Sunday, August 16, 2015

Labeling animal genes in plants

A while back, a student I spoke to asked me how GMOs would be labeled if an animal gene was added to a plant. She was a vegetarian and was concerned about this. I told her that I didn't know, but thinking about it now, I would have challenged the notion of labeling something as an "animal" gene. In this post, I'm going to explain the concept of common DNA between species, a topic that I touched on briefly in an earlier post. This post will also explain at a genetic level how agriculture is not natural, a topic that I also described in an earlier post, but will go in more detail here.

You may have read that "humans share ~50% of their DNA with bananas" or that we share around 99% of our DNA with chimpanzees. What does this mean? Before I delve deeply into the topic, I need to remind everyone that DNA is the blueprint for proteins. Proteins are the building blocks of our cells. As such, the same protein can be found in different organisms. For example: we have livers and mice have livers, so it would make sense that many of the proteins that are involved in developing the liver and are involved in the liver's metabolic functions would be similar between mice and humans.

As I've mentioned before, changes in DNA are normal. Each one of us has a few differences that we didn't inherit from our parents. These are known as mutations. We tend to think of mutations as negative things: they can cause cancer or genetic disorders. But mutations can also be beneficial. In our species, mutations have allowed for adaptation to high altitude in Tibetans or have protected individuals from heart disease. The same is true in nature: mutations allow for plants to develop resistance to pests, or in the case of weeds, to pesticides.

When a mutation takes place, there are several things that can happen: if the mutation is "bad", then it won't propagate to the next generation. If a mutation is "good", then it gives the organism a selective advantage and it propagates. As an example, if a mutation gives an organism a leg up against a predator, then odds are that the "mutant" will live longer and have more kids. Some of the kids will inherit the mutation, and they in turn will live longer and have more kids. Pretty soon, there will be more individuals in the population that have the awesome mutation, because they've all lived longer and had more kids. After many generations, that mutation might spread throughout an entire population so that everyone has it. Sometimes a mutation is just neutral: it doesn't hurt the organism nor does it improve matters.

Throughout evolution, each species will have developed unique mutations that make that species what it is. Different populations of the same species will have also developed unique mutations to help the population adjust to the region, such as mutations in certain human populations that have allowed them to develop resistance against regional diseases.

So, I thought I'd share an example and I'm taking the easy way out and will share an image from my thesis. In grad school, I was working on a gene and we thought that it might be involved in autism (ASD - or autism spectrum disorder). So I examined the DNA from that gene in a few hundred individuals with ASD. I found quite a few mutations and got really excited, so the next step was to do the same study in controls (i.e. individuals who didn't have ASD). I found that my controls had just as many variations. This graphic has the results from all that work:

Spouse, don't freak out!! I know that it's a really crowded graphic and you want to shut down the computer and never look at the image again, but I'll walk you through it. You're looking at a bunch of rows with really small A, C, T, and Gs. That's the DNA sequence for the gene I was working on in various ethnic populations around the world. What the DNA sequence is doesn't matter for the point I'm trying to make so quit trying to squint at the screen. Each row is a different human population: Japanese, Caucasian, etc. There are also a few other primates included: Chimp and Gorilla. This is commonly done when we study evolution in humans so that we can figure out how ancient a mutation might be. You'll also see a row with letters other than A,C,T,G: that's the protein (i.e. amino acid) that is encoded for by the DNA sequence. Then, you see a few boxes: those are the parts of the DNA/protein that are thought to be crucial for the protein's function. Next, you'll see that there are a few bases that are highlighted: those are the bases that are different between human populations. The shaded letters are what I want you to focus on.

Keep in mind that these shaded letters were in my controls. These individual don't have any diseases (that we know of), and it just goes to show that differences between populations is "normal". But you may also have noted that there aren't any variations in those boxes: the parts of the protein that we think are crucial for its function. There aren't even any differences in these boxes between humans and other primates. So by looking at this example, you can see how similar we are to chimps: much more than we'd like to believe.

As to difference between species (i.e. not just between different populations of the same species), this is what that exact same gene looks like at the protein level between many different species (below). In this graphic, you're not looking for shading, rather, you're looking for stars along the bottom, indicating that there's no difference in the protein in all the different species indicated at that spot.

Published with my own permission. Original is here.  
Again, you can see that the regions of the protein in the boxes have lots of stars along the bottom, indicating that through the millions of years of mammalian evolution between mice and human, not much has changed in the "important bits" of this particular protein.

Of course, there are genes unique to each species and there are scientists who dedicate their research to studying those differences in attempts to better understand, for example, what makes Homo sapiens so different from our other primate relatives.

Now, here's a key point: could you say that this particular gene was a dog gene? Could you say that it was a human gene? Not really. Which one of them is "right"? Which version of the human gene in all the different populations is "right"? The example I've provided is for a gene that is unique to mammals, but there are genes that are shared from bacteria all the way up to humans. There are genes that are shared in plants and humans. So it's very difficult to use the term "belong" when we talk about proteins and genes.

And now we move into the next topic: if you take the rat version of the gene and add it to a dog, is it unnatural?

The evolutionary process that I've described throughout this piece doesn't really apply to agriculture or domestic animals including cows, horses, or common household pets. Think about it this way: if you take a chihuahua and abandon it in the forest, do you think that it could fend for itself? Is the chihuahua best adapted to the environment and predators that a dog faces? Not really. It needs this $2600 Gucci dog carrier to survive in this cruel world. We've bred our pets and selected our crops to meet OUR needs, not theirs. We have bred and selected our dogs to be docile and to shed less, when they should have evolved to be better hunters and faster runners.

The same goes with our crops. We've bred our crops for taste, flavor, and size. Plants in the wild are poison filled, disgusting things that no predator would want to eat. The mutations that we've selected for aren't the ones that nature would have selected had we let her do her thing.

So when someone states that the Innate Potato is unnatural because we've taken a segment of a wild potato gene and have added it to another potato, how is it more unnatural than what we've already done in agriculture? Even transgenesis (taking one gene from a species and adding it to another), happens naturally, as was recently found in the case of the sweet potato where bacterial genes were "added" by nature to the tuber.

Genes are genes: they change, get copied, erased, and broken apart throughout evolution, but we can also choose how to change, copy, erase, and break them apart to meet our needs. These needs are getting more difficult to meet as our environment changes and our population grows, so we should have all forms of trait development available at our disposal, including transgenesis.

Feel free to ask email questions or to comment below.

Sunday, August 9, 2015

The funding of science: public & private sector collaborations

Hi all,

There's been a storm in the science communication world over this article. In case you've missed it, several public sector scientists who are outspoken proponents of biotech crops have been targeted by anti-GMO activists, and have had their emails seized and read under freedom of information laws. The argument is that as public sector scientists, the public should be able to read their emails and know if they have been cooperating with private sector businesses (i.e. Monsanto). One of these scientists is Dr Kevin Folta.

Dr Folta has superstar status in the GMO world. I've emailed him a handful of times and each time, I've been painfully nervous. Saying that he has been a target of anti-GMO activist activity is putting it lightly. He has constantly disavowed receiving any sort of funding from Big Ag. The article I posted at the beginning outlines that the emails uncovered that he received 25K from Monsanto, which Dr Folta says was used for outreach activities, and that he had travel expenses covered when doing public communication. This has raised a veritable poopoo-storm in anti-GMO groups, who are claiming that Dr Folta personally received 25K from Monsanto.

As you may know, I'm currently doing R&D in assay development for a private company completely unaffiliated with Ag. I do hands-on work and I've been back at the bench for almost 2 years now. But before that, I used to work more closely with customers, representing their voice and concerns during product development. So I want to provide a brief explanation on why and how a private sector scientist such as myself needs to collaborate with public sector scientists, and vice versa. I think that this relationship is extremely difficult to understand unless you're in this area of work, so I hope to provide a little bit of insight. I also hope that other scientists in the private and public sector speak up about this to educate the public, and if you need a platform, I'm making my blog available for it.

As a company goes about developing a product, at some point it needs to start generating data outside of the company. There are several reasons for this: a) the company wants to put the product through its paces to make sure that it works well in different settings and environments, b) it wants to generate marketing material to sell the product. No matter how much data you generate within the company, it doesn't carry nearly as much weight as data generated by someone from outside the company. Sometimes it also has to do with samples/materials: if you're developing an assay for a disease, where are you going to get the patient samples to make sure your product works? A public sector scientist would be interested in such a collaboration because if the product DOES indeed work, then the scientist could get a very good publication out of it. How the product is provided, the timeline, the reagents, funding (if any), how the data will be shared, etc. are all decided and agreed upon in advance between the groups, and much of it depends on the type of collaboration (whether it's a trial, a beta test, or a pre-commercial agreement).

If such a collaboration does lead to a publication, it is common that someone from product development will be listed as an author on the paper. If not, the company's role in the collaboration is outlined in the funding sources. In my experience, I have not seen a scientist get personally paid for such a collaboration, but that is not to say that it would not happen.

There are other types of collaborations: sometimes a public lab will contact a product developer to find out if a certain application of a technology is possible. If the company thinks that it might be, a collaboration might be set up following the same principles outlined above.

In my experience, the times in which a public scientist actually gets paid by a private company is when they are engaged as an expert or as a consultant. I worked on a project designing an assay where we hired a few people from the public sector, who were experts in that particular field, to help with the assay design and provide us with guidance.

Could the public sector scientists have conducted the research and done the work on their own? Possibly. But it costs a lot of money which the public lab may not have, a lot of internal knowledge about how the product works which the lab may not have, and other resources which may not be accessible to them.

Another very common practice in the industry is conferences and seminars organized by a company to allow clinicians and scientists to share their research into products or applications of a product. Of course, companies will try to select speakers that are pleased with the performance of the product, but in no way do they control what is said. I actually helped organize one such seminar while my sales-rep was on maternity leave. Of the speakers invited to attend, I gave them the option of sending me their slides so that they were pre-loaded or bringing their own laptop. Most chose to bring their own laptop, so I didn't even see the slides that the speakers were going to use until the day of.

In no shape or form did the speakers get coached. In fact, one of the speakers mentioned that he preferred a product from another vendor for one of the applications he spoke about. All the speakers were offered reimbursement for their travel expenses getting to and from the seminar.

Why would a scientist accept to speak in such a forum? First, the scientist gets to share his or her research with a very broad audience. Second, many individuals in that audience are working with the exact same products, so they can discuss and offer recommendations to one another. Why would a company sponsor such an event? It allows scientists to better understand a technology or assay which they may not be familiar with. Hopefully, the scientists will come up with ideas on how they could use that assay in their research, or will walk away impressed enough with the applications that they'll consider using it. It's a risk. If scientists aren't pleased with the product, make no mistake about it: they will tell everyone.

In addition, private industry sponsors many other "marketing" type activities. For example, a company might sponsor a coffee break at a conference, sponsor the printing of conference material, sponsor an evening mixer at a conference, etc.

Do I think that these activities cross some sort of line and are "bribes" of some sort or that they could buy a scientist's opinion on a topic? Absolutely not. If you think that's the case, then you do not know how expensive it is to run a lab. Check out to get an idea of how much common reagents, plasticware, and equipment costs.

At the same time, I am fully aware that I design assays for evidence-based people with little brand loyalty: if I build something that sucks, no one will use it. Unlike a sports team (who can lose for years, but still have a sell-out crowd), a consumer electronics brand (who can make a product that isn't as good as a competitor's), or a clothing brand (who can make a delicate piece of clothing that you have to dry clean if  you want to wear if more than one time), if it doesn't work, if it doesn't do its job, then customers will go elsewhere.

That's my personal experience as a private sector scientist working with the public sector. My guess that much of it applies to many other companies and segments of the biotech world.

Dr Folta has clarified that he received money from Monsanto for his public outreach efforts and that this has been spent organizing talks, coffee, and getting to and from the places he speaks. His critics have said that this just highlights that he's been lying for all these years after constantly disavowing that he doesn't receive money from "Big Ag". In case it needs to be said, there's a difference between funding someone's research and funding someone's outreach activities. Think about it this way: if Monsanto had organized the session, bought the coffee, and Dr Folta had simply showed up, given a talk, and then walked away, would you think that he was "bought"? So what's the difference? Or better yet, if Dr Folta held a seminar for students to teach them how to use Excel, and Microsoft sponsored the event, would you have a problem with it? My guess is "no".

Public research scientists struggle to get their funding. One of the main reasons (if not THE main reason) I didn't go into the public sector was because in grad school it seemed that most of my prof's time was spent securing grants. That didn't seem like the life I wanted to lead: I wanted to DO the science, not just sit down and write about it. If we want our public scientists to be completely detached from the private sector in their funding, in their outreach activities, in their conferences, in their seminars, in college campuses (including infrastructure such as arenas and stadiums), then we need to provide them with more public funds. And how do we do that? We increase taxes. There's pretty much no way around it.

Whether or not we increase taxes and better fund our public scientists, there's one thing that bears repeating: science is science. Regardless of who you are, where you work or who funds you, if your data sucks then your data sucks. If your data's awesome then your data's awesome.

One final thing: as I've been following the story of the US-Right to Know's actions against biotech advocates, I've thought at many points in time "I'm so happy I'm in the private sector and don't have to deal with this. If I were one of those scientists, I'd probably just quit engaging with the public." And that's probably what the aim of these Freedom of Information requests is: to exhaust our public sector scientists to the point that they just collapse. A public sector scientist running a blog similar to mine would be way more effective because, in the public's perspective, private sector scientists are considered less ethical. So support public sector scientists, donate to their granting/funding agencies, and call out US-RTK in their efforts which are nothing short of a witch-hunt.