Natural genetic engineering (NGE) is a class of process proposed by molecular biologist James A. Shapiro to account for novelty created in the course of biological evolution. Shapiro developed this work in several peer-reviewed publications from 1992 onwards, and later in his 2011 book ''Evolution: A View from the 21st Century'', which has been updated with a second edition in 2022. He uses NGE to account for several proposed counterexamples to the central dogma of molecular biology (Francis Crick's proposal of 1957 that the direction of the flow of sequence information is only from nucleic acid to proteins, and never the reverse). Shapiro drew from work as diverse as the adaptivity of the mammalian immune system,

ciliate The ciliates are a group of alveolates characterized by the presence of hair-like organelles called cilia, which are identical in structure to eukaryotic flagella, but are in general shorter and present in much larger numbers, with a differen ...

macronuclei A macronucleus (formerly also meganucleus) is the larger type of nucleus in ciliates. Macronuclei are polyploid and undergo direct division without mitosis. It controls the non-reproductive cell functions, such as metabolism. During conjugation, t ...

and

epigenetics In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are ...

. The work gained some measure of notoriety after being championed by proponents of

Intelligent Design Intelligent design (ID) is a pseudoscientific argument for the existence of God, presented by its proponents as "an evidence-based scientific theory about life's origins". Numbers 2006, p. 373; " Dcaptured headlines for its bold attempt to ...

, despite Shapiro's explicit repudiation of that movement.

Concept

Shapiro first laid out his ideas of natural genetic engineering in 1992 and has continued to develop them in both the primary scientific literature and in work directed to wider audiences, culminating in the 2011 publication of ''Evolution: A View from the 21st Century'' (second edition in 2022.). Natural genetic engineering is a reaction against the

modern synthesis Modern synthesis or modern evolutionary synthesis refers to several perspectives on evolutionary biology, namely: * Modern synthesis (20th century), the term coined by Julian Huxley in 1942 to denote the synthesis between Mendelian genetics and s ...

and the central dogma of molecular biology. The modern synthesis was formulated before the elucidation of the double-helix structure of DNA and the establishment of

molecular biology Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...

in its current status of prominence. Given what was known at the time a simple, powerful model of genetic change through undirected mutation (loosely described as "

random In common usage, randomness is the apparent or actual lack of pattern or predictability in events. A random sequence of events, symbols or steps often has no order and does not follow an intelligible pattern or combination. Individual ra ...

") and natural selection, was seen as sufficient to explain evolution as observed in nature. With the discovery of the nature and roles of nucleic acids in genetics, this model prompted Francis Crick's so-called Central Dogma of Molecular Biology: " equentialinformation cannot be transferred back from protein to either protein or nucleic acid."Crick, F.H.C. (1958)
On Protein Synthesis.
Symp. Soc. Exp. Biol. XII, 139-163. (pdf, early draft of original article) Shapiro points out that multiple cellular systems can affect DNA in response to specific environmental stimuli. These "directed" changes stand in contrast to both the undirected mutations in the modern synthesis and (in Shapiro's interpretation) the ban on information flowing from the environment into the genome. In the 1992 '' Genetica'' paper that introduced the concept, Shapiro begins by listing three lessons from molecular genetics: * there is a surprising amount of genetic conservation across taxonomic boundaries, * the mosaic structure of the genome results in multiple nonlocal genes having multiple phylogenic effects, and, drawing on the work of his friend and collaborator Barbara McClintock, * the existence of multiple cellular mechanisms (including

mobile genetic elements Mobile genetic elements (MGEs) sometimes called selfish genetic elements are a type of genetic material that can move around within a genome, or that can be transferred from one species or replicon to another. MGEs are found in all organisms. In ...

) that can restructure DNA. From these, Shapiro concludes:

can be argued that much of genome change in evolution results from a genetic engineering process utilizing the biochemical systems for mobilizing and reorganizing DNA structures present in living cells.

Relation with Intelligent Design

In a 1997

Boston Review ''Boston Review'' is an American quarterly political and literary magazine. It publishes political, social, and historical analysis, literary and cultural criticism, book reviews, fiction, and poetry, both online and in print. Its signature form ...

article, Shapiro lists four categories of discoveries made in molecular biology that, in his estimation, are not adequately accounted for by the

Modern Synthesis Modern synthesis or modern evolutionary synthesis refers to several perspectives on evolutionary biology, namely: * Modern synthesis (20th century), the term coined by Julian Huxley in 1942 to denote the synthesis between Mendelian genetics and s ...

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding g ...

organization, cellular repair capabilities,

and cellular information processing. Shapiro concludes:

What significance does an emerging interface between biology and information science hold for thinking about evolution? It opens up the possibility of addressing scientifically rather than ideologically the central issue so hotly contested by fundamentalists on both sides of the Creationist-Darwinist debate: Is there any guiding intelligence at work in the origin of species displaying exquisite adaptations that range from lambda prophage repression and the Krebs cycle through the mitotic apparatus and the eye to the immune system, mimicry, and social organization?

Within the context of the article in particular and Shapiro's work on Natural Genetic Engineering in general, the "guiding intelligence" is to be found within the cell. (For example, in a Huffington Post essay entitle
Cell Cognition and Cell Decision-Making
ref name="Shapiro 2012a" /> Shapiro defines cognitive actions as those that are "knowledge-based and involve decisions appropriate to acquired information," arguing that cells meet this criteria.) However, the combination of disagreement with the Modern Synthesis and discussion of a creative intelligence has brought his work to the attention of advocates of

. Natural genetic engineering has been cited as a legitimate scientific controversy (in contrast to the controversies raised by various branches of creationism). While Shapiro considers the questions raised by Intelligent Design to be interesting, he parts ways with creationists by considering these problems to be scientifically tractable (specifically by understanding how NGE plays a role in the evolution of novelty). With the publication of ''Evolution: A View from the 21st Century'', Shapiro's work again came under discussion in the Intelligent design community. In a conversation with Shapiro,

William Dembski William Albert Dembski (born July 18, 1960) is an American mathematician, philosopher and theologian. He was a proponent of intelligent design (ID) pseudoscience, specifically the concept of specified complexity, and was a senior fellow of the ...

asked for Shapiro's thoughts on the origins of natural genetic engineering systems. Shapiro replied that "where they come from in the first place is not a question we can realistically answer right now." While Dembski sees this position as at least not inconsistent with Intelligent Design, Shapiro has explicitly and repeatedly rejected both creationism in general and Intelligent Design in particular.

Criticism

While Shapiro developed NGE in the peer-reviewed literature, the idea attracted far more attention when he summarized his work in his book ''Evolution: A View from the 21st Century''. In part due to its discussion of the Intelligent Design movement, the book was widely and critically reviewed. Criticism falls into two main categories: :# ''The theory crosses the line into

teleology Teleology (from and )Partridge, Eric. 1977''Origins: A Short Etymological Dictionary of Modern English'' London: Routledge, p. 4187. or finalityDubray, Charles. 2020 912Teleology" In ''The Catholic Encyclopedia'' 14. New York: Robert Appleton ...

'', a line exemplified by the review written by Larry Moran. The form of Shapiro's argument has points of resemblance to several creationist arguments to the effect that observed biology cannot be explained by a combination of "random" (undirected) mutation and natural selection. One of the many standard responses to these arguments is that biology can be sufficiently explained without invoking higher causes. Shapiro's view differs significantly from that of creationists, not the least because his higher causes exist only at the level of cellular machinery. However, to a critic unpersuaded of the need for higher causes, it is not persuasive to substitute material higher causes for the supernatural. :# ''Shapiro does not give a fair reading of the central dogma.'' Shapiro's reading of the central dogma requires that ''only'' random mutations can be the root of evolutionary change. If this reading is correct, then, ignoring the looseness of such an application of the term "

", the several mechanisms identified by Shapiro (''e.g.'',

) do indeed falsify this theory. However, Crick and geneticists in general had long been well aware of the existence of mutagens at the time of the formulation and restatement of the central dogma, and in fact before the discovery of the mechanisms of biological heredity.Morgan, Thomas Hunt. The mechanism of Mendelian heredity New York, Holt, 191

/ref> A more conservative interpretation, in the words of

Marshall Nirenberg Marshall Warren Nirenberg (April 10, 1927 – January 15, 2010) was an American biochemist and geneticist. He shared a Nobel Prize in Physiology or Medicine in 1968 with Har Gobind Khorana and Robert W. Holley for "breaking the genetic code" ...

, is simply that "DNA makes RNA makes protein." Under this reading, proteins would not be expected to modify DNA, but Shapiro provides multiple examples of where this occurs, including

histone modification In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn are w ...

, mutagenic subclasses of excision and repair enzymes, extensive regulation of mobile genetic elements, and various classes of RNA regulation, and direct modification of nucleotides via

cytosine methylation DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts t ...

and enzymatic deamination. Shapiro responded to the review in ''Evolutionary Intelligence''.

References

{{Reflist , refs= {{cite journal , last=Shapiro , first=James A. , title=Natural genetic engineering in evolution , url=http://shapiro.bsd.uchicago.edu/Shapiro.1992.Gentica.NatGenEngInEvo.pdf , journal=Genetica , year=1992 , volume=86 , number=1–3 , pages=99–111 , doi=10.1007/BF00133714, pmid=1334920 , s2cid=5983884 {{cite journal , last=Shapiro , first=James A. , url=http://shapiro.bsd.uchicago.edu/Shapiro1997TIG.pdf , title=Genome organization, natural genetic engineering and adaptive mutation , journal=Trends in Genetics , volume=13 , number=3 , pages=98–104 , doi=10.1016/S0168-9525(97)01058-5, pmid=9066268 , year=1997 {{cite journal , url=http://www.bostonreview.net/BR22.1/shapiro.html , title=A Third Way , last=Shapiro , first=James , date=February–March 1997 , journal=

, access-date=2012-09-29 , archive-url=https://web.archive.org/web/20120304013501/http://www.bostonreview.net/BR22.1/shapiro.html , archive-date=2012-03-04 , url-status=dead {{cite journal , last=Shapiro , first=James A. , url=https://rowan.biology.ualberta.ca/courses/genet302/uploads/winter06/lecture/b1/shelagh_campbell/lecture_outlines/topic_1/TEgenomeevol.pdf , title=A 21st century view of evolution: genome system architecture, repetitive DNA, and natural genetic engineering , journal=Gene , volume=345 , issue=1 , pages=91–100 , doi=10.1016/j.gene.2004.11.020 , pmid=15716117 , date=January 2005 {{dead link, date=February 2018 , bot=InternetArchiveBot , fix-attempted=yes {{cite journal , last=Shapiro , first=James A. , url=http://shapiro.bsd.uchicago.edu/Shapiro_1999_Genetica.pdf , title=Transposable elements as the key to a 21st century view of evolution , journal=Genetica , volume=107 , number=1–3 , pages=171–179 , doi=10.1023/A:1003977827511 , pmid=10952210 , year=1999, s2cid=7952900 {{cite journal , url=http://shapiro.bsd.uchicago.edu/shapiro2002.AnnNYAS.pdf , title=Genome Organization and Reorganization in Evolution: Formatting for Computation and Function , author=Shapiro, James A. , journal=Annals of the New York Academy of Sciences , year=2002 , volume=981 , pages=111–134 , doi = 10.1111/j.1749-6632.2002.tb04915.x, pmid=12547677 , s2cid=5296727 {{cite journal , last=Shapiro , first=James A. , journal=Annals of the New York Academy of Sciences , volume=870 , issue=1 , pages=23–35 , date=May 1999 , title=Genome System Architecture and Natural Genetic Engineering in Evolution , doi=10.1111/j.1749-6632.1999.tb08862.x, pmid=10415470 , bibcode = 1999NYASA.870...23S , s2cid=21506885 {{cite journal , last=Shapiro , first=James A. , journal=Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences , volume=38 , number=4 , date=December 2007 , pages=807–819 , url=http://shapiro.bsd.uchicago.edu/Shapiro2007.SHPSC_370.pdf , title=Bacteria are small but not stupid: cognition, naturalgeneticengineering and socio-bacteriology , doi=10.1016/j.shpsc.2007.09.010 , pmid=18053935 , url-status=dead , archiveurl=https://web.archive.org/web/20110727223515/http://shapiro.bsd.uchicago.edu/Shapiro2007.SHPSC_370.pdf , archivedate=2011-07-27 , citeseerx=10.1.1.371.1320 {{cite book , title=Evolution: A View from the 21st Century , publisher=FT Press , author=Shapiro, James A. , year=2011 , pages=272 , isbn=978-0132780933, author-link=James A. Shapiro {{cite web , url=http://www.huffingtonpost.com/james-a-shapiro/cell-cognition_b_1354889.html , title=Cell Cognition and Cell Decision-Making , publisher= Huffington Post , last=Shapiro , first=James A. , date=19 March 2012 {{cite journal , url=http://vcp.med.harvard.edu/papers/shapiro-read-write-genome.pdf , title=How life changes itself: The Read-Write (RW) Genome , author=Shapiro, James A. , journal=Physics of Life Reviews , volume=10 , issue=3 , pages=287–323 , date=July 2013 , doi=10.1016/j.plrev.2013.07.001, pmid=23876611 , bibcode=2013PhLRv..10..287S , citeseerx=10.1.1.371.35 {{cite journal , url=http://www8.svsu.edu/~koperski/Two%20Bad%20Ways%20to%20Attack%20Intelligent%20Design%20and%20Two%20Good%20Ones.pdf , title=Two bad ways to attack intelligent design and two good ones , author=Koperski, Jeffrey , journal=Zygon , date=June 2008 , volume=43 , issue=2 , pages=443–449 , doi=10.1111/j.1467-9744.2008.00926.x {{dead link, date=February 2018 , bot=InternetArchiveBot , fix-attempted=yes {{cite web , title=Is James Shapiro a Design Theorist? , author=Dembski, William , publisher= Evolution News and Views , date=12 January 2012, author-link=William A. 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(Review) Evolution: A View from the 21st Century
, last=Kutschera , first=Ulrich , title=Newsletter of the International History, Philosophy and Science Teaching Group , editor-first=Dietmar , editor-last=Höttecke , date=September 2012 , volume=21 , number=9 {{cite journal , title=Response to Pauline Hogeweg's review of my book, "Evolution: a view from the 21st century" , author=Shapiro, James A. , journal=Evolutionary Intelligence , year=2012 , doi=10.1007/s12065-012-0074-7 , volume=5 , issue=3 , page=211, doi-access=free Evolutionary processes Non-Darwinian evolution