Designing the Fittest

Genetic engineering is a technique for improving the Instruction Books of living things, as are natural selection or artificial selection. Like artificial selection, genetic engineering changes living things by deliberate selection for particular traits. It differs from artificial selection in one important respect: genetic engineering allows people to select for traits by changing the Instructions living things contain directly, rather than selecting for new traits produced randomly by mutation.

For genetic engineering to produce a desired trait, we need to know which Instructions produce that trait. When working with traits that are produced by only one or two Instructions, the traits can be successfully modified even without knowing much about the rest of the Instructions in the organism's Instruction Book. This is like adding Instructions for a headlight to the end of a bicycle's assembly manual; we really don't need to know much about how the rest of the bicycle was made to do it. As the number of Instructions that produce the desired trait increases, we need to know more and more about the organism's Instruction Book to genetically engineer it: In these cases, we need to know all of the Instructions that produce the trait, and sometimes the Instructions for the transcription factors that turn it on.

Since genetic engineering allows us to add precisely which Instructions we want, we can precisely control the traits we produce by carefully designing the workers the Instruction will produce and by choosing promoters that turn on the Instruction when we want.

Presently, there are three tools used for adding Instructions to living things via genetic engineering: gene guns, retro viruses, and a bacterium called agrobacter. While these three methods are very different, they all serve one goal: getting new Instructions into the nucleus of the organism's cells, so that the Instructions can be added to the organism's Instruction Book.

All three of these techniques start with the same raw material: a piece of DNA containing Instructions for workers that will paste it into an organism's Instruction Book. These bits of DNA are called vectors. Vectors are often plasmids, and are similar in function to conjugation factors and transposons. The vector contains, in addition to the Instructions for pasting-it-in workers, the Instructions the genetic engineer wants to add to the organism, and a reporter gene. The reporter gene lets the engineer know that the vector has made it into the organism. Originally, these were Instructions for workers that gave the organism resistance to an antibiotic, but more recently, the reporter Instructions call for workers to turn a colorless test molecule into a colored dye.

The details of the vector and how it is used distinguish the three techniques.

To be used in gene gunning, the vector is coated onto gold dust "bullets". These bullets are loaded into the gene gun -- a tiny air-pressure cannon -- and fired at the cells to be transformed. Sometimes, the bullets end up in the cells' nuclei, and the cells express the vector's Instructions. Since these Instructions include making a worker that pastes the vector into the organism's Instruction Book, the organism ends up with new Instructions. Let's see how this works:

On the left, we see a plant and its Instructions color-coded for some desirable trait (for example, an insect resistance trait like the one lost in the artificial selection example). In the middle is the gold dust bullet with a few Instructions stuck to it. These Instructions include the Instruction for the desirable trait (in green), a reporter gene (in white), and the Instructions for pasting this scrap of DNA into the plant's Instruction Book (in magenta). On the right, we see the transformed plant. It now expresses the desired trait, and contains all the Instructions that were stuck to the bullet. The new Instructions are inserted into the plant's Instruction Book, but they don't erase any that were there before.

We use gold dust because it's biologically inert. This is important because the bullet ends up lodged in the nuclei of transformed cells -- we wouldn't want to go to all the trouble of transforming a plant and then end up making it sick in the process.

When vectors are used with agrobacter, this bacterium is tricked into taking up the vector through a method like conjugation. When agrobacter infects plants, it forces the vector into the infected cells' nuclei. (For this to work, the vector has to resemble a natural one agrobacter usually inflicts on plants, so it contains a few Instructions the bacterium needs.) Once in a nucleus, the vector has itself pasted into the cell's Instruction Book, as happens with gene gunning:

In the wild, the two kinds species of agrobacter, Agrobacter tumefaciens and Agrobacter rhizogenes, cause disease in some plants. The first causes galls, the second causes unusual root growth. Neither one infects any animals. Fortunately, there doesn't seem to be any bacteria that can transform animals.

This picture is like the one above, except that the agrobacter doing the work is shown in aqua, as is its Instruction Book. This color code indicates that neither the agrobacter's Instruction Book nor any of its traits are present in the transformed plant. Only the vector is added to the plant's Instruction Book. (The vector is shown with more Instructions in magenta -- these are the ones agrobacter needs to insert it into the plant.)

Scientists have used agrobacter to add Instructions for the four workers that make up the vitamin A pathway to one line of rice. This rice now produces vitamin A in its grains. Rapid adoption of this rice, called Golden Rice, could eliminate vitamin A deficiency in poor countries and prevent many cases of night blindness, total blindness, and childhood death.

The vectors used with retro viruses are the most specialized. These consist of the normal vector, plus most of the Instructions that make up a retro virus. Of course, since the genetic engineer doesn't want the retro virus to run rampant with its new Instructions, he removes the Instructions that produce the virus's coat and a few other Instructions the virus needs to take over cells. This vector -- now containing a "safe" virus Instruction book -- is put into the virus's coat, turning it into a "sterile" virus. This sterile virus is then allowed to infect an organism, adding its Instructions to it.

In this case, the retro virus's entire tiny, "safe" Instruction Book is added to the plant's Instruction Book. Since this book lacks the Instructions the virus needs to spread, the plant doesn't infect others, and so is shown without the aqua color for the virus's traits.

Once added to an organism, the vector's Instructions act just like the ones the organism started with -- the organism has no way to tell the difference.

In order for the new Instructions to be passed on to the organism's offspring, the new Instructions must be added to its germ plasm. This is usually done by adding the Instructions to each of the organism's cells very early in development, since some of those cells will later differentiate into the organism's gonads. (If the new Instructions are added only into somatic cells, the Instructions aren't passed on to the plant's descendents, and we've just accomplished gene therapy rather than genetic engineering.)

At present, genetic engineering permits only small changes to living things. None of the vectors are big enough to hold more than a few new Instructions. To make bigger changes, we have to use artificial selection and selective breeding.

Although genetic engineering is much better than artificial selection for making these small changes, there is one thing that can go wrong: the vector can land in the middle of an Instruction. This usually breaks the Instruction, so that it doesn't produce a functional worker. Since plants' and animals' Instruction Books contain mostly stuff that isn't Instructions, this is rare. It also makes little or no difference to the organism, since the organism has another copy of the Instruction in its other Instruction Book, and may have still more copies in both Books. In the worst case, it changes the allele for that Instruction; if this changes a trait, it can be seen, and we can decide whether we like it or not.

Our ability to change Life's Instruction Books through artificial selection and genetic engineering is dwarfed by Nature's ability to change Instruction Books by natural selection. Natural selection is always at work, whereas people only rarely try to change living things through either of our methods. The sheer number of living things mutating, reproducing, growing, and struggling for survival guarantees that Nature's library of Instruction Books will always be very diverse. Unfortunately, there's no similar guarantee for the library of Instruction Books in domestic plants and animals: with or without artificial selection or genetic engineering, it's all too easy for us to allow that library to shrink to just a few Volumes. Of course, catastrophes like asteroid impacts can wipe out nearly all living things (and thus nearly all the diversity among them). Fortunately, these sorts of mass extinctions are very infrequent.

Part One: Reading the Book

Part Two: Copying the Book

Part Three: Improving the Book
Better Books by Trial and Error
Survival of the Fittest
Choosing the Fittest
Designing the Fittest
Instruction Books at Your Fingertips

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