Genome projects and gene therapy: Gateways to next generation biological weapons

Military Medicine, Nov 2003 by Black, John Logan III

Genomic and gene therapy research promise important gains into the treatment of human, animal, and plant diseases. However, there is a military aspect to this research that must be recognized. This research enables a new form of biological warfare named genomic warfare. This is the first peer-reviewed scientific article to discuss this threat in-depth. This article advocates that we begin to deal with this threat. Despite that the United States and many signatories of previous bioweapons treaties have agreed not to use biological weapons, mankind has a track record of using all of the weapons at its disposal. This article has a review of the literature and a basic overview of genomic research and gene therapy, which is followed by a discussion of how this therapy can be weaponized. How genomic warfare weapons might be deployed, how deployment may be detected, and the policies and research that would reduce this threat will be described. It is the aim of this article to clearly articulate that this risk exists and to encourage public health, scientific, political, and military leaders to take action to deal with the risk.

Introduction

There are many genomic projects that have the initial aim of sequencing and characterizing the genes of a given species. These projects, including the human genome project when combined with gene therapy, present new ethical, legal, and social implications. One ethical, legal, and social implication is the use of this newly acquired information to develop advanced biological weapons.1 To date, little literature exists on the misuse of genomic research in tandem with gene therapy for military purposes. The goal of this article is not to interfere with the benefit that this research promises but to stimulate thought and discussion about the threat that this technology poses for a new type of biological warfare, which is referred to as "genomic warfare." The term genomic warfare is selected over the term gene warfare, which has been mentioned in the lay press and some articles,2 because the word "gene" implies that only the part of DNA in the nucleus of the cell that encodes proteins is a target of these weapons. This definition is too narrow because strategies targeting other regions of the genome can also be used. Furthermore, genomic sequences from other species, especially those causing disease, are a viable source of potential warfare agents.

The present state of genomic research will be reviewed first. Next, gene therapy will be reviewed, and the common vectors used in gene therapy experiments will be described. These basics are essential to understanding the risk. The theoretical characteristics of a weaponized vector for use against man and some scenarios of a genomic warfare attack will follow. The epidemiological clues of such an attack will then be discussed. Finally, there will be a list of initial steps that should be taken to defend against genomic warfare weapons.

Overview of Genome Projects

Genomic research has ushered in an era of profound change in medicine and society. The initial draft of the human genome was completed in June 2000, and two descriptions and an analyses of the draft were published in articles by researchers from the International Human Genome Sequence Consortium3 and Celera Genomics4 in February 2001. Work continues to produce a completed sequence of the human genome in 2003. Parallel efforts are ongoing to identify variations in nucleotides within the sequence of the human genome (called single nucleotide polymorphisms) and to identify the position, sequence, and function for all of the genes of the human genome. Even before the function of all of the human genes is known, linkage analyses are being done to identify which parts of the genome are associated with human traits and illnesses. Subsequent detailed analysis will be done to find the specific DNA sequences responsible for these diseases. Mutational analysis and identification of gene polymorphisms and allele frequencies are expected to eventually determine susceptibility to a large number of human diseases. Identification of gene expression characteristics in response to exogenous agents, such as drugs, or environmental and pathological variables is expected to expedite drug discovery and therapeutics. Up to the time that the human genome was published, only 483 drug targets accounted for virtually all of the drugs on the market, but there are probably more than 50,000 genes in the human genome, many of which may be new drug targets.3,5,6 Over the next few decades, many new therapeutic agents will be developed, perhaps at a rate that will prove bewildering to practitioners.

Many other genomic sequencing projects are completed including Haemophilus influenzae,7 Mycoplasma genitalium,8 Saccharomuces cerevisiae,9 Methanococcus jannaschi,10 Escherichia coli,11 Mycobacterium tuberculosis,12 Caenorhabditis elegans,13 Drosophila melanogaster,14 Yersinia pestis,15 and many others. These genomes are now being compared with the human genome to provide important insights into the similarities between species, the age of genes, their rate of change, and how unique genes, including those toxic to man, function. Many other species are being studied including genomes of organisms that are responsible for the production of disease states in man. Much of the information mentioned above is deposited in the National Center for Biotechnology Information databases (http://www. ncbi.nlm.nih.gov/), which is available to anyone with Internet access worldwide.