John Hardy on Genetics-Based Alzheimer's Disease Research
Special Topic of Alzheimer's Disease Interview, April 2011
Photo credit: The Royal Society. |
According to our Special Topics analysis on Alzheimer's Disease research over the past decade, the work of Professor John Hardy ranks at #9 by total cites, based on 138 papers cited a total of 10,749 times. Three of these papers rank among the top 20 over the past decade or over the past two years. In our 2003 analysis, Prof. Hardy ranked at #13 by total cites. In Essential Science IndicatorsSM from Thomson Reuters, Prof. Hardy is among the top 1% of scientists in the field of Neuroscience & Behavior, Clinical Medicine, and Molecular Biology & Genetics. His current overall record in the database includes 425 papers cited a total of 17,828 times between January 1, 2000 and December 31, 2010. He is currently Professor at UCL's Institute of Neurology, in the Reta Lila Weston Institute of Neurological Sciences. In 2009, he was named a Fellow of the Royal Society. |
Here, ScienceWatch.com talks with Prof. Hardy about his highly cited research as it pertains to Alzheimer's.
Please tell us about your educational
background and research experiences.
I did my undergraduate work at Leeds University in Biochemistry. A key person there for me was (and still is) Professor Anthony Turner, who helped me in my finals project and helped me get a Ph.D. place. He remains a colleague and friend to this day doing excellent work on alpha secretase.
I did my Ph.D. in Neuropharmacology on glutamate and dopamine with Harry Bradford at Imperial College, and then got a postdoc at the MRC Neuropathogenesis Unit in Newcastle, where I worked with Peter Dodd, Jim Edwardson, and Bob and Elaine Perry. This is where we started to do some Alzheimer work. Newcastle was and is a major center for dementia work. From there, I was very lucky to get a postdoc position with Bengt Winblad, and had two fun years in Sweden in his group doing neuropharmacology.
"Alzheimer's disease research has changed enormously over the 25 years I have been doing it: when I started we knew almost nothing. Now we really have an outline understanding of the disease."
I was then exceptionally lucky to get a Lecturer's job in Bob Williamson's department in Imperial College. He had set up an excellent human genetics department but needed someone to teach biochemistry and that was why I was hired, but the opportunity to learn genetics and start to apply it to Alzheimer's and other diseases was fantastic, and I was also lucky in hiring Alison Goate as my first postdoc. It was a great and productive time and, after we found APP gene mutations, I never looked back really.
What first drew you to Alzheimer's disease research?
Moving to Newcastle and then to Sweden gave me the chance to work on AD, and being in Bob's department with Alison Goate and other great colleagues helped me switch to genetics effectively.
Your most-cited original article in our
analysis is the December 2000 Nature paper, "A beta peptide
vaccination prevents memory loss in an animal model of Alzheimer's
disease," (Morgan D, et al., 408[6815]: 982-5). Would you tell
us a bit about this paper – your expectations going in, your
findings, where this work has gone since this publication (for example,
clinical trials)?
Well, first I am a bit embarrassed to be on the list because of this paper, which is really Dave Morgan's from start to finish. Dave and I had been postdocs and friends together in Sweden and we both moved to the University of South Florida (USF) at the same time. We were doing genetics, Karen Duff was in my group and was setting up transgenics using mutations we found, and Dave was a (then rat) behavioral guy. So this was a natural collaboration which Dave led and both Dave and Karen have effectively continued: transgenic modeling of neurodegenerative disease.
The paper was submitted after I left USF for Mayo, and frankly Dave need not have had me as a coauthor. It was really a "thank you" for Karen and I helping him set up the whole system there. It has been an enormously influential paper, though I now worry about what exactly is the relevance of the rather subtle memory problems we saw in the mice to the situation in the human disease where there is massive cell loss.
You're also a coauthor on the most-cited
paper from the past two years on our list—the October 2009
Nature Genetics study, "Genome-wide association study
identifies variants at CLU and PICALM associated with Alzheimer's
disease," (Harold D, et al., 41[10]: 1088-93). What is it about
this paper that is causing it to become so highly cited so
quickly?
"Genetics has changed. We used to do 'solo efforts': one lab sorting out one set of families, but now, the groups who do well are those who can effectively collaborate."
Genetics has changed. We used to do "solo efforts": one lab sorting out one set of families, but now, the groups who do well are those who can effectively collaborate. This paper, led by Julie Williams, is enormously important, detailing two new AD genes (and many more subsequently by the same approach). We were a small part of this study.
Even more recently, you were part of the
group that published the November 2010 PLoS One article,
"Genetic evidence implicates the immune system and cholesterol
metabolism in the aetiology of Alzheimer's disease," (Jones L, et
al., 5[11]: art. no. e13950). What can you tell us about this
work?
Again, I think this is a very important paper. Lesley Jones led it, and she had a terrible time publishing it. I think it offers a glimpse of how we will be doing genetic analysis from now on: we are trying to work out not what individual genes are involved in disease, but what pathways are important. Lesley's analysis was the first attempt at doing this, and I think it will be very influential.
Your work ranked among the top 20 researchers
in our earlier analysis of AD, which covered the 1992-2002 period, and
now this one, which covers 2000-2010. How has the focus of your work
changed over these periods?
Alzheimer's disease research has changed enormously over the 25 years I have been doing it: when I started we knew almost nothing. Now we really have an outline understanding of the disease. Research has changed—in the obvious technical ways, but also in research philosophy. The groups who succeed now are the groups who are good collaborators and who make their data available to others. We have been doing this for genetic data for five years and Alzheimer's Disease Neuroimaging Initiative (ADNI) has pioneered this for clinical data. This is the future—data sharing and co-operation.
How has the field changed over these years?
Would you say we are in a better position today in terms of our
knowledge of AD and its genetics, than we were in the 1990s? Why or why
not?
We know a huge amount more. I wrote a review about this (Hardy J, "A hundred years of Alzheimer's disease research," Neuron 52[1]: 3-13, 5 October 2006). And now is a golden age for genetics-based biomedical research.
Where do you hope to see this research go in
the next decade?
I hope we will progress from understanding to
treatments!!!
John Hardy PhD, MD (Hon), DSc, FMedSci, FRS
Department of Molecular Neuroscience and Reta Lila Weston
Laboratories
Institute of Neurology
University College London
London, England
JOHN HARDY'S MOST CURRENT MOST-CITED PAPER IN ESSENTIAL SCIENCE INDICATORS:
Hardy J, Selkoe DJ, "Medicine—the amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics," Science 297(5580): 353-6, 19 July 2002 with 2,569 cites. Source: Essential Science Indicators from Clarivate.
ADDITIONAL INFORMATION:
- Read a interview with coauthor Dennis J. Selkoe.
KEYWORDS: ALZHEIMER’S DISEASE, DEMENTIA, NEUROPHARMACOLOGY, HUMAN GENETICS, BIOCHEMISTRY, APP GENE MUTATIONS, BETA PEPTIDE VACCINATION, TRANSGENIC MODELING, COLLABORATIVE EFFORTS, GENETIC PATHWAYS, RESEARCH PHILOSOPHY, DATA SHARING.