Thursday, December 27, 2007

The Genomics Revolution and the State of Personalized Medicine

The seeds of the Human Genome Project (HGP) were laid during the 1984 Alta Summit in the Wasatch Mountains of Utah. Scientists gathered as part of a meeting sponsored by the Department of Energy (DOE) and the International Commission for Protection Against Environmental Mutagens and Carcinogens. They came with the specific question: "Could new methods permit direct detection of mutations, and more specifically could any increase in the mutation rate among survivors of the Hiroshima and Nagasaki bombings be detected (in them or in their children)?" [1] Seventeen years after that summit the first publications on the preliminary analyses on the working drafts human genome were published by Nature and Science journals in February 2001 by two competing groups: the International Human Genome Mapping Consortium and the Celera Genomics Sequencing Team. [2-3] The same issue of Nature featured a perspective on the potential importance to medicine of the 1.4 million single nucleotide polymorphisms (SNPs) mapped in the genome [4]. One pragmatic approach in interpreting the success of the HGP is in determining its current impact on medicine.

Overall, the project took 13 years to complete in 2003; whereby basic science has benefited from the HGP [5]. Research in surrounding fields has progressed at an incredible rate creating a veritable alphabet soup of -omics-related projects: peptidomics, proteomics, genomics, lipidomics, transcriptomics, metabolomics, metallomics, glycomics, interactomics, spliceomics, and ORFeomics. Researchers who worked on the original effort to sequence the genome turned their efforts to sequencing the genome of one individual since the HGP dealt with a conglomeration of DNA from several individuals. Personalized genomes are able to provide more relevant information about specific conditions in individuals. J. Craig Venter was the first individual for which a diploid genome sequence was characterized in September 2007 [6]. In the publication on Venter's genome, a table is provided containing many markers for common diseases and traits showing the potential for self-examination possible from knowing our genetic sequence. For instance, the list revealed that Venter is more likely to have wet earwax due to the sequence of his ABCC11 gene [6]. It also reveals that Venter is at a higher risk of Alzhimer's disease; information, which may be relevant to health-practitioners diagnosing aliments.

Unfortunately, much of the genomics revolution in science has side-stepped health-practitioners in part due to cost. Venter's genome cost about $70 million to sequence [7]. His genome was followed shortly thereafter by the genome of James Watson employing the sequencing technology of 454 Life Sciences which cost less than $1 million dollars [8]. Estimated costs for a sequencing an individual's genome is approximately $100,000 using the most current technology [7]. The X-Prize Foundation has set up an a genomics X-Prize worth $10 million for the first team able to sequence the genomes of 100 individuals in 10 days; any technologies borne from this accomplishment would almost certainly drive costs down further [8].

There is tension between those geneticists that feel that publicity gained from the sequencing of the genomes of the wealthy and celebrities will garner more attention and support from the public and those who feel that it a misuse of genomics. A news article in the May 2007 issue of Nature shows this unease; Francis Collins, director of the National Human Genome Research Institute (NHGRI), was quoted as saying that sequencing of scientists with "strong financial positions ... [is] contrary to what the genome project aimed to achieve." The NHGRI plans to sequence 100 individual genomes in the next several years and wants to maximize the information obtained from these individuals. Ideas for candidates include those individuals with rare genetic disorders and individuals who have already been studied as part of the International HapMap Project, which published its analyses in the October 2007 [8-9].

Genomics in clinical settings is not routinely utilized, but it is an area that deserves increasing focus at medical schools and continuing education programs. Essential knowledge for current health-practitioners includes understanding available genetic tests for common diseases in pre-symptomatic patients and their uses in diagnoses of symptomatic patients. Our current understanding of the interactions between environmental and genetic factors and the small role that any individual genetic marker may make to complex human diseases undercuts the possibilities for determining more from genetic tests [10]. In a survey study conducted by Finn et al. of US and Canadian psychiatrists, it was shown that fewer than 25% of those surveyed felt prepared or competent to discuss information from genetic analyses with patients and their families [11]. Furthermore, the attitudes of many health-practitioners can be summarized as the HGP as being interesting and potentially useful one day, but having no dramatic effects on health-care in the near future, which has left many wondering "What will genetics and genomics do for me now, and how will they improve patient outcomes?" [12]. Guttenmacher proposes several recommendations to bridge the gap between the basic sciences and medical training, including increased focus on the relationship between common diseases (as opposed to rare Mendelian diseases) and genetics so that health-practitioners begin to think about the genetic factors contributing to the expression of diseases in patients [12].

Science tends to work in leaps and bounds, and while the cost has been prohibitive up to this point, two companies have recently announced new genotyping services for about $1,000. On November 17, 2007, the New York Times contained an article about two new companies; deCODE Genetics, an Icelandic company, will offer to genotype 1 million SNPs from cheek scrapings for $985, and a Google-financed company, 23andMe, will soon announce a similar service that will test 650,000 SNPs [13]. But given the caution with which trained genetic counselors approach genomic information one wonders the use of this data to the average person and the misinformation that might arise from misreading.

[1] Robert Cook-Deegan. The Alta Summit, December 1984. Genomics 5. 661-663 (1989)
[2] The International Human Genome Mapping Consortium. A physical map of the human genome. Nature 409, 934-941 (2001).
[3] The Celera Genomics Sequencing Team. The sequence of the human genome. Science. 291(5507):1304-51. (2001).
[4] Chakravarti, A. Single nucleotide polymorphisms: . . .to a future of genetic medicine. Nature. 409(6822):822-3 (2001).
[5] Francis S. Collins, Michael Morgan, Aristides Patrinos. The Human Genome Project: Lessons from Large-Scale Biology. Science. 300(5617):286-90 (2003).
[6] Levy, S. et al. The Diploid Genome Sequence of an Individual Human. PLoS Biol. 5(10):e254 (2007).
[7] May, M. Venter Sequenced. Nature. Vol 25 10. 1071 (2007).
[8] Check, E. Celebrity genomes alarm researchers. Nature 447, 358-359 (2007).
[9] The International SNP Map Working Group. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature. 409(6822):928-33 (2001).
[10] McGuire. A.L. Medicine. The Future of Personal Genomics. Science. 317(5845):1687 (2007).
[11] Finn, C. T. et al. Psychiatric genetics: a survey of psychiatrists’ knowledge, attitudes, opinions, and practice patterns. J. Clin. Psychiatry 66, 821–830 (2005).
[12] Guttmacher AE, Porteous ME, McInerney JD. Educating health-care professionals about genetics and genomics. Nat Rev Genet. 8(2):151-7 (2007).
[13] Wade, N. Experts Advise a Grain of Salt With Mail-Order Genomes, at $1,000 a Pop. New York Times. 17 Nov. 2007. Accessed:

1 comment:

Harry said...

There are two other companies and that also provide personal genomic information (and both seem to be more medically oriented)...