Effect Measure

Genetically modified crops is not a special interest of mine, which is a good thing because once you get into that controversy you are like the worker who gets his sleeve caught in the machine: before long you are dragged into the gears and badly mauled. I’m not reflexively against it. I recognize that what GM advocates have been saying has more than a grain of truth: we’ve been engaged in genetic engineering of crops since agriculture was domesticated. Modern genetic techniques have amplified that ability by orders of magnitude, but the result is the same. We are purposely altering the genetic make-up of an organism to serve human purposes. But of course it isn’t as simple as that. I am broaching the subject, with some trepidation, because now the subject of GM chickens designed to be resistant to avian influenza has entered the argument:

John Lowenthal is praising chickens – in particular the broiler variety which takes just 42 days to grow from egg to maturity. The extraordinary bird, bred to grow big, fast and plump for our dinner tables, could undoubtedly play a significant role in fighting world hunger.

Especially because the Australian scientist and his CSIRO research team at the high security Australian Animal Health Laboratory in Victoria may just have the technology to breed an avian flu-resistant chicken.

It’s early days, he tells his audience at last week’s 10th International Symposium on the Biosafety of Genetically Modified Organisms in Wellington.

But the proof of concept project signals the cutting edge of genetic modification – gene silencing to create a resistance to viral infection which is then integrated into DNA, so it’s passed on in future generations through normal breeding.

If it works, the avian influenza virus – which in its H5N1 strain has led to 240 reported human deaths in 15 countries – could be stopped in its tracks. (Chris Barton, New Zealand Herald)

These are the first four paragraphs of a pretty long article, so I kept reading to find out exactly how this was to be done. It turns out, however, this article is a puff piece for GM advocates and uses the bird flu example as a typical bait and switch tactic. You want to be protected against avian flu? Then let us march full bore into a GM future, few strings attached. There are 37 more paragraphs and avian flu is not mentioned again, not even once. Instead we get a steady diet of GM advocate talking points, with occasional anti-GM counterpoints (usually with a swift rebuttal quote).

This is by way of saying that while I am not anti-GM (it is used to make useful pharmaceuticals, as the article observes, and the anti-bird flu scenario is a possibility, although apparently still a long way off), I don’t trust most GM advocates. Talk is cheap, but their products aren’t. And they don’t want anybody to interfere. The article complains that New Zealand’s regulations are far too strict:

The legislation – the Hazardous Substances and New Organisms (HSNO) Act overseen by the Environmental Risk Management Authority (Erma) – is seen by many as a defacto [sic] moratorium on genetic modification. Since provisions relating to new organisms took effect in July 1998, just 16 GM contained field tests have been approved. Prior to this 50 GM field tests had been approved by the Minister for the Environment.

I agree this is good evidence that the regulations have slowed (but not stopped) field tests of GM organisms but not that the regs are too strict. If anything, the 50 field tests done prior to regulation seem far too many. The promise of this technology comes from its great power. And its great power is the best reason I can think of to go cautiously.

The problem of commercial chicken monoculture is now a concern for agricultural scientists. It isn’t hard to imagine what would happen if Monsanto or another GM behemoth came up with a single chicken breed resistant to avian influenza. We’d have one chicken breed all over Africa and Asia. Until, that is, that flu or another virus figured out how to get around it. Then we’d have no chickens. Anywhere.

The chances it would turn out that way may be small. We really don’t know. How big a risk do we want to take? One in a hundred? One in a thousand? It’s all about balancing one risk against another, and as the situation changes so does the risk – risk equation. Right now, it’s not even a question. And the bird flu promise is a Trojan horse for too much stuff I don’t trust.

Comments

#1 Mike
November 29, 2008

We’d need to support chicken genome storage just like the seed banks now.

One problem you address is the secrecy and lack of oversight but that is at the core of this: Protect Potential Profits. If you run a privately (or mostly privately) run research facility, you only survive when you make money. Public funding for science, either through grants or university facilities reduces the greed that hides information. When what you earn is not tied to what you find, you get information that you can trust.
#2 Mike Haubrich, FCD
November 29, 2008

For an approach on GMO by a researcher in the field at Iowa State University, I recommend the blog Genetic Maize, but Anastasia Bodnar. This post in particular discusses the issue of invoking “Frankenstein” to create fear of GMO.

Some may see Anastasia as a “Cheerleader” for GMO, but I see her approaching it as a true skeptic and scientist should. And I mean no disrepect, but your final paragraph in this post uses the same sort of fear-mongering in regards to GMO as anti-vaxxers take. “How big of a risk?” The ethicists should really wait to try to answer the question until after more of the science is in.

What I am seeing is the attitude that since Monsanto is involved, then it must be bad and so we should try to stop it. I agree that the promise of the end of the bird flu virus is really just a pie-in-the-sky propaganda tool to promote GMO, but I also think that dismissing the overall promise of developing drought and weevil resistant crops because we are afraid there is a tiny risk of destroying all poultry smacks of the same sort of denialist approach as the anti-vaxxers use.
#3 revere
November 29, 2008

Mike H.: Thanks for your thoughtful comments. You make some good points to which I must plead guilty. But let me try and react in a thoughtful way, too.

I am not reflexively anti-GMO but I am reflexively distrustful of many who are promoting it. The article in question I take as a case in point. I read it to learn something about what was a GM application of interest to me. It occupied the lede of the article (first 4 paragraphs). It then disappeared completely into an argument for loosening GM regs in New Zealand. I, as a reader, learned nothing about the ostensible subject, which was just a pretext to preach against the regs. Unfortunately, this is not uncommon.

Let me respond to the accusation I am engaged in fear mongering. I’ll admit that it is a plausible way to read what I wrote, so maybe I subconsciously engaged in it because of my distrust (BTW, the fact that Monsanto is engaging in GMO promotion and research is in my mind an argument to distrust it; I don’t trust them). Anyway, I’ll have to think about that more. You may have a point about what I wrote. But let me take the opportunity to clarify what was on my mind.

High consequence but unknown risk events seem to me to be of a different sort than the vaccine controversy. Even in the worst case, for vaccines (a worst case I see no evidence for), we are not talking about high consequence events for the globe as a whole, even if the events are devastating for some individuals. We are also talking about balancing risks, however, and in that case the risk balance seems quite clear. There is no comparable risk balance equation here, since we are not talking about a particular vaccine or even a particular GMO application, just about a very powerful technology. The idea that we wouldn’t regulate a very powerful technology seems insane to me. The comparable argument about vaccines is that we shouldn’t have any vaccines because they might pose a risk. I know some people hold to that absurd position, but most of the vaccine argument isn’t couched in those terms, nor is my GMO argument.

One similarity is that many anti-vaxxers also distrust Big Pharma, an attitude for which I can’t blame them. As a physician, however, the risk – risk equation is overwhelmingly clear. That is not the case for GMO. Far from it. There are a number of genetic engineering applications which we accept and appear worth it. Many more are being suggested without being properly thought out (my my view). I am in favor of not doing irrevocable things without thinking them through, and if needed, testing them thoroughly under tightly controlled conditions. I made that point in the post but it is not as clear as I would have liked and you point out it could have been interpreted differently. However I am not advocating we stop work on developing resistant crops, although I will point out that the idea of making crops that are resistant to pesticides has the added effect of increasing the use of pesticides, so the risk – risk equation has to be considered carefully.

My final point in the post is that as of this point things that might not seem worth the risk could become worth the risk (even if we don’t know how big that risk is) if the situation changes. However we now have enough experience to proceed cautiously until that equation does change drastically.

Anyway, thanks for the comment.
#4 Jody Lanard M.D.
November 29, 2008

Two comments about your blog entry: “Bird flu resistant GM chickens?”

1. on GM food proponents’ disdain for public concerns, and
2. on Australian AHL candor and intellectual property assertions.

1. Proponents of GM foods are simultaneously confident about the safety of their products, and contemptuous of the public’s ability to judge the worthiness of the products.

Aside from legislation about research and monitoring, there is one crystal clear way to resolve public concern about the food itself: labeling.

But most GM food producers fight long and hard against labeling. They use probably true but highly disingenuous arguments — such as: “there is no difference in the healthfulness of GM vs. non-GM food, and therefore there is no need for a GM label.”

This argument instantly falls apart when you examine other well-accepted reasons for labeling products — values-based reasons.

In 2003, I wrote:

“I am neutral — due to being rather uninformed — about the scientific aspects of GMO’s. But I am militant about the labelling issue. Some people really care about whether their food is genetically modified. Some people care how their beef is slaughtered — Muslims and halal; Jews and kosher methods. Some people want to know if their food is “organically” grown. Some want to know if McDonalds’ french fries are 100% vegetarian, or if some animal fat has snuck in. Some, but not all, of these desires are for health reasons. Mostly they are for values reasons — things people believe deeply for reasons beyond morbidity and mortality.” ( http://tinyurl.com/5mcblx )

Why is this so hard for officials to understand?

2. In terms of the candor of some scientists working on H5N1 infectivity in animals, EffectMeasure readers may recall an incident at Australia’s Animal Health Lab, reported March 8, 2007. ( http://tinyurl.com/6jg7nw )

A couple lab workers were found to have improperly used personal protective equipment while working with avian influenza. They were subsequently isolated, and fortunately found to be free of avian influenza.

The announcements from the AHL (same lab referenced in Revere’s story above) did not reveal the strain of avian influenza used in the experiments, nor from what country the samples were obtained, nor whether the country-of-origin gave permission for the strain to be used for proprietary Australian research.

I asked the lab director, Martyn Jeggo, what strain it was, and where it was from. March 8 2007:

“could you please let me know with what strain of [H5N1] avian influenza the technician and animal handlers were working?”

Response from Martyn Jeggo March 8 2007:

“The strain of avian influenza virus used in this experiment was a Southeast Asian isolate from ducks that has no known links to human cases that have occurred in this region or elsewhere”

Second Query to Martyn Jeggo March 8 2007:

“If you have a chance, could you let me know what exact AI strain(s) and subtype(s) were used to try to infect the animals with which the three lab techs were working?”

Second Response from Martyn Jeggo, March 8 2007:

“you will appreciate that as with much of the research at AAHL [Australian Animal Health Laboratory] and indeed, similar institutes, research of this nature has issues of commercial in confidence and IP [intellectual property] that restrict what can be released until the work is published or patents lodged.”

Ah — intellectual property rights for Australian scientists! But still no answer about whether the sample-donors — whoever they were — received any benefit for providing the samples. (And did they even know they were providing samples for another country’s proprietary research? Not one word about that.)
#5 Tom DVM
November 29, 2008

Human manipulation of nature can end with un-intended consequences.

We may have to manipulate crops or animals to feed the world in the future…but we should do so with our eyes wide open…

…complete wipe-outs of plant or animal crops can occur.

ie. sterile cytoplasm in corn 1973.
#6 Jonathon Singleton
November 29, 2008

Revere, what a surreal Shakespearean insult whilst “Rome” burns inexorably into a human H5N1 pandemic — thanks, largely, to the unstable viral promoters which have been used in GM crops since the 1990s… Frankly, I think Australian CSIRO scientist, John Lowenthal

is a misinformed delusional tosser more interested in shoring up his pathetic Aussie male ego… Who gives a rats ass ’bout the kids, it’s all about insecure Australian men and their tiny little cocks (ooops, I mean “genetically modifed H5N1 resistant” chickens).
#7 Lea
November 29, 2008

It should read: “Human manipulation of nature WILL end with un-intended consequences.”

Would love to hear your take on this K.

GM all the way around is a disaster and will only end in destruction. GMO farming in Brazil between 2006 and 2007 was only less than in India, where the GMO area increased from 3.8 million hectares to 6.2 million hectares, or 63 percent. The greatest increase of these crops occurred under the government of President Luiz Incio Lula da Silva, despite growing opposition from Brazilian farmers and environmentalists.

And then there’s this disgusting story:

The GM genocide: Thousands of Indian farmers are committing suicide after using genetically modified crops
03rd November 2008

http://www.dailymail.co.uk/news/worldnews/article-1082559/The-GM-genocide-Thousands-Indian-farmers-committing-suicide-using-genetically-modified-crops.html

When Prince Charles claimed thousands of Indian farmers were killing themselves after using GM crops, he was branded a scaremonger. In fact, as this chilling dispatch reveals, it’s even WORSE than he feared.

The children were inconsolable. Mute with shock and fighting back tears, they huddled beside their mother as friends and neighbours prepared their father’s body for cremation on a blazing bonfire built on the cracked, barren fields near their home.
As flames consumed the corpse, Ganjanan, 12, and Kalpana, 14, faced a grim future. While Shankara Mandaukar had hoped his son and daughter would have a better life under India’s economic boom, they now face working as slave labour for a few pence a day. Landless and homeless, they will be the lowest of the low.
Shankara, respected farmer, loving husband and father, had taken his own life. Less than 24 hours earlier, facing the loss of his land due to debt, he drank a cupful of chemical insecticide.
Unable to pay back the equivalent of two years’ earnings, he was in despair. He could see no way out.
………….

There’s more or you can google indian farmers killing themselves.
____________________________________________

First plants, now chickens, what’s next? Or should I say who’s next?
#8 M. Randolph Kruger
November 30, 2008

More like what time do the Blade Runners show up to check your DNA out?
#9 Lora
November 30, 2008

So, what they are saying is this:

We know what particular gene is needed for resistance to avian flu. However, we are choosing to ignore the many breed preservation organizations that already exist with a vast amount of genetic diversity in poultry, and we are not going to trouble ourselves to run a high throughput sequencing experiment for the purpose of finding a naturally occurring mutant (or set of mutants) in this locus, as we couldn’t sell you anything by doing that. Instead, we are going to make a set of constructs and attempt to get one of ‘em to work in vivo.

I’m not sure if my faith in the transfection skills of Monsanto et al. is so low that I have little confidence they’ll be able to get this to work, or if I’m worried that with unemployment so high, they might accidentally hire someone with a brain who could get it to work.

All I can say scientifically is that they are doing this the hard way. It’s way easier to find things naturally occurring–we’ve tried to do this sort of thing for biotech pharmaceuticals, and the crap people come up with isn’t nearly as good as the naturally occurring stuff. There’s a lot of constructs that look like they should work, but just don’t for some reason.
#10 revere
November 30, 2008

Lora: I really don’t know what they are saying, scientifically. This was picked up at an int’l meeting and reported as the lede in a news article in NZ. I took the opportunity to comment on the bait and switch aspect of bird flu vs. regulating GMO. The underlying science is not spelled out for the bird flu angle, but the idea that it involved a “proof of principle” implies it is very, very far from fruition.
#11 Lora
November 30, 2008

Yeah, I am making some guesses on their technique. Some of my colleagues-n-neighbors make transgenic farm animals for pharmaceutical production, and I know what a misery they go through just to make, like, one goat. And I know all the negative results my fellow Big Pharma colleagues have generated for proteins by design vs. basic biology. The economy is in favor of them finding someone with really good hands, but nothing else is going their way. So I can see where they might reason that by shouting “BIRD FLU! BOOGA BOOGA BOOGA!” they might improve their recruiting efforts; if you happen to be a molecular biologist with the ability to do this sort of thing, would you rather work on a cure for cancer or work on the latest KFC product?

Maybe this is what companies mean when they say there is a shortage of science/technology trained graduates? We all want to cure horrible diseases and save the planet, but coming up with a new KFC Bird Flu Free Bucket-o-Grease, not so much…?
#12 K
November 30, 2008

Hmmm look how long it took for H1N1 to get tamiflu resistant. How long would it take for it to get around the resistant gene in the GM chickens?? Meanwhile we would have sunk our wad in that gene line and then be up a creek without a paddle.

Lora is right that the heritage breeds at least represent some long standing lines and more diversity. But I still maintain that there are risks there if the goal of preserving Java’s separate from RIR separate from Leghorns becomes the overriding principle. There is the risk of inbreeding but also if we mix up these lines at least in some flocks we might get a bird with multiple resistances that would outperform the heritage breeds and not carry the heavy load of negative genes from inbreeding.

At any rate I hope any breeders who are trying to maintain a flock of a variety of heritage breeds study what is needed to prevent inbreeding, tag your birds so you know individuals (almost never a problem for us with our diversity of sizes, combs, colors) and keep detailed records. Find out how much back breeding of related birds is safe to do, what crosses are more dangerous (cousins, sister/brother, half sibs, parent to child etc) and regularly import birds of the breed from other flocks.
#13 K
November 30, 2008

Laura, Pics of our mutts
http://home-and-garden.webshots.com/album/569009566GmvJQs
http://pets.webshots.com/album/14856857ujvYRuXyzU
http://home-and-garden.webshots.com/album/37056725roubZB
#14 Lora
November 30, 2008

K–Very pretty! I like Gracy, nice silver markings.

In this case, I’m arguing more that a naturally occurring resistance gene from any existing avian source is likely to be more successful than attempting to engineer a viral vector for some sort of RNAi/transgene therapy (what his CV indicates he is trying to do) to get flu resistance. It doesn’t particularly bother me where he finds such a naturally occurring resistance gene, whether it’s in your mutts or in my Phoenix, I’m just suggesting he will have far better luck finding one in any of the various existing heritage breed banks due to their diversity, than he would in, say, a battery egg farm.

In my experience as a professional biotech geek, he’s going about this the hard way specifically so he can get the IP on this particular vector system. Bully for him, but if I were the technology acquisitions manager of a veterinary corporation, I’d tell him we don’t fund longshots in this economic climate. You don’t ignore a massive existing source of genes that can be screened high-throughput in a few weeks just so you can do five years’ worth of work.

It takes, oh, I dunno, let’s say you can get blood samples from a population of 5000 chickens in a year, assuming you have a couple of grad students to help and you have a pretty slick labeling system. You can PCR and sequence that much in about three months, if you’ve got a decent capillary chromatography system. You set up the HTS robot to notify you by email of any mismatches to (base sequence) in that PCR, and then go do something else for a while. When you get hits on the mismatch, you return to the breeder and see if the chicken is still around, if it has offspring, if you can buy the chicken or its offspring. You can take primary cell cultures from the chicken/offspring and immortalize them, then test them for resistance in a handy 96 well plate format. When you get good matches, just breed out that chicken and its offspring to any cross you like, and there’s your resistant population. Even if there are only two resistant chickens in 5000, you’ll still catch those two. Time, start to finish: about 2 years.

The designer chicken way is much harder. You’re looking at a 2% – 0.1% chance of any of your constructs working to confer resistance in a test transfection. Multiply by the chances of a vector being a good vector–seems like he has a sort of lentivirus idea, and those can be a real pain in the ass to make work, even with good hands, so multiply by another 1%. Then there’s the bit about not actually killing or injuring the chicken in the process, because chickens covered in tumors are a Bad Thing, and that’s a complete unknown–let’s compare w/ mammalian stable transfections and say perhaps 2 – 5% are successful. That’s, what, a 0.0004% chance of success? And time, start to finish, even using HTS for the construct screening, is more like 5 – 7 years.
#15 Lea
November 30, 2008

Reading what Lora and K have written this past week has been fascinating. Thanks for taking the time to do so ladies.
#16 M. Randolph Kruger
November 30, 2008

That was funny Lora on the first one. Our resident “Them GM crops are going to stick it up our butts someday” doomsayer friend Jonny S. down in OZ seems to be coming more true each day.

GM anything and I dont mean to be biblical about it is flirting with the end of man. Some jerk will come by someday and say, “we have a cure for aging”. Great, so the population of the earth explodes and we die of starvation. You look great when you go. Or to go after the resources we attack some nation that has them (iraq). I make no political statement there. I think we would have gone there anyway but thats for another blog.

What do we do if they make a GM chicken that can feed that world… Should we? It takes bio-ethics to a new level. If you feed Ethiopians say, they are only going to go out and make more babies that will draw in even more resources.

It would seem that our problems began in the world when we tried to save the world. Each time we saved 100,000, nature would kill one million. This i the reason that I fear twhat could happen with GM chickens and GM anything for that matter. The idea is that they could make things better, but in reality they could make it worse. If we ever get a bug that got around their superchicken then we would be gone and fast. Bio-engineering is a nice idea and limited use of it should be entertained. What if some of those compounds that Jonny cites all the time actually turn out to be modifying the of every bug out there? MRSA, worms, flu, TB etc. We are seeing resurgences of this stuff everywhere. Is it a natural reoccurrence or is it an already genetically mutated group of things out to get us?

I honestly dont know. I also honestly dont want to find out the hard way if it is either. We could be setting ourselves up for a God trap. We play God, God is smart and he knows we are going to tinker. We get to a level of intelligence to be able to manipulate things genetically and then the GM whatever functions beautifully. Then it turns or something it harbors like a flu comes roaring back at us, kills us all and then God laughs. If you pull God out of it the concept is very likely plausible to Revere too.

Something to think about.
#17 K
December 1, 2008

Lora, we probably agree more than we disagree. Mostly I fear that heritage breeds which are grand old birds will get inbred. Since they have been created by crossing other breeds it really can’t hurt to cross in other breeds once again and then cross back to insure the traits you are trying to preserve. Luckily since no one keeps breed registries on chickens this can be done. By and large if it looks like a RIR for all intents and purposes it is a RIR in the chicken world. We could do that and work to keep some breed strong while mixing in genetic diversity but we find homozygous birds boring.

Glad you like Gracey – she is a grand one, good brood mother and genetic mother too. Phoenix are lovely birds but I really couldn’t deal with the tails!!!

Phoenix. Hmm
#18 Susan Och
December 1, 2008

K: You couldn’t have the flock you have today if it weren’t for breed preservationists of a few decades ago bringing breeds like the Orpingtons back from the brink of extinction. I’m concerned about inbreeding to dead-ends as well, which is why I’m excited about the existence of the ALBC, an umbrella organization that catalogs isolated populations of heirloom breeds and devises preservation and breeding plans to insure both the future and health of each breed.

Chickens are easy compared to the challenges of dairy cattle or pigs whole herds of which are likely to go straight to slaughter if the farm, or farmer falls on hard times. We might someday want pigs that are smart enough to nurse their young without crushing them or cows that can make thrive without heavy corn rations and barns.

Environmentalists tend to envision a “perfect world” that looks like nature without any evidence of humans. Thus there is a lot of concern about extinctions in species which are perceived to have evolved independently of humans, while livestock breds, which obviously evolved alongside humans, is considered disposable or replaceable or are just not considered at all.

Of course if you are lucky enough to have a flock or a herd that has been improved or handed down through the generations, that flock or herd is your intellectual property, is your wealth, even if you live in a place with nothing resembling a GMO lab. Yet, if you resist a sudden call to cull all poultry within miles, you are considered “backwards”, and the researchers protecting their own samples (that came from from your birds) get to invoke their intellectual property rights instead of sharing.

It seems that a little humility and some respect for the work of past generations and other cultures would go a long way.
#19 Susan Och
December 3, 2008

It’s odd how a genome produced by a genetic engineer is a patentable item, but a genome produced by the combined efforts of yourself and your ancestors is just a chicken.

(Also odd how my comments have been “held for moderation” and never published. That’s why this one is late and short.)
#20 revere
December 4, 2008

Susan: The system is responsible for holding comments (usually because they have a lot of links in them and are suspected comment spam) and I try to check periodically to see if any have gone unpublished pending approval. I didn’t see any of yours in that category (sometimes I am late but they do get published), but my apologies if this has happened to you. Sometimes I am better at it than others. I am in the midst of writing a grant at the moment, an occupation which always makes me distracted.

I always value your comments which are informative and often present a different and interesting perspective for me. Today’s comment is a lovely case in point.
#21 M. Randolph Kruger
December 4, 2008

Revere, I think it only holds them for a week at the most. Thats how mine works, probably the same for yours. It may go back to the old Darpanet thing too to prevent clutter in the system from facilities that might not have been there any longer. Message queue thing. Roten might know more on this.