Okay, so what the heck are “omics”?

In the National Academy of Science’s genetically engineered crop study report released a few days ago, they proposed a new regulatory framework for analyzing the safety of any crop variety that relies on a technology called “omics”? So what in the world is an omic and how is it useful?

There are many different types of “omics”. It all started with GENomics which involves figuring out and comparing the GENES between organisms. This has allowed scientists to identify different genetic “markers” associated with diseases and other traits. However, genomics are only part of the story. Just because a gene is present doesn’t mean it is active.

Active genes are used as a template to TRANSCRIBE molecular messengers called RNA. Analyses of the levels of RNA within an organism in a given tissue or in response to a certain stimulus are known as TRANSCRIPTomics, but it doesn’t stop there.

RNA transcripts serve as instructions that enable cells to build PROTEINS. Proteins are the real workhorses of the cell, and are largely responsible for an organism’s traits. Comparisons of the protein landscape in an organism are accomplished by PROTEomics.

But what about all the other cool stuff floating around in cells? Hormones, pigments, vitamins, ethanol? These molecules are assembled within cells and are called METABOLITES (and plants have way way way more of them than people: nicotine, caffeine, capsaicin…..). And guess what? Where there’s a molecule there’s an “omics”, so now we’ve got METABOLomics.

So omics includes the study of the genes, RNA, proteins, and metabolites in an organism (there are even more, but I won’t go there). Sound complicated? It gets worse. When scientists gather data for omics studies, they get it in pieces.

So you know the human genome project? It’s not like somebody scanned a human blood sample and printed out the entire genome. To put it into perspective, if the human genome was unravelled and blown up to the diameter of a strand of hair, that hair would be 30 miles long and form a wad the size of a volleyball.

The genome had to be sequences piece by piece (not particularly systematically) and then those pieces had to be reassembled. To put it into perspective, Dr. Keith Bradnom uses the following analogy: Take 100 identical jigsaw sets, mix all the pieces together, throw away 10% of the pieces, randomly mix in the contents of an unrelated puzzle, throw away the cover of the box, and assemble!

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Some scientists on twitter even called this analogy an over-simplification! As you can imagine, this takes not only a lot of brain power, but also a lot of computing power. Then once you finally get it assembled….

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So that’s why the National Academy of Sciences said that we need to further develop these technologies. The idea is that we could compare the “omics” between new crop varieties and existing varieties and analyze any significant differences for potential safety concerns. As you can see, this is no small project, and that’s why they call it “big data”.

If you are a non-scientist, I hope you found this explanation helpful. If you are a scientist, particularly a computational scientist, please let me know in the comments if I’ve made any mistakes or am missing important details.

Editorial Summary of the National Academy of Science’s Consensus Report on Genetically Engineered Foods

This morning, the National Academy of Sciences (NAS) released a consensus report titled “Genetically Engineered (GE) Crops: Experiences & Prospects”. You can download the full 400 page report which includes a four page summary here. The public release of the report was accompanied by a webcast including a presentation of the report followed by a question and answer session. My notes on the webcast including screen shots of many of the slides are synthesized below. I apologize for any missing slides or points. None were omitted intentionally. As a scientist, I tended to focus my notes more on human health and the environment and less on social/economic points.

The NAS is a private, non-profit organization that “is charged with providing independent, objective advice to the nation on matters related to science and technology. Scientists are elected by their peers to membership in the NAS for outstanding contributions to research. “

Volunteers for the NAS committee to assemble the consensus report were vetted for potential conflicts of interest. The committee was composed of a very diverse range of scientists and experts from a variety of different topic areas ranging from entomology to science communication. The committee was initially divided, as there were many different views on the prospects and progress of genetically engineered crops. However, all members were required to back their claims with evidence as the discussion progressed, and they ultimately came to a consensus that best reflects the available data.

Committeemethods

In analyzing the issue, the committee looked to two decades of scientific literature including nearly 1000 articles. They also listened to input from 80 diverse speakers, and reviewed over 700 public comments. These videos and other materials have all been archived and are publicly available. The study was sponsored by the New Venture Fund, the Gordon and Betty Moore Foundation, the Burroughs Wellcome Fund, the U.S. Department of Agriculture, and the National Academy of Sciences. The report had 26 diverse reviewers. The committee had to respond to each of their comments and defend their conclusions with evidence.

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The first key message from the committee emphasized the increasing difficulty of differentiating crop improvement technologies that qualify as GE from those that do not (you can read my personal explanation of this issue here). The chair of the committee Dr. Fred Gould likened this to the invention of cell-phones, cameras, and lap-tops which were once all distinct technologies that now have overlapping functions.

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For this reason, the committee contends that it is impossible to “make sweeping generalizations about the benefits and risks of GE crops”. For the report, they mainly focused on three of the most widely grown GE crops: corn, cotton, and soybeans. The report also focused on the two most commonly utilized traits: insect (BT crops) and herbicide (RoundUp-Ready crops) resistance.

The committee generally concluded that insect resistant crops result in increased yields due to fewer losses from pests. Planting of insect resistant crops also correlates with a decrease in the application of synthetic pesticides and an increase in biodiversity. However, improper management of insect-resistant crops can and has resulted in the evolution of resistant insects.

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They also concluded that the planting of herbicide-resistant crops can lead to an increase in yield. Beyond yield, the technology is substantially useful to farmers for several reasons. Herbicide-resistant crops allow farmers to apply a single herbicide where they might before have used many at a time when it is optimally convenient, safe, and physiologically advantageous for their crops.

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My screenshot of this slide did not turn out, so I looked it up in the archives

The committee also notes that weeds (like the insects) have evolved resistance to this herbicide creating a huge challenge for farmers who will need to change their management strategies. The committee also made a point to emphasize that comparisons of kilograms of herbicide use before and after herbicide-resistant crops were widely adopted is not meaningful unless the health and environmental impacts of those herbicides are also compared.

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The committee’s analysis of the environmental impact of GMOs, revealed some evidence of gene flow from GE crops into wild ecotypes, but only under experimental conditions. The committee in general found that there was no evidence of environmental problems caused by growing GE crops. There was also no direct connection between the use of herbicide-resistance crops and no-till practices as farmers had already begun to move away from tilling prior to the advent of GE crops.

GENE FLOW:ENVIRO

In response to the question of whether or not GMO crops are contributing to yield increases, the committee contends that they are. They acknowledge that what’s good for one farmer is not good for another, but farmers in general are gaining from the technology.

yield rate

That said, as these graphs show, there is not a spike in yield increase following the advent of GE crops (indicated by the vertical purple line). This likely demonstrates that changes in management practices and genetics through conventional breeding and other crop genetic improvement methods are equally as important for increasing crop yield. New types of GE crops could potentially contribute to the rate of increase depending on the traits introduced and the socioeconomic/cultural/legal factors that influence the adoption of new GE crops.

yield 2

To assess the impacts of GE crops on human health, the committee analyzed over 200 existing studies, looked for changes in patterns of human health before and after the adoption of GE foods, and compared the overall health of people in the United States and Canada (where GE crops are widely grown) with the health of people in Europe (where they are not). The committee reported that many of the existing animal studies were not optimally designed.

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Reports of long-term health of livestock fed GE diets and studies comparing nutrient and chemical compositions of GE food were more reliable. From these, they did not find any reliable evidence linking GE foods to health concerns. They also did not find any differences in human health that correlated with the adoption of GE crops.

human health 2

Given the lack of legitimate health concerns associated with GE foods in general, the NAS proposed a new system for regulating future GE foods. The proposed regulatory approach would compare the “omics” (levels of various compounds including nucleic acids, proteins, and metabolites) of new crops with the same levels in existing varieties.

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New crops would then be categorized as Tier 1 if there are no differences or Tier 2 if there are differences that have no expected health or environmental effects. Tier 1 or 2 crops would not require any further testing. If the new crops have differences with potential for health or environmental effects or differences that cannot be interpreted, they would be classified as Tier 3 or Tier 4 respectively and would require further testing. Under this system, most new varieties would fall under the category of Tier 1 or Tier 2.

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On the issue of labeling, the committee concluded that because there are no health effects associated with GE food, there is no justification for labeling them on the basis of food safety. There are, however, policy reasons for which labels might be instituted such as consumer autonomy. It is outside of the legal authority of the FDA to institute a label for policy/cultural reasons, so labels would need to be mandated at the congressional level.

Read what a handful of other academic scientists had to say about the report here.

 

What’s everyone’s beef with beef?

I grew up on a cattle ranch, which means I ate beef for every meal. My plates included parts of a cow that would make most readers blush. Chicken might as well have been a vegetable.

When I left rural eastern Colorado, I was surprised to meet people who considered my family’s beef dependance not only unusual but also unethical. My college roommate, who also moved to Boulder from a cattle ranch, actually had tofu thrown at her because she wasn’t a vegetarian. Even the meat-eaters  insisted on purchasing only grass-fed, organic beef. Talk about a culture shock.

The reasons for animosity towards omnivores range from trendiness to animal welfare, but often included an argument that meat-consumption is less environmentally friendly. There are at least two reasons cited for this. For one, the calorie conversion by animals, particularly cows, is not very efficient. That is, we get more calories out of eating the corn that a cow would eat than by eating the cow. Additionally, cows and other ruminants literally burp greenhouse gases (GHGs).

As I read an NPR article about cow belches, I found myself wondering whether adjusting the cow’s diet would reduce emissions. If rumination leads to GHG emissions, might strictly grass-fed cows be less environmentally friendly since they ruminate more? To find out, I took to twitter, and asked Amy Young, a staff research associate in a beef cattle genomics and biotechnology lab at UC Davis.

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Amy responded with an extensive review of research comparing the carbon footprint of different protein sources, as well as a reader-friendly synthesis of these and other data into a consumer info handout by the primary investigator in Amy’s lab, Dr. Alison Van Eenennaam.

The simple answer to my question provided by these data is yes, cows on a strictly grass-fed diet produce more GHGs; however, the reasons behind my prediction might not be correct. Grass-fed beef, when compared with intensively raised, corn-fattened beef, have a higher emission to protein ratio because they spend more of their life out walking around burning off calories. Strictly range-fed beef take longer to get to market weight, which means more time spent burping methane.

But the issue gets more complicated. For cows fed corn, the environmental impact of growing the corn has to be taken account. If the cows are pasture grazed, then what type of pasture? If the cows feed on dry grasslands not useful for farming, and only eat forage, then there is no loss in terms of land use or wasted calories. But for cows fed on irrigated pasture as many of the happy cows in California are, water use has to be considered. And cows that live in colder states have to be fed bailed hay during the winter to qualify as grass-fed, which means farmland that could be used to grow food is growing feed.

Confused yet? Me too, but the major take home message is simple. There’s a huge range of environmental impact for beef depending on where/when/what/and how they’re fed. The same is true of every single prospective protein source, flora or fauna. Dr. Van Eenennaam summarizes this concept beautifully:

There is no one sustainable source of protein, and depending upon the question that is being asked (e.g. carbon emissions/water use/land use/energy use per calorie/unit weight/unit protein), different food products will look like the “most sustainable” choice. There are also ethical and religious concerns around animal welfare and/or consuming meat and/or animal products (e.g. eggs, milk). Often there are direct conflicts between what is perceived as the most sustainable production system. Is it the one that best protects animal health/welfare, the one with the lowest environmental footprint per unit of product, or the most efficient? As with all dietary decisions there are tradeoffs among the various pillars of sustainability, and consumers will need to make the choices they consider to be best for their particular family values, budget, and circumstances.”

When it comes to making environmentally conscious dietary decisions in the United States, possibly the most important point to remember is that, regardless of our specific diets, most American’s consume way more protein than they actually need. Perhaps instead of focusing so much on which particular food sources are the most environmentally friendly, we should try to remember that everything we eat has some impact on the environment. Restricting total calorie and protein intake to not surpass what is essential is probably the single clearest dietary step the average westerner can take to decrease their environmental footprint.

So you heard GMOs are banned in Europe…

The lowdown: The European Union has approved the cultivation of one GMO and importation of many (with more on the horizon). The European Commission and European Academies Science Advisory Council, like other government and scientific associations around the world, supports the evidence-based conclusion that GMOs currently on the market are not any less safe than  their conventionally bred counterparts. Nonetheless, certain member states within the EU have elected to ban cultivation of EU-approved GMOs on political/cultural grounds.

The details: Headlines claiming that GMOs are banned in Europe abound. These are often accompanied by an assertion that the United States should follow suit. Does the EU know something the US does not? Where are these claims coming from?

In response to the question “why are GMOs banned in other countries,” Dr. Robert Paarlberg, Professor of Political Science at Wellesley College and Adjunct Professor of Public Policy at the Harvard Kennedy School, clarified:

Very few countries explicitly ‘ban’ GMOs. In most cases, governments have simply not yet ‘approved’ various GMO crops for cultivation, or for import, or for human consumption. The presumption that each separate GMO should require case-by-case and use-by-use approval, by national government regulatory committees, has greatly slowed down the uptake of the technology. In effect, GMO foods and crops are being regulated as strictly as medical drugs, even though there is no evidence that they carry more risks than conventional foods and crops (in the official opinion of the EU Research Directorate, for example). Critics of GMO crops have promoted highly precautionary regulatory systems as one way to slow down the spread of the technology, and in large parts of the developing world governments have not yet given any cultivation approvals at all

As has been previously noted, Europe is not a unified country, but a continent made up of separate countries, many of which participate as member states in the coalitional European Union. The  EU as a whole has established directives regarding the import and cultivation of GMOs, and, like the US, requires pre-market safety testing and post-market environmental monitoring of GMOs. The EU has only authorized one crop for cultivation, pest-resistant Bt corn (Mon-810), however 58 GMOs have been approved for import as food and feed, and 58 more are awaiting regulatory approval. 17 of these have received a positive European Food Safety Authority (EFSA) assessment, and one is inconclusive. Applications for cultivation of 8 additional GMOs (including one renewal of Mon-810) are pending, and 4 have received a positive EFSA opinion.  Furthermore, the EU relies heavily on external sources for soymeal, and imports more than 60% of plant protein needs. 90% of these imports originate from countries where GE soybeans cover 90% of total soybean acreage.

Within the EU, member states can choose to ban the cultivation of GMOs that have been approved by the European Commission. Previously, a member state could elect to ban cultivation of approved GMOs only “if they had new evidence that the organism concerned constitutes a risk to human health or the environment or in the case of an emergency”. No such evidence has ever been presented. In response to a series of legal battles, the EU revised its guidelines to grant member states more freedom over decisions to ban GMO cultivation. Under the new (2015) directive:

a Member State may prohibit or restrict the cultivation of the crop based on grounds related amongst others to environmental or agricultural policy objectives, or other compelling grounds such as town and country-planning, land use, socio-economic impacts, co-existence and public policy.

Reluctance of some European countries to cultivate GMOs is often cited as evidence that European scientists and authorities are uncertain of their safety:

Washington wants Europe to ease restrictions on imports of these foods, commonly known as GMOs for genetically modified organisms, but the EU is skeptical they are safe.

However, according to an extensive European Commission Report on EU-funded GMO research:

The main conclusion to be drawn from the efforts of more than 130 research projects, covering a period of more than 25 years of research, and involving more than 500 independent research groups, is that biotechnology, and in particular GMOs, are not per se more risky than e.g. conventional plant breeding technologies.

Within the report, Marc Van Montague Chairman of the Institute of Plant Biotechnology for Developing Countries (IPBO) at Ghent University in Belgium goes on to say:

Now, after 25 years of field trials without evidence of harm, fears continue to trigger the Precautionary Principle. But Europeans need to abandon this knowingly one-sided stance and strike a balance between the advantages

Further, the European Academies Science Advisory Council has stated:

The scientific literature shows no compelling evidence to associate such crops, now cultivated worldwide for more than 15 years, with risks to the environment or with safety hazards for food and animal feed greater than might be expected from conventionally bred varieties of the same crop.

Despite approval of GMOs, much of the food in EU member-state grocery stores is GMO-free, because, according to the European Commission:

Many food business operators have made the choice of not placing GM food on the shelves. This may be linked to the labelling obligations of the GMO legal framework, as well as the availability of non-GM alternatives.

 

Here are a few other helpful resources on GMO regulation in the EU:

GMOs: EU decision-making process explained

Fact Sheet: Questions and Answers on EU’s policies on GMOs. April 22, 2015

A decade of EU-funded GMO research

European Academies Science Advisory Council: Planting the Future

A look at GMO policies in different nations. Layla Katiraee, July 6, 2015

Where are GMOs grown and banned? Genetic Literacy Project, Accessed April 27th, 2016

 

It’s the plants. They’re learning. They…remember

 

Sorry Mark Wahlberg, this is not a prequel to the 2008 sci-fi thriller “The Happening,” but maybe M. Night Shyamalan was onto something. Could plants learn that large groups of people are threatening, then kill them with an aerosol neurotoxin? Probably not. But they do learn, remember, forget, and even make decisions in some capacity.

If you’ve ever touched a mimosa pudica, the so-called sensitive plant, you know that plants can freak out. They sense a disturbance and react, possibly to protect themselves from hungry insects. Could they learn to tell the difference between threatening and non-threatening stimuli?

To find out, Dr. Monica Gangliano, associate professor in the school of animal sciences at the University of Western Australia, stimulated mimosa plants repeatedly with water droplets. After several showers, the plants stopped responding. Remarkably, months later, the same plants still didn’t recoil from a water droplet. The plants seemingly learned the water was not a threat, and remembered, even in the absence of stimuli.

These results are striking, but discoveries of learning and memory in plants are not new. Plants are exposed to a variety of stresses. Some are enduring like the cold of winter. Others are transient like heat stress in the late afternoon. Responding to stress requires energy, and often stalls growth. Thus it is beneficial for plants to remember and respond quickly to some stresses while learning to ignore others.

Plants have several strategies for recording memories and passing them on to future generations. In response to stress, plants can reorganize their DNA to activate or inactivate certain genes in a semi-permanent and heritable way. Plants can also store molecules of RNA, which act like molecular messages to enable a rapid response to future threats. A recent discovery by Dr. Susan Lindquist’s group at Massachusetts Institute of Technology suggests that plants may also store and transmit memories using proteins called prions

Prions are best known as the causal agent for mad cow disease (scrapies in sheep and Creutxfeldt-Jakob Disease in humans), but they are also associated with long-term memory storage in animals. Prions are able to adopt unique folding patterns. These patterns can be inherited and transmitted to neighboring proteins like a molecular switch that causes cascading and permanent changes.

Lindquist’s group used computational methods to look for genes in plants that resembled those encoding prion proteins in yeast. They then expressed the functional domain of what appeared to be a plant prion in yeast. The plant domain was able to functionally replace an analogous domain in a yeast prion protein. This strongly suggests that plants have prions or prion-like proteins.

Does this mean plants have brains, or plant neurobiology is the next big field of study? Doubtful. What some have called plant neurobiology is remarkably similar to what has always been recognized as stress response. To say that plants are making decisions probably gives them a bit too much credit. Decision-making is a more-or-less voluntary response. Plant reflexes might be a more appropriate term to describe the changes that occur in a plant in response to stress.

Nonetheless, similarities between plants and animals should not be ignored. Gangliano and Lindquist’s studies demonstrate the value of breaking down organism barriers in science. In the current structure, plant scientists go to plant science meetings, veterinary/livestock researchers go to animal meetings, and everyone else goes to meetings focused primarily on human health. Plants, humans, and other animals coexist in an interdependent web, so should our approaches to studying them.

Sources

S Chakrabortee, C Kayatekin, GA Newby, ML Mendillo, A Lancaster, S Lindquist. Luminidependens (LD) is an Arabidopsis protein with prion behavior..Proc Natl Acad Sci U S A , (2016).

PA Crisp, D Ganguly, SR Eichten, JO Borevitz, BJ Pogson. Reconsidering plant memory: Intersections between stress recovery, RNA turnover, and epigenetics.. Sci Adv 2, e1501340 (2016).

S Berry, C Dean. Environmental perception and epigenetic memory: mechanistic insight through FLC.. Plant J 83, 133-48 (2015).

M Gagliano, M Renton, M Depczynski, S Mancuso. Experience teaches plants to learn faster and forget slower in environments where it matters..Oecologia 175, 63-72 (2014).