Table of contents

Nature Biotechnology 20th Anniversary

Nature Biotechnology is 20! We have brought together a collection of Features celebrating two decades of the science and business of biotech, with an eye on the future.


In This Issue

In this issue pvii




Focus on Nature Biotechnology 20th Anniversary

Breaking out of the bubble p213


The biotech community has made remarkable progress over the past 20 years. Now it needs to break out of its bubble.

Immune profiling players shift gear to guide cancer drug development pp215 - 216

Michael Eisenstein


Drug developers refocus efforts on RAS pp217 - 218

Cormac Sheridan


Natural killer cells blaze into immuno-oncology pp219 - 220

Ken Garber


FDA head Califf spurned p220


GM salmon shut out of US p220


GM mosquitoes fire first salvo against Zika virus pp221 - 222

Emily Waltz


Bial incident raises FAAH suspicions p223

Eva von Schaper


Seed spy pleads guilty p223

Emily Waltz


Sanofi drops MannKind's inhaled insulin p224

Mark Ratner


Around the world in a month p225




Building a business

Aligning needs pp226 - 230

Dennis Ford & William Kohlbrenner


The best way for aspiring entrepreneurs to achieve their financing goals is to understand what investors and partners want.


Opinion and Comment


Deciphering the EU clinical trials regulation pp231 - 233

Mohamed Abou-El-Enein & Christian K Schneider


A call for industry to embrace green biopharma pp234 - 235

Kristi L Budzinski, Stefan G Koenig, Deborah A O'Connor & Tse-Sung Wu


Marketplace response to GM animal products pp236 - 238

Damien Mather, Rasmus Vikan & John Knight



Digital medicine's march on chronic disease pp239 - 246

Joseph C Kvedar, Alexander L Fogel, Eric Elenko & Daphne Zohar


Digital medicine offers the possibility of continuous monitoring, behavior modification and personalized interventions at low cost, potentially easing the burden of chronic disease in cost-constrained healthcare systems.



Focus on Nature Biotechnology 20th Anniversary

Estimating the biotech sector's contribution to the US economy pp247 - 255

Robert Carlson


US biotech sector revenue is estimated to have grown on average >10% each year over the past decade—much faster than the rest of the economy. A more comprehensive assessment of biotech's economic contribution, however, will require improved data collection, classification and analysis.

Focus on Nature Biotechnology 20th Anniversary

20 years of Nature Biotechnology research tools pp256 - 261

Anna Azvolinsky, Laura DeFrancesco, Emily Waltz & Sarah Webb


Authors of some of the most highly cited Nature Biotechnology papers that describe research tools discuss their work and challenges for their fields.

Focus on Nature Biotechnology 20th Anniversary

20 years of Nature Biotechnology biomedical research pp262 - 266

Anna Azvolinsky, Charles Schmidt, Emily Waltz & Sarah Webb


Authors of some of the most highly cited Nature Biotechnology biomedical papers from the past 20 years discuss their work and challenges for their fields.

Focus on Nature Biotechnology 20th Anniversary

20 years of Nature Biotechnology bioengineering research pp267 - 269

Laura DeFrancesco, Charles Schmidt & Emily Waltz


Authors of some of the most highly cited Nature Biotechnology nonbiomedical papers from the past 20 years discuss their work and challenges for their fields.

Focus on Nature Biotechnology 20th Anniversary

Voices of biotech pp270 - 275

Ido Amit, David Baker, Roger Barker, Bonnie Berger, Carolyn Bertozzi, Sangeeta Bhatia, Alessandra Biffi, Francesca Demichelis, Jennifer Doudna, Steven F Dowdy, Drew Endy, Moritz Helmstaedter, Howard Junca, Carl June, Sasha Kamb, Anastasia Khvorova, Dae-hyeong Kim, Jin-Soo Kim, Yamuna Krishnan, Melike Lakadamyali, Tuuli Lappalainen, Sharon Lewin, James Liao, Nick Loman, Emma Lundberg, Lee Lynd, Cathie Martin, Ira Mellman, Atsushi Miyawaki, Christine Mummery, Karen Nelson, Jeanne Paz, Pamela Peralta-Yahya, Paola Picotti, Kornelia Polyak, Kristala Prather, Jun Qin, Stephen Quake, Aviv Regev, John A Rogers, Reshma Shetty, Morten Sommer, Molly Stevens, Gustavo Stolovitzky, Masayo Takahashi, Fuchou Tang, Sarah Teichmann, Maria-Elena Torres-Padilla, Leena Tripathi, Praveen Vemula, Greg Verdine, Frank Vollmer, Jun Wang, Jackie Y Ying, Feng Zhang & Tian Zhang


Nature Biotechnology asks a selection of researchers about the most exciting frontier in their field and the most needed technologies for advancing knowledge and applications.

Focus on Nature Biotechnology 20th Anniversary

Community crystal gazing pp276 - 283

Anu Acharya, Kate Bingham, Jay Bradner, Wylie Burke, R Alta Charo, Joel Cherry, André Choulika, Tony Coles, Robert Cook-Deegan, Stanley T Crooke, Emilia Díaz, Brent Erickson, L Val Giddings, Sebastian Eriksson Giwa, James C Greenwood, Vishal Gulati, Sam Hall, John Harris, Jamie Heywood, Colin Hill, Jeremy Levin, Adina Mangubat, John Maraganore, Giovanni Mariggi, Barbara J Mazur, Amy L McGuire, Nathalie Moll, Jonathan Moreno, Gail Naughton, Lita Nelsen, Jane Osbourn, Daniel Perez, John Reed, Eric Schmidt, Vicki Seyfert-Margolis, Paul Stoffels, Jørgen Thorball, Tara O'Toole, Indrek Vainu, Sander van Deventer, Elias Zerhouni & Daphne Zohar


A selection of individuals from the biotech ecosystem give their views on the challenges facing the sector over the coming years.

Focus on Nature Biotechnology 20th Anniversary

When biotech goes bad pp284 - 291

John Hodgson


A look at 20 years of the dark side of biotech.


Focus on Nature Biotechnology 20th Anniversary

The changing life science patent landscape pp292 - 294

Arti K Rai & Jacob S Sherkow


What have we learned from 20 tumultuous years of patent law in the life sciences? Is patenting likely to be as important for the industry in the future?


News and Views

From clinical imaging to implantation of 3D printed tissues pp295 - 296

E Thomas Pashuck & Molly Stevens


Mechanically stable bone, cartilage and muscle tissues are printed in custom shapes.

See also: Research by Kang et al.

Haplotypes drop by drop pp296 - 298

Jacob O Kitzman


Short-read sequencing provides haplotype information when long DNA fragments are barcoded in microfluidic droplets.

See also: Research by Zheng et al.

Cas9 loosens its grip on off-target sites pp298 - 299

Christopher E Nelson & Charles A Gersbach


Two new variants of the Cas9 nuclease have minimal activity at off-target DNA sites.

Research Highlights p299





Fast search of thousands of short-read sequencing experiments pp300 - 302

Brad Solomon & Carl Kingsford


A data indexing method enables fast and computationally efficient searching of short-read sequencing archives.


Haplotyping germline and cancer genomes with high-throughput linked-read sequencing pp303 - 311

Grace X Y Zheng, Billy T Lau, Michael Schnall-Levin, Mirna Jarosz, John M Bell, Christopher M Hindson, Sofia Kyriazopoulou-Panagiotopoulou, Donald A Masquelier, Landon Merrill, Jessica M Terry, Patrice A Mudivarti, Paul W Wyatt, Rajiv Bharadwaj, Anthony J Makarewicz, Yuan Li, Phillip Belgrader, Andrew D Price, Adam J Lowe, Patrick Marks, Gerard M Vurens, Paul Hardenbol, Luz Montesclaros, Melissa Luo, Lawrence Greenfield, Alexander Wong, David E Birch, Steven W Short, Keith P Bjornson, Pranav Patel, Erik S Hopmans, Christina Wood, Sukhvinder Kaur, Glenn K Lockwood, David Stafford, Joshua P Delaney, Indira Wu, Heather S Ordonez, Susan M Grimes, Stephanie Greer, Josephine Y Lee, Kamila Belhocine, Kristina M Giorda, William H Heaton, Geoffrey P McDermott, Zachary W Bent, Francesca Meschi, Nikola O Kondov, Ryan Wilson, Jorge A Bernate, Shawn Gauby, Alex Kindwall, Clara Bermejo, Adrian N Fehr, Adrian Chan, Serge Saxonov, Kevin D Ness, Benjamin J Hindson & Hanlee P Ji


A microfluidics approach that links short sequence reads enables haplotype construction and complex variation identification from tiny amounts of input DNA.

See also: News and Views by Kitzman

A 3D bioprinting system to produce human-scale tissue constructs with structural integrity pp312 - 319

Hyun-Wook Kang, Sang Jin Lee, In Kap Ko, Carlos Kengla, James J Yoo & Anthony Atala


A new bioprinting system produces large tissue constructs with enough structural stability for surgical implantation.

See also: News and Views by Pashuck & Stevens

Minimally invasive endovascular stent-electrode array for high-fidelity, chronic recordings of cortical neural activity pp320 - 327

Thomas J Oxley, Nicholas L Opie, Sam E John, Gil S Rind, Stephen M Ronayne, Tracey L Wheeler, Jack W Judy, Alan J McDonald, Anthony Dornom, Timothy J H Lovell, Christopher Steward, David J Garrett, Bradford A Moffat, Elaine H Lui, Nawaf Yassi, Bruce C V Campbell, Yan T Wong, Kate E Fox, Ewan S Nurse, Iwan E Bennett, Sébastien H Bauquier, Kishan A Liyanage, Nicole R van der Nagel, Piero Perucca, Arman Ahnood, Katherine P Gill, Bernard Yan, Leonid Churilov, Christopher R French, Patricia M Desmond, Malcolm K Horne, Lynette Kiers, Steven Prawer, Stephen M Davis, Anthony N Burkitt, Peter J Mitchell, David B Grayden, Clive N May & Terence J O'Brien


Cortical activity can be monitored for 6 months or longer from within the brain vasculature using an endovascular stent-electrode array.


Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo pp328 - 333

Hao Yin, Chun-Qing Song, Joseph R Dorkin, Lihua J Zhu, Yingxiang Li, Qiongqiong Wu, Angela Park, Junghoon Yang, Sneha Suresh, Aizhan Bizhanova, Ankit Gupta, Mehmet F Bolukbasi, Stephen Walsh, Roman L Bogorad, Guangping Gao, Zhiping Weng, Yizhou Dong, Victor Koteliansky, Scot A Wolfe, Robert Langer, Wen Xue & Daniel G Anderson


Cas9-mediated gene editing corrects hereditary tyrosinemia in a mouse model.

A dual AAV system enables the Cas9-mediated correction of a metabolic liver disease in newborn mice pp334 - 338

Yang Yang, Lili Wang, Peter Bell, Deirdre McMenamin, Zhenning He, John White, Hongwei Yu, Chenyu Xu, Hiroki Morizono, Kiran Musunuru, Mark L Batshaw & James M Wilson


In vivo delivery of CRISPR-Cas9 corrects mutation in newborn mouse liver.

Enhancing homology-directed genome editing by catalytically active and inactive CRISPR-Cas9 using asymmetric donor DNA pp339 - 344

Christopher D Richardson, Graham J Ray, Mark A DeWitt, Gemma L Curie & Jacob E Corn


The efficiency of homology-directed genome editing with CRISPR-Cas9 is boosted through improved design of donor DNA.

Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates pp345 - 352

Arturo J Vegas, Omid Veiseh, Joshua C Doloff, Minglin Ma, Hok Hei Tam, Kaitlin Bratlie, Jie Li, Andrew R Bader, Erin Langan, Karsten Olejnik, Patrick Fenton, Jeon Woong Kang, Jennifer Hollister-Locke, Matthew A Bochenek, Alan Chiu, Sean Siebert, Katherine Tang, Siddharth Jhunjhunwala, Stephanie Aresta-Dasilva, Nimit Dholakia, Raj Thakrar, Thema Vietti, Michael Chen, Josh Cohen, Karolina Siniakowicz, Meirigeng Qi, James McGarrigle, Adam C Graham, Stephen Lyle, David M Harlan, Dale L Greiner, Jose Oberholzer, Gordon C Weir, Robert Langer & Daniel G Anderson


In vivo screening of a large combinatorial library of alginates identifies materials that elicit a substantially reduced foreign body response.


Careers and Recruitment

Towards sustaining a culture of mental health and wellness for trainees in the biosciences pp353 - 355

Jessica W Tsai & Fanuel Muindi


Addressing the mental health of graduate and postdoctoral trainees in the biosciences will substantially benefit the scientific community at large.


People p356