And the Oscar of Science Goes to …

It took Sergey to get John into a suit. [Editor’s note: Now we know it can be done.] At a glitzy awards gala swarming with movie stars, musicians, and Silicon Valley elite, John Hardy of University College London accepted the 2016 Breakthrough Prize in Life Sciences on November 8. The award—established three years ago by founders of Google, Facebook, and other tech powerhouses—honors scientists who have made game-changing discoveries in life sciences, physics, and mathematics. Awardees receive $3 million. Hardy was one of five researchers to win the award in life sciences this year. He was recognized for discovering that genetic mutations in the amyloid precursor protein (APP) cause familial Alzheimer’s disease, formulating the amyloid cascade hypothesis, and driving many subsequent advances in AD research that resulted from that early success.

Hardy was quick to point out that he accomplished none of this alone. In his acceptance remarks, he thanked a long list of co-workers, competitors, mentors, and families who participated in research. “Perhaps my greatest gift is that I’m good at picking smart people to work with,” he told Alzforum.

On the Red Carpet.

John Hardy cradles the toroid-shaped trophy, designed by sculptor Olafur Eliasson to represent forms found throughout nature—from galaxies to DNA. [Courtesy of Kimberley White, Getty Images 2015.]

With the goal of encouraging bold innovation in science and attracting young whippersnappers into the fold, the Breakthrough Prize was founded in 2012 by Google co-founder Sergey Brin; 23andMe CEO Anne Wojcicki; Jack Ma, founder of Chinese internet retailer Alibaba, his wife, Cathy Zhang; venture capitalist Yuri Milner and his wife, Julia; and Facebook’s Mark Zuckerberg and his wife, Priscilla Chan.

This year’s $22 million in prizes went to researchers who span the scientific gamut. Along with Hardy in the life science camp, Karl Deisseroth of Stanford University in Palo Alto, California, and Edward Boyden of Massachusetts Institute of Technology each received a prize for their development of optogenetics. On the other end of the spectrum, an international group of 1,377 researchers shared the Breakthrough Prize in Fundamental Physics for their discovery that subatomic particles called neutrinos can oscillate between three different forms. Past award recipients include Jennifer Doudna of the University of California, Berkeley, for her discovery of the now famous gene-editing tool CRISPR, and a cadre of scientists, including Berkeley’s Saul Perlmutter, for unveiling the “dark energy” that drives the accelerating expansion of the universe. 

A Hollywood feel permeates Breakthrough Prize awards ceremonies. This year’s event at NASA’s Ames Research Center in Mountain View, California, aired on the National Geographic channel. Comedian Seth MacFarlane, who previously hosted the Oscars, ran the proceedings. Celebrities such as Russell Crowe, Hilary Swank, and Lily Collins introduced the prize winners, and a performance by Pharrell Williams livened up the crowd. Hardy, along with his wife and three children, shared a table with singer and songwriter Lana Del Rey, among others. Hardy said he was enthused by the level of excitement about science that reverberated through the mostly non-scientist crowd. The following day, last year’s recipients presented their work at a symposium at the University of California, Berkeley. Next year, Hardy and his fellow honorees will do the same.

Hardy won the award for achievements spanning a prolific career, but his role in the 1991 report of APP mutations that caused familial AD was the catalyst for his later achievements (Goate et al., 1991; Chartier-Harlin et al., 1991). This find set the stage for the amyloid hypothesis, which Hardy co-drafted the following year (see Hardy and Higgins, 1992). Hardy and his colleagues also unveiled mutations in tau that cause frontotemporal dementia, and ultimately developed a model in which tauopathy fit squarely into the amyloid cascade (see Hardy et al., 1998; and Morris et al., 1999). His and his colleagues’ extensive network analyses of mouse models delineated specific roles of amyloid and tau in driving both synaptic dysfunction and neuroinflammatory aspects of AD (see Jan 2015 news). 

Hardy is equally active in Parkinson’s research, having discovered triplication in the α-synuclein gene as a genetic cause of an early onset form of this disease, and formulating a hypothesis of mass action, whereby increasing amounts of certain proteins prone to misfolding and deposition hasten neurodegeneration (Singleton et al, 2003; Singleton et al., 2004). Hardy is a co-author on many milestone discoveries, including one of tau mutations causing frontotemporal dementia (Hutton et al., 1998). 

Hardy’s recent discovery of AD risk mutations in the microglial receptor TREM2 rekindled interest in the role of neuroinflammation, another key component of the AD riddle (see Nov 2012 news). These genetic findings not only point to new targets and treatment strategies, but also offer ways to better select clinical trial participants most likely to benefit from treatments, Hardy said. This, along with some promising results from recent trials testing anti-amyloid therapies, may explain renewed optimism currently animating the AD research field, Hardy said. “There has been a sea change over the last 18 months or so,” he told Alzforum. “People are starting to embrace the idea that amyloid-targeted therapies may actually work.”

Hardy will donate part of his $3 million prize to the construction of the Dementia Research Institute at University College London. He also plans to buy a new house, which will certainly not be a mansion, he added.

Among the many Hardy credited with his success, he made sure to mention his undergraduate mentor, Anthony Turner of Leeds University, who convinced the 21-year-old Hardy not to leave academia for a career as a truck driver. Turner surreptitiously arranged an interview for Hardy with Harry Bradford at Imperial College, who would ultimately become his graduate school advisor.

Hardy has no regrets about his decision to forgo the brawn of the big rig in pursuit of brain science. “I love my job,” Hardy said. “The AD research community is like a village, and I like most of my neighbors.”—Jessica Shugart

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References

News Citations

  1. Network Analysis Points to Distinct Effects of Amyloid, Tau
  2. Enter the New Alzheimer’s Gene: TREM2 Variant Triples Risk

Paper Citations

  1. Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature. 1991 Feb 21;349(6311):704-6. PubMed.
  2. Chartier-Harlin MC, Crawford F, Houlden H, Warren A, Hughes D, Fidani L, Goate A, Rossor M, Roques P, Hardy J. Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene. Nature. 1991 Oct 31;353(6347):844-6. PubMed.
  3. Hardy JA, Higgins GA. Alzheimer's disease: the amyloid cascade hypothesis. Science. 1992 Apr 10;256(5054):184-5. PubMed.
  4. Hardy J, Duff K, Hardy KG, Perez-Tur J, Hutton M. Genetic dissection of Alzheimer's disease and related dementias: amyloid and its relationship to tau. Nat Neurosci. 1998 Sep;1(5):355-8. PubMed.
  5. Morris HR, Perez-Tur J, Janssen JC, Brown J, Lees AJ, Wood NW, Hardy J, Hutton M, Rossor MN. Mutation in the tau exon 10 splice site region in familial frontotemporal dementia. Ann Neurol. 1999 Feb;45(2):270-1. PubMed.
  6. Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, Hulihan M, Peuralinna T, Dutra A, Nussbaum R, Lincoln S, Crawley A, Hanson M, Maraganore D, Adler C, Cookson MR, Muenter M, Baptista M, Miller D, Blancato J, Hardy J, Gwinn-Hardy K. alpha-Synuclein locus triplication causes Parkinson's disease. Science. 2003 Oct 31;302(5646):841. PubMed.
  7. Singleton A, Myers A, Hardy J. The law of mass action applied to neurodegenerative disease: a hypothesis concerning the etiology and pathogenesis of complex diseases. Hum Mol Genet. 2004 Apr 1;13 Spec No 1:R123-6. PubMed.
  8. Hutton M, Lendon CL, Rizzu P, Baker M, Froelich S, Houlden H, Pickering-Brown S, Chakraverty S, Isaacs A, Grover A, Hackett J, Adamson J, Lincoln S, Dickson D, Davies P, Petersen RC, Stevens M, de Graaff E, Wauters E, van Baren J, Hillebrand M, Joosse M, Kwon JM, Nowotny P, Che LK, Norton J, Morris JC, Reed LA, Trojanowski J, Basun H, Lannfelt L, Neystat M, Fahn S, Dark F, Tannenberg T, Dodd PR, Hayward N, Kwok JB, Schofield PR, Andreadis A, Snowden J, Craufurd D, Neary D, Owen F, Oostra BA, Hardy J, Goate A, van Swieten J, Mann D, Lynch T, Heutink P. Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17. Nature. 1998 Jun 18;393(6686):702-5. PubMed.

External Citations

  1. acceptance remarks

Further Reading

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