PhD student working on the C4 rice project here. On the road right now but happy to answer questions when I can find a moment.
I genuinely think C4 rice the best shot we've got at alleviating a huge chunk of world hunger in one (extremely difficult) move.
Some key points:
- C4 plants (like maize and sugarcane) are generally about 50% more efficient at biomass accumulation than C3 plants (like rice and wheat). C4 rice could mean a yield increase for rice of up to 50% _with no increase in inputs_
- RuBisCO is by far the most abundant protein in plants. It accounts for the majority of the nitrogen required by C3 plants, and the inefficiency of C3 is the reason we have to use so much nitrogen fertiliser. C4 rice would require considerably less fertiliser than C3 rice.
- C4 plants use CO2 much more efficiently that C3 plants. This allows them to keep their stomata closed much more of the time, so they lose less water through transpiration. This makes C4 plants much more water efficient - C4 rice could require much less water than C3 rice, meaning it could be grown on land that is currently unsuitable for rice production.
- C4 is probably the most interesting example of convergent evolution we know about. It has evolved over 70 times independently. This is quite amazing - it's a complex trait that requires dozens of proteins to be organised in a particular temporal and spatial pattern, and needs a new cell type to be made. Yet it has evolved 70+ times.
- We are using the recurrent evolution pattern as our 'way in' to the problem of figuring out how to control C4 at the molecular level. We analyse gene expression on a massive scale in C4 and C3 sister species from all the evolutionary origins of the trait.
- This involves a lot of interesting software challenges that hn might be interested in. For example, we're working with so many species that we can't sequence all their genomes. But we can sequence their _transcriptomes_, which is all the genes that are expressed at a given time. The sequencing technology produces millions of tiny fragments of the original sequences, which have to be pieced back together to be useful (an NP-hard problem).
I work at a company in the Silicon Valley that provides some of the computational firepower and software expertise used to analyze transcriptomes for this project. We're hiring engineers and scientists. Email in profile for more info on that, otherwise I'm happy to answer questions as well.
> Are you talking about sequencing enough to get adequate coverage for reconstruction?
Yes. Assembling a genome requires a lot of sequencing data or different kinds, and is expensive. Genomes (especially in plants) can be huge. We're only interested, at least in this specific example, in the things that are expressed. These make up a small proportion of the genome, and so we sequence only those things.
> Also, what do you think of the criticism that it is difficult to know the potential effects of GMO on their ecosystems in the wild?
Agriculture in general has a vast impact on the environment. This is true across the board - including organic, GMOs, 'conventional', etc. By its very nature agriculture is about shaping the environment so we can control a piece of it to optimise it for food production. Our responsibility is to try to predict and minimise the effects that might cause problems.
So far, GMOs have proven to have relatively little effect on the environment (compared to other drivers of agricultural productivity, like pesticide and herbicide use, for example).
In the case of C4 rice we can predict what the major potential issue might be: C4 rice plants might perform so well that they outcompete wild plants outside the field setting. `There are some technological tricks we can use to try to ensure plants don't do well outside the field.
When you say "relatively little", what does that mean? I can't see why there would be any difference at all that comes from some (plant) being GMO in itself.
Some plants developed with GMO technology might of course behave differently from other variants of same species; for instance if some GMO variantg grows up faster than previous seeds and is harvested faster and you can grow another crop in the same season and get a better yield, then there is of course more need for fertilizing etc. But that in itself does not come from something being GMO.
Well, with first-generation GMOs, a single gene was inserted into a crop. This is totally unlike all previous crop breeding, where changes were complex and no single gene was likely to control the trait. So before GMOs, there was basically no chance that a trait bred into crops could escape into the wild by gene flow, but with first-gen GMOs that became a real possibility. It has indeed been recorded happening a bunch of times, leading to, for example, herbicide resistance in weeds.
I should point out that herbicide resistance in weeds was widespread before GMOs by other mechanisms, and in fact the switch to glyphosate has been a great thing because we've massively reduced the application of harmful chemicals, while glyphosate is benign. But the fact remains that GMOs do carry their own specific risks that are a result of the technology and methodology, rather than the specific application.
It's been a few years, but the plant geneticists I used to work with until 2012 seemed to have to solve a lot of problems to get reliable full-genome sequences of de novo species (these have no reference assemblies to go by).
Including what I had until then assumed was the simple act of just sampling DNA material: multiple consistent sites on the plants were sampled and this context was important not just for gene expression, but overall sanity checking of final assemblies (speaking of sanity checks: flow cytometry as well). Then there was setting up Illumina and 454 sequencing experiments, which seemed to involve quite a few iterations/experimentation in developing primers, choosing bead configuration, amplification procedures and a whole lot of other stuff I don't understand...
And still, after all that, the literature did have a bunch of species that had already had a few genes sequenced using earlier methods and traditional PCRs, so the whole sample set was given this treatment as well, again as a sanity check and to get a strong reference to earlier results (1000+ of species, thousands of individual plants, each with multiple samples as I mentioned).
And still, after all that... the evolutionary history of this group of plants still looks slightly different depending on which genes you looked at.
And so now I know what a consensus tree is... and how much fun it is to see researchers have their software doing MCMC tree building run in just a few days on HPC compute clusters when they'd previously waited months :-)
In my experience most systems are a series of tradeoffs. Even though C4 has evolved over 70 times, are there advantages conveyed by C3 or is C3 just easier to evolve?
C3 is the ancestral system - 45 million years ago, all plants were C3. C4 is a relatively new evolutionary innovation.
The evolutionary history goes something like this. 3.6 billion years ago, Earth's atmosphere was very rich in CO2 and had basically no O2. Then photosynthesis evolved in bacteria in the ocean, using the enzyme RuBisCO to trap CO2 into sugars. Those bacteria became incredibly successful and in the process released a lot of O2 into the atmosphere - over the next 2 billion years the atmosphere became oxygenated. Unfortunately, RuBisCO sometimes mistakes O2 for CO2 and accidentally creates a toxic product that wastes energy instead of storing it. So this new oxygen-rich atmosphere started to make photosynthesis more efficient. Eventually (42 million years ago) the atmosphere became so oxygen rich and CO2-depleted that this inefficiency was a major evolutionary pressure, and C4 started to pop up.
There's very little compromise with C4 - it's just better in a very wide range of commonly occurring environmental conditions.
Well, the project is likely to take another 15 years until we have the system bred into local varieties. This gives us a lot of time for building confidence in what we're doing, and learning from previous failures.
Part of the issue with 'GMO' is that many people see it as a way for 'Big Ag' to tighten its control on the food supply. This project is an example of GMO being used for humanitarian benefit on a massive scale, with no benefit to 'Big Ag'. However, that's not enough - Golden rice for example has been met with a deliberate campaign of resistance by Greenpeace.
The fundamentally important thing is that the farmers don't get fed misinformation. IRRI, who coordinate the C4 rice project, have a huge community outreach and participation program, and do an incredible amount of education with farmers. If the farmers want the technology, it will happen. And in the market, if people want the food, it will happen. Hungry people don't give a crap what Greenpeace say.
Golden rice would allow "Big Ag" to tighten their control on the food supply if it was actually useful, which seems unlikely at the moment. About 30 or so of the biggest agricultural technology companies hold patents vital to it, including Monsanto and Bayer, and Golden Rice itself is patented with the patents controlled by Syngenta. They've granted a limited free license for humanitarian use[1], but only for countries that can't grow enough calories of food to feed their population[2] and small-scale subsistence farmers, and only if they don't export the rice. As far as I can tell it's basically impossible to grow enough rice to make a difference under the terms of the agreement, which isn't surprising as the whole thing's basically a PR stunt for big agri. (Even the creator of golden rice reckons the main reason everyone was so willing to license their patents was because it makes a good PR weapon against anti-GMO activists - now they can accuse them of wanting the third world to starve.)
Those restrictions are pretty much exactly what is needed - the vast majority of malnourished asians grow their own food on very small plots. Golden rice would be available to them. It's not available for commercial exploitation by anyone, including Syngenta.
Chances of pulling it off eventually are very high - I started my PhD with naive prior of around 0.5, and I'm converging on something like 0.9 now.
The hardest thing is discovering how the system is fundamentally regulated, and we are making rapid progress. Our massively high throughput approach gives us huge lists of candidate genes with probabilities, so we can rank them and process them through a biological testing pipeline quite fast. Using this process we've discovered a whole lot in the last two years - for example we now have a toolbox of genes we can use to precisely time gene expression in the bundle sheath cell (the cell C4 plants concentrate RuBisCO in). Our computational systems are rapidly improving, and I think 2015 will be a big year for us. Final year of my PhD, and I intend to go out with a bang :).
The secondary challenge is building the system in rice, but unless everything we know about molecular biology is wrong, this will work. We've already started by putting the parts we do know about in the right places in separate plants, then breeding them together ('gene stacking'). This happens in parallel with the discovery.
The major uncertainty is in the timescale - 15 years is ambitious, but not unlikely. 20 years is likely. With a colleague at LSE, I did some simulations of what the impact of success would be at various timescales, and 20 years would still be a vast humanitarian win. Every year we can shave off the time to delivery potentially saves tens of thousands of lives and lifts another hundreds thousand or so people out of food scarcity.
The first two stages of the project have proceeded in parallel, so we've been doing gene discovery and stacking in rice at the same time. I think we're probably 3 years behind schedule - the gene discovery part of that original pyramid is very optimistic.
A combination of education and (mostly) ignoring them, I would hope. Such screaming comes from people who expect to have food available for their next meal, and tends to evaporate when hungry.
I couldn't agree more. I really hope this rampant science denialism that is getting traction in American society is just profoundly ignored by those in power.
I think your position is unscientific. First, there's enough food to feed everybody on this planet already, but the "economical science" is not in favor of distributing resources evenly. Second, it's highly unscientific to start feeding a large population with foods that haven't passed any testing, and, no, 5-10-year trials are not enough. So, instead of solving problems we've created, the only solution is change the system that's highly unfair and that's build around the idea that only a small percentage of the world population will live well, will be wasteful, and destroying the entire planet with it's pathological consumerism and the rest will be "servicing" them or, at least, not getting hold of their resources, but suffering from their unhealthy for the environment lifestyle. Also, although I understand the positive sides of the GMOs, introducing them to our ecosystem is something, which short- and long-term consequences we cannot predict. So, if you want to help the hungry, re-engineer the political and the economical system (like The Venus Project), which corrupt system allows this global unfairness and leave the organisms (in "GMO") alone! I personally don't mind planting GMOs on Mars, just not on Earth, please, or not outside of strictly-controlled environments!
> it's highly unscientific to start feeding a large population with foods that haven't passed any testing
It's not unscientific at all. Whether to perform extensive testing on foods is not a function of science but of public opinion.
The science tells us that all plant-derived foods outside a very small group of sources are extremely likely to be safe for the vast majority of people. There are very few exceptions, but there are some, like potatoes and tomatoes, which are both derived from poisonous wild ancestors so new strains need to be checked for reversion to the wild state. I say 'the vast majority of people', because some tiny number of people can have allergic reactions to any food, whether derived from a GMO or not.
We don't perform any testing at all on the majority of new foods introduced. This includes new plant strains bred by various mutagenesis strategies, where vast numbers of mutations are induced by chemicals or with x-rays. By comparison, GMO-derived foods receive extensive testing, but only due to public opinion, not because they are inherently more dangerous. They are in fact inherently more safe. In the process of producing a new strain by genetic modification, very few changes will be made to the genome, and they will tend to be highly predictable, whereas the conventional breeding process is highly unpredictable and introduces lots of unwanted effects. This has been demonstrated in dozens of studies.
> So, if you want to help the hungry, re-engineer the political and the economical system
This can only be said from a position of first-world comfort. It would be wonderful if we could solve the resource distribution problem. But let's not kid ourselves: it would be crazy to only try to fix the economics. What's the timescale on that change? A very long time. How likely is it to work? Not at all likely. Improving agricultural yields through technology is something we definitely can achieve, and the timescale is predictable. Hungry people will choose the technology that allows them to feed themselves now, not the promise that if the entire world economy changes they may one day get some food.
On the last point: This kind of reasoning has been repeated over and over again with any "food technology" rolled out since the beginning of agriculture 12,000 years ago. Still people are hungry. Maybe it is time to find out whether working on the root cause actually fixes the hunger in the world.
Food technology has, in the last 100 years, almost completely eradicated famine and has raised over a billion people out of severe nutritional deficit.
I'm not saying don't try to fix other things. I'm saying do both.
In the last 100 years food waste has amounted to 1.3 billion tons per year. That's almost half of the global production. There is clearly no need to produce more food to solve hunger.
That would only be true if the food wasted would otherwise be going to the world's hungry. This is not the case.
Most of the world's poor do not import food, they grow it in their immediate vicinity. Increased yields help them directly.
If you have a solution to the food distribution problem, by all means let's work on that at the same time. But there's no reason not to work on crop efficiency.
I genuinely think C4 rice the best shot we've got at alleviating a huge chunk of world hunger in one (extremely difficult) move.
Some key points:
- C4 plants (like maize and sugarcane) are generally about 50% more efficient at biomass accumulation than C3 plants (like rice and wheat). C4 rice could mean a yield increase for rice of up to 50% _with no increase in inputs_
- RuBisCO is by far the most abundant protein in plants. It accounts for the majority of the nitrogen required by C3 plants, and the inefficiency of C3 is the reason we have to use so much nitrogen fertiliser. C4 rice would require considerably less fertiliser than C3 rice.
- C4 plants use CO2 much more efficiently that C3 plants. This allows them to keep their stomata closed much more of the time, so they lose less water through transpiration. This makes C4 plants much more water efficient - C4 rice could require much less water than C3 rice, meaning it could be grown on land that is currently unsuitable for rice production.
- C4 is probably the most interesting example of convergent evolution we know about. It has evolved over 70 times independently. This is quite amazing - it's a complex trait that requires dozens of proteins to be organised in a particular temporal and spatial pattern, and needs a new cell type to be made. Yet it has evolved 70+ times.
- We are using the recurrent evolution pattern as our 'way in' to the problem of figuring out how to control C4 at the molecular level. We analyse gene expression on a massive scale in C4 and C3 sister species from all the evolutionary origins of the trait.
- This involves a lot of interesting software challenges that hn might be interested in. For example, we're working with so many species that we can't sequence all their genomes. But we can sequence their _transcriptomes_, which is all the genes that are expressed at a given time. The sequencing technology produces millions of tiny fragments of the original sequences, which have to be pieced back together to be useful (an NP-hard problem).