Craig Venter Mycoplasma Laboratorium

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Contents Articles Mycoplasma laboratorium 1 Mycoplasma 8 Craig Venter 13 References Article Sources and Contributors 21 Image Sources, Licenses and Contributors 22 Article Licenses License 23

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Page 1: Craig Venter Mycoplasma Laboratorium

ContentsArticles

Mycoplasma laboratorium 1Mycoplasma 8Craig Venter 13

ReferencesArticle Sources and Contributors 21Image Sources, Licenses and Contributors 22

Article LicensesLicense 23

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Mycoplasma laboratorium 1

Mycoplasma laboratoriumMycoplasma laboratorium is a planned partially synthetic species of bacterium derived from the genome ofMycoplasma genitalium. This effort in synthetic biology is being undertaken at the J. Craig Venter Institute by ateam of approximately twenty scientists headed by Nobel laureate Hamilton Smith, and including DNA researcherCraig Venter and microbiologist Clyde A. Hutchison III.

MycoplasmaMycoplasma is a genus of bacteria of the class Mollicutes in the division Tenericutes, characterised by the lack of acell wall (making it Gram negative) due to their parasitic or commensal lifestyle (extracellular and intracellular). Inmolecular biology, the genus has received much attention. Apart from being a notorious and hard to eradicate(immune to beta-lactam and other antibiotics) contaminant in mammalian cell cultures,[1] It has also been used as amodel organism: the second published complete bacterial genome sequence was that of Mycoplasma genitalium,which has one of the smallest genomes of free-living organisms.[2] The M. pneumoniae genome sequence waspublished soon afterward and was the first genome sequence determined by primer walking of a cosmid libraryinstead of the whole-genome shotgun method.[3] Consequently this species was chosen as a model for the minimalcell project,[4] catalog the entire protein content of a cell.[5]

Pelagibacter ubique (an α-proteobacterion of the order Rickettsiales) has the smallest known genome (1,308,759base pairs) of any free living organism and is one of the smallest self-replicating cells known. It is possibly the mostnumerous bacterion in the world (perhaps 1028 individual cells) and, along with other members of the SAR11 clade,are estimated to make up between a quarter and a half of all bacterial or archaeal cells in the ocean.[6] However, thisspecies was identified only in 2002 by rRNA sequences and was fully sequenced in 2005,[7] being an extremely hardto cultivate species which does not reach a high growth density,[8] [9] therefore mycoplasma are used as a tool insteaddue to their ease and speed of growth.Additionally, as of November 2010, there are 1363 sequenced prokaryotic genomes in NCBI and 4 newly discoveredspecies have less genes than M. genitalium, but many essential genes are missing in Hodgkinia cicadicola , Sulciamuelleri, Baumannia cicadellinicola (symbionts of cicadas) and Carsonella ruddi (symbiote of hackberry petiolegall psyllid, Pachypsylla venusta[10] ) may be encoded in the host nucleus.[11]

species name number of genes size (Mbp)

Candidatus Hodgkinia cicadicola Dsem [12] 169 0.14

Candidatus Carsonella ruddii PV [13] 182 0.16

Candidatus Sulcia muelleri GWSS [14] 227 0.25

Candidatus Sulcia muelleri SMDSEM [15] 242 0.28

Buchnera aphidicola str. Cinara cedri [16] 357 0.4261

Mycoplasma genitalium G37[17] 475 0.58

Candidatus Phytoplasma mali [18] 479 0.6

Buchnera aphidicola str. Baizongia pistaciae [19] 504 0.6224

Nanoarchaeum equitans Kin4-M [20] 540 0.49

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Minimal genome projectThe team started with the bacterium M. genitalium, an obligate intracellular parasite whose genome consists of 482genes comprising 582,970 base pairs, arranged on one circular chromosome (the smallest genome of any knownnatural organism that can be grown in free culture). They then systematically removed genes to find a minimal set of382 genes that can sustain life.[21] This effort was also known as the Minimal Genome Project.The team intends to synthesize chromosome DNA sequences consisting of these 382 genes. Once a version of theminimal 382-gene chromosome has been synthesized, it is intended to be transplanted into a M. genitalium cell tocreate M. laboratorium.The resulting M. laboratorium bacterium is expected to be able to replicate itself with its man-made DNA, making itthe most synthetic organism to date, although the molecular machinery and chemical environment that would allowit to replicate would not be synthetic.[22]

In December 2003, the team had reported a fast method of synthesizing a genome from scratch, producing the5386-base genome of the bacteriophage Phi X 174 in about two weeks.[23] However, the genome of M. laboratoriumis about 50 times larger. In January 2008, the team reported to have synthesized the complete 582,970 base pairchromosome of M. genitalium, with small modifications so that it won't be infectious and can be distinguished fromthe wild type. They named this genome Mycoplasma genitalium JCVI-1.0.[24] [25] The team had also demonstratedthe process of transplanting a (non-synthetic) genome from one Mycoplasma species to another in June 2007.[26] InMay 2010 they showed that they were able to synthesize the 1,200,000 base pair genome of Mycoplasma mycoidesfrom scratch and transplant it into a Mycoplasma capricolum cell; the new genome then took over the cell and thenew organism multiplied.[27] The new organism was nicknamed Synthia.The J. Craig Venter Institute filed patents for the Mycoplasma laboratorium genome (the "minimal bacterialgenome") in the U.S. and internationally in 2006.[28] [29] [30] This extension of the domain of biological patents isbeing challenged by the watchdog organization Action Group on Erosion, Technology and Concentration.[31]

Venter hopes to eventually synthesize bacteria to manufacture hydrogen and biofuels, and also to absorb carbondioxide and other greenhouse gases. George Church, another pioneer in synthetic biology, holds that E. coli is a moreefficient organism than M. genitalium and that creating a fully synthetic genome is not necessary and too costly forsuch tasks; he points out that synthetic genes have already been incorporated into E.coli to perform some of theabove tasks.[25] On June 28, 2007, a team at the J. Craig Venter Institute published an article in Science Express,saying that they had successfully transplanted the natural DNA from a Mycoplasma mycoides bacterium into aMycoplasma capricolum cell, creating a bacterium which behaved like a M. mycoides.[32]

On Oct 6, 2007, Craig Venter announced in an interview with UK's The Guardian newspaper that the same team hadsynthesized a modified version of the single chromosome of Mycoplasma genitalium using chemicals. Thechromosome was modified to eliminate all genes which tests in live bacteria had shown to be unnecessary. The nextplanned step in this minimal genome project is to transplant the synthesized minimal genome into a bacterial cellwith its old DNA removed; the resulting bacterium will be called Mycoplasma laboratorium. The next day theCanadian bioethics group, ETC Group issued a statement through their representative, Pat Mooney, saying Venter's"creation" was "a chassis on which you could build almost anything". The synthesized genome had not yet beentransplanted into a working cell.[33]

On May 21, 2010, Science reported that the Venter group had successfully synthesized the genome of the bacterium Mycoplasma mycoides from a computer record, and transplanted the synthesized genome into the existing cell of a Mycoplasma capricolum bacterium that had had its DNA removed. The "synthetic" bacterium was viable, i.e. capable of replicating billions of times. The team had originally planned to use the M. genitalium bacterium they had previously been working with, but switched to M. mycoides because the latter bacterium grows much faster, which translated into quicker experiments.[34] Venter describes it as "the first species.... to have its parents be a computer".[35] The transformed bacterium is dubbed "Synthia" by ETC. A Venter spokesperson has declined to

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confirm any breakthrough at the time of this writing, likely because similar genetic introduction techniques such astransfection, transformation, transduction and protofection have been a standard research practice for many years.Now that the technique has been proven to work with the M. mycoides genome, the next project is presumably to goback to the minimized M. genitalium and transplant it into a cell to create the previously mentioned M. laboratorium.

Bacterial genome transplantationIn order to propagate a synthetic genome the technique to transplant an intact whole bacterial genome into anotherhad to be developed. Oswal Avery's pioneering experiments in the 1940s showed that some bacteria could taken upnaked DNA[36] and with the advent of molecular cloning techniques DNA elements could be transformed intocompetent cells, typically cloning vectors, around 5-20 kbp long, and even bacterial artificial chromosomes can bemaintained. In 2007, Venter's team reported that they had managed to transfer the chromosome of one species,Mycoplasma mycoides to Mycoplasma capricolum by means of:• isolating the genome of M. mycoides: gentle lysis of cells trapped in agar — molten agar mixed with cells and let

to gelled—, followed by pulse field gel electroporation and the band of the correct size (circular 1.25Mbp) beingisolated.

• making the recipient cells of M. capricolum competent: growth in rich media followed starvation in poor mediawhere the nucleotide starvation results in inhibition of DNA replication and change of morphology.

• polyethylene glycol-mediated transformation of the circular chromosome to the DNA-free cells followed byselection.[37]

The term transformation is used to refer to insertion of a vector into a bacterial cell (by electroporation or heatshock),here transplantation is used akin to nuclear transplantation.The switch from M.genitalium to M.mycoides was spurred due to the faster growth of the latter [38]

Bacterial chromosome synthesisIt is possible to create DNA sequences chemically (Oligonucleotide synthesis) which is achieved by successiverounds of deprotection and coupling of protected phosphoramidite nucleotides with geometrically decreasing yieldsto length, making sequences longer than 1kb unfeasible. For longer sequences, DNA ligation is required. In 2008Venter's group published a paper showing that they had managed to create a synthetic genome (a copy of M.mycoides sequence CP001621 [39]) by means of a hierarchical strategy. [24] :• Synthesis ->1kbp: The genome sequence was synthesised by Blue Heron [40] in 1078 1080bp cassettes with 80bp

overlap and NotI restriction sites (inefficient but rare cutter).• Ligation -> 10kbp: 109 Groups of a series of 10 consecutive cassettes were ligatated and cloned in E.coli on a

plasmid and the correct permutation checked by sequencing, this would follow a geometric distribution withexpected number of trials of 10.

• Multiplex PCR -> 100kbp: 11 Groups of a series of 10 consecutive 10kbp assemblies (grown in yeast) werejoined by multiplex PCR, using a primer pair for each 10kbp assembly.

• Isolation and recombination -> secondary assemblies were isolated by means of the plug method above andjoining and transformed into yeast spheroplasts without a vector sequence (present in assembly 811-900).

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Synthetic genomeIn 2010, using the methods described above Venter and colleagues created a strain of Mycoplasma mycoides calledJCVI-syn1.0, with a synthetic genome.[41] Initially the synthetic construct did not work so to pin point the error —which caused a delay of 3 months in the whole project[38] — a series of semi-synthetic constructs were created giventhe fact than the natural genome worked, the cause of the failed growth was an frameshift mutation in DnaA, anreplication initiation factor, which once corrected worked and was verified.[41]

The construction of a cell with a synthetic genome was done to test the methodology in order to allow more modifiedgenomes to be created in future, consequently to minimise sources of failure the genome was created using a naturalgenome as a template. Due to the large size of a genome, apart from the elements required for propagation in yeastand residues from restriction sites, several differences are present in Mycoplasma mycoides JCVI-syn1.0 notably anE.coli transposon IS1 (an infection from the 10kb stage) and an 85bp duplication.[41]

However, the project has received heavy criticism as it claims to the press to have created a synthetic organisms,given the fact that the genome, was synthesized chemically in many pieces (a synthetic method) and joined togetherby means of molecular biological techniques (an artificial method), and transplanted into the cytoplasm of a naturalcell (after a few generations, though, the original protein content is undetectable). The two species used as donor andrecipient are of the same genus as the more distant two species are, the less the correct protein interactions aremaintained, such as binding factors and binding sites, which mutate together (epistasis),[42] consequently, Paul Keim(a molecular geneticist at Northern Arizona University in Flagstaff) notes that "there are great challenges aheadbefore genetic engineers can mix match, and fully design an organism's genome from scratch" [38] due to this issue.DNA is the template for protein construction and requires protein to do so, a chicken-and-egg conundrum solved bythe RNA world hypothesis, consequently synthetic naked DNA would require several protein to kick start a viablecell. In 2002 a team lead by E Wimmer synthesised a replication poliovirus (one of the largest viruses),[43] viruses,however, duplicate by disabling and utilising host protein expression machinery. Furthermore, whereas DNA caneasily be amplified (PCR using Taq polymerase), ligated (ligase) and transcribed (T4 polymerase), current in vitrotranslation kits utilise yeast extracts and a cell wall cannot be synthesised ex novo not even in a water-in-oilemulsion. An interesting parallel of the requirement of protein to kickstart a cell's DNA is in mathematical models ofthe cell cycle in mathematical biology, which, as they rely on a systems of ordinary differential equations to modelthe cell cycle, require initial conditions to be set, which if not within the robustness range of the strain (wild-type ormultant) do not allow it to survive.[44]

WatermarksA much publicised feature of the M. laboratorium is the presence of watermark sequences as an ultimate proof of theachievement and as a publicity stunt — it's a common tradition in the semiconductor industry to have latininscriptions in unused portions of the microchip, visible only by electron microscopy. The 4 watermarks (present infigure 1 in supplementary material of [41] ) are coded messages in the form of DNA base pairs, of 1246, 1081, 1109and 1222 base pairs respectively, in natural peptides the 4 nucleotides encode in sets of 3 the 20 natural amino acidsby means of the universal genetic code. Each amino acid by convention is represented by a letter, but in nature thereis nothing which ties Alanine, a molecule, to the latin letter A, a vowel, so this convention was disregarded in thelatter watermarks. In the minimal genome organism the watermark were encoded as amino acids, with V as U, bothin reference to Latin inscriptions (U started to appear only in carolingian manuscripts) and the lack of a standardamino acid for U (selenocysteine is U but is non-standardly encoded) containing the names of the researchers:• VENTERINSTITVTE• CRAIGVENTER• HAMSMITH• CINDIANDCLYDE• GLASSANDCLYDE

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In the synthetic organism, instead the Latin alphabet — which in English has 26 letters, which is covered only inbase 4 with 3 or more digits — was encoded by a undisclosed encoding. The encoding is fixed and 3 digits make anuppercase letter or Ascii symbol, possibly randomly allocated (not Ascii table, frequency or keyboard order).[45] Thecontent of the watermarks is as follows:1. watermark 1 an Html script which reads to a browser as text congratulating the decoder with an email link

([email protected]) to click to prove the decoding.2. watermark 2 contains a list of authors and a quote from James Joyce: "To live to err, to fall, to triumph, to

recreate life out of life".3. watermark 3 contains more authors and a quote from Robert Oppenheimer (uncredited): "See things not as they

are, but as they might be".4. watermark 4 contains yet more authors and a quote from Richard Feynman: "What I cannot build, I cannot

understand".

Concerns and controversy

Press coverage

The main controversy from the project is the undue amount of publicity it received from the press due to Venter'sshowmanship, to the degree that Jay Keasling, a pioneering synthetic biologist and founder of Amyris says “The onlyregulation we need is of my colleague’s mouth”.[46] The Vatican has not condemmed the discovery, but claims it isnot a new life [47]

Cost

It is estimated that the synthetic genome cost US$40 million and took 20 people more than a decade of work.,[38]

despite the controversy, Venter has attracted over $110 million in investments so far for Synthetic Genomics, with afuture deal with Exxon Mobil of $300 million in research to design algae for diesel fuel[46]

Utility

Despite the funding for practical applications, as stressed by George Church, one of the main players in the field ofsynthetic biology, a few changes are required to obtain useful organisms now, such as biofuel production orbioremediation.[46] However, speculation of the distant future possible application is rife. Venter himself is prone tosuch speculations such as “What if we can make algae taste like beef?”.[46] If it were possible to create a syntheticcell without the use of preexisting recipient cells, however, many applications would be achievable which would beotherwise unattainable, such as a completely overhauled bacterium that works in a logically controlled way—,removing what has been described as 'evolutionary messiness'[48] — with lower mutation rates, categorical genearrangement (colinearity), with adding novel nucleotides to increase encoding, a feat achieved in vitro (PCR) or witha completely novel genetic code, such as has been achieved by experiments in which a few additional non-canonicalamino acids were added.

Bioterrorism and bioterror

Craig Venter has funded ethical studies, but has been criticised by scientists for over-dramatising the risks ofbioerror or bioterrorism,[38] which are misunderstood by the general public. One argument regarding bioterrorism isin regards to smallpox, which could be synthesised and insertion into existing related pox viruses could theoreticallybe used to recreate the virus, which has been completely eradicated, except for in two BSL-4 laboratories and digitalgenomes.[49] Most countries stopped vaccination programs for smallpox by the late 1970s, making a major part ofthe current world population susceptible to the virus.[49] However, just like the 2001 anthrax attacks, the SARS virus,Ebola scares in the west or other outbreaks scares the damages would be in reality limited and quickly contained.

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Similar projectsA team at the Hungarian Academy of Science, created a strain of Escherichia coli called MDS42 and sold under thename of "clean genome" [50], where 15% of the genome of the parental strain (E. coli K-12 MG1655 ) wereremoved to aim in molecular biology efficiency, removing IS elements, pseudogenes and phages, resulting in bettermaintenance of plasmid-encoded toxic genes, which are often inactivated by transposons. [51] (biochemistry andreplication machinery were not altered)

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[23] Smith, Hamilton O.; Clyde A. Hutchison, Cynthia Pfannkoch, J. Craig Venter (2003-12-23). "Generating a synthetic genome by wholegenome assembly: {phi}X174 bacteriophage from synthetic oligonucleotides" (http:/ / www. pnas. org/ cgi/ content/ abstract/ 100/ 26/ 15440).Proceedings of the National Academy of Sciences 100 (26): 15440–15445. doi:10.1073/pnas.2237126100. . Retrieved 2007-10-08.

[24] Gibson, B; Clyde A. Hutchison, Cynthia Pfannkoch, J. Craig Venter, et al. (2008-01-24). "Complete Chemical Synthesis, Assembly, andCloning of a Mycoplasma genitalium Genome" (http:/ / www. sciencemag. org/ cgi/ content/ abstract/ 1151721). Science 319 (5867): 1215.doi:10.1126/science.1151721. PMID 18218864. . Retrieved 2008-01-24.

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[45] Ken Shirriff (2010-06-10). "Using Arc to decode Venter's secret DNA watermark" (http:/ / www. arcfn. com/ 2010/ 06/using-arc-to-decode-venters-secret-dna. html). Ken Shirriff's blog. . Retrieved 2010-10-29.

[46] ANDREW POLLACK, His Corporate Strategy: The Scientific Method, NYTimes, September 4, 2010[47] "Vatican Greets Development of First Synthetic Cell with Caution" (http:/ / www. americancatholic. org/ news/ report. aspx?id=2641).

American Catholic. 2010-05-25. . Retrieved 2010-10-29.[48] Dan S Tawfik, Messy biology and the origins of evolutionary innovations Nature Chemical Biology 6 , 692–696 (2010)

doi:10.1038/nchembio.441[49] The Genetic Engineering of Smallpox. WHO’s Retreat from the Eradication of Smallpox Virus and Why it Should be Stopped (http:/ / www.

biosafety-info. net/ file_dir/ 413148854af122567. pdf) A BRIEFING PAPER BY THE SUNSHINE PROJECT. 2002.[50] http:/ / www. scarabgenomics. com/[51] Umenhoffer, K.; Fehér, T. �S.; Balikó, G.; Ayaydin, F.; Pósfai, J. �N.; Blattner, F. R.; Pósfai, G. �R. (2010). "Reduced evolvability of

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Popular press

External links• J. Craig Venter Institute: Research Groups (http:/ / www. jcvi. org/ research/ )• NCBI prokaryotic genome database (http:/ / www. ncbi. nlm. nih. gov/ genomes/ lproks. cgi)

Mycoplasma

Mycoplasma

Scientific classification

Kingdom: Bacteria Phylum: Tenericutes  or

Firmicutes Class: Mollicutes Order: Mycoplasmatales Family: Mycoplasmataceae Genus: Mycoplasma

Nowak 1929 Species

M. gallisepticumM. genitaliumM. hominisM. hyopneumoniaeM. laboratoriumM. ovipneumoniaeM. pneumoniaeetc.

MycoplasmosisClassification and external resources

ICD-10 A49.3

ICD-9 041.81 [1]

Mycoplasma is a genus of bacteria that lack a cell wall.[2] Without a cell wall, they are unaffected by many commonantibiotics such as penicillin or other beta-lactam antibiotics that target cell wall synthesis. They can be parasitic orsaprotrophic. Several species are pathogenic in humans, including M. pneumoniae, which is an important cause ofatypical pneumonia and other respiratory disorders, and M. genitalium, which is believed to be involved in pelvicinflammatory diseases.

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Origin of the nameThe name Mycoplasma, from the Greek mykes (fungus) and plasma (formed), was first used by A. B. Frank in 1889.He thought it was a fungus, due to fungus-like characteristics .[3]

An older name for Mycoplasma was Pleuropneumonia-Like Organisms (PPLO), referring to organisms similar tothe causative agent of contagious bovine pleuropneumonia (CBPP).[4] It was later found that the fungus-like growthpattern of M. mycoides is unique to that species.

CharacteristicsThere are over 100 recognized species of the genus Mycoplasma, one of several genera within the bacterial classMollicutes. Mollicutes are parasites or commensals of humans, other animals (including insects), and plants; thegenus Mycoplasma is by definition restricted to vertebrate hosts. Cholesterol is required for the growth of species ofthe genus Mycoplasma as well as certain other genera of mollicutes. Their optimum growth temperature is often thetemperature of their host if warmbodied (e. g. 37° C in humans) or ambient temperature if the host is unable toregulate its own internal temperature. Analysis of 16S ribosomal RNA sequences as well as gene content stronglysuggest that the mollicutes, including the mycoplasmas, are closely related to either the Lactobacillus or theClostridium branch of the phylogenetic tree (Firmicutes sensu stricto).

Cell morphologyThe bacteria of the genus Mycoplasma (trivial name: mycoplasmas) and their close relatives are characterized bylack of a cell wall. Despite this, the cells often present a certain shape, with a characteristic small size, with typicallyabout 10% of the volume of an Escherichia coli cell. These cell shapes presumably contribute to the ability ofmycoplasmas to thrive in their respective environments. Most are pseudococcoidal, but there are notable exceptions.Species of the M. fastidiosum cluster are rod-shaped. Species of the M. pneumoniae cluster, including M.pneumoniae, possess a polar extension protruding from the pseudococcoidal cell body. This tip structure, designatedan attachment organelle or terminal organelle, is essential for adherence to host cells and for movement along solidsurfaces (gliding motility), and is implicated in normal cell division. M. pneumoniae cells are pleomorphic, with anattachment organelle of regular dimensions at one pole and a trailing filament of variable length and uncertainfunction at the other end, whereas other species in the cluster typically lack the trailing filament. Other species likeM. mobile and M. pulmonis have similar structures with similar functions.Mycoplasmas are unusual among bacteria in that most require sterols for the stability of their cytoplasmicmembrane. Sterols are acquired from the environment, usually as cholesterol from the animal host. Mycoplasmasgenerally possess a relatively small genome of 0.58-1.38 megabases, which results in drastically reducedbiosynthetic capabilities and explains their dependence on a host. Additionally they use an alternate genetic codewhere the codon UGA is encoding for the amino acid tryptophan instead of the usual opal stop codon. They have alow GC-content (23-40 mol %).

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First isolationIn 1898 Nocard and Roux reported the cultivation of the causative agent of CBPP, which was at that time a graveand widespread disease in cattle herds. [5] [6] The disease is caused by M. mycoides subsp. mycoides SC(small-colony type), and the work of Nocard and Roux represented the first isolation of a mycoplasma species.Cultivation was, and still is difficult because of the complex growth requirements.These researchers succeeded by inoculating a semi-permeable pouch of sterile medium with pulmonary fluid from aninfected animal and depositing this pouch intraperitoneally into a live rabbit. After fifteen to twenty days, the fluidinside of the recovered pouch was opaque, indicating the growth of a microorganism. Opacity of the fluid was notseen in the control. This turbid broth could then be used to inoculate a second and third round and subsequentlyintroduced into a healthy animal, causing disease. However, this did not work if the material was heated, indicating abiological agent at work. Uninoculated media in the pouch, after removal from the rabbit, could be used to grow theorganism in vitro, demonstrating the possibility of cell-free cultivation and ruling out viral causes, although this wasnot fully appreciated at the time (Nocard and Roux, 1890).

Small genomeRecent advances in molecular biology and genomics have brought the genetically simple mycoplasmas, particularlyM. pneumoniae and its close relative M. genitalium, to a larger audience. The second published complete bacterialgenome sequence was that of M. genitalium, which has one of the smallest genomes of free-living organisms.[7] TheM. pneumoniae genome sequence was published soon afterwards and was the first genome sequence determined byprimer walking of a cosmid library instead of the whole-genome shotgun method.[8] Mycoplasma genomics andproteomics continue in efforts to understand the so-called minimal cell,[9] catalog the entire protein content of acell,[10] and generally continue to take advantage of the small genome of these organisms to understand broadbiological concepts.

TaxonomyThe medical and agricultural importance of members of the genus Mycoplasma and related genera has led to theextensive cataloging of many of these organisms by culture, serology, and small subunit rRNA gene and wholegenome sequencing. A recent focus in the sub-discipline of molecular phylogenetics has both clarified and confusedcertain aspects of the organization of the class Mollicutes.[11]

Originally the trivial name "mycoplasmas" has commonly denoted all members of the class Mollicutes. The name"Mollicutes" is derived from the Latin mollis (soft) and cutes (skin), and all of these bacteria do lack a cell wall andthe genetic capability to synthesize peptidoglycan. Now Mycoplasma is a genus in Mollicutes. Despite the lack of acell wall, many taxonomists have classified Mycoplasma and relatives in the phylum Firmicutes, consisting of lowG+C Gram-positive bacteria such as Clostridium, Lactobacillus, and Streptococcus based on 16S rRNA geneanalysis. The order Mycoplasmatales contains a single family, Mycoplasmataceae, comprising two genera:Mycoplasma and Ureaplasma.Historically, the description of a bacterium lacking a cell wall was sufficient to classify it to the genus Mycoplasmaand as such it is the oldest and largest genus of the class with about half of the class' species (107 validly described),each usually limited to a specific host and with many hosts harboring more than one species, some pathogenic andsome commensal. In later studies, many of these species were found to be phylogenetically distributed among atleast three separate orders.A limiting criterion for inclusion within the genus Mycoplasma is that the organism have a vertebrate host. In fact, the type species, M. mycoides, along with other significant mycoplasma species like M. capricolum, is evolutionarily more closely related to the genus Spiroplasma in the order Entomoplasmatales than to the other members of the Mycoplasma genus. This and other discrepancies will likely remain unresolved because of the extreme confusion that

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change could engender among the medical and agricultural communities.The remaining species in the genus Mycoplasma are divided into three non-taxonomic groups, hominis, pneumoniaeand fermentans, based on 16S rRNA gene sequences.The hominis group contains the phylogenetic clusters of M. bovis, M. pulmonis, and M. hominis, among others. M.hyopneumoniae is a primary bacterial agent of the porcine respiratory disease complex.The pneumoniae group contains the clusters of M. muris, M. fastidiosum, U. urealyticum, the currently unculturablehaemotrophic mollicutes, informally referred to as haemoplasmas (recently transferred from the generaHaemobartonella and Eperythrozoon), and the M. pneumoniae cluster. This cluster contains the species (and theusual or likely host) M. alvi (bovine), M. amphoriforme (human), M. gallisepticum (avian), M. genitalium (human),M. imitans (avian), M. pirum (uncertain/human), M. testudinis (tortoises), and M. pneumoniae (human). Most if notall of these species share some otherwise unique characteristics including an attachment organelle, homologs of theM. pneumoniae cytadherence-accessory proteins, and specialized modifications of the cell division apparatus.

Laboratory contaminantMycoplasma species are often found in research laboratories as contaminants in cell culture. Mycoplasmal cellculture contamination occurs due to contamination from individuals or contaminated cell culture mediumingredients. Mycoplasma cells are physically small – less than 1 µm – and they are therefore difficult to detect with aconventional microscope. Mycoplasmas may induce cellular changes, including chromosome aberrations, changes inmetabolism and cell growth. Severe Mycoplasma infections may destroy a cell line. Detection techniques includeDNA Probe, enzyme immunoassays, PCR, plating on sensitive agar and staining with a DNA stain including DAPIor Hoechst.It has been estimated that at least 11 to 15% of U.S. laboratory cells cultures are contaminated with mycoplasma.(bywhom?) A Corning study showed that half of U.S. scientists did not test for mycoplasma contamination in their cellcultures. The study also stated that, in Czechoslovakia, 100% of cell cultures that were not routinely tested werecontaminated while only 2% of those routinely tested were contaminated. (study page 6) Since the U.S.contamination rate was based on a study of companies that routinely checked for mycoplasma, the actualcontamination rate may be higher. European contamination rates are higher and that of other countries are higher still(up to 80% of Japanese cell cultures).[12]

First synthetic genome synthesizedOn 20 May 2010, Gibson et al. reported that they had created the first synthetic genome of a mycoplasmal cell.[13]

References[1] http:/ / www. icd9data. com/ getICD9Code. ashx?icd9=041. 81[2] Ryan KJ, Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. pp. 409–12. ISBN 0838585299.[3] Conrad J. Krass and Max W. Gardner Etymology of the Term Mycoplasma (http:/ / ijs. sgmjournals. org/ cgi/ reprint/ 23/ 1/ 62. pdf) Int. J. of

Syst. Bact.; Jan 1973, p. 62-64; Vol. 23, No. 1[4] Edward DG, Freundt EA (February 1956). "The classification and nomenclature of organisms of the pleuropneumonia group". J. Gen.

Microbiol. 14 (1): 197–207. PMID 13306904.pdf (http:/ / mic. sgmjournals. org/ cgi/ reprint/ 14/ 1/ 197. pdf)[5] Nocard, E.I.E. & Roux, E.; Le microbe de la péripneumonie. Ann Inst Pasteur 12, 240-262. (Translated as ‘The microbe of pleuropneumonia’

in Rev Infect Dis 12, 354-358 (1990))[6] Hayflick L. & Chanock, R.M. (1965). "Mycoplasma Species of Man" (http:/ / mmbr. asm. org/ cgi/ reprint/ 29/ 2/ 185. pdf). Bacteriol.

Reviews 29 (2): 185–221. .[7] Fraser CM, Gocayne JD, White O, et al. (October 1995). "The minimal gene complement of Mycoplasma genitalium" (http:/ / www.

sciencemag. org/ cgi/ pmidlookup?view=long& pmid=7569993). Science (journal) 270 (5235): 397–403. doi:10.1126/science.270.5235.397.PMID 7569993. .

[8] Himmelreich R, Hilbert H, Plagens H, Pirkl E, Li BC, Herrmann R (November 1996). pmid=8948633 "Complete sequence analysis of the genome of the bacterium Mycoplasma pneumoniae" (http:/ / nar. oxfordjournals. org/ cgi/ pmidlookup?view=long& ). Nucleic Acids Res. 24

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(22): 4420–49. doi:10.1093/nar/24.22.4420. PMID 8948633. PMC 146264. pmid=8948633.[9] Hutchison CA, Montague MG (2002). "Mycoplasmas and the minimal genome concept". Molecular Biology and Pathogenicity of

Mycoplasmas (Razin S, Herrmann R, eds.). New York: Kluwer Academic/Plenum. pp. 221–54. ISBN 0306472872.[10] Regula JT, Ueberle B, Boguth G, et al. (November 2000). "Towards a two-dimensional proteome map of Mycoplasma pneumoniae".

Electrophoresis 21 (17): 3765–80. doi:10.1002/1522-2683(200011)21:17<3765::AID-ELPS3765>3.0.CO;2-6. PMID 11271496.[11] Johansson K-E, Pettersson B (2002). "Taxonomy of Mollicutes". Molecular Biology and Pathogenicity of Mycoplasmas (Razin S, Herrmann

R, eds.). New York: Kluwer Academic/Plenum. pp. 1–30. ISBN 0306472872.[12] John Ryan (2008). "Understanding and Managing Cell Culture Contamination" (http:/ / catalog2. corning. com/ Lifesciences/ media/ pdf/

cccontamination. pdf). Corning Incorporated. pp. 24. .[13] Daniel G. Gibson, John I. Glass, Carole Lartigue, Vladimir N. Noskov, Ray-Yuan Chuang, Mikkel A. Algire, Gwynedd A. Benders,

Michael G. Montague, Li Ma, Monzia M. Moodie, Chuck Merryman, Sanjay Vashee, Radha Krishnakumar, Nacyra Assad-Garcia, CynthiaAndrews-Pfannkoch, Evgeniya A. Denisova, Lei Young, Zhi-Qing Qi, Thomas H. Segall-Shapiro, Christopher H. Calvey, Prashanth P.Parmar, Clyde A. Hutchison, III, Hamilton O. Smith, J. Craig Venter (2010). "Creation of a Bacterial Cell Controlled by a ChemicallySynthesized Genome" (http:/ / www. sciencemag. org/ cgi/ content/ abstract/ science. 1190719). Science (sciencemag.org) 329 (5987): 52–6.doi:10.1126/science.1190719. PMID 20488990. .

External links• Compare (http:/ / en. wikibooks. org/ wiki/ Cell_Biology/ Introduction/ Cell_size) the size of these small bacteria

to the sizes of other cells and viruses.• MedPix(r)Images (http:/ / rad. usuhs. mil/ medpix/ medpix. html?mode=slide_sorter& pt_id=12564#top)

Mycoplasma Pneumonia• Ureaplasma Infection: eMedicine Infectious Diseases (http:/ / emedicine. medscape. com/ article/

231470-overview)

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Craig Venter

J. Craig Venter

Craig Venter in 2007

Born October 14, 1946Salt Lake City, Utah, USA

Institutions State University of New York at BuffaloNational Institutes of HealthJ. Craig Venter Institute

Alma mater University of California, San Diego

Known for DNAHuman genomeMetagenomicsSynthetic genomicsShotgun approach to genome sequencing

Notable awards Kistler Prize (2008), ENI award (2008), National Medal of Science (2008)

John Craig Venter (born October 14, 1946) is an American biologist and entrepreneur, most famous for his role inbeing one of the first to sequence the human genome[1] and for his role in creating the first cell with a syntheticgenome in 2010.[2] [3] Venter founded Celera Genomics, The Institute for Genomic Research and the J. Craig VenterInstitute, now working at the latter to create synthetic biological organisms and to document genetic diversity in theworld's oceans. He was listed on Time magazine's 2007 and 2008 Time 100 list of the most influential people in theworld. In 2010, the British magazine New Statesman listed Craig Venter at 14th in the list of "The World's 50 MostInfluential Figures 2010".[4]

Early lifeVenter was born in Salt Lake City, Utah. In his youth, he did not take his education seriously, preferring to spend histime on the water in boats or surfing. According to his biography, A Life Decoded, he was said to never be a terriblyengaged student, having Cs and Ds on his eighth-grade report cards.[5] According to Time Magazine, it was notalways evident that Venter would become a transformative figure, particularly when he was a boy.Although he was against the Vietnam War,[6] Venter was drafted and enlisted in the United States Navy where heworked in the intensive-care ward of a field hospital.[7] While in Vietnam, he attempted to commit suicide byswimming out to sea, but changed his mind more than a mile out.[8] Being confronted with wounded, maimed, anddying soldiers on a daily basis instilled in him a desire to study medicine[9] — although he later switched to scientificmedical research.

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EducationVenter graduated from Mills High School and began his college career at a community college, College of SanMateo in California. He received his B.S. degree in biochemistry in 1972, and his Ph.D. degree in physiology andpharmacology in 1975, both from the University of California, San Diego. At UCSD, he studied under biochemistNathan O. Kaplan,[10] and married former Ph.D. candidate Barbara Rae.[11] [12] [13] [14] After working as an associateprofessor, and later as full professor, at the State University of New York at Buffalo, he joined the National Institutesof Health in 1984. In Buffalo, he divorced Dr. Rae-Venter and married his student, Claire M. Fraser,[12] remainingmarried to her until 2005.[15]

DiscoveryWhile at the NIH, Venter learned of a technique for rapidly identifying all of the mRNAs present in a cell and beganto use it to identify human brain genes. The short cDNA sequence fragments discovered by this method are calledexpressed sequence tags (ESTs) a name coined by Anthony Kerlavage at The Institute for Genomic Research. TheNIH initially led an effort to patent these gene fragments, in which Venter coincidentally and controversially becameinvolved.[16] The NIH later withdrew the patent applications, following public outcry. Subsequent court casesdeclared that ESTs were not directly patentable.[17]

Human Genome ProjectVenter was passionate about the power of genomics to radically transform healthcare. Venter believed that shotgunsequencing was the fastest and most effective way to get useful human genome data.[18] The method wascontroversial, however, since some geneticists felt it would not be accurate enough for a genome as complicated asthat of humans.[19] Frustrated with what Venter viewed as the slow pace of progress in the Human Genome project,and unable to get funds for his ideas, he sought funding from the private sector to fund Celera Genomics.[20] Thegoal of the company was to sequence the entire human genome and release it into the public domain fornon-commercial use in much less time and for much less cost than the public human genome project. The companyplanned to monetize their work by creating a value-added database of genomic data to which users could subscribefor a fee. The goal consequently put pressure on the public genome program and spurred several groups to redoubletheir efforts to produce the full sequence. DNA from five demographically different individuals was used by Celerato generate the sequence of the human genome; one of the individuals was Venter himself. In 2000, Venter andFrancis Collins of the National Institutes of Health and U.S. Public Genome Project jointly made the announcementof the mapping of the human genome in 2000, a full three years ahead of the expected end of the Public GenomeProgram. The announcement was made along with US President Bill Clinton, and U.K. Prime Minister TonyBlair.[21] Venter and Collins thus shared an award for "Biography of the Year" from A&E Network.[22] Celerapublished the first Human Genome in the journal Science, and was soon followed by a Human Genome ProjectPublication in Nature.[23] [24] Despite some claims that shotgun sequencing was in some ways less accurate than theclone-by-clone method chosen by the Human Genome Project,[25] the technique became widely accepted by thescientific community and is still the de facto standard used today.Although Celera was originally set to sequence a composite of DNA samples, partway through the sequencing,Venter switched the samples for his own DNA.[26]

After contributing to the Human Genome, and its release into the public domain, Venter was fired by Celera in early2002.[27] According to his biography, Venter was ready to leave Celera, and was fired due to conflict with the maininvestor, Tony White, that had existed since day one of the project. Venter writes that his main goal was always toaccelerate science and thereby discovery, and he only sought help from the corporate world when he couldn't findfunding in the public sector.

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Ocean samplingThe Global Ocean Sampling Expedition (GOS) is an ocean exploration genome project with the goal of assessing thegenetic diversity in marine microbial communities and to understand their role in nature's fundamental processes.Begun as a Sargasso Sea pilot sampling project in August 2003,Craig Venter announced the full Expedition on 4March 2004. The project, which used Craig Venter's personal yacht, Sorcerer II, started in Halifax,Canada,circumnavigated the globe and returned to the U.S. in January 2006.[28]

Current workVenter is currently the president of the J. Craig Venter Institute, which conducts research in synthetic biology. InJune 2005, he co-founded Synthetic Genomics, a firm dedicated to using modified microorganisms to produce cleanfuels and biochemicals. In July 2009, ExxonMobil announced a $600 million collaboration with Synthetic Genomicsto research and develop next-generation biofuels.[29]

Venter is a member of the USA Science and Engineering Festival's Advisory Board.[30]

Media coverageVenter has been the subject of articles in several magazines, including Wired,[31] The Economist,[32] Australianscience magazine Cosmos,[33] [34] and The Atlantic.[35] Additionally, he was featured on The Colbert Report on bothFebruary 27, 2007, and October 30, 2007.Venter appeared in the "Evolution" episode of the documentary television series Understanding.On May 16, 2004, Venter gave the commencement speech at Boston University.[36]

In a 2007 interview with New Scientist when asked "Assuming you can make synthetic bacteria, what will you dowith them?", Venter replied:

Over the next 20 years, synthetic genomics is going to become the standard for making anything. Thechemical industry will depend on it. Hopefully, a large part of the energy industry will depend on it. We reallyneed to find an alternative to taking carbon out of the ground, burning it, and putting it into the atmosphere.That is the single biggest contribution I could make.

Furthermore it suggests that one of the main purposes for creating synthetic bacteria would be to reduce thedependence on fossil fuels through bioremediation.[37]

On May 10, 2007, Venter was awarded an honorary doctorate from Arizona State University.,[38] and on October 24of the same year, he received an honorary doctorate from Imperial College London.[39]

He was on the 2007 Time 100 most influential people in the world list made by Time magazine. In 2007 he alsoreceived the Golden Eurydice Award for contributions to Biophilosophy.On September 4, 2007, a team led by Venter published the first complete (six-billion-letter) genome of an individualhuman — Venter's own DNA sequence.[40] When on BBC News on October 22, 2007, when asked about hisreligious view he replied that he thought that a true scientist could not believe in supernatural explanations.On December 4, 2007, Venter gave the Dimbleby lecture for the BBC in London. He outlined his current work andfuture developments in genetics.In February 2008, he gave a speech about his current work at the TED conference.[41]

Venter delivered the 2008 convocation speech for Faculty of Science honours and specialization students at theUniversity of Alberta. A transcription of the speech is available here [42].[43]

Dr. Venter was featured in Time Magazine's "The Top 10 Everything of 2008" article. Number three in 2008's Top10 Scientific Discoveries was a piece outlining his work stitching together the 582,000 base pairs necessary to inventthe genetic information for a whole new bacterium.[44]

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Dr. Venter took part in the inaugural San Diego Science Festival [45] and spoke at its press conference on February26, 2009.On April 6, 2009, Venter gave a speech at Arizona State University as part of the Origins Symposium.For an episode aired on July 27, 2009, Venter was interviewed on his boat by BBC One for the first episode of TVshow Bang Goes the Theory.On May 20, 2010, Venter announced the creation of first self-replicating synthetic bacterial cell.[46]

On November 21, 2010 Steve Kroft profiled J. Craig Venter and his research on 60 minutes.

Individual human genome sequencedOn September 4, 2007, a team led by Sam Levy published the first complete (six-billion-letter) genome of anindividual human—Venter's own DNA sequence.[40] Some of the sequences in Venter's genome are associated withwet earwax,[47] increased risk of antisocial behavior, Alzheimer's and cardiovascular diseases.[48] This publicationwas especially interesting since it contained a diploid instead of a haploid genome and shows promise forpersonalized medicine via genotyping. This genome, rather immodestly dubbed HuRef by Levy et al., was alandmark accomplishment and as of mid-2010 is probably the highest quality personal genome sequence yetcompleted.The Human Reference Genome Browser is a web application for the navigation and analysis of Venter's recentlypublished genome. The HuRef database consists of approximately 32 million DNA reads sequenced usingmicrofluidic Sanger sequencing, assembled into 4,528 scaffolds and 4.1 million DNA variations identified bygenome analysis. These variants include single-nucleotide polymorphisms (SNPs), block substitutions, short andlarge indels, and structural variations like insertions, deletions, inversions and copy number changes.The browser enables scientists to navigate the HuRef genome assembly and sequence variations, and to compare itwith the NCBI human build 36 assembly in the context of the NCBI and Ensembl annotations. The browser providesa comparative view between NCBI and HuRef consensus sequences, the sequence multi-alignment of the HuRefassembly, Ensembl and dbSNP annotations, HuRef variants, and the underlying variant evidence and functionalanalysis. The interface also represents the haplotype blocks from which diploid genome sequence can be inferred andthe relation of variants to gene annotations. The display of variants and gene annotations are linked to external publicresources including dbSNP, Ensembl, Online Mendelian Inheritance in Man (OMIM) and Gene Ontology (GO).Users can search the HuRef genome using HUGO gene names, Ensembl and dbSNP identifiers, HuRef contig orscaffold locations, or NCBI chromosome locations. Users can then easily and quickly browse any genomic regionvia the simple and intuitive pan and zoom controls; furthermore, data relevant to specific loci can be exported forfurther analysis.

Mycoplasma laboratoriumVenter is seeking to patent the first life form created by humanity, possibly to be named Mycoplasmalaboratorium.[49] There is speculation that this line of research could lead to producing bacteria that have beenengineered to perform specific reactions, e.g. produce fuels, make medicines, combat global warming, etc.[50]

In May 2010, a team of scientists led by Venter became the first to successfully create what was described as"synthetic life".[51] [52] This was done by synthesizing a very long DNA molecule containing an entire bacteriumgenome, and introducing this into another cell, analogous to the accomplishment of Eckard Wimmer's group, whosynthesized and ligated an RNA virus genome and "booted" it in cell lysate.[53] The single-celled organism containsfour "watermarks"[54] written into its DNA to identify it as synthetic and to help trace its descendants. Thewatermarks include1. Code table for entire alphabet with punctuations

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2. Names of 46 contributing scientists3. Three quotations4. The web address for the cell.[55]

Selected bibliographyVenter is an ISI highly cited researcher and has authored over 200 publications in scientific journals.[56]

• Fleischmann, Robert D.; Adams, Mark D.; White, Owen; Clayton, Rebecca; . . . Venter, J. Craig (July 28, 1995)."Whole-Genome Random Sequencing and Assembly of Haemophilus influenzae Rd.". Science (Washington, DC:American Association for the Advancement of Science) 269 (5223): 496–512. doi:10.1126/science.7542800.PMID 7542800.

• Tomb, Jean-F.; White, Owen; Kerlavage, Anthony R.; Clayton, Rebecca A.; Sutton, Granger G.; Fleischmann,Robert D.; . . . Venter, J. Craig (August 7, 1997). "The complete genome sequence of the gastric pathogenHelicobacter pylori". Nature (London, England: Nature Publishing Group) 388 (6642): 539–47.doi:10.1038/41483. PMID 9252185.

• Adams, Mark D.; Celniker, Susan E.; Holt, Robert A.; Evans, Cheryl A.; Goccayne, Jeannine A.; Amanatides,Peter G.; . . . Venter, J. Craig (March 24, 2000). "The genome sequence of Drosophila melanogaster". Science(Washington, DC: American Association for the Advancement of Science) 287 (5461): 2185–95.doi:10.1126/science.287.5461.2185. PMID 10731132.

• Venter, J. Craig; et al. (February 16, 2001). "The Sequence of the Human Genome". Science (journal)(Washington, DC: American Association for the Advancement of Science) 291 (5507): 1304–51.doi:10.1126/science.1058040. ISSN 0036-8075. PMID 11181995.

• Venter, J. Craig; Remington, Karin; Heidelberg, John F.; Halpern, Aaron L.; Rusch, Doug; Eisen, Jonathan A.;Wu, Dongying; Paulsen, Ian et al. (April 2, 2004). "Environmental Genome Shotgun Sequencing of the SargassoSea". Science (Washington, DC: American Association for the Advancement of Science) 304 (5667): 66–74.doi:10.1126/science.1093857. PMID 15001713.

• Rusch, Donald B.; Halpern, Aaron L.; Sutton, Granger; Heidelberg, Karla B.; Williamson, Shannon; Yooseph,Shibu; Wu, Dongying; . . . Venter, J. Craig (March 13, 2007). "The Sorcerer II Global Ocean Samplingexpedition: Northwest Atlantic through Eastern Tropical Pacific" [57]. PLoS Biology (Public Library of Science) 5(3): 398–431. doi:10.1371/journal.pbio.0050077. PMID 17355176. PMC 1821060.

• Yooseph, Shibu; Sutton, Granger; Rusch, Donald B.; Halpern, Aaron L.; Williamson, Shannon; Remington,Karin; Eisen, Jonathan A.; . . . Venter, J. Craig (March 13, 2007). "The Sorcerer II Global Ocean SamplingExpedition: Expanding the Universe of Protein Families" [58]. PLoS Biology (Public Library of Science) 5 (3):432–466. doi:10.1371/journal.pbio.0050016. PMID 17355171. PMC 1821046.

• Venter, J. Craig (October 18, 2007). A Life Decoded: My Genome: My Life. New York, New York: Viking Adult.ISBN 0670063584. OCLC 165048736.

References[1] Shreeve, Jamie (October 31, 2005). "The Blueprint Of Life" (http:/ / www. usnews. com/ usnews/ news/ articles/ 051031/ 31genome. htm). .

Retrieved December 6, 2007.[2] Fox, Stuart (May 21, 2010). "J. Craig Venter Institute creates first synthetic life form" (http:/ / www. csmonitor. com/ Science/ 2010/ 0521/ J.

-Craig-Venter-Institute-creates-first-synthetic-life-form). . Retrieved May 21, 2010.[3] http:/ / www. jcvi. org/ cms/ research/ projects/ first-self-replicating-synthetic-bacterial-cell/ overview/[4] "14. Craig Venter - 50 People Who Matter 2010 |" (http:/ / www. newstatesman. com/ global-issues/ 2010/ 09/ gene-genius-craig-venter-life).

New Statesman. . Retrieved 21 October 2010.[5] Venter, J. Craig. (2007-11-19). Authors@Google: J. Craig Venter (http:/ / www. youtube. com/ watch?v=bqRJL7PveWs#t=1m40s). United

States. Event occurs at 1:40-2:25. .[6] J. Craig Venter (2007). "Introduction" (http:/ / www. npr. org/ templates/ story/ story. php?storyId=16004438). A Life Decoded.

ISBN 9780670063581. OCLC 165048736. . "For many years I have been trying to make sense and meaning out of the lives I saw destroyed or

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maimed due to the government policies that involved us in the war in Vietnam."[7] Ward, Logan (2010-11). "Breakthrough Awards 2010: Pioneering New Life" (Print). Popular Mechanics 187 (11): 62–5.[8] Ross Douthat (January/February 2007). "The God of Small Things" (http:/ / www. theatlantic. com/ magazine/ archive/ 2007/ 01/

the-god-of-small-things/ 5556/ ). Atlantic Magazine. . Retrieved 2011-01-28.[9] 'Artificial life' breakthrough announced by scientists, BBC, 21 May 2010. http:/ / news. bbc. co. uk/ 2/ hi/ science_and_environment/

10138849. stm[10] "Craig Venter Takes Aim at the Big Questions" (http:/ / archive. sciencewatch. com/ sept-oct97/ sw_sep-oct97_page3. htm). ScienceWatch 8

(5). September/October 1997. . Retrieved June 7, 2009.[11] Rae-Venter Law Group (http:/ / www. rae-venterlaw. com/ who. htm)[12] "The god of small things" (http:/ / www. smh. com. au/ news/ science/ the-god-of-small-things/ 2007/ 01/ 25/ 1169594430068.

html?page=fullpage). The Sydney Morning Herald. January 26, 2007. .[13] http:/ / people. famouswhy. com/ craig_venter/[14] http:/ / www. nndb. com/ people/ 832/ 000163343/[15] Wadman, Meredith (May 2007). "High-profile departure ends genome institute's charmed run". Nature Medicine 13 (5): 518.

doi:10.1038/nm1594. PMID 17479082.[16] Roberts, Leslie (October 11, 1991). "Genome patent fight erupts: an NIH plan to patent thousands of random DNA sequences will

discourage industrial investment and undercut the Genome Project itself, the plan's critics charge.". Science 254 (5029): 184–186.doi:10.1126/science.1925568.

[17] "Patent Law—Utility—Federal Circuit holds that expressed sequence tags lack substantial and specific utility unless underlying genefunction is identified.—In re Fisher, 421 F.3d 1365 (Fed. Cir. 2005)." (http:/ / www. harvardlawreview. org/ issues/ 119/ june06/recent_cases/ in_re_fisher. pdf). Harvard Law Review 119 (8): 2604–2611. 2006. .

[18] Weber, James L.; Myers, Eugene W. (1997). "Human Whole-Genome Shotgun Sequencing" (http:/ / genome. cshlp. org/ content/ 7/ 5/ 401.full). Genome Research 7 (5): 401–409. doi:10.1101/gr.7.5.401 (inactive 2010-05-20). PMID 9149936. .

[19] Green, Philip (1997). "Against a Whole-Genome Shotgun" (http:/ / genome. cshlp. org/ content/ 7/ 5/ 410. full). Genome Research 7 (5):410–417. doi:10.1101/gr.7.5.410 (inactive 2010-05-20). PMID 9149937. .

[20] See Victor McElheny, Drawing the Map of Life: Inside the Human Genome Project, New York, Basic Books, 2010. ISBN978-0-465-04333-0

[21] Shreeve, Jamie (October 31, 2005). "The Blueprint of Life" (http:/ / www. usnews. com/ usnews/ news/ articles/ 051031/ 31genome. htm).U.S. News and World Report. . Retrieved January 30, 2007.

[22] "Montgomery County, Maryland Government (December 19, 2000). "Time Magazine Dubs Montgomery County "DNA Alley"" (http:/ /www. montgomerycountymd. gov/ mc/ news/ press/ 00-463. html). Press release. . Retrieved January 30, 2007.

[23] Others, J. Craig; Adams, Mark D.; Myers, Eugene W.; Li, Peter W.; Mural, Richard J.; Sutton, Granger G.; Smith, Hamilton O.; Yandell,Mark et al. (2001). "The Sequence of the Human Genome". Science 291 (5507): 1304–1351. doi:10.1126/science.1058040. PMID 11181995.

[24] Others, E.S.; Linton, L.M.; Birren, B.; Nusbaum, C.; Zody, M.C.; Baldwin, J.; Devon, K.; Dewar, K. et al. (2001). "International HumanGenome Sequencing Consortium (2001) Initial sequencing and analysis of the human …". Nature 409 (6822): 860–921.doi:10.1038/35057062. PMID 11237011.

[25] Olson, M.V. (2002). "The Human Genome Project: A Player's Perspective" (http:/ / www. sciencedirect. com/ science?_ob=ArticleURL&_udi=B6WK7-462733V-D& _user=10& _rdoc=1& _fmt=& _orig=search& _sort=d& _docanchor=& view=c& _acct=C000050221&_version=1& _urlVersion=0& _userid=10& md5=2756b52b46093f7dbc0b492540267ac6). Journal of Molecular Biology 319 (4): 931–942.doi:10.1016/S0022-2836(02)00333-9. PMID 12079320. .

[26] Singer, Emily (September 4, 2007). "Technology Review" (http:/ / www. technologyreview. com/ biomedicine/ 19328/ ?a=f). Technologyreview. . Retrieved May 25, 2010.

[27] Regalo, Antonio (July 24, 2005). "Maverick biologist at work on next goal: creating life". Seattle Times.[28] Larkman, Kirell (September 7, 2007). "Yacht for Sale: Suited for Sailing, Surfing, and Seaborne Metagenomics". GenomeWeb.com

(GenomeWeb News).[29] Howell, Katie (July 14, 2009). "Exxon Sinks $600M Into Algae-Based Biofuels in Major Strategy Shift" (http:/ / www. nytimes. com/

gwire/ 2009/ 07/ 14/ 14greenwire-exxon-sinks-600m-into-algae-based-biofuels-in-33562. html). NYTimes.com (New York Times). .[30] http:/ / www. usasciencefestival. org/ about/ advisors retrieved 2010-07-05[31] Shreeve, James. " Craig Venter's Epic Voyage to Redefine the Origin of the Species (http:/ / www. wired. com/ wired/ archive/ 12. 08/

venter. html)," Wired, August 2004. Accessed June 7, 2007.[32] "The Journey of the Sorcerer", The Economist, December 4, 2004.[33] First individual person's genome decoded (http:/ / www. cosmosmagazine. com/ node/ 1561) - Cosmos Magazine. September 4, 2007.[34] Geneticists on verge of creating artificial life (http:/ / www. cosmosmagazine. com/ node/ 1642) - Cosmos Magazine. October 8, 2007.[35] Douthat, Ross. "The God of Small Things," The Atlantic, Jan/Feb 2007.[36] Warren, Jessica. April 30: Genome scientist to speak at Commencement (http:/ / www. dailyfreepress. com/ news/

april-30-genome-scientist-to-speak-at-commencement-1. 932055), The Daily Free Press, April 28, 2004. Accessed August 2, 2008.[37] Aldhous, Peter (2007). "Interview: DNA's messengers". New Scientist (2626): 57.[38] Aufrett, Sarah. "ASU Celebrates Spring Graduates" (http:/ / asunews. asu. edu/ stories/ 200705/ 20070511_grad. htm), ASU Insight, May 11,

2007. Accessed June 7, 2007.

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[39] "Honorary degrees awarded to Browne, Venter and Rausing" (http:/ / www3. imperial. ac. uk/ newsandeventspggrp/ imperialcollege/newssummary/ news_24-10-2007-11-2-43), Imperial College, October 24, 2007. Accessed May 21, 2010.

[40] Levy S, Sutton G, Ng PC, Feuk L, Halpern AL, et al. (2007). "The Diploid Genome Sequence of an Individual Human" (http:/ / www.plosbiology. org/ article/ info:doi/ 10. 1371/ journal. pbio. 0050254). PLoS Biology 5 (10): e254. doi:10.1371/journal.pbio.0050254.PMID 17803354. PMC 1964779. .

[41] TED | Talks | Craig Venter: On the verge of creating synthetic life (video) (http:/ / www. ted. com/ talks/craig_venter_is_on_the_verge_of_creating_synthetic_life. html)

[42] http:/ / venter2008conv. jottit. com/[43] Brown, M.: "Genomics leader accepts U of A honorary degree" (http:/ / www. expressnews. ualberta. ca/ article. cfm?id=9399), "UofA

ExpressNews"; retrieved on June 7, 2009.[44] "The Top 10 Everything Of 2008" (http:/ / www. time. com/ time/ specials/ 2008/ top10/ article/ 0,30583,1855948_1863947,00. html). Time.

November 3, 2008. . Retrieved April 30, 2010.[45] http:/ / mysdscience. com/[46] http:/ / www. ted. com/ talks/ lang/ eng/ craig_venter_unveils_synthetic_life. html[47] Omim - Ear Wax, Wet/Dry (http:/ / www. ncbi. nlm. nih. gov/ entrez/ dispomim. cgi?id=117800)[48] Venter, J.C. (2007). A Life Decoded. New York: Viking. ISBN 978-0-670-06358-1.[49] Regalado, Antonio (June 29, 2005). "Biologist Venter aims to create life from scratch" (http:/ / www. post-gazette. com/ pg/ 05180/ 530330.

stm). Pittsburgh Post-Gazette. .[50] Highfield, Roger (June 8, 2007). "Man-made microbe 'to create endless biofuel'" (http:/ / www. telegraph. co. uk/ news/ uknews/ 1553919/

Man-made-microbe-to-create-endless-biofuel. html). The Daily Telegraph (London). . Retrieved April 30, 2010.[51] Gibson, DG; Glass, JI; Lartigue, C; Noskov, VN; Chuang, RY; Algire, MA; Benders, GA; Montague, MG et al. (2010). "Creation of a

Bacterial Cell Controlled by a Chemically Synthesized Genome." (http:/ / www. sciencemag. org/ cgi/ content/ abstract/ science. 1190719).Science (Science (journal)) 329 (5987): 52–6. doi:10.1126/science.1190719. PMID 20488990. .

[52] "Scientists Create First Self-Replicating Synthetic Life" (http:/ / www. wired. com/ wiredscience/ 2010/ 05/scientists-create-first-self-replicating-synthetic-life/ ). .

[53] . 27. December 2009. pp. 1163–72. doi:10.1038/nbt.1593. PMID 20010599.[54] Using Arc to decode Venter's secret DNA watermark by Ken Shirriff (http:/ / www. arcfn. com/ 2010/ 06/

using-arc-to-decode-venters-secret-dna. html)[55] Sample, Ian (May 20, 2010). "Craig Venter creates synthetic life form" (http:/ / www. guardian. co. uk/ science/ 2010/ may/ 20/

craig-venter-synthetic-life-form). The Guardian (London). .[56] "Venter, J. Craig" (http:/ / hcr3. isiknowledge. com/ author. cgi?& link1=Browse& link2=Results& id=770) (restricted access).

ISIHighlyCited.com. August 19, 2003. . Retrieved October 17, 2009.[57] http:/ / www. pubmedcentral. nih. gov/ articlerender. fcgi?tool=pmcentrez& artid=1821060[58] http:/ / www. pubmedcentral. nih. gov/ articlerender. fcgi?tool=pmcentrez& artid=1821046

Further reading• Ewing-Duncan, David (2006). Masterminds: Genius, DNA, and the Quest to Rewrite Life. New York, New York:

Harper Perennial. ISBN 9780007161843.• Shreeve, James (2004). The Genome War: How Craig Venter Tried to Capture the Code of Life and Save the

World. New York, New York: Alfred A. Knopf. ISBN 0375406298.• Spufford, Francis (2003). The Backroom Boys: The Secret Return of the British Boffin. London, England: Faber.

ISBN 0571214975.• Sulston, John (2002). The Common Thread: A Story of Science, Politics, Ethics and the Human Genome.

Washington, DC, USA: Joseph Henry Press. ISBN 0309084091.

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External links• J. Craig Venter Institute (http:/ / www. jcvi. org/ )• Sorcerer II Expedition (http:/ / www. sorcerer2expedition. org/ version1/ HTML/ main. htm)• Synthetic Genomics (http:/ / www. syntheticgenomics. com/ )• The Institute for Genomic Research (TIGR) (http:/ / www. jcvi. org)• HuRef Genome Browser (http:/ / huref. jcvi. org)

Media• Craig Venter (http:/ / www. charlierose. com/ guest/ view/ 81) on Charlie Rose• Cracking the code to life (http:/ / www. guardian. co. uk/ science/ 2007/ oct/ 08/ genetics. scienceandnature), The

Guardian, October 8, 2007• Craig Venter interview (http:/ / www. pbs. org/ kcet/ wiredscience/ video/ 289-craig_venter. html), Wired

Science, December 2007 (video)• Radio interview (http:/ / philosophytalk. org/ pastShows/ Genomics. html) on Philosophy Talk• Video of interview/discussion with Craig Venter (http:/ / bloggingheads. tv/ diavlogs/ 398) by Carl Zimmer on

Bloggingheads.tv• Craig Venter: A voyage of DNA, genes and the sea (http:/ / www. youtube. com/ watch?v=E5X6Qy772YU) -

TED (Technology Entertainment Design) conference (video)• Webcast of Venter talk 'Genomics: From humans to the environment' (http:/ / www. 21school. ox. ac. uk/ video/

200710_venter. cfm) at The James Martin 21st Century School• The Richard Dimbleby Lecture 2007 - Dr. J. Craig Venter - A DNA Driven World (http:/ / video. google. com/

videoplay?docid=4893602463025557866)• A short course on synthetic genomics. Edge Master Class 2009 (http:/ / www. edge. org/ 3rd_culture/

church_venter09/ church_venter09_index. html)• Craig Venter: On the Verge of Creating Synthetic Life (http:/ / www. ted. com/ talks/

craig_venter_is_on_the_verge_of_creating_synthetic_life. html) - TED (Technology Entertainment Design)conference (video)

• Craig Venter unveils "synthetic life" (http:/ / www. ted. com/ talks/ craig_venter_unveils_synthetic_life. html) -TED (Technology Entertainment Design) conference (video)

• " J. Craig Venter: Designing Life (http:/ / www. cbs. com/ primetime/ 60_minutes/ )". 60 Minutes. CBS.2010-11-21.

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Article Sources and Contributors 21

Article Sources and ContributorsMycoplasma laboratorium  Source: http://en.wikipedia.org/w/index.php?oldid=413469038  Contributors: Adventhesis, Aircorn, Alison, Andy120290, Antony-22, AxelBoldt, Craigboy, Dlungo,Drsamir, Elconejo, Enzino, Evercat, Flakinho, GoingBatty, Grundle2600, JWSchmidt, Jakobkennedy, Kleopatra, Kubiak200, Marshallsumter, Mgiganteus1, Ragesoss, Sabedon, Sasata, Serpent'sChoice, Smartse, Sophos II, Soporaeternus, Squidonius, Velho, Wasell, Yellowdesk, АлександрВв, 33 anonymous edits

Mycoplasma  Source: http://en.wikipedia.org/w/index.php?oldid=410152509  Contributors: A-Day, Adeliine, Alansohn, Anna Frodesiak, Aranel, Arcadian, Bob Blaylock, Bobblewik, Bobo192,Can't sleep, clown will eat me, CanisRufus, ChyranandChloe, Cnairne, Cst17, D99figge, DO11.10, Danierrr, Dianamirkin, Discospinster, Doagie, Doseiai2, Esowteric, Excirial, Fanghong,Fivemack, Fram, Gould363, Gruntmonk, Haham hanuka, Happymercury, Ilikeeatingwaffles, IvanShim, JWSchmidt, Jason Quinn, Jimquinlan, Josh Grosse, Lavateraguy, Lightmouse, MER-C,Mani1, MarcoTolo, Mathias71, Mboverload, Mburger, Mdsam2, Metallion, Mgiganteus1, MicroProf, Million Moments, Mre 888, My Core Competency is Competency, NebuchadnezzarN,NewEnglandYankee, Nickptar, Occamsrazorwit, Ogrinus, OlavN, Onco p53, PancakesMan, Peter G Werner, Pkaz, Renice, Rich Farmbrough, RitRat, Rjwilmsi, Rmosler2100, Robwaldo,Ronsword, Sabedon, Seglea, ShadowRangerRIT, Shirulashem, Sournick3, Squidonius, TeamZissou, TimVickers, Una Smith, Wickey-nl, 91 anonymous edits

Craig Venter  Source: http://en.wikipedia.org/w/index.php?oldid=413963400  Contributors: * and Obelisk, 123kevin123, A5db26od, AManWithNoPlan, Abhishikt, Acampbell70, Adammajewski, Ahimsa52, Airplaneman, Aitias, Akriasas, Alansohn, Albertmost, Alexf, Alison, All Hallow's Wraith, Allissonn, AlphaEta, AmigoNico, Anaxial, Andrew c, Andrewdt85, Andycjp,Anna Frodesiak, Antony-22, Apokrif, Aufidius, Avb, Avono, BrightBlackHeaven, Brossow, Bryan Derksen, Bueller 007, Caldwa, CanadianCaesar, CanisRufus, CapitalR, Cardsplayer4life,Cariaso, Centralhawk3, Chase me ladies, I'm the Cavalry, Chenzw, ConfusedVorlon, Conversion script, Cthunter01, D rholambda, D6, Da monster under your bed, Dane Sorensen, David fromDownunder, Demophon, Dismas, Dj123wind, DoctorDNA, Dogah, EdBever, Eep², Elencalime, Enzino, Episiarch, Eric Brummer, Erkcan, Esteban Zissou, Etacar11, Everard Proudfoot, Evilsaltine, Famousdog, FastLizard4, Favonian, Fingerz, Fishwristwatch, Flatterworld, Flex, Florentino floro, Frasor, Frzl, Gcm, GhanaDa, Giftlite, Good Olfactory, Graham, GregorB, Hakan Kayı,Hans Dunkelberg, Happysailor, Hgilbert, Hohanyao, Htanna, IALTO, II MusLiM HyBRiD II, Idyll M, Infliv, J-stan, Javaweb, Jigorou, Jmichaelrosenberg, JohnnyGerms, Johntex, Jonas AGX,Jonathan B, Julia Rossi, Jusdafax, Jwillbur, Jxramos, Katharineamy, Kazkaskazkasako, Kirachinmoku, Kpjas, Kringz, Kumioko, LaurenRueda, Lexor, Lfstevens, Linmhall, Llull, Lofhlou,Loremaster, Lumos3, Macrakis, Malcolmxl5, Manway, Marcolop, Masparasol, Masterpiece2000, Metsfanmax, Mgalle, Mhardcastle, MichaelJanich, Miguel Andrade, Mwng, Myasuda, Naddy,Nerak99, Nickjacksonza, Niharikatandon, Nihil novi, Nishkid64, Nobunaga24, Nomad, Nono64, Nymf, OldRightist, Ombudswiki, Outreachscientist, PDH, Pb30, Peter G Werner, PeterH2,Pgr94, PhilKnight, Philip Trueman, Phollands, Physicistjedi, Pinktulip, Plindenbaum, Plumbago, Prowsej, RNAgirl, Ragesoss, Rainer Wasserfuhr, Raj2004, Rajah, Rangline, Ras, Raudys,RedAndr, Remember, Rich Farmbrough, Richard Arthur Norton (1958- ), Richard001, Rjwilmsi, Rl, Robbie098, Robinatron, Ruralgirl, Rwmacleod, SDC, Saintrain, Salmon78, Sarbruis,Seaphoto, SergeyKurdakov, Sfmammamia, Sgb235, Sharmistha1, Shawnc, ShelfSkewed, Skepticsteve, Skittleys, Skomorokh, Slixi, Snowmanradio, Snowolf, Soporaeternus, Spencergreenwood,Sq327, Srlasky, Sterichinderance, Suomi Finland 2009, Tangent747, TheRealNightRider, Tom harrison, TreasuryTag, UDScott, USNews, VK35, Versus22, Vespristiano, Vigeesh, WAS 4.250,Wcoenen, Whizzball, Wolbo, Wuhwuzdat, YUL89YYZ, YowiePower, ZephyrAnycon, Zero Gravity, Zigzig20s, ZimZalaBim, Zipzipzip, Zondi, 282 ,کشرز anonymous edits

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Image Sources, Licenses and Contributors 22

Image Sources, Licenses and ContributorsImage:Craigventer2.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Craigventer2.jpg  License: unknown  Contributors: Article by Liza Gross, but no photo credit given

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License 23

LicenseCreative Commons Attribution-Share Alike 3.0 Unportedhttp:/ / creativecommons. org/ licenses/ by-sa/ 3. 0/