Fundamental to the myriad of genomic research efforts in operation around the world is the mapping and sequencing of whole genomes . The entire genomes of more than seventy organisms had been completed by early 2002, including the working drafts of the human genome, first published in 2001. The successful completion of the sequencing of these genomes was made possible in part by companies developing and utilizing new technologies and processes to increase the speed and accuracy of mapping and sequencing. This effort has also spawned entire new fields that aim, in various ways, to capitalize on genomics and identify disease-causing genes and new therapeutic strategies.
The advent of the global Human Genome Project in 1989 provided significant, additional incentive for the development of a variety of new genomics-based companies. These companies can be loosely divided into seven major types: large-scale sequencing companies, gene mining companies, functional genomics companies, population-based genomics companies, bioinformatics companies, established pharmaceutical companies, and new biopharmaceutical companies. These are general distinctions and are not absolute, since many companies are blending and using a variety of these technologies with overlapping applications.
Large-Scale Sequencing Companies
Early stages of the human genome project involved the physical mapping and subsequent sequencing of genes and intervening segments. A number of companies were founded specifically to identify genes, sequence them, and determine their function as a means to lead to new diagnostics and pharmaceuticals. These companies include Incyte, Human Genome Sciences, and Celera Genomics. This group of companies has contributed to public and private databases millions of bases of sequence data not only for the human genome, but for many microorganisms as well.
Gene Mining Companies
Now that the sequence data is available and placed in the public domain, companies have been created to "mine" the data, that is, to analyze the genomic sequences to identify genes, their function, and their relationships to health and disease processes. Companies pioneering in this area included Sequana and Millennium Pharmaceuticals (although Sequana did not survive as an independent company). Once genes were identified as relevant to specific disease processes, some of the companies in this sector focused on discovering and developing small molecules, antibodies , proteins, or a combination of the three, in search of drugs that will target the consequences of the defective gene or dysregulated pathways.
Functional Genomics Companies
The challenge of the postgenomics era has been to identify those genes that are of clinical value for drug development. Inherent to that is a basic understanding of the function of all genes. Using industrialized biology approaches, these companies develop technologies for their own use or for sale to other companies. These new technologies are designed to pinpoint specific genes associated with disease and to determine causal relationships with pathology . Companies specializing in this area include Affymetrix, Excelesis, and Lexicon. In addition, most major pharmaceutical companies have established functional genomics departments.
Population-Based Genomics Companies
In order to determine which genes are relevant and underlie complex human diseases such as diabetes mellitus, Alzheimer's disease, or hypertension, companies have been created to collect patient materials. These firms collect relevant clinical information and DNA on people suffering from defined disease as well as people who have no known disorders. They then look at DNA sequence variations in an attempt to identify the genetic factors that may predispose an individual to develop these types of disorders, or factors that directly lead to the development of disease. One company working in this area is deCODE, which has access to the genetic and health data of the entire population of Iceland.
In order to extract the maximum amount of information from genomic sequence data, a new discipline has emerged, called bioinformatics. Bioinformaticians are involved in the capture and interpretation of biological data. The need for bioinformatics support throughout the genomics industry is significant and, as a result, a number of companies have been started that provide these services. Companies engaged in this type of research include DoubleTwist, Genomica, and Spotfire. Because genomics has created terabytes (a trillion bytes) of data, virtually all genomics efforts now require a substantial investment in in-house bioinformatics.
Established Pharmaceutical Companies
The pharmaceutical industry has been working to integrate genetic and genomic information into the drug discovery process. Essentially all of the major pharmaceutical companies have such programs, including GlaxoSmithKline, Merck, and Novartis. From the beginning of compound synthesis through the identification of drug targets, genomics is changing the traditional drug development process. Understanding the influence of polymorphisms on drug target binding is critical to optimizing drug development. This is especially important now, because successes in combinatorial chemistry have given rise to a tremendous increase in the number compounds to be analyzed.
New Biopharmaceutical Companies
As a result of molecular biology and genomics, a number of new companies have been formed that focus on creating drugs from specific genes. As genes are identified and the function of the protein is learned, these companies manufacture the proteins made by specific genes for use in the treatment of human disease. This includes a variety of drugs made through recombinant DNA technology, such as insulin and growth hormone. These new drugs provide patients with a safer therapeutic alternative to other protein sources. Companies working in this sector include Genentech and Amgen. In addition, some companies focus on making protein therapeutics in novel ways. One such company is Genzyme Transgenics, which has genetically altered livestock to produce therapeutic protein in their milk. Other companies focus on producing artificial antibodies that are engineered to look just like normal human antibodies. These so called humanized antibodies, produced by companies such as Protein Design Laboratories, are already on the market for use in treating diseases such as cancer and arthritis.
From Present to Future
Technological advances clearly drive innovation in the pharmaceutical and health-care industries. Advances in the speed and accuracy of DNA sequencing and the growing understanding of the genome have created hundreds of companies, with billions of dollars in assets, that are using this information to contribute to the creation of new diagnostic and therapeutic agents. This has been accomplished even before science has achieved full knowledge of the human DNA sequence or a complete understanding of the function of most human genes. It is expected that the next decade will provide the remaining human genomic information, which will enable a breathtaking array of new therapeutic and preventive options for the treatment of human disease.
see also Bioinformatics; Biotechnology; Combinatorial Chemistry; Genome; High-throughput Screening; Human Genome Project; Pharmacogenetics and Pharmacogenomics.
Kenneth W. Culver
and Mark A. Labow
Genomic Industry Web Guide. <http://www.business2business.com/webguide/o,1660,49834, ff.html>.