Wiley Podcast · Keith Matthews and Chris Wozniak: Talking Ag Biotech Episode 2

Keith Matthews

So, this is Keith Matthews and Chris Wozniak with the second episode of Keith Matthews and Chris Wozniak talking Ag Biotech. Good morning, Chris.

Chris Wozniak

Good morning, Keith, how are you?

Keith Matthews

I'm doing well. I'm doing well. I am really, really very excited to get together this morning and talk about Ag Biotech because we had some really significant developments since the last time we talked. It's interesting because we said that we were going to plan to have some future episodes of the podcast and we kind of had a little outline or a game plan of what we were going to talk about and then, voila! President Biden released his executive order and I think that's really big news. I was very excited about that. And then we also have USDA Animal and Plant Health Inspection Service (APHIS).

Keith Matthews

APHIS came out with a determination on a purple tomato which actually got a fair amount of news and visibility. People are kind of excited about that. So, I thought that sounds like a really good couple of topics for us to delve into.

Chris Wozniak

Sure, I agree.

Keith Matthews

So, the interesting thing about the executive order. So, the last three administrations each have had actions related to biotechnology. So as folks will recall President Obama initiated a modernization and update of the coordinated framework close to the end of his administration. And then during the Trump Administration there was an executive order which basically further confirmed U.S. executive government executive grant support for biotechnology. And now, President Biden has come out with executive order 14081, which I think is actually fairly significant and that there's a lot there in terms of what this whole of government approach to promoting biotechnology and “biomanufacturing.” What are your thoughts on these actions? What do you think about this?

Chris Wozniak

Generally, I'm supportive of all three of those executive orders, in that, as you know, over the last 25 or more years there's been a lot of consternation and debate about the place of biotechnology. A lot of fear mongering, etc. So, anything to me that shows that we, as a government, are standing behind the technology and there are really many technologies involved for things like AG food and feed production as well as biomedical. Even some things that are structural dealing with concrete, etc. I think that it gives the citizenry of the country, you know, reason to think and pause and say well “Is this being regulated appropriately?” “Can I feel safe feeding this to my family?” And I think the answer is becoming, increasingly, yes. There are still some naysayers, some NGOs and things that my opinion, they strive to disrupt the process but, after more and more time goes by, and we see the positive aspects of biotechnology, and very, very little that's really been run afoul or unpredictable or anything like that, that this latest executive order, I think does a good job talking about things like education. To me that's one of the keys.

We can talk about this more, but I was pleased to see in the briefing, that some of the folks present from Office of Science and Technology Policy (OSTP) as well as other both government and private companies really pushing the idea that education - k to 12 - and beyond. Not just supporting PhD students and postdocs. But starting young. And I can see it in my own experience. I've done some, I won't call them lectures, that sounds too formal but speaking with third graders, fourth graders, and high school students both in Fargo, North Dakota and here in Arlington and Alexandria, Virginia. And I'm amazed at the difference between what these children know at these young ages compared to what I knew at that age. I mean some of the things they were talking about were things I learned as a freshman student in college in biology.

Keith Matthews

Absolutely.

Chris Wozniak

And so, I'm happy to see that in education. Because to me that's the game changer. It takes some time. But that's the game changer. In addition, from what I understand, they're putting some real money behind this as well and that's obviously key to getting these programs moving.

Keith Matthews

Yeah, you speak about the White House briefing that was held on the executive order. And it's interesting because, for anyone who hasn't done so, you can actually go to the White House webpage, to the website, and there's a link to the brief. It was three and a half hours and actually may not even have to go to the web page, but it's on YouTube. So maybe you can find it through YouTube.

But it's three and a half hours of folks talking about this and talking about the significance of biotechnology to this administration. And one of the speaking in terms of AG Biotech, one of the persons who spoke was USDA Deputy Secretary Jewell Bronaugh, who gave some examples of specific actions that USDA is going to take. And you speak of education, well, apparently USDA has said they're going to invest $68,000,000 in training the next generation of AG researchers, educators, and extension specialists. One thing that I was actually very pleased to hear is that USDA says they're going to put $500,000,000 into the development of new sustainable fertilizers. And there is no question whatsoever as to the importance of fertilizers to improving crop yield. Fertilizers, biostimulants, that whole range of crop inputs. But a lot of your fossil fuel based fertilizers are not the nicest chemicals in the world. So, it's great to hear that USDA is going to put some money into developing sustainable, hopefully biologically based, type fertilizers that will be more environmentally friendly in helping us to grow the food that we need.

Chris Wozniak

Oh yeah, definitely. And I'm happy to see it as someone who used to work for USDA and funding competitive grant proposals on things like biotech, risk to the environment, food, safety, etc. and I can tell you in talking with colleagues at National Institute of Health (NIH) and National Science Foundation (NSF) and looked at the amount of money that was directly, in my opinion, going to, what I call, real agriculture. People had problems that needed to be solved - whether it's pests or disease resistance or whatever it is - and we had somewhat of a pittance compared to what the folks at NSF and NIH were seeing. And I'm happy to say, if they're going to put this kind of money behind some of the programs that nationalize food and AG, and really push the biotech angle. They've had for close to 15 years now, a program that specifically deals with organic agriculture. And they were able to come up with $40,000,000 back in 2007 or 2008 to fund that. Whereas, in the biotech realm, we were looking at $3,000,000. So, I think it's high past time that the biotech sector and - doesn't have to be exclusively biotech. I think it has the most potential in the next 10 to 20 years to really revolutionize. Because as folks in that briefing pointed out, we're looking at the potential of 10,000,000,000 people by 2050. We have a lot of work to do to grow more on less land. And I think biotech is one of the key tools in the toolbox, so to speak, to make that happen.

Keith Matthews

Yeah, absolutely. Absolutely. Well, one of the other things. The agencies, the executive branch, they’re always saying this. This is something that we're going to do. We're going to streamline regulations, we're going to try to streamline the regulatory process, make it easier to bring these sorts of products to market to get them approved or bring in the market. Well, that's always a nice sentiment. It's a sentiment that you hear every year for the last 12 years, if not longer. But in fact, how does that really happen. So, the first thing I'd like to focus on is an actual streamlining of the regulations and now it seems like it may be bearing fruit, pun intended. Which is APHIS and their amendments to part 34070 for part 340 and some of the things that are happening there. So, what are your some of your thoughts on that?

Chris Wozniak

Well, from what I've read about the secure rule that APHIS has put forth and it's in action. We've seen that already, starting with this regulatory review process where they look at a product before they start the formal environmental review or anything like that or the Plant Protection Act. Just look and say “is this something we need to regulate”? And to me that is an absolutely crucial step in moving regulation forward in the sense that, not everything needs to be regulated the way we've been doing it the last, you know, 25 years. So, in and these cases if you look at something like this gene edited purple tomato. And can say well you know there's no good reason for us, it's not a plant pest, which is one of the regulatory triggers for APHIS, then we don't need to spend a lot of time on this. And they put it out there on their website, and they're keeping a list of trait and crop combinations. And in the past APHIS has referred to this as sort of an extension process which may not be the most accurate term. But, basically, what it says is if we see something that looks very similar to something we've already done the environmental assessment on, etc., it's already been - their old terminology was deregulated so they deregulated - it's no longer a regulated article. Then when we see the next one, we don't have to go through all that. And I applaud that wholeheartedly. I think that makes perfect sense. I wish that was the case also at EPA with plant corporate protectants. It seems like at times we've done so much work on BT-corn, BT-cotton, and BT-Soybean, that when the next one comes in, it should really be simplified both in terms of the timeline and the amount of data generation. But my understanding is it's generally not.

And so, you know that's one of the things about the APHIS rule I think is a big step forward in that realm. The only one thing I'll say that was a little disappointing, in one part they stipulate that if you're going to do a homology directed gene editing, where you have a template to prescribe what type of DNA changes you want, you're limited to a single base pair.

Keith Matthews

Yeah, I going to ask about that.

Chris Wozniak

And so, when I, I queried a colleague there who shall remain nameless, and I said “well, how did you come up with one base pair?” And he said, “well, they had to pick a number.” And, to me, that's just not…

Keith Matthews

It's better than zero.

Chris Wozniak

Well, true. It is better than zero. But see the other thing in that rule, if you read the detail, if you do a cut with cast nine or whatever your favorite enzyme is. Double-stranded DNA cut. And then you get this non-homology directed replication. So, it's repaired with nucleotides that are available, there's no template. You might get two, three, four, eight different nucleotides in an order that weren't there before. And that's acceptable. That's okay. But if you direct it, then apparently, you're limited to a single base parent and I hope they see with time that we can venture a little further than that. The key is, there, you don't do a traditional food safety assessment at APHIS. That's not sort of their job, so to speak. FDA would look at that or, if it's a pesticidal trait, EPA would weigh in.

But it's fairly simple and straightforward to do bioinformatics, homology to toxins, homology to allergens kind of assessment. And just say “yeah, that 30 base pair gene editing you did? That's fine.” In general, I want to say, and reiterate, I'm positive about the steps they're moving forward with, with a couple of caveats and hopes for the future.

Keith Matthews

Yeah, just follow up a little bit on that though, from a legal standpoint. I do find that a bit…because I really focused on that when the when the rule was promulgated a couple of years ago. That they limit it to site-directed changes to one base pair. And I know that they put that out for comment. They took comments and they explain why they did that if you look at the preamble, they explain that. But the problem with that is you put that in a regulation, and then that regulation is enshrined in law until the regulation is amended. For those who are aware of the long, long history of the part 340 amendments, you have my sympathy. For those who aren't aware of it, that process started in 2008 and there were at least three proposed rules that took comment. And so you know there were two iterations where they put out a proposal, they took comments, and then they decided they couldn't go forward and they finally went forward with the with the final rule in 2020.

But, that just is an indication of…rulemaking is so cumbersome, and it takes so long, and to put something like that, that is so prescriptive in a rule that then, to change it, you're going to have to go through a rulemaking process - an APA notice and comment rulemaking process. Heaven forbid that that takes another twelve years. I don't think that it would, but still, you know that's my suggestion when I was in the EPA's Office of General Counsel (OGC), was always my recommendation to the agency was always - to my agency clients - was always if you're doing a rulemaking, make it as…give yourself as much discretion as you possibly can. Not completely open ended, because avoiding for vagueness. But, to the extent that you set up the structure, make sure if you can that you have some ability, that you have some leeway for discretion in there, because if you just say one and that's it and when somebody comes in they have two or three, then they've got to go through a completely different process. And what's the justification for that?

Chris Wozniak

Yeah, I personally don't know that there is a scientific justification for that. I think that you mentioned discretion, and to me that's one of the keys. For example, the FDA Center for Veterinary Medicine has practiced enforcement discretion in the past. I had this Glofish come on the market many years ago. They said there's no need for us to regulate that, and, end of story. And to some degree APHIS has been able to do that with certain products where they feel, again, “we don't need to reinvent the wheel here.” I haven't really seen that as much at EPA. And, to me, that's one thing you have to remember - that those three agencies I just spoke of deal with a qualitative risk assessment. It's not quantitative with biological or biotech products now. Certainly, some of the conventional chemicals, they do the quantitative risk assessment, a probabilistic risk assessment. The difference being that the probabilistic risk assessment relies on lots of preexisting data and further data generation to model what may or may not happen. Whereas with the qualitative, it's really based on the expertise of those risk assessors and the risk managers as to whether something meets the statutory standard. Whether it's no unreasonable adverse effect on man or the environment, or whatever it is. And, to me, that's the way it should be. I mean I think you need to be able, as professionals, particularly when you have a group of these folks who've been working on these kinds of products, should be able to say, “there's really nothing here.” We can do a note to file, do a public notice in the Federal Register, whatever, that this is going out.

And we're done. Another example, quickly, is when the FDA's Center for Food Safety and Applied Nutrition looked at the protein that's in the Impossible Burger meat. It's based on a plant based version of hemoglobin, leg hemoglobin. And they didn't have to do tons of studies that required data generation. They looked at the structure of the protein, looked at the amino acid sequence, and compared it to hemoglobin, which is in every mammal and some non-vertebrates as well, and said “this is similar enough. We're good.” Yes, and that's the kind of regulatory change that I would like to see effected across the board because, to me, if you have these professionals and they're experts and well-educated and have great experience in the job, then allow them to exercise that and move forward. Now I realized it makes some attorneys in OGC a little nervous.

Keith Matthews

Yeah.

Chris Wozniak

I get that. But, by the same token, I don't think we have all the time in the world. We have a real need, whether it's climate change, whether it's feeding the folks, as we look at population increases. We need to get moving and some of the current timelines for these regulatory actions are incongruous with that.

Keith Matthews

Yeah, and we really do have to get back to that concept first articulated back in the mid-80s in the coordinated framework. Articulated, but I think never really put into effect of regulating product, not the process. You don’t have to regulate the process.

So, speaking of that. The fact sheet that came out with the executive order with respect to regulations said “advances in biotechnology are rapidly altering the agricultural industrial technological and medical products landscape. This can create challenges for developers and innovators that your initiative will improve the clarity and efficiency of the regulatory process for products of biotechnology.” So, as I said, every administration says that they're going to do that. I think a significant issue that we, certainly in the United States, clearly in other areas in other parts of the world like the EU, clearly have more problems, you know in this respect than we do here in the United States. But one of the things is that the science of biotechnology is advancing so rapidly. What scientists are able to do and the kinds of changes and the products that they can develop. It's just really, I struggle to see how we come up with a regulatory system that in fact, can safeguard the public health and the safety and the environment. And, at the same time, not produce just almost intolerable delays and hindrances to the development of biotechnology.

Chris Wozniak

Yeah, no, it's a difficult question for sure in the sense that you're always trying to balance the public good and safety etc. And as we talked about earlier today, that perception is key. If people whether - they're consumers of foods or farmers using AG products inputs of various kinds - if they're not confident that those are able to be used in a safe manner and in some case with food in a nutritious manner, a wholesome manner, then the products simply aren't going to prosper. The good news in my opinion, is that thanks in small part to these executive orders, but also a lot of other efforts and just demonstration equality products, I do think the tide is turning. I think we will see more and more folks accepting biotechnology. That doesn't mean everything that's labeled biotech. There are some people, for example it was talked about in the White House briefing, who are growing bones in a lab that can be used in joint repair. So, instead of getting a metal knee replacement or a replacement, you get one made of real bone. I have no doubt there are some people just really uncomfortable with that if they thought of it. But, if you think about it, it makes a lot of sense. And I think some of these companies are really doing some amazing work. Particularly in the area too of microbes. We've talked about this before where, genetically speaking, it's much easier to tweak a bacterium, or even a yeast or other eukaryote, as compared to breeding a plant. It's 13+ years from identification of a trait in a plant to commercialization for transgenic or biotech trait. At least that's been the history. And with these microbes, you can make these changes in a couple of months and get out in the field with them and test them. And I think that's one aspect that's really going to push the regulatory system. More and more folks are to be working with microbes. Some people will be comfortable with that. Some may be not as much. But I think with the right regulation, the right approach to the regulation, and following guidance from people like the NIH, for example, has their list of microbes to avoid etc. I think that's really one of the main aspects of the future. But I mean it's already here. It's not just the future. We're already seeing an uptick in applications for AG purposes. But there are, as I mentioned here earlier, there are people at Defense Advanced Research Projects Agency (DARPA) for example, have a program that deals with repairing concrete. Strengthening concrete with synthetic biology- derived microbes. And so those are the kinds of things that I think the regulatory system is going to have to deal with in whatever manner. I think, right now, it's going to be perhaps a bit of a wakeup call when these kinds of things start coming in.

But I think that, as they said early on with the coordinated framework back in 1985-1986, when they were formulating it. These organisms that are some already in field trials and testing and some forthcoming that have a variety of different purposes and capabilities. Some are for everything from repairing and strengthening concrete. Some for fixing nitrogen from the atmosphere in the soil around plant roots. And others have a variety of what we would think of as plant regulator type influences on plant root architecture. And these are already here, I say in field trials, some are entering the market. But there are many more coming where folks you know are putting tens, if not hundreds of millions of dollars, in on these projects to move into a whole realm of microbes that do a variety of things in the soil. And some of them you can think of more of like a soil amendment helping with soil structure, mobilization of phosphorus, etc. Others may be for plant disease resistance, reducing root rots, or crown rots, etc. So, I think that's really the immediate future, at least in AG Biotech and food biotech, is microbial.

Keith Matthews

Yeah. I agree. There's so much going on now related to the Phyto biome and the microbiome. The Phyto biome, the microbiomes, the rhizobiome. And, since we last talked, I was in Denver at a conference of the Phytobiomes Alliance. And they asked me to come out and talk about the regulatory structure that's applicable to microbes in the EPA for a regulatory structure and also USDA regulatory structure applicable to microbes. And I really enjoyed that meeting, I stayed out for the entire two and a half days of a meeting. And it was, aside from the regulatory session that they had, I gave a talk on FIFRA regulation, USDA regulation, there was another gentleman that talked about TSCA regulation of microbes and then we had a panel of industry representatives that talked about what they were doing. But, aside from that session, it was mostly basic science. And it was really fascinating. And it's not very often nowadays that I go to a meeting that I get to have the opportunity to go to meetings that are just basic science. But it's just really fascinating. Some of the things that are going on, some of the research that's going on, some of the discoveries that are going on related to the microbiome, the rhizobium phytobiomass and so, there's a lot that's going on there. But one of the things very important for product developers to realize and recognize is that the regulatory structure that they will face depends upon what their product - what their microbial product - is intended to do. And from a scientific standpoint, speaking as a lawyer, to a scientist, it doesn't necessarily make a whole lot of sense, but the statute and the regulations are what they are. So, if you're making claims that your microbe impacts the plant's physiology that enables it to take up nutrients, or to withstand abiotic stress for example, that could very well be a pesticide claim.

Whereas if, for the example you just gave, if you have a microbe and it makes nutrients in the soil more available to the plant for uptake, well that could be a soil amendment, or a plan inoculant, or a plant inoculant that has soil amendment properties.

That's not regulated as a pesticide. So, it's not easy for folks to kind of understand that. Particularly when you're a scientist and you don't focus on the law. So, that's something that I actually spend a fair amount of time working with just explaining to people and also working with clients to make sure that they understand that particular claims that you're making will have different regulatory impacts.

Chris Wozniak

Yes, clearly. And this new executive order seeks to provide a portal or channel through the unified biotech website that USDA hosts for the three principal regulatory agencies, such that a person could get - in a timely manner - an answer as to who would regulate their product. Or if it's regulated at all. Now, it's a very laudable goal. And it may sound simple, but it's not. One of my first questions when I saw that paragraph in the EO was, “well how does this mesh, for example, with the Pesticide Registration Improvement Act (PRIA)?” There are defined timelines, for example, under category M009, it says “Here's your fee, and, in whatever it is, three months, we'll tell you whether you're regulated as a pesticide or not.” Well, that's not going to jive with this portal concept very well. So, I'm not sure how they're going to work out the details of that. PRIA is a statute you can't just ignore the dictates of that act.

And so, I think though, that that is an important goal. I can't give you details, but I've spent roughly the last month working for a client where I'm trying to find out who would regulate their product. And I'm still working on it. So, just trying to find an answer. Which agency will take this, if any? And I worked for the system for 35 years so, I should have a better handle on it. And even after the coordinated framework update that finished up in 2016, and the agencies identified the areas that are germane to their jurisdiction and their statutes, there are some new products that will challenge that and cause somebody to think. Which is a way to open. But there are some others that are still kind of less clear and one of the, again, goals of this EO is to clear up ambiguities. And as you mentioned, mosquitoes are a good example. So, if you make some claim you're reducing a viral titer in a mosquito or maybe it'll impact dengue or yellow fever or something. FDA regulates it. But if you just say I want to kill mosquitoes, it's EPA’s. And that makes sense to us in the regulatory arena because we're familiar with those documents that laid that out. But, to the average scientist on the outside, like why? Why does FDA do one, EPA do the other, and at some point, I think there's going to have to be some sort of a reckoning.

That we as a regulatory system need to clarify and simplify “who does what?” Give up the turf battles and maybe work coordinately. When I worked for EPA, I also did some technical support work for FDA on one of the first generation engineered mosquitoes. It worked out fine. I mean there should be more of that kind of cooperation going on instead of it being a special case.

Keith Matthews

Well in terms of people asking those questions as to “Why is it like that?” or “How does it work?” It's not just the scientists. Also, the product developers. But that's a good segue and a good way to end this episode of our podcast, which is to say, that if you are a product developer out there and you have questions about which agency regulates your product or where do you go where to go to figure out which regulations apply to your product. The best place you can go is to Keith Matthews at Wiley Rein (kmatthews@wiley.law). Give me a call, send me an email and we will get you headed in the right direction. Well with that Chris, thank you very much this has been great again and we will look forward to doing it again very soon.

Chris Wozniak

Sounds good my pleasure, Keith.

Keith Matthews

 All right, take care.

Chris Wozniak

You too bye.