with Dr. Story C. Landis, the newly appointed Director of the National Institute of Neurological Disorders and Stroke (NINDS). Our questions were focused and direct; her answers, forthcoming and optimistic. Here we bring readers of PDF News & Review an edited version of the interview.

Q: How can a person in your position do exciting new things in research when the federal budget scenarios are so bleak?

We have been fortunate at NINDS to have extraordinary increases in funding in recent years. Now we know that this country has many new obligations and that NIH will have only modest increases in 2004 and 2005. This means that we will have to choose carefully among our investment opportunities and be more creative than before about how we use the funds we do have.

Static budgetary conditions often force you to test new approaches. We're starting to be more radical in our thinking - working to identify ways of allowing investigators to do the work faster, better and more efficiently. We've used pilot experiments to improve mechanisms and frameworks. One example of this is our program for screening FDA approved compounds. This was an interesting pilot and good things came out of it. Another is the neuroprotection trial, under the direction of Dr. Bernard Ravina. It represents a new design for trials and I am optimistic about its potential.

We need to take a good hard look at what NINDS is doing and why. For every new program we take on we may have to give up an old one - even some long-standing initiatives. The challenge is to undertake thoughtful evaluation of the old and new, balancing each against our obligation to support the best possible science. This is a spectacular time for translational and clinical neurosciences and the Institute has to facilitate ways to take advantage of it.

Q: How will Dr. Zerhouni's "Roadmap" play out in these plans?

A: The NIH Roadmap is a product of teams of investigators and directors and represents their notions of the big, broad directions that could be taken to advance biomedical research. The challenges laid out in the roadmap are large - in most cases, too large for a single institute to tackle alone.

One idea is to build a better research 'toolbox' for today's medical researcher and make it widely available - for example, to establish and improve access to 3D structures of membrane proteins. This type of protein is difficult to purify and crystallize, but once we have crystals, scientists can determine their structures. A project like this will give the research community more robust scientific resources that they can then adapt to their own needs. It has the potential to rapidly accelerate the pace of many neuroscience research projects since communication in the nervous system is mediated by membrane proteins and knowing their structure is critical to understanding how they function.

Another tool is the 'molecular library' which can store thousands of FDA-approved compounds. Following the roadmap will ultimately mean that we can do this for hundreds of thousands of compounds. The initiative will provide new ways to explore the functions of cells at molecular levels in health and disease. This is a good example of how pooling our resources in an NIH-wide initiative can help NINDS and the other institutes to mount projects on a grander scale.

We also want to facilitate the process of patient-based research. This will require nothing less than reorganizing the entire clinical enterprise, everything from looking at the approval processes, re-engineering trial design, harmonizing regulations, improving training and providing infrastructure. NINDS as a single organization clearly couldn't do all this on its own; the process needs to be NIH-wide.

Q: There seem to be signs that NIH is moving more heavily into clinical and translational research. What are your own views on this given your background as a basic scientist?

NIH has always had a very active clinical and translational program. What is new is an effort to make clinical trials more rational and more likely to yield positive benefits and this means a greater focus on translational research. We know that translation from basic science into clinical research doesn't happen naturally. Findings should flow from one area to the next, but they don't always do this. The challenge is to help make this happen.

You have to approach a problem like this in a concrete and constructive fashion by putting in place programs that will encourage translational research. In 2002, we set up a special program to support investigators who are interested in pursuing translational research with grants of up to $1 million. To date, seven such grants have been awarded. In Parkinson's, we awarded a major grant to Dr. Howard Federoff at the University of Rochester to take advantage of scientific advances in gene transfer methods. By helping to identify more effective viral vectors for GDNF we will be able to better ensure the safe and effective transfer of therapeutic genes in patients.

We also have to change perceptions about clinical research which basic scientists sometimes see as being less prestigious. We need to identify a climate for better collaboration and incentives can play a part in this.

Q: You have a gifted and hardworking professional staff but they seem stretched very thin. Is there anything you can do about this?

Yes, I most certainly have gifted professional staff. And yes, they are stretched too thin. Part of the reason for this is the burden of history. Ten years ago, NINDS was not as active in the community as it is today and demands on our staff were less. More recently, there have been efforts throughout the federal government to become more efficient. To achieve this goal, the staff who support the scientific program directors are being reorganized and their numbers reduced. It will be a big challenge to make this work but we will do our best.

Q: What do you consider to be the two or three most important areas in Parkinson's science that show the most promise?

In the short-term, one of the most interesting areas for me is glial cell-line-derived neurotrophic factor (GDNF). GDNF is a growth factor that has been shown in animal studies to promote the growth of neurons when it is delivered in tiny amounts to nerve cells growing in a dish or to the brain using a pump. The primate studies look spectacular and what we have learned from a small clinical trial in England shows promise. But even with GDNF, there are still problems that we haven't solved yet - for example, how do you provide it long-term, in a way that is safe? And how do we reconcile the reality that GDNF only deals with one neuron type (dopamine) with our knowledge that Parkinson's goes beyond the dopaminergic system? We have to answer some of these longer-term questions and keep refining our strategies.

In the longer term, I think we'll learn a great deal by building on our knowledge of defects in protein processing. Understanding these mechanisms is likely to yield important answers to questions about the pathology of PD - it's a great credit to basic science that no one would have guessed even 10 years ago.

Cell replacement, using neural stem cells, is another key area for the future. We should be able to learn enough about stem cells to make it work. We have enough cell lines available to explore the potential of stem cells for PD and other diseases, but it's not clear yet whether there are enough stem cell lines for therapeutic use. And, I am concerned that this approach is specific to the dopaminergic system whereas we now know that Parkinson's goes beyond that system.

Finally, I think that it will be important to improve early diagnosis and translational science may be able to play a crucial part here.

Q: What made you take the job? And how do you think it will change your life?

It's an incredibly important position which presents wonderful opportunities and interesting challenges. I didn't apply for it until the search for the position was opened for the third time. This gave me the chance to grow in the position of Intramural Science Director and equipped me with a clearer vision about what needs to be done. Now I'm three times busier than ever before, it's a much bigger job and I'm working as hard as I can to learn as much as possible about the responsibilities of the Institute.

A critical step in this process has been the opportunity to meet with voluntary organizations, to learn about the expectations from their constituencies, and to develop a clearer idea about what doctors and scientist expect from NINDS. To date, I have met with thirty-five different advocacy groups.

My new role involves more public relations for the Institute than my previous position. We have to make a compelling argument for what has been done at NIH with the money that we've been given and to showcase achievements without being perceived as boastful. Investigators supported by NINDS have done some wonderful things over the past decade. One example is the new brain attack therapy for stroke which if administered within three hours can reverse the effects of a stroke. There are eight new drugs for epilepsy. We don't yet have a cure for Parkinson's, but we do have one major therapeutic advancement in Deep Brain Stimulation surgery.

Q: What role do you believe the advocacy community can play in assisting research?

Advocacy groups can play a huge part in the providing the broader perspective. For example, PDF and other Parkinson's advocacy groups can play a crucial role in recruitment and retention of patients for Parkinson's clinical trials. Recruitment can be an extraordinary problem. In those cases where we have worked closely with advocacy groups, trials have been on schedule. This means that they've been on budget for recruitment and therefore do not have to divert funds from future research opportunities. We would also like to encourage patient representation on the institutional review boards that oversee animal research and clinical trials at the universities and medical schools in their communities. These boards all have lay members and patients bring an important perspective to their deliberations. Giant strides in research will be reached through a partnership - between scientists, advocacy groups, industry, M.D.'s and government.