Written by Matt DiLeo
“Many administrators, private and public, have decided that the future of plant breeding lies in genomics, relying on claims that molecular genetics has revolutionized the time frame for product development. ‘Seldom has it been pointed out that it is going to take as long to breed a molecular engineering gene into a successful cultivar as it takes for a natural gene’” – Goodman 2002
Traditional breeding essentially consists of the repeated selection of the best individuals of a plant population over time. This can be accomplished by farmers, hobbyists or professionals and ranges radically in sophistication from the inadvertent selection of genotypes that grow best in a given cultivated environment to massive multi-year statistical studies on large pedigreed families grown in multi-location trials. Regardless of the methods used, breeders are unified in their selection of traits based on phenotype and NOT on genotype (with some limited MAS). Breeders generally don’t know (or care) why a plant has a certain trait. They just want it to work. This approach is the strategic opposite of genetic engineering, which aims to first understand the specific mechanism of a given trait first so that it can be consciously and directly modified.
New Sources of Germplasm: Lines, Transgenes, and Breeders*
The end of breeding has been repeatedly and falsely prophesied for going on two decades now – yet even after hundreds and hundreds of millions of dollars of research, only a handful of transgenic traits have been successful. To some extent, it’s an unfair comparison as applied genetic engineering has been virtually crippled by regulation. Yet all the same, the above paper by Goodman (2002) does a nice job of outlining all the complications that genetic engineering enthusiasts tend to gloss over in their zeal to take crop improvement beyond breeding.
Far and away, I think the most important reason that genetic engineering has not replaced breeding is that overenthusiastic proponents fail to understand how much of the genetics upon which breeding is built remains unknown. Genotypes can perform radically different in very similar environments and genes can perform radically different within similar genotypes (and of the tens of thousands of genes in any crop, we have a hint of only what a few of them do). Breeding succeeds in the face of these tremendous unknowns because it selects blindly based on phenotypic results.
This distinction between consciously engineering a system and improving it by trial and error (generating many, possibly random iterations and just seeing which works best) is a fundamental distinction seen in many fields from drug discovery to mechanical engineering (to evolving computational cars!). Whether you’re trying to improve biological, technological or social systems, iterative selection is best when you don’t really understand how your system works – but once you do understand it well enough to make accurate predictions, rational engineering allows massive leaps in what you can accomplish.
Currently, our knowledge of plant biology is nowhere near complete enough to allow wholesale engineering – but it does allow us to make some very small, targeted changes that can occasionally have very big effects (e.g. herbicide and pest resistance). Ten years after Goodman’s paper, there is still much that we can hope that genetic engineering will accomplish – but breeding will continue to be the bread and butter of crop adaptation and yield improvement for the foreseeable future.** In 2002, he warned:
“Plagiarizing N.W. Simmonds (1991), we can add MAS, genomics, and possibly even transgenics to the bandwagons we have known. These include (but are certainly not restricted to): induced polyploids, haploids, mutations, overdominance, genetic variances harvest index, high-lysine, small tassels, nitrogen fixation, nitrate reductase, somaclonal variation, bracytic dwarfs, leafy hybrids, precision agriculture, high-oil topcrosses, ag chemical/seed synergy.
Simmonds’ observations merit repeating even after more than a decade, “The bandwagon, as it applies to plant breeding, is expensive and damaging. Resources are being diverted from doing genuinely useful jobs to the pursuit of trendy irrelevance; biotechnology is, I think, accelerating the collapse of proper agricultural research.”
Clearly this is an overstatement (now that we’re in the future). In particular precision agriculture has gone mainstream and genomics and MAS have been paying dividends. All the same, his ending plea to remember that breeding is the core of crop improvement holds true. Private companies haven’t forgotten this (for the few crops and market classes they work on), but our public breeding programs (that cover every other crop) are being rapidly hollowed out and dissolved.
I once heard a nice analogy of genetic engineering vs. breeding.*** Emphasis on genetic engineered “traits” are like drop-in widgets for cars: electric starters, GPS, halogen headlights, etc. But breeding is what shapes the chassis, drivetrain and body. It’s great to have all those bells and whistles, but they’re more useful on some cars than others…
* Goodman, M.M. (2002). New Sources of Germplasm: Lines, Transgenes, and Breeders Memoria congresso nacional de fitogenetica
** Of course my department, Applied Systems Biology, is one of many groups trying to change this…
*** Rabobank presentation from Genomics in Business, 2011
Written by Guest Expert
Matt DiLeo has a PhD in Plant Pathology from UC, Davis. During his postdoctoral research at Boyce Thompson Institute, he researched unintentional effects of genetic engineering. Matt builds R&D teams and biotech platforms: genome editing, gene discovery, microbials, and controlled environment agriculture.
This post can get a good discussion going. Over the weekend, I was thinking about some of the same issues, and the kinds of distinctions made between breeding and genetic engineering.
It seems that the form of genetic engineering being discussed in this post refers to an advanced form where genomes are cut apart and pasted together to achieve a desired result – essentially the synthetic biology of plants. The kind of genetic engineering we have today is a simpler kind – where it is used to introduce or deactivate a few genes. Breeding is still essential to genetic engineering today, for the reasons stated above about regional adaptation, environmental differences, etc. It would be silly for anyone to say that breeding cannot do anything more, and that genetic engineering can just ‘take over from here.’ I haven’t heard anyone say that, although Doug Gurian-Sherman (of UCS) says that he heard Nina Fedoroff say essentially that, but I have my doubts about this claim.
I think the distinction between Breeding as the unconscious selection and Genetic Engineering as the conscious design approach is not quite right. Breeding increasingly involves conscious selection of particular genes, alleles, or genetic regions that have desirable characteristics in addition to the final phenotype. Marker Assisted Selection is being used to select particular components of the genotype, while leaving the remainder up to random chance and selection. With genetically engineered plants, particular genetic constructs or insertion sites could affect the resulting phenotype, along with the genetic background of the plant it is in. So, genetic engineering as it is currently practiced in plants also still involves a selection process. It would be no different in concept between selecting between different red peppers to see which ones perform best in a location versus selecting between different transgenic peppers to see which ones perform best.
It is also conceivable and probably practiced to some extent that somewhat random genetic engineering can be used to discover potentially valuable new traits. Genetic Engineering can be entirely random. On the nonrandom breeding side, we have examples of concerted metabolic engineering in crops such as orange maize, using breeding and MAS to bring alleles together to create a desired biochemical result. There is also a ton of MAS being done at large breeding companies.
The scale between observing what works and selecting it from a random breeding process, versus trying to consciously set up a molecular pathway to achieve a desired result – is a continuum going from little to a lot of knowledge about the underlying mechanisms. Breeding and Genetic Engineering both lie on this continuum, but have significant overlap – making a clear distinction between them on this issue impossible in my opinion. I was thinking about this issue this weekend because I have not only heard a few staff and grad students around me express a similar opinion, but also a sociologist of science – along with a very prominent plant breeder. It is a topic that I find interesting and philosophical – and integral to understanding what it is that a plant breeder does.
Perhaps the question is not so much Genetic Engineering vs Breeding but instead Breeding With Genetic Engineering vs Breeding Without Genetic Engineering. Can traits generated through transgenesis be used to enhance the breeding process by providing genetic diversity for important traits that breeders can use to improve crops beyond what breeding without it can do?
As genetic engineering (the copy and paste variety) and breeding become more advanced the lines will become more blurry – already breeders can essentially copy and paste sections of geneome within a species to wherever they want within the same species(you just need big honking populations, big honking sequencing pipelines, and big honking computers to turn around your data) – this, I think, is the only way that breeding would ever go away – by becoming so like genetic engineering, so intertwined, that purists refuse to see it as such – otherwise it will be here to stay – it is no mistake that 50% of R&D costs (approximately) for companies like Monsanto go straight into breeding programs (market share in seeds is utterly reliant on a good breeding program in a world where traits are licensed far and wide) – public research should perhaps take this lesson to heart.
Also one needs top notch breeding techniques to properly introgress transgenic traits from transformation backgrounds to commercially relevant germplasm anyway – without these techniques you could be lagging by years in getting a commercially useful trait into a commercially useful germ, which in terms of corporations hurts the pocket book and is time spent losing money while the patent expires – for public research it is simply time spent not doing whatever noble thing your trait was meant to do.
I agree with all of that. The inspiration for my post was that there are many lab-based ways to conciously “engineer” a crop that aren’t legally and popularly referred to as “genetic engineering”: eg MAS or targeted mutation of known genes. Likewise there are high tech ways to generate new genetic variation for that are philosophically closer to trad prebreeding than genetic engineering as it has been practiced to get pest/icide resistance: eg screening massive numbers of random cobalt/somaclonal/ems mutants or very long lists of weakly supported ‘candidate genes.’
I thought it was an interesting contrast to compare concious engineering with a priori knowledge vs trial and error – especially since our legal system is oblivious to this and other biologically meaningful ways to evaluate risk.
It reminded me of when my brother was working on building robotic dragonflies in that mech E lab: he said you can design wings and their movements in CAD based on equations or you can just play around with pieces of material – which approach is faster and more accurate ultimately depends on how well you know your system.
Craig Venter’s development of a synthetic organism (microbe) definitely points in the direction of “the end of breeding” but says little about the usefulness of a fully synthetic/engineering approach.
Let’s imagine a future, an increasingly likely one, where the functions of all corn genes are known. With the proper enabling technology, one could theoretically stitch together synthetic corn. Yet, given that state of knowledge, it’s not obvious that the same bundle of traits couldn’t just as easily be achieved with MAS/selective breeding.
One thing that’s obvious, both currently and in that imagined future, is that engineering is required to introduce traits produced by genes that are not present in the gene pool. If you want corn expressing e.g. Bt toxin, you need engineering.
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