The Facts on Indian Farmer Suicides and GMO

This Talking Biotech Podcast features Dr. Ron Herring from Cornell University, a sociologist that carefully examined the claims that seed companies drive farmers in India to take their own lives.  Hosted by Kavin Senapathy. 

Unfilled Glowing Plant Promises Harm Science Perception

About two years ago the internet erupted with a cool kickstarter campaign.  The Glowing Plant Project claimed to want to create trees that would light the streets. The concept spread quickly, with prominent pieces on major websites that stoked contributions to the project.  It would ultimately raise $484,013.

Years later there are no glowing plants even in service as dim nightlights, let alone illuminating our cities.  The overselling of this concept was recently reviewed by Antonio Regalato at MIT Technology Review.

Natural lighting?  That implies using it as a light.  Not quite. 

Today's blog expands on the comments made in Regalato's wonderful article. The Glowing Plant Project thrived on the hype, and did not do itself any favors with a few bad moves that I feel were a bit deceptive, and in the long run, it could have a very negative impact on the perception of edgy science at the public interface. 

Even today the website makes a very strong claim, and presents a picture that must be an artistic rendering or an enhancement of any minor glow that would be captured with long exposures. It is likely GFP, which is a much simpler solution but not "glowing" (producing its own light).  GFP "fluoresces", that is, it gives off light, but only after you excite it with energy. Big difference. 

The hype is deep, the results disappointing.

The Concept

It is completely feasible to add the hardware that makes fireflies and jellyfish glow, thereby giving the plant the materials to make a few photons.  It has been used to monitor plant behaviors with highly-sensitive cooled CCD cameras. However, there are some extreme limitations that break the reality of lighting streets, or even dim rooms, that have been obvious to me from the start. 

The Chemistry Problem

The bioluminescence they speak of is actually quite old technology in the lab.  It is a tool available to scientists for decades. The enzyme luciferase (from "light giver" enzyme) mediates a chemical reaction in critters like fireflies.  It is a two-step reaction requiring adenosine triphosphate (ATP) and oxygen (two things a plant has available in some amount) but also requires a chemical called luciferin.  Luciferin is synthesized by fireflies and some other bioluminescent organisms, but you don't see it in plants.

The plants would have to manufacture the luciferin, which would be a feat of metabolic engineering, at least to make the high levels needed to sustain a glow visible to the human eye. 

There are some important constraints to consider.  When one molecule of luciferin is combined with ATP, it creates a compound called luciferyl adenylate and pyrophosphate. This compound then reacts with oxygen to form an energetically excited compound called oxyluciferin which then fires off a photon of light to regain its ground state.  There's more to it, but that's the skeleton. Invest ATP, oxygen, and a non-resident chemical called luciferin to produce one photon. 

Room lighting typically runs at 20 micromoles (2,000,000,000,000,000,000 photons) per square meter, per second, so you can have a handle on the number of chemical reactions and the amount of factors that would be required to pull this off. 

I have practical experience with this system.  Back in the early 1990's we'd hook up gene regulatory sequences to the luciferase gene (the blueprint of the protein) to test if these regulatory sequences functioned in plants.  If they did, the gene would be turned on, the plant would make the enzyme, and we could take plant powder and test for luciferase activity.  We'd crush the powder in liquid nitrogen, then incubate it with luciferin and ATP.  You had to work fast, and keep things cold. There was no visible glow of the powder, even in the darkest darkroom.

To test the powder we'd load that reaction into a luminometer.  The machine has an extremely sensitive photomultiplier or photodiode that can detect photons at 10(-21)-ish level.  It is much more sensitive than the human eye by a longshot. There we could measure the spritz of photons emitted. 

The Glowing Plant Project would also have to have the plant manufacture massive amounts of luciferin, and then count on massive amounts of ATP and oxygen.  Metabolically, this might not work so well. 

The other issue is the chemistry of the reaction.  Luciferase activity is down-regulated by its own products, meaning that you can't generate a lot of the intermediates without impeding the process. This is great to measure a snapshot of gene activity in a luminometer, but not great to light a street. 

It seems like some fundamental limits of the system were not well considered when the campaign was initiated. 

Images Used

The images used on the website looked strangely familiar to me. I was really disappointed to find the original images.  The glowing plant they show on their t-shirts and other swag is not their work.  It is not a plant they created, and they do not credit where the photo was originally posted.  The original work was done by David Ow and colleagues in 1986.  You can see that paper and the image here. 

Here's the picture in its original presentation. (D. W. Ow et al. Science 234, 856–859; 1986)

It seems a bit slimy to use that image on t-shirts and the website without a clear statement that it is not their work.  

In fact, the image was produced by watering a plant transformed with the luciferase enzyme with a solution containing luciferin, waiting six hours, and then laying the plant in contact with a 4 x 5 inch piece of Kodak Ektachrome 200 film for 24 hours, as cited in the above-referenced manuscript. 

Moving Forward

The group has now moved to raising cash for this campaign using Wefunder, which sells shares in a company rather than just committing cash.  From the company's Facebook page it is evident that they are exploring other options, such as a fragrant moss, which is beyond feasible, as plants make lots of volatiles we appreciate. Maybe they can use these more do-able projects to salvage a broken campaign and some fractured trust. 

Conclusion

This Kickstarter campaign reminds us that there is an excited community that wants to get cozy with synthetic biology and novel solutions to human problems. That's a good thing.

Maybe there's a little sour grapes in there too, because I see so many great projects in so many labs that can solve actual problems, and $20,000 would be a huge help. These projects remain underfunded, but are real, do-able and have public benefit.   

And that's the best punchline.  If we're going to continue parlaying this excitement in biology into new frontiers, we need to deliver on our promises. This visible Kickstarter campaign began with an idea that was scientifically DOA, yet captured the curiosity of many.  The marketing arm, use of others' images and enhanced photos, is not the way to build trust about public investment in technology. 

In the end, I'd be glad to be proven wrong.  I'm a geek too, and have a soft spot for those that think out of the box.  But remember, we're dealing with the public's trust.  It is a fragile thing.  It is hard to earn and easy to lose. 

Unfilled Glowing Plant Promises Harm Science Perception

About two years ago the internet erupted with a cool kickstarter campaign.  The Glowing Plant Project claimed to want to create trees that would light the streets. The concept spread quickly, with prominent pieces on major websites that stoked contributions to the project.  It would ultimately raise $484,013.

Years later there are no glowing plants even in service as dim nightlights, let alone illuminating our cities.  The overselling of this concept was recently reviewed by Antonio Regalato at MIT Technology Review.

Natural lighting?  That implies using it as a light.  Not quite. 

Today's blog expands on the comments made in Regalato's wonderful article. The Glowing Plant Project thrived on the hype, and did not do itself any favors with a few bad moves that I feel were a bit deceptive, and in the long run, it could have a very negative impact on the perception of edgy science at the public interface. 

Even today the website makes a very strong claim, and presents a picture that must be an artistic rendering or an enhancement of any minor glow that would be captured with long exposures. It is likely GFP, which is a much simpler solution but not "glowing" (producing its own light).  GFP "fluoresces", that is, it gives off light, but only after you excite it with energy. Big difference. 

The hype is deep, the results disappointing.

The Concept

It is completely feasible to add the hardware that makes fireflies and jellyfish glow, thereby giving the plant the materials to make a few photons.  It has been used to monitor plant behaviors with highly-sensitive cooled CCD cameras. However, there are some extreme limitations that break the reality of lighting streets, or even dim rooms, that have been obvious to me from the start. 

The Chemistry Problem

The bioluminescence they speak of is actually quite old technology in the lab.  It is a tool available to scientists for decades. The enzyme luciferase (from "light giver" enzyme) mediates a chemical reaction in critters like fireflies.  It is a two-step reaction requiring adenosine triphosphate (ATP) and oxygen (two things a plant has available in some amount) but also requires a chemical called luciferin.  Luciferin is synthesized by fireflies and some other bioluminescent organisms, but you don't see it in plants.

The plants would have to manufacture the luciferin, which would be a feat of metabolic engineering, at least to make the high levels needed to sustain a glow visible to the human eye. 

There are some important constraints to consider.  When one molecule of luciferin is combined with ATP, it creates a compound called luciferyl adenylate and pyrophosphate. This compound then reacts with oxygen to form an energetically excited compound called oxyluciferin which then fires off a photon of light to regain its ground state.  There's more to it, but that's the skeleton. Invest ATP, oxygen, and a non-resident chemical called luciferin to produce one photon. 

Room lighting typically runs at 20 micromoles (2,000,000,000,000,000,000 photons) per square meter, per second, so you can have a handle on the number of chemical reactions and the amount of factors that would be required to pull this off. 

I have practical experience with this system.  Back in the early 1990's we'd hook up gene regulatory sequences to the luciferase gene (the blueprint of the protein) to test if these regulatory sequences functioned in plants.  If they did, the gene would be turned on, the plant would make the enzyme, and we could take plant powder and test for luciferase activity.  We'd crush the powder in liquid nitrogen, then incubate it with luciferin and ATP.  You had to work fast, and keep things cold. There was no visible glow of the powder, even in the darkest darkroom.

To test the powder we'd load that reaction into a luminometer.  The machine has an extremely sensitive photomultiplier or photodiode that can detect photons at 10(-21)-ish level.  It is much more sensitive than the human eye by a longshot. There we could measure the spritz of photons emitted. 

The Glowing Plant Project would also have to have the plant manufacture massive amounts of luciferin, and then count on massive amounts of ATP and oxygen.  Metabolically, this might not work so well. 

The other issue is the chemistry of the reaction.  Luciferase activity is down-regulated by its own products, meaning that you can't generate a lot of the intermediates without impeding the process. This is great to measure a snapshot of gene activity in a luminometer, but not great to light a street. 

It seems like some fundamental limits of the system were not well considered when the campaign was initiated. 

Images Used

The images used on the website looked strangely familiar to me. I was really disappointed to find the original images.  The glowing plant they show on their t-shirts and other swag is not their work.  It is not a plant they created, and they do not credit where the photo was originally posted.  The original work was done by David Ow and colleagues in 1986.  You can see that paper and the image here. 

Here's the picture in its original presentation. (D. W. Ow et al. Science 234, 856–859; 1986)

It seems a bit slimy to use that image on t-shirts and the website without a clear statement that it is not their work.  

In fact, the image was produced by watering a plant transformed with the luciferase enzyme with a solution containing luciferin, waiting six hours, and then laying the plant in contact with a 4 x 5 inch piece of Kodak Ektachrome 200 film for 24 hours, as cited in the above-referenced manuscript. 

Moving Forward

The group has now moved to raising cash for this campaign using Wefunder, which sells shares in a company rather than just committing cash.  From the company's Facebook page it is evident that they are exploring other options, such as a fragrant moss, which is beyond feasible, as plants make lots of volatiles we appreciate. Maybe they can use these more do-able projects to salvage a broken campaign and some fractured trust. 

Conclusion

This Kickstarter campaign reminds us that there is an excited community that wants to get cozy with synthetic biology and novel solutions to human problems. That's a good thing.

Maybe there's a little sour grapes in there too, because I see so many great projects in so many labs that can solve actual problems, and $20,000 would be a huge help. These projects remain underfunded, but are real, do-able and have public benefit.   

And that's the best punchline.  If we're going to continue parlaying this excitement in biology into new frontiers, we need to deliver on our promises. This visible Kickstarter campaign began with an idea that was scientifically DOA, yet captured the curiosity of many.  The marketing arm, use of others' images and enhanced photos, is not the way to build trust about public investment in technology. 

In the end, I'd be glad to be proven wrong.  I'm a geek too, and have a soft spot for those that think out of the box.  But remember, we're dealing with the public's trust.  It is a fragile thing.  It is hard to earn and easy to lose. 

Disgusted with (Some) Science Advocates

Just when you think the social media discussion of science can't get any more gross, it does.  This is no longer a discussion about science, about whether to play with DNA or vaccinate kids, about climates changing or chemtrails overhead.  What we are witnessing is a new low by a tiny sub-population of out-of-hand science advocates. The brutality, harassment and name-calling scientists have had to endure, is now going back the other way from those that claim to represent a science-minded community. 

Stop now. It is not the way we teach. It is not the way we share what we know.  It is not the way you will represent ideas I hold dear.  

Some folks need to rethink their direction if they want to get where they are trying to go.

This is no longer about science. It has entered a realm of basic right and wrong. The day science advocates start denigrating others in our name, we've lost, and you shift the focus from bad science to me as your central problem.  Stop wasting my time. 

I'm not mentioning names. I received a tweet early this AM stating that we need to use social media to drive mass reporting of a popular alternative health website, in the interest of getting it banned. After all, that's what they did, apparently. 

I visited the associated Facebook page only to see that some had already boasted about recommending it for shut down.  Specious reporting because they disagreed with content, or in retaliation for the fact that that website was apparently used in the same take down of a 70k-member science-advocacy site. 

I expect this from the anti-GMO, anti-whatever communities.  They have ridden me to the point where I was ready to  quit science, where I wanted to just disappear.  I have been personally harassed to the point where I sat in a plane, off to another talk, and hoped it would crash in a ball of flames.  No kidding. 

Harassment continues to this day.  They just broke into my office two weeks ago. They reference the damaging false claims about me, the endless images attached to me forever on the internet, the slander, the hate.  I don't want anyone to endure what I deal with, and I don't want anyone claiming to stand up for science and reason to ever harm others in this way. 

Trust me. It sucks. Don't do to others what they did to me. Don't be them.

You will win this the right way, with data and evidence, by being a teacher.  

I'm disgusted.  When I see allegedly science-minded people using FOIA to interrogate the records of those they disagree with, when I see science advocates coordinating mass reporting of websites they don't like, when I see harmful epithets and four-letter words being used to personally harm those they disagree with...  I'm out.  I do not want to be part of that tribe. 

Raise your damn game.  This is too important, you are turning off the people we need to reach.  You are making my job harder.  If we are going to change to hearts and minds, we are going to win the heart and appeal to the mind. 

Tearing down others does not make us bigger. Raise your game. Elevate this conversation.  Remember that you represent something important.  Truth.  Deliver it on a silver platter to those that need to know it, not with a four-letter word or fist to those you don't like. 

That's how we'll create the change we need to see. 

Disgusted with (Some) Science Advocates

Just when you think the social media discussion of science can't get any more gross, it does.  This is no longer a discussion about science, about whether to play with DNA or vaccinate kids, about climates changing or chemtrails overhead.  What we are witnessing is a new low by a tiny sub-population of out-of-hand science advocates. The brutality, harassment and name-calling scientists have had to endure, is now going back the other way from those that claim to represent a science-minded community. 

Stop now. It is not the way we teach. It is not the way we share what we know.  It is not the way you will represent ideas I hold dear.  

Some folks need to rethink their direction if they want to get where they are trying to go.

This is no longer about science. It has entered a realm of basic right and wrong. The day science advocates start denigrating others in our name, we've lost, and you shift the focus from bad science to me as your central problem.  Stop wasting my time. 

I'm not mentioning names. I received a tweet early this AM stating that we need to use social media to drive mass reporting of a popular alternative health website, in the interest of getting it banned. After all, that's what they did, apparently. 

I visited the associated Facebook page only to see that some had already boasted about recommending it for shut down.  Specious reporting because they disagreed with content, or in retaliation for the fact that that website was apparently used in the same take down of a 70k-member science-advocacy site. 

I expect this from the anti-GMO, anti-whatever communities.  They have ridden me to the point where I was ready to  quit science, where I wanted to just disappear.  I have been personally harassed to the point where I sat in a plane, off to another talk, and hoped it would crash in a ball of flames.  No kidding. 

Harassment continues to this day.  They just broke into my office two weeks ago. They reference the damaging false claims about me, the endless images attached to me forever on the internet, the slander, the hate.  I don't want anyone to endure what I deal with, and I don't want anyone claiming to stand up for science and reason to ever harm others in this way. 

Trust me. It sucks. Don't do to others what they did to me. Don't be them.

You will win this the right way, with data and evidence, by being a teacher.  

I'm disgusted.  When I see allegedly science-minded people using FOIA to interrogate the records of those they disagree with, when I see science advocates coordinating mass reporting of websites they don't like, when I see harmful epithets and four-letter words being used to personally harm those they disagree with...  I'm out.  I do not want to be part of that tribe. 

Raise your damn game.  This is too important, you are turning off the people we need to reach.  You are making my job harder.  If we are going to change to hearts and minds, we are going to win the heart and appeal to the mind. 

Tearing down others does not make us bigger. Raise your game. Elevate this conversation.  Remember that you represent something important.  Truth.  Deliver it on a silver platter to those that need to know it, not with a four-letter word or fist to those you don't like. 

That's how we'll create the change we need to see. 

Another Downside of Glyphosate

Dr. Stephanie Seneff is famous for her observation that autism rates track glyphosate, leading her to the conclusion that glyphosate causes autism and that 50% of children will be autistic in 2025.  At that rate, and logic, every kid will be autistic in 2045. 

In looking at statistics, I found another confounding contributor.  Enjoy. 

The trend is undeniable.

The numbers of UFO sightings are increasing, no doubt brought on by the use of glyphosate.  Or maybe UFOs make kids autistic.  Or UFOs cause glyphosate. It is so hard for me to think wrong! 

When you look at a heat map of where the most sightings occur, look what is at the end of that yellow arrow.... You guessed it.  Monsanto World HQ.  Coincidence?

Happy Friday. Enjoy the weekend, listen to the podcast... covering the NAS Report with Dr. Neal Stewart. 

National Academies Report Summaried

A subset of the panel that met to synthesize the science on genetic engineering in crops convened at the American Society of Plant Biologists 2016 conference in Austin, TX.  Drs. Robin Buell, Rick Dixon and Neal Stewart discussed the results and process of the panel's conclusions.

There were 20 people on the committee from diverse backgrounds and looked at a wide variety of literature and testimony.  Testimony came from "individuals who have been directly involved in, or who have special knowledge of the question" and they were charged to examine "all credible views".

The committee examined relevant literature, over 1000 publications, saw ~80 personal interviews. Interviews were conducted with many non-scientists with strong anti-GMO views. The entire process was transparent and all information presented was available to the public. Any member of the public could access the information.  All of this was a first for a National Academies Report. 

The central synthesis is that there is no easy differentiation between genetic improvement methods. Any method, including traditional breeding, mutation breeding, transgenics, all have an equal potential to produce deleterious outcomes. 

Environmental, health, social and economic effects were considered in the synthesis of the report. 

Outcomes were from a consensus of 20 diverse individuals with a range of scientific sophistication:


Insect resistance:

• Reduction in yield losses from insects. 
• Reduction in the use of synthetic insecticides.
• Evidence of higher diversity of insects in GE crop areas. This "halo effect" allows farmers that are not growing Bt crops to experience benefits from GE crop production. This was documented in Wan et al, 2012 PLoS One, 7 (7):e42004. 

Herbicide Resistance:

• Can affect yield positively, but increase flexibility for farmer.
• Weeds are evolving resistance to glyphosate
• Integrated weed management approaches were recommended. 
• Herbicide use in cotton, corn and soybean is generally flat.
• The rate of resistance to glyphosate is consistent with the trend of weed resistance from any herbicide. 
• The glyphosate patent expired in 2000 which cut price, and likely contributed to wider use, wider GE crop adoption.
• Herbicide tolerant crops allow no-till ag and cuts soil loss. 

Yield:

Yield increase rates are not affected on a large scale from biotech plants. However, genes were not added to increase yields, plants were changed so farming can be more predictable and cost less.

The Seralini rats make an appearance in the discussion.

Human Health Effects:

• The committee went back through negative animal studies and noted how they were not well designed and statistically underpowered.    
• Feed conversion and other animal metrics did not reflect a problem.
• Epidemiological data from GE consuming and non-GE consuming countries did not show a difference. 
• The conclusion was that there was no evidence of adverse health effects. 
• Seralini was invited to give a presentation, and disappeared from his video screen during the discussion.

Social and economic effects were discussed, and concluded generally favorable economic impacts for farm producers, but there was a lot of heterogeneity in the data.  One issue is that traits are stacked and that not all farmers want stacked traits. There is a difficulty to find some kinds of non-GE seed in certain crops. Future considerations need to be considered with respect to patents, regulation and other product restrictions.

There is concern about how gene editing may be over-regulated.  It is a powerful and successful technology with huge numbers of studies emerging using it.  Cebus has even generated a CRISPR-based herbicide tolerant crop. 

The committee also looked to -omics technologies and how they might work in helping with the safe and effective regulation of genetically engineered crops. Can such technologies be used to really define the composition of plants to ensure more confidence in their safety?  There was a discussion that the public sector could do this job well.  

Predictions suggest that there will be great strides in disease resistance and output traits.  There will be gains in forage crops and crops generated for biofuels.  The long-term reality and environmental impacts are of course not known, but will always be considered.  There also was a recommendation that the pubilc sector play a bigger role in commercialization, and also funds available for examination of potential problems. 

The final synthesis is that it is about the product, not the process, and that the safety focus should be most focused on novel traits. Also that -omics technologies should be used more frequently in safety assessments to have a greater confidence in product equivalence.

The strength of the report comes from its careful language and nuance. There's no evidence that it will solve every problem and no evidence that it is dangerous. The technology has strengths and limitations and when we discuss it we need to consider evidence carefully and look at individual traits. 

This work is a tremendous synthesis from a massive amount of information and a lot of hours from experts in the field. It was a landmark report that will stand as a part of the history of this discussion.

Follow on Twitter at #GEcropstudy

I'm Not Pro-GMO

For years I've had to make that clarification.  I'm not pro-GMO.  I never would characterize myself as pro-GMO. 

Last week Mark Lynas and I answered questions for an audience in Belfast, Northern Ireland. At the end the moderator polled the audience for who was "anti-GMO" and who was "pro-GMO". Mark and I sat quietly and did not raise our hands.  

That's me, Mark and Prof. Chris Elliot at the event in Belfast.

The moderator quipped, "Obviously both of you are pro-GMO." 

Mark and I both rejected that categorization. 

As a scientist, I find such terms of ideological grounding quite troubling.  Genetic engineering is a technology.  I can think of good applications, I can think of evil applications.  My synthesis of four decades of literature and a deep understanding of the technology says that the applications have been overwhelmingly positive. 

Consistent with the recent interpretations of the National Academies of Science, there is no evidence of health problems, no plausible mechanism for health related-issues, and environmental concerns that must be monitored and addressed. 

That's it. Not pro-GMO. 

Also, my views could change later today if evidence is presented. 

Most of this blog's readers likely feel the same way-- that we want to understand technology and stand by a scientific synthesis.  

But remember, this is a question of perception, especially to the folks on the fence that are not sure what to believe.  You are less likely to earn their trust by taking any position that seems ideological. 

Dr. Steven Novella came to a similar conclusion recently.  He said something like, "I'm not pro-GMO like I'm not pro-UFO... it all boils down to evidence." 

Remember, this is about communication, and taking a side can alienate us from those that want to understand the science.  It is our duty to be objective, fair and scientific. That has no pro or anti side.