INNOVATION | NATURE INDEX
David Lipman, who co-authored the BLAST paper, which has been cited in at least 4,900 inventions according to patent documents in the Lens database. GAME-CHANGERS Some papers have a profound and obvious influence on future research and industry applications. Patents citing these life science papers indicate their bearing on developments which have widespread health implications.
ists of the most highly cited academic patents are a general indicator of the dynamic selected from the Lens platform, based on articles garner considerable attention between science and technology, and can articles cited in patents. Each paper had been from the research community. But infer that a piece of research has influenced cited in more than 1,000 patent families by Larticles that are highly cited in patents don’t an invention (see Patently clear). Here, the 2016. Patent families represent a single inven- BILL REITZEL receive the same attention. This is surprising index profiles three life science articles that tion. Inventors often file patents in multiple given the demand from governments that sci- have been highly cited in patents. Each arti- countries, which is why the number of citing entists demonstrate the societal or economic cle has had profound impact on industry and, patents is larger than the number of patent value of their research. Citations of articles in eventually, consumers. These papers were families.
NATURE INDEX 2017 | INNOVATION | S9 NATURE INDEX | INNOVATION
Basic Local Alignment Search Tool (BLAST) THE GOOGLE OF GENOMES used pattern recognition software to perform ANTIBODIES AS THERAPY faster sequence comparisons. It could calculate Basic Local Alignment Search Tool the statistical level of similarity between two Replacing the complementarity- published in the Journal of Molecular sequences, says Lipman, who recently left the determining regions in a human Biology in 1990. NCBI after 28 years as its director. antibody with those from a mouse Within 10 years automated DNA sequenc- published in Nature in 1986. › CITED IN 4,900 PATENT FAMILIES ing machines had also gained a foothold and some 50,000 nucleotide sequences from plants › CITED IN 2,089 PATENT FAMILIES nferring the function of a protein 40 years and animals were stored in the NCBI-owned ago required finding a related protein with genetic sequence database known as Genbank. n 1986, Greg Winter and colleagues at the a known function. To determine the simi- BLAST enabled researchers to search for, or UK’s Medical Research Council (MRC) Ilarity between two proteins meant comparing compare, DNA sequences. Just five years after described in Nature a method for swapping their amino acid sequences using a time- its release, BLAST was handling about 200,000 Ipieces of a mouse antibody with those from a consuming algorithm. queries a week. These comparisons could human to create a chimeric antibody. This was In 1983, biologist David Lipman and col- yield several types of clues: what organism the the second essential step in the development of league W. John Wilbur reported a faster sequence probably came from, its evolutionary antibody-based therapies for human disease, method to identify the similarity between origin, and potential function. which represented more than 40% of total sales two unrelated sections of DNA or protein. A BLAST has since evolved into a family of free of biopharmaceutical products in 2016. year later, a global team of scientists used the web-based bioinformatics search tools that are The first step occurred a decade earlier when technique to show that amino acid sequences still widely used. Since 1990, the BLAST paper Nobel prize winning researchers Georges from a human growth factor closely resembled has been cited by at least 4,900 new inventions, Köhler and César Milstein developed mouse sequences from a cancer gene in a chicken according to patent documents in the Lens antibodies that recognize a single foreign virus. The paper marked significant progress database. Chemical giant Dupont and several molecule. While such monoclonal antibod- in the basic understanding of cancer develop- of its subsidiaries own the most patents that ies, had a wide range of applications in medical ment and revealed the value of computational cite the paper. research and diagnostics, their use in medicine tools for making biological discoveries. The NCBI team have created a new pro- was limited. Mouse antibodies are different Lipman, then based at the National Institute gramme within the BLAST toolkit that they from human ones — even when they target of Arthritis, Diabetes, and Digestive and Kid- hope to publish by September that will assist and bind to the same part of a protein. “Anti- ney Diseases, says this unexpected discovery with finding small genetic variations in bacte- bodies that are generated in another species prompted him to find how to detect more dis- ria, which may be linked to traits such as anti- cause side-effects in humans,” says vaccinolo- tant relationships between proteins. In 1990, biotic resistance. ■ gist, Ursula Wiedermann, of the Medical Uni- Lipman and colleagues Stephen Altschul and versity of Vienna. Indeed, the first US Food Warren Gish, along with collaborators Webb By Branwen Morgan and Drug Administration (FDA) approved Miller, at Pennsylvania State University, and therapeutic antibody, CD3, is no longer used Eugene Myers at the University of Arizona, pub- 1. Altschul et al. Journal of Molecular Biology for this reason. lished details of a more advanced algorithm. The 215,403-410 (1990) Winter’s method for creating chimeric
PAPERS IN 1,200 PATENTS Lines represent 1,100 the number Source: Lens.org Source: o patent 1,000 documents that The 1990 paper by Lipman and cited one o three 900 li e science colleagues has been cited in papers b 0 . 6,807 patent documents to 2016, The number o 800 totalling 4,900 new inventions. patent amilies re ers to the 700 number o new inventions. 600 The 1986 paper by inter and colleagues has been cited in 500 3,182 patent documents, totalling 2,089 new inventions.
Lipman-citing 400 patents umber o citing patents per ear
300 inter-citing The 1999 paper by Golub has been patents cited in 2,031 patent documents, 200 totalling 1,278 new inventions. olub-citing patents 100
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