Delta Scan: The Future of Science and Technology, 2005-2055: Advances in DNA Microarray Technology

Key Pages

Category:
Science and Technology

Domain:
Biology and Biotechnology

Keywords:
Biotechnology & genetics - DNA microarrays, DNA chips, genomics, pharmacogenomics, research technology

Outlook:
Advances in the next 3 to 10 years are expected to make DNA microarray technology ever more widely accessible, potentially reaching a commercial scale that could speed the discovery of new biomedical applications in the next several decades.

Summary Analysis:
A DNA microarray, also known as a DNA chip or sometimes 'laboratory on a chip', is a small glass slide imprinted with hundreds of 'dots' of genetic material. The primary application of microarrays is gene expression profiling, determining which genes are 'turned on' in a particular biological state. A microarray might contain 10,000 dots, giving it the experimental power of racks and racks of test tubes, and allowing the screening of thousands of genes in a single experiment. The microarray has applications in a broad range of biological research and in toxicological screening, pharmaceutical screening and drug development, and disease characterisation.

Microarrays were developed in the mid-1990s, and the technology has progressed rapidly. The first account of using the technology for gene expression research was published in the journal Science in 1995. The commercial stage of this technology has already arrived, and investment by companies such as Affymetrix and CombiMatrix ensures further opportunities for small academic research groups and large industry research teams alike. In the next 3 to 10 years, further progress is expected in the development of hardware, procedures, and analytic methods.

• Hardware - Fundamentally different, and proprietary, microarray production techniques have been developed, such as the use of inkjet technology and robotic pins, to place the genetic material on the glass slides. Production can presently be done on a small scale by individual university research laboratories, offering flexibility and customisability, or on a commercial scale, along with cost savings and standardisation. As production techniques are developed further, competition is likely to exist between commercial attempts that standardise the chips around a particular propriety design and 'open-source' models that can be created by individual laboratories.

• Procedures - Quality control and assurance procedures will need to be standardised for results to be reviewed by scientists and regulatory authorities. Collective efforts are already under way and can be expected to be worked out in the next 5 years, with regulations taking longer. Reliable and valid data collection is a frequent challenge, as researchers must contend with technical difficulties with the sensitivity and accuracy of specific biological targets and probes.

• Analytic methods -- Because the experiments generate more data than can be managed easily using conventional methods, the use of microarrays is closely tied to developments in bioinformatics, and more generally to the integration of biological information and computing power.

There is considerable potential for biomedical applications in the next 10 to 20 years . This has stimulated the research and development interests of the biotechnology industry and already produced a marketable product (Roche's AmpliChip CYP450, based on Affymetrix technology and used to predict the rate at which a patient clears drugs based on the detection of altered versions of liver enzymes). By comparing gene activity in healthy and diseased cells, DNA microarrays offer a tool for understanding the genetic basis of some diseases. The technology could also be used to gather information on an individual's genetic susceptibility to certain diseases as well as metabolism of pharmaceuticals.

Implications:

Potential for new kinds of genome-scale questions to be asked based on scanning and screening of large amounts of data
Alteration of organisational structure and management of laboratories to accommodate reliance on automated and high-throughput technology and increased data generation
Potential for the expansion of the era of 'big biology' to create financial inequities between small laboratories and privately funded research centers
Advancement of pharmacogenomics and the notion of 'personalized medicine'

Early Indicators:

The journal Nature Genetics' publication in January 1999 of a special supplement devoted to the future of microarrays, 'The Chipping Forecast'
The US Food and Drug Adminstration's approval in February 2005 of the AmpliChip CYP450, the first diagnostic to be based on DNA microarray technology
CombiMatrix's formation in May 2005 of a molecular diagnostics subsidiary
CombiMatrix's marketing of 'CustomArray' made-to-order chips

What to Watch:

International standards are developed for quality control and assurance procedures.
Specialized diagnostic tests for susceptibility to certain classes of drugs become available.
Affymetrix strikes development and marketing partnerships, sharing its vast portfolio of intellectual property, or is very successful in developing the market by itself.
Industry announcements of new ways of placing and probing the genetic material on a chip are made.
Pharmaceutical manufacturers begin to outnumber academic and research institutes as customers for microarrays.

Parallels/Precedents:

Advent of automated DNA sequencers, which accelerated the speed of results for an otherwise known but time-consuming procedure
Increase in processing power of silicon chips over time with advances in technology

Enablers/Drivers:

Development of new computational and statistical methods to manage vast quantities of experimental data
Advances in fluorescent chemistry and other probe technology
Movement toward simplified and standardised array data, design, and analysis
Continued cooperation on the part of scientists, technology producers, and regulators
Publication of positive clinical results, motivating investment in biotechnology applications

Leaders:
Regions:

US

Institutions:

Affymetrix (development of commercial microarray production technology) [link]
GE/Amersham (development of CodeLink bioarray system, acquired from Motorola) [link]
CombiMatrix (development of commercial microarray production technology) [link]
Agilent (development of commercial microarray production technology)
Applied Biosystems (development of chemiluminescence-based system to measure gene expression levels in cells and tissues) [link]
Netherlands Cancer Institute [link]
Genome-based Therapeutic Drugs for Depression (GENDEP), Institute of Psychiatry, UK [link]
Population Genetics Technologies, Cambridge, UK [link]
European Bioinformatics Institute Microarray Informatics Group [link]
The Paterson Institute Bioinformatics Group, UK [link]
DNA Databank of Japan (DDBJ) [link]

Figures:

Sources:

The Economic and Social Research Council (ESRC) Genomics Network [link]
Hopkins, M et al. 'Putting Pharmacogenetics into Practice.' Nature Biotechnology. 2006. April 24 403-410
"Pharmacogenetics and Pharmacogenomics: State of the Art and Socio-economic Impacts." Institute for Prospective Technological Studies, Barcelona, Spain. 2006 [link]
Greer, B. and Khan, J. "Diagnostic Classification of Cancer using DNA Microarrays and Artificial Intelligence." 2004. Ann. N.Y. Acad. Sci. 1020 49-66.
Miller, C. and Attwood, T. "Bioinformatics Goes Back to the Future." Nature Reviews Molecular Cell Biology. 2003. 4, 157-162 [link]
Van't Veer L. "Gene Expression Profiling Predicts Clinical Outcome of Breast Cancer." 2002. January 31. Nature. [link]
"The Cancer Revolution." August 23 2003. New Scientist [link]
Gibson, Greg. 2003. Microarray analysis: genome-scale hypothesis scanning. PLoS Biology 1 (1):E15.
Interview with Gregg Whitworth. 7 June 2005.
Shoemaker, D. D., E. E. Schadt, C. D. Armour, Y. D., He, P. Garrett-Engele, P. D. McDonagh, P. M. Loer .... 2001. "Experimental annotation of the human genome using microarray technology." Nature 409, no. 6822: 922-927.
Tansey, Bernadette. "Power Tools for the Gene Age: New Test Can Help Doctors in Prescribing Medications." The San Francisco Chronicle, 7 February 2005, E-1.
"Microarray Gene Expression Data Society" Microarray Gene Expression Data Society [link]
Ball, CA, et al. 2002. "A Guide to Microarray Experiments: An Open Letter to the Scientific Journals." Lancet 360: 1019.
"The Chipping Forecast II." Nature Genetics 32 (2002), no. 4.

At A Glance:
When:
11–20 years

Where:
Global

How Fast:
Years

Likelihood:
Medium-High

Impact:
Medium-Low

Controversy:
Medium

Related Outlooks:

About this outlook: An outlook is an internally consistent, plausible view of the future based on the best expertise available. It is not a prediction of the future. The AT-A-GLANCE ratings suggest the scope, scale, and uncertainty associated with this outlook. Each outlook is also a working document, with contributors adding comments and edits to improve the forecast over time. Please see the revision history for earlier versions.

Category:	Science and Technology
Domain:	Biology and Biotechnology
Keywords:	Biotechnology & genetics - DNA microarrays, DNA chips, genomics, pharmacogenomics, research technology
Outlook:	Advances in the next 3 to 10 years are expected to make DNA microarray technology ever more widely accessible, potentially reaching a commercial scale that could speed the discovery of new biomedical applications in the next several decades.
Summary Analysis:	A DNA microarray, also known as a DNA chip or sometimes 'laboratory on a chip', is a small glass slide imprinted with hundreds of 'dots' of genetic material. The primary application of microarrays is gene expression profiling, determining which genes are 'turned on' in a particular biological state. A microarray might contain 10,000 dots, giving it the experimental power of racks and racks of test tubes, and allowing the screening of thousands of genes in a single experiment. The microarray has applications in a broad range of biological research and in toxicological screening, pharmaceutical screening and drug development, and disease characterisation. Microarrays were developed in the mid-1990s, and the technology has progressed rapidly. The first account of using the technology for gene expression research was published in the journal Science in 1995. The commercial stage of this technology has already arrived, and investment by companies such as Affymetrix and CombiMatrix ensures further opportunities for small academic research groups and large industry research teams alike. In the next 3 to 10 years, further progress is expected in the development of hardware, procedures, and analytic methods. • Hardware - Fundamentally different, and proprietary, microarray production techniques have been developed, such as the use of inkjet technology and robotic pins, to place the genetic material on the glass slides. Production can presently be done on a small scale by individual university research laboratories, offering flexibility and customisability, or on a commercial scale, along with cost savings and standardisation. As production techniques are developed further, competition is likely to exist between commercial attempts that standardise the chips around a particular propriety design and 'open-source' models that can be created by individual laboratories. • Procedures - Quality control and assurance procedures will need to be standardised for results to be reviewed by scientists and regulatory authorities. Collective efforts are already under way and can be expected to be worked out in the next 5 years, with regulations taking longer. Reliable and valid data collection is a frequent challenge, as researchers must contend with technical difficulties with the sensitivity and accuracy of specific biological targets and probes. • Analytic methods -- Because the experiments generate more data than can be managed easily using conventional methods, the use of microarrays is closely tied to developments in bioinformatics, and more generally to the integration of biological information and computing power. There is considerable potential for biomedical applications in the next 10 to 20 years . This has stimulated the research and development interests of the biotechnology industry and already produced a marketable product (Roche's AmpliChip CYP450, based on Affymetrix technology and used to predict the rate at which a patient clears drugs based on the detection of altered versions of liver enzymes). By comparing gene activity in healthy and diseased cells, DNA microarrays offer a tool for understanding the genetic basis of some diseases. The technology could also be used to gather information on an individual's genetic susceptibility to certain diseases as well as metabolism of pharmaceuticals.

	Implications:	Potential for new kinds of genome-scale questions to be asked based on scanning and screening of large amounts of data Alteration of organisational structure and management of laboratories to accommodate reliance on automated and high-throughput technology and increased data generation Potential for the expansion of the era of 'big biology' to create financial inequities between small laboratories and privately funded research centers Advancement of pharmacogenomics and the notion of 'personalized medicine'
	Early Indicators:	The journal Nature Genetics' publication in January 1999 of a special supplement devoted to the future of microarrays, 'The Chipping Forecast' The US Food and Drug Adminstration's approval in February 2005 of the AmpliChip CYP450, the first diagnostic to be based on DNA microarray technology CombiMatrix's formation in May 2005 of a molecular diagnostics subsidiary CombiMatrix's marketing of 'CustomArray' made-to-order chips
	What to Watch:	International standards are developed for quality control and assurance procedures. Specialized diagnostic tests for susceptibility to certain classes of drugs become available. Affymetrix strikes development and marketing partnerships, sharing its vast portfolio of intellectual property, or is very successful in developing the market by itself. Industry announcements of new ways of placing and probing the genetic material on a chip are made. Pharmaceutical manufacturers begin to outnumber academic and research institutes as customers for microarrays.
	Parallels/Precedents:	Advent of automated DNA sequencers, which accelerated the speed of results for an otherwise known but time-consuming procedure Increase in processing power of silicon chips over time with advances in technology
	Enablers/Drivers:	Development of new computational and statistical methods to manage vast quantities of experimental data Advances in fluorescent chemistry and other probe technology Movement toward simplified and standardised array data, design, and analysis Continued cooperation on the part of scientists, technology producers, and regulators Publication of positive clinical results, motivating investment in biotechnology applications
	Leaders:	Regions: US Institutions: Affymetrix (development of commercial microarray production technology) [link] GE/Amersham (development of CodeLink bioarray system, acquired from Motorola) [link] CombiMatrix (development of commercial microarray production technology) [link] Agilent (development of commercial microarray production technology) Applied Biosystems (development of chemiluminescence-based system to measure gene expression levels in cells and tissues) [link] Netherlands Cancer Institute [link] Genome-based Therapeutic Drugs for Depression (GENDEP), Institute of Psychiatry, UK [link] Population Genetics Technologies, Cambridge, UK [link] European Bioinformatics Institute Microarray Informatics Group [link] The Paterson Institute Bioinformatics Group, UK [link] DNA Databank of Japan (DDBJ) [link]
	Figures:
	Sources:	The Economic and Social Research Council (ESRC) Genomics Network [link] Hopkins, M et al. 'Putting Pharmacogenetics into Practice.' Nature Biotechnology. 2006. April 24 403-410 "Pharmacogenetics and Pharmacogenomics: State of the Art and Socio-economic Impacts." Institute for Prospective Technological Studies, Barcelona, Spain. 2006 [link] Greer, B. and Khan, J. "Diagnostic Classification of Cancer using DNA Microarrays and Artificial Intelligence." 2004. Ann. N.Y. Acad. Sci. 1020 49-66. Miller, C. and Attwood, T. "Bioinformatics Goes Back to the Future." Nature Reviews Molecular Cell Biology. 2003. 4, 157-162 [link] Van't Veer L. "Gene Expression Profiling Predicts Clinical Outcome of Breast Cancer." 2002. January 31. Nature. [link] "The Cancer Revolution." August 23 2003. New Scientist [link] Gibson, Greg. 2003. Microarray analysis: genome-scale hypothesis scanning. PLoS Biology 1 (1):E15. Interview with Gregg Whitworth. 7 June 2005. Shoemaker, D. D., E. E. Schadt, C. D. Armour, Y. D., He, P. Garrett-Engele, P. D. McDonagh, P. M. Loer .... 2001. "Experimental annotation of the human genome using microarray technology." Nature 409, no. 6822: 922-927. Tansey, Bernadette. "Power Tools for the Gene Age: New Test Can Help Doctors in Prescribing Medications." The San Francisco Chronicle, 7 February 2005, E-1. "Microarray Gene Expression Data Society" Microarray Gene Expression Data Society [link] Ball, CA, et al. 2002. "A Guide to Microarray Experiments: An Open Letter to the Scientific Journals." Lancet 360: 1019. "The Chipping Forecast II." Nature Genetics 32 (2002), no. 4.

At A Glance:	When:	11–20 years
	Where:	Global
	How Fast:	Years
	Likelihood:	Medium-High
	Impact:	Medium-Low
	Controversy:	Medium