nature and artifice: a reflection on domestication and gmosadanchin/.../gmos06_final.pdf ·...
TRANSCRIPT
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
Nature and Artifice:A reflection on
domestication and GMOs
Ambassade de France, Copenhagen23 november 2006
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
Take home message
Culture, not Nature, is the hallmark of humanity
Culture differentiates Man from Nature Initially, humans protect Nature against humans (« Tristes tropiques »
C. Lévy-Strauss); Artifice is still perceived as dangerous Nature has no purpose, it is not friendly, but needs to be tamed Domestication of plants and animals marks humanisation, starting the
Neolithic Age GMOs are the latest avatar of domestication The fear of Artifice leads to the dangerous thought that plant GMOs are
dangerous while animal GMOs are safe Often, going to Artifice is safer
The next revolution will be synthetic biology
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
A few dates 200,000-100,000 BP Birth of Homo sapiens ssp. Sapiens 17,000-12,000 BP Domestication of dog (Canis canis) 12,000 BP Domestication of fermentation microbes (lactobacilli and fungi) 10,000-9,000 BP Domestication of rice (Oryza sativa) and wheat (Triticum
aestivum) 10,000 BP Domestication of cattle (Bos taurus) 9,500 BP Domestigation of pig (Sus scrofa) 9,000 BP Domestication of maize (Zea mays ssp. Parviglumis) 6,000 BP Domestication of horse (Equus caballus) 5,000 BP Domestication of silkworm (Bombyx mori)
-------------------------------------------------------------------------------------------------------- 1764 Kolreuter fertilizes plants artificially 1866 Mendel establishes the first laws of genetics 1940-1960 The Green Revolution (maize and wheat breeding, irrigation, fertilizer,
and seed development based on irradiation and chemical mutagenesis) 1973 The first bacterial GMO 1984 The first transgenic mice 1987 Quantitative Trait Loci are used to speed up selection of crop seeds 1994 The first GMO food reaches the food market
1800 1 billion1928 2 billion1961 3 billion1974 4 billion
1987 5 billion1999 6 billion
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
What life is Living and computing Biological information Genetically Modified Organisms
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
Three processes make life:
Information transfer => genomics decyphers the programmeassociated to the cell
Forces coupling the genome structure to the structure of the cell:
MetabolismCompartmentalisation
The cell is the atom of life, with two compartmentalisation strategies: asimple envelope (bacteria...), or the multiplication of membranes and skins(plants and animals...)
What life is
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
Information transfermanipulates strings of
symbols
Replication (law: “complementarity”)
Transcription (law: “complementarity”)
Translation (law: a cypher, the “genetic code”)
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
Deoxyribonucleic acid (DNA) stores the memory of the geneticprogramme. It chains four types of basic building blocks. Twostrands are intertwined, making a double helix.
Informationtransfer
....GCGGTATTTTGATGGAGTTATACGGAAGGGATGTTC....
....CGCCATAAAACTACCTCAATATGCCTTCCCTACAAG....
Remarkably, the genome programme reads like a text:
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
DNA
A => T
C => G
T => A
G => C
Complementarity:DNA replication
=>
<=
The text of one half ofthe helix entirelyspecifies the text ofthe other half, as thepositive and negativeviews of a photographspecify each other
Errors resultin evolution
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
5’
5’5’
3’
3’
3’
3’
3’
5’
5’leading lagging
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
The objects of the cellfactory
The factory readsa « magnetictape » DNA,which chainsfour types ofchemicals, notedA, T, C and G,the bases.
The machine is enclosed in a solidcasing, the membrane (connectingthe inside with the outside) andsmall « heads » read the messageand transform it into activecomponent, the proteins. Theproteins are also chains ofstandard chemicals, of twentytypes, the amino acids.
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
From the geneticprogramme to the cell
When the machine readsthe programme, itperforms actions. Aspecial machinery readsthe DNA and copies itinto active objets, theproteins (enzymes
are proteins).
DNA
protein
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
The genetic code
Only meaningful parts of the four-letter DNA text(genes) are translated into a twenty letters text,the text of a protein. The cypher driving thecorrespondence is named the genetic code.
For example “ TCA ” in DNA means “ S ” (achemical residue, “Serine”, among the twentyamino acid types) in the protein.
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
The cell factory
A cell looks like acomputer whichwould programmethe construction ofsimilar computers
It has a magnetic tape,or hard disk (the« genetic programme »)and reading deviceswhich allow it to readthe programme and putit into action
The « cloning » of the ewe Dolly performed thataction: moving the programme from a machine (acell) to another one (an egg without a nucleus)
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
What life is Living and computing Biological information Genetically Modified Organisms
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
Information Transfer
As for building up a machine, one needs a bookof recipe to build up a cell.
This construction changes the text of the recipeinto something concrete: this transfers« information ».
In a cell, information transfer is managed by thegenetic programme
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
Context: the “geneticprogramme”
Physics: matter, energy, timeStatistical physics: Physics + informationBiology: Physics + information, coding, control...Arithmetics: sequences of integers, recursivity,coding…Computation: Arithmetics + programmes +machine...
The « genetic programme » metaphor has practicalconsequences: we know how to manipulate genes andgene products, can we push the metaphor to its ultimateconsequences?
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
A genetic computer
In a computer the machine is separatedfrom the data and the programme
Data and programme play the samerole (i.e. they can be thought of as‘ declarations ’)
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
Two processes are needed for computing:
A machine able to read and write
A programme on a physical support (a perforated ormagnetic tape illustrates the sequence of symbols thatmake the programme), split (in practice, but notconceptually) into two entities :
Programme (providing the goal)Data (providing the context)
The machine is distinct from the programme
What is computing?
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
Cells and computersGenetics describes genomes as texts written with a four letter
alphabet: do cells behave as computers?
Horizontal Gene TransferVirusesGenetic engineeringAnimal cloning
all points to separation between
« Machine » (the cell factory)andData + programme
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The Turing machine
programme(data)in the formof a linearsequenceof symbols
machine(read/write)
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An algorithmic view ofbiological actions
Replication, transcription, translation: high parallelism
“Begin, Repeat, Check Points, End”
The action is always oriented, with a beginning and an end
The processes of time control (check points) are essentialto allow coordination of multiple actions in parallel
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
What life is Living and computing Biological information Genetically Modified Organisms
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
Three types ofinformation
Biology is an abstract science (!) and you need toprepare to make a considerable effort of abstractionto understand it
Information is at its core, but what is information?
Three types of information (not exhaustive!):
1. Shannon’s information (Shannon’s entropy)2. Algorithmic complexity3. Logical depth4. Critical depth
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
Shannon’s entropy (1)The information in a string of symbols (a sequence) can be
appreciated by some measure of the probability of occurrence ofparticular motifs
A commonplace description of genome sequences calls « entropy » theinformation of the sequence, assuming that life is a fight againstentropy: both are wrong assignments
Caveat: Myron Tribus relates that von Neumann, to whom Shannonhad turned to help him find a name for his information, proposedprophetically: “You should call it entropy for two reasons. In thefirst place your uncertainty function has been used in statisticalmechanics under that name, so it already has a name. In thesecond place, and more important, no one knows what entropyreally is, so in a debate you will always have the advantage”, thusopening a Pandora’s box of intellectual confusion.
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Shannon’s probability law is similar to that writtenon the grave of Ludwig Bolzmann. This is thesource of enormous confusion
H(pi) = – Σ {pi log2 pi | i ∈ I }
The validity of this formula rests on very stronghypotheses about the nature of the signals (forexample, the signals should fit standard Laplace-Gauss probability laws)
Shannon’s entropy (2)
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Algorithmiccomplexity
Shannon’s « entropy » does not care about the meaning ofa sequence (it can represent replication, however)
Algorithmic complexity is the length of the shortestprogramme needed to generate the sequence. A sequenceis random if it cannot be described by a programme with alength shorter than the sequence (Kolmogorov and others);e.g. 0101010101... has a low complexity
Bacterial genomes look « random »; plant and animalgenomes look « repeated » => both look « uninteresting »!
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
Unexpected propertiesof strings of symbols
The DNA « text » can be considered as a string ofsymbolsStrings can play the role of « programmes » withremarkable properties (e.g. when « recursive », i.e.calling themselves as routines). A machine run by arecursive programme usually does not have standardmechanistic (i.e. predictable) properties
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Logical Depth (1)
A very short programme (low algorithmic complexity)can describe a repeated sequence (trivial), but also afractal figure such as Koch’s snowflake: as shown in thefigure, this is a stepwise process, asking for time to beintroduced into the concept of information
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Logical Depth (2)
The consequence of logical depth is that, when aprogramme is complicated enough (branching andrecursive), it becomes impossible to predict its outcome.The only way to know it is to run the programme…
Evolution has evolved DNA from DNA, from DNA... insuch a way that every single base has a certain « depth »,that makes that living organisms are, in principle and byconstruction, poised to be ultimately unpredictable…
This allows them to create some progeny that cansurvive in an unpredictable future.
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
What life is Living and computing Biological information Genetically Modified Organisms
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
A general constraint hinderingengineering: evolution
Variation / Selection / Amplification Stabilisation
Evolution creates
Function capture (recruits)
Structure codes
Sequence
5
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Plant GMOs: improving cropyields and product quality
After Kolreuter fertilized plants, Mendel found how characters areinherited, starting the first green revolution. Crosses between variantspermitted screening for new breedsPlants are mutagenized (often irradiation) to produce more variantsVariants are unpredictable. Together with « useful » mutations theycarry many other mutations, often deleterious, requiring a long selectionprocess to obtain the required plantsGenetic engineering modifies only one, or a small number oftargeted genes, directly going to the desired properties. GMOs are morepredictable than mutants obtained by the more traditional (alsoartificial!) approachesGenetic engineering aims at stabilizing the phenotype: this goes againstthe ability of plants to evolve. Hence, GMOs are less fit to the non-humanized (wild) environment
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
Animal GMOs:humanisation of organs
The initial goal of animal GMOs was similar to that of plant GMOs,improving quality of animal products, or using the animal as a factoryInterest for health care created a new Unmet Need, associated tophylogenetic proximity between animals and humans: using GMOs asproviding tissue substitutes.Humanizing organs is widely accepted by the public, despite itsobvious danger:
Animal tissues contain retrovirusesEmerging diseases are often caused by transfer from animals tohumans (eg HIV, SARS, Hantah etc)
Nature is preadapted through evolution, it canbe more dangerous in principle than Artifice
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Nature and Artifice
Biological adaptation is the easier, the closer the organismfrom humansComing from Humans, human blood is dangerousNatural processes are more difficult to control than artificialprocessesProgress in applications of biological knowledge is linkedto increasing our control over the processes, i.e. gettingever more artificial, e.g. inventing efficient artificial bloodwould be an immense progress (cf HIV, BSE, Hepatitis,etc)Future progresses will go to « synthetic biology », wherethe evolution potential of artificial organisms will be lower
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
Caveat:The Delphic Boat
We spoke of isolatedgenesBut genes do not operatein isolation!Proteins are part ofcomplexes, as are partsin an engineIt is important tounderstand theirrelationships, as those inthe planks which make aboat
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Genetics of Bacterial Genomeshttp://www.pasteur.fr/recherche/unites/REG/ [email protected]
Thank you