Cadmium, Arsenic, and glass manufacturing in Portland: What do the test results mean?

Tonight at Cleveland High School (in Portland, OR) the Multnomah County government convened a public meeting to discuss the recent pinpointing of elevated cadmium (Cd) and arsenic (As) levels in Portland to the Bullseye Glass manufacturing facility at 3722 SE 21st. Avenue. I was frankly hoping that the representatives of the Department of Environmental Quality (DEQ) and Oregon Health Authority (OHA) would put the levels DEQ measured of those metals in October into a health context. Unfortunately, they did not, and the meeting degenerated into an expression of public anger that didn't answer many questions.

Fortunately, we have well-established models of cancer risk from the Environmental Protection Agency (EPA) and reference exposures from the California EPA for the threshold of likely health risks in general. Those models and exposures are based on data from industrial use of Cd and As, as well as documented environmental exposures from published studies. In other words, we have an evidence-based context for the numbers DEQ measured in the air outside Bullseye's production facility. In hopes of helping people understand the big question voiced at the meeting tonight ("What do the emissions mean for my family?"),  I've compiled the results from air quality monitoring with those reference levels.

To make things easier to compare, I've put all the exposure data and relevant reference levels in a table with everything in the same units (micrograms per cubic meter).

Let's break these numbers down a bit. First off, the DEQ numbers come from the agency's monitoring station in the parking lot of Fred Meyer corporate headquaters, 120 meters from the Bullseye Glass factory. You can get those numbers here. Note: DEQ reported nanograms per cubic meter, so you have to divide those numbers by 1,000 to get micrograms per cubic meter.

The Oregon DEQ benchmarks are reported here. These numbers are set based on the EPA lung-cancer model, where the benchmark is the level at which exposure would increase cancer risk by 1 in one million for a person who breathed that air for their entire lifetime (chronic exposure).

The EPA cancer risk and CalEPA reference exposures come from this page (arsenic) and this page (cadmium). I used the 1 in 10,000 lung cancer risk estimate from EPA because it was closest to the exposures reported near Bullseye. It's a linear model, so it shouldn't be surprising that you can just multiply the DEQ benchmark by 100 to get that number as well. Note: The CalEPA reference exposures are given in milligrams per cubic meter, so you have to multiply those numbers by 1,000 to get to micrograms per cubic meter.

From a first look, you may notice that the average exposure DEQ measured falls near the 1 in 10,000 risk for lung cancer from the EPA model (it's actually about 1 in 6,300 for As, and 1 in 20,400 for Cd). The averages are also 2-3 times the CalEPA threshold below which no health effects at all are expected.

Hopefully you've noticed something else from the table above: the DEQ benchmarks are quite stringent. They are far below the CalEPA thresholds for any likely health effects at all from inhaling either cadmium or arsenic, and they correspond to a 1 in one million increase in lung cancer risk (based on the EPA models). For some perspective, men have a 1 in 13 chance of developing lung cancer in their lifetime (and a 1 in 2 chance of any cancer), while women have a 1 in 16 lifetime chance for lung cancer and a 1 in 3 lifetime chance for all cancers (check out the data from the American Cancer Society). Taken another way, if one million people lived at the DEQ benchmark, we would expect one lung cancer due to cadmium exposure, and about 70,000 lung cancers from other causes. Even going up to the 1 in 10,000 risk in the table above, you would expect around 50 cadmium-related lung cancers in a population of one million who all lived at the monitoring station, as compared to the 70,000 cases from other causes. Did I say stringent?

It's important to repeat that the data above come from right next to Bullseye. If you go even a short distance away, mixing in the atmosphere will lower the concentration of arsenic and cadmium. DEQ has even published a preliminary map of expected cadmium exposures here, based on relative concentrations of the elements in moss samples collected by the US Forest Service. Here's a screenshot:

These numbers are in nanograms per cubic meter again, so you have to divide by 1,000 to compare with the table. It may help to think of the boundary between the highest two concentrations (around 30 ng/cubic meter) as the average from monitoring (29.4 ng/cubic meter). By the time you get to the Fred Meyer day care, the estimated levels have dropped to about 0.01 micrograms/cubic meter - or right at the CalEPA threshold below which any health effects are unlikely. Farther out, at Cleveland HS or Winterhaven Elementary, levels are more like 0.005 micrograms/cubic meter, half the CalEPA health threshold and in the 1 in 100,000 probability of cancer in an individual due to the cadmium exposure. You may also notice a smaller point-source in north Portland, which looks like it's at Ostrom Glass and Metal Works.

So what's the conclusion?

Even for students at the Fred Meyer day care facility, inhaling the air is unlikely to cause any ill effects at all based on the CalEPA threshold and EPA cancer models. The cancer risk estimate is already down to 1 in 60,000. In other words, if there were 60,000 students in that day care, we would expect one of them to get a lung cancer from Cd exposure. There are in fact approximately 100 children who attend the facility, and they will not breathe this air 24/7 for 70 years (the assumptions of the EPA model). As for other health effects, the exposure looks like it would be right at the CalEPA threshold outside (and probably lower inside).

Further away (for example, in the residential neighborhoods east of 26th Ave. and south of Gladstone St., exposures should be lower. While there are reports of a detectable level of Cd and As in the soil at the day care facility, soil and air tests at Cleveland HS and Winterhaven Elementary ordered by Portland Public Schools did not detect any Cd or As. (I hope to link to those results if and when they are released).

In short, the levels DEQ detected are at or below where one would expect much of an elevation in lung cancer risk or other health consequences. Personally, I don't see grounds to get particularly worried about human health given the numbers that have been reported.

Let me be clear: It would be great to get cadmium and arsenic exposures down to the DEQ benchmarks, especially since they are elements and do not "break down" in the environment the way molecular toxins can. Given the possibility of soil accumulation, DEQ's efforts make sense. I hope that the employees at Bullseye are being evaluated for As and Cd exposure, since their exposures are potentially much higher inside the factory. And re-evaluating the pollution control measures at Bullseye is a no-brainer, since we now know that it is a significant point source for As and Cd. There is lots of work to be done.

However, the community anger expressed at tonight's meeting is, in my opinion, totally unjustified. It was clear from DEQ and Forest Service presentations that sleuthing out the source of Cd and As was an involved process, from DEQ identifying the two elements as more concentrated in monitoring than predicted from modeling known sources, to the Forest Service using a moss and lichen model to establish relative exposures throughout the City, to the DEQ doing targeted monitoring near Bullseye to confirm the source and document the exposure levels. Put simply, government agencies discovered the problem and tracked it to its source before anybody noticed any consequences. To me, that looks like effective detective work on the part of DEQ and USFS. The first commenter, reading a prepared statement from Neighbors for Clean Air, characterized the process as "an abysmal failure of government." While I understand that many of my neighbors are worried and angry, I think we can do better than that.


UPDATES:
As the conversation has broadened to include emissions of hexavalent chromium, I've written another post dealing with that metal.

Also, soil testing results from the nearby daycare have been released, and I've worked through those in another post.

The OR state cancer registry (OSCaR) has released the results of an analysis of lung and bladder cancer in the area around Bullseye glass; here are those results with my analysis.

Does Eric Metaxas really have comprehensive imagination?

Recently an opinion piece by Eric Metaxas, "Science Increasingly Makes the Case for God," caused a bit of a storm after the Wall Street Journal ran it on Christmas Day. The argument it makes - that the physical world is fine-tuned to match the needs of living things - is nothing new; similar claims from authors such as Michael Behe, William Dembski, and Michael Denton were part of founding the Intelligent Design movement in the early 1990s. The fact that Metaxas can still get publicity from his claims suggests a serious examination is in order.

The foundation of Metaxas's argument is the striking correlation between the physical conditions of the Earth and the needs of organisms that live on that Earth. As he puts it:

Today there are more than 200 known parameters necessary for a planet to support life—every single one of which must be perfectly met, or the whole thing falls apart.

This correlation is something any knowledgeable observer should accept; the match between organisms and their environments is quite striking. Given that correlation, we naturally want to understand the cause, and that is where Metaxas's views differ so radically from those of most scientists.

There are really two possibilities. The first explanation argues that life is picky, fragile, and static, and that the universe must have been adjusted to the particular needs of living things. This is where Metaxas's description, that "every single [parameter] must be perfectly met" comes from. If the universe needed adjusting (often called "fine-tuning" when describing the constants of physics), then there must have been an intelligent being doing the adjusting - hence "the Case for God."

The other possibility is that the conditions of the universe are relatively static and not "adjusted" to benefit life, but that living things are capable of evolving so that they can tolerate those conditions (at least in a few places like Earth). Either explanation could produce the striking correlation; how do we choose between them?

Each explanation makes strong demands on our understanding. One particularly strong demand for the fine-tuning explanation, often unstated or ignored, is a complete understanding of the possible ways living things could exist. Arguing that the universe has to be adjusted to the requirements of Earth life includes the implicit assumption that the Earth includes the complete sweep of potential living things. If you want to argue that Metaxas's "200 parameters" have to be the way they are, you have to argue that the only way living things could possibly exist is pretty much just the way they do here on Earth.

As an example, if you insist that life absolutely requires liquid water, having planets with liquid water on their surface seems like a reasonable demand of the universe. Can you be sure of that assumption when the only examples of living things you know of all come from a planet with oceans? It's rather like insisting that all mammals deliver well-developed live young, completely ignorant of the marsupial branch of the mammal family tree. Time has not been kind to this assumption of "comprehensive imagination." That living things could survive in deep oceanic hydrothermal vents (way too deep to get energy from the sun), at the near-boiling temperatures of hot springs,  or in extremely acidic conditions were all hardly conceived (not even taken seriously enough to be considered impossible) until the organisms living in those environments were discovered. Claiming to imagine every possible way of being alive seems both remarkably arrogant and extremely unlikely. To borrow from Daniel Kahneman's remarkable book, this explanation suffers from the "WYSIATI" fallacy: What You See Is All There Is.

But what about the other explanation - that life has evolved to match the conditions in which it finds itself? That lineages of organisms can change over time was once considered an extraordinary idea, and one might rightfully demand some pretty strong evidence of its reality. After over 150 years with the idea of natural selection, the evolutionary biologist can point to a range of different types of evidence, from change in fossil lineages, to the hierarchical pattern of diversity of living things, to the underlying biochemical similarity of all living things. One can observe the evolutionary process in the lab with organisms whose generation times are conveniently short, as well as in decades-long studies of wild populations. We even know that life on Earth has adjusted to huge shifts in the composition of its atmosphere caused by living things themselves! In short, that lineages of living things on Earth can change over time is a well-documented fact. That other forms of life could evolve does not seem far-fetched, since there is no apparent reason the conditions for evolution (reproduction, a genetic system, and differential survival) could not be fulfilled in radically different forms of life.

So in understanding the strong correlation between environment and living things, we can either claim that life is inherently dependent on the conditions here on Earth (again, a claim of comprehensive imagination for which we cannot have any real basis) or claim that life can adapt to at least some of the environments available (for which we have abundant evidence, at least for Earth-life). If we are really honest about the limitations of our examples of life - and the limits of our imaginations - we should see the absurdity of the assumptions necessary to claim proof of supernatural fine-tuning. The far more plausible explanation is the evolutionary one, and it is the only one with sound empirical evidence.

(note: not long after I wrote this post, the AAAS hosted a session on what a "shadow biosphere" (i.e. not based on DNA/protein) might be like. There's an account of the session here, if you're curious.)

What would an Intelligent Design theory look like?

When I first read about the "hypothesis" of Intelligent Design, I figured it would go away soon enough. Clearly, I underestimated the degree to which a vocal segment of society will prioritize their personal beliefs in a Designer over all the evidence that suggests there is no design in nature (and yes, I know people talk about natural "designs" all the time in a casual way, just like we use the term natural "selection," when both are mere metaphors that save a lot of verbiage). Advocates of "ID" are constantly claiming it is science (it helps justify putting it in a public school science classroom), so I'm going to take the intelligent design argument seriously enough to put it in scientific terms. What would a theory of Intelligent Design look like, and what testable predictions would it make?

1. If natural structures are the result of a design process rather than undirected evolution, they should be consistently optimal. An entity intelligent enough to design any of the complex creatures we see around us (and powerful enough to put those designs into use) would be expected to do a good job, and the designs should be really good. As a corollary, we shouldn't see a lot of designs that mere humans like us could easily improve.

2. Good designs should not be limited to one taxonomic group. If it's a good design - one that solves a problem well - it should be widely used.

3. We shouldn't see a lot of history in an intelligently designed world. There's no reason a designer would need to provide continuity between the organisms it designed, especially if the intermediate forms between current organisms (what we call common ancestors in evolution) did not perform as well as the ones we see today. (If you like, you could call this prediction a more general version of #2).

4. An intelligent designer would try to make its different designs compatible. In other words, an designer with any intelligence would never design parasites. Why would such a creative and intelligent entity go to all the trouble to design an fancy multicellular creature, then toss in some single-celled bacteria (or even viruses) that could take that creature down?

Now I'm sure some of the folks on the ID side of things will find fault with these predictions; they may say that I'm limiting the mystery of how a Designer would have worked, or its purpose in creating living things, etc. But I'm trying to do science here, and if ID is to be a scientific hypothesis, it has to have specific testable predictions, just like all the great scientific explanations.

So how well does the evidence from nature match these predictions? Not very well. Starting with prediction #1 (designs should be consistently optimal), there's lots of non-optimal design out there. Using our own bodies as an example, humans have this terrible design in our throat, where we cross swallowed food with inhaled air and occasionally choke to death because of it. We also have chronic back difficulties from standing on two legs with a spine that works just fine for animals on four. Childbirth in humans is much more difficult than other mammals, because moms push our babies' big, brainy heads through a small opening in the pelvis (caesarian sections work in difficult deliveries because removing a baby through the big abdominal opening is far easier than the natural route for birth). And finally, anyone who has studied the hormonal mechanism for regulating blood pressure ends up with a big facepalm; the kidneys respond to an decrease in blood pressure by modifying a hormone made by the liver, which is then modified again in the lungs and kidneys, which then both goes back to the adrenal glands to make another hormone which tells the kidneys to increase salt retention in the urine, while all the while the third version of the liver hormone goes to the brain, which makes another hormone to tell the kidneys to absorb more water from the urine. In simpler terms, the kidneys use the liver, lungs, brain, and adrenal glands as intermediaries in the process of the kidney telling itself to absorb more salt and water from the urine. NOBODY would call that a good design. In each case, I'd say we humble humans could have done much better. And those are just a few examples from one species (us).

So how about prediction #2 (good designs should be used all over the place)? There are a lot of species out there that could really benefit from some traits from other groups. Gliding snakes and squirrels are pretty cool for snakes and squirrels, but they are awful compared to true fliers like birds or bats (feathers would be helpful). We mammals would be much better at long aerobic efforts if we had the flow-through lungs that birds do. Those birds would benefit from better recognition of their chicks than just "it hatched in my nest" (you did know that cuckoos are nest parasites, right)? And there are the marine mammals, which do remarkably well given the fact that they have to routinely return to the ocean's surface to breathe ("I could sure use some gills, Shamu!"). Examples of good "designs" limited to one group of organisms abound here.

Now for prediction #3 (we should not see history). I'll just come out and say it: history pervades the record of life on Earth. Extinction has eliminated most of the intermediate ancestors between the species we see today, but we know they were there from fossils. It seems very strange that a designer would respect the ancestry of its various groups so carefully ("no nursing for you - you're a bird!" or "yes, whale, I know you have fins, but they still have to have all the fingers inside"). It also seems strange that a designer would put out an Archaeopteryx - a stepping-stone species between dinosaurs and birds that could never compete against a modern bird, but could make it without any true birds around yet. Why design a cobbled-together intermediate when you could just do real birds?

I can imagine someone arguing that a designer was learning as it went, and that the various groups of organisms were somehow the "rough drafts" along the way (no doubt arguing that we humans are the polished final draft). But that means that this intelligent designer didn't just publish the best designs, but all the "rough drafts." Does that make any sense?

And finally, prediction #4 (different designs should be compatible). I'll leave predators and prey aside, and just point out that there are roughly four species of parasite on earth for every non-parasite species (and plants may justly feel that most of those animals are also parasites as well - at least the ones that aren't helping them with pollination). While parasites certainly have ecological roles and big effects, it's hard to see those roles as necessary ones. Ultimately, why would any intelligent designer handicap its designs with so many effective parasites?

So there you have it. Some realistic and rational predictions from intelligent design, none of which match the actual world we have. I'm sure that ID advocates will argue that I'm setting up a straw man, and trot out their own prediction that they see "complex specified information" or "irreducible complexity" as predictions of the model. You should realize, however, that ID is not the only theory that predicts "CSI" (evolution would do the same), so it hardly qualifies as a prediction that discriminates ID from other explanations. As for "irreducible complexity," every time the ID folks argue something is "irreducibly complex," patient biologists point out the "reducibility" to simpler forms, at which point the ID movement abandons the case and picks out something else. Camera eyes, bacterial flagellae...it's like a big game of evidentiary whack-a-mole. I'm just going to ask you to judge my predictions on their own merits, and remind you that there's this other theory that would predict that organisms would often be bolted together in funny ways, that ancestry would be central to what features those organisms would have, and that struggling to survive would put organisms at cross-purposes all the time. I bet you've even heard of it...

A metaphor for the anti-vaccination crowd

I'm perpetually amazed that we still have to discuss this, but the anti-vaccination movement still hasn't faded into deserved obscurity. For example, the keynote speaker for this year's National Science Teachers Association conference is Dr. Mayim Bialik - you probably know her as an actress on Big Bang Theory - who, despite a neuroscience degree, has not vaccinated her kids. She gave a very non-committal answer to a question from Ira Flatow about vaccination, arguing that it's just a personal choice for each family.

Of course, that's simply not true, if you understand epidemiology. Take, as an example, the fact that outbreaks of whooping cough (pertussis) are geographically connected to places where higher numbers of parents opt out of giving their kids the vaccine for non-medical reasons. In other words, everybody is put at higher risk of getting whooping cough in places where parents don't vaccinate, even in a state with a 91% average rate of vaccination for kindergartners. And yes, it's the unvaccinated who are at most risk, leading to the remarkable result that "with vaccine-preventable infectious diseases, the risk is higher for those higher in socioeconomic status" (Dr. Kenneth Bromberg, director of The Vaccine Research Center). After all, it's those with time on their hands who have the luxury of delving into the kinds of conspiracy theories that fuel the pseudoscience of the anti-vaccination movement. Yet the neighbors of those who do not vaccinate are put at higher risk, as are the kids who go to school with unvaccinated children, their infant siblings and grandparents, and anybody who has a compromised immune system who comes into contact with the unvaccinated kids. The primary risk is personal, but secondary risk to the community is really significant.

Yet even with all the data that show the effectiveness of vaccines (heck, the field tests of the Salk polio vaccine lay the groundwork for modern double-blind clinical trials) a public figure with a science doctorate can somehow remain equivocal and see it as a matter of personal freedom. So here's a simple analogy that may help readers understand why the rest of us don't just say "OK, don't vaccinate your kids."

If you drive at night, you can turn on the headlights (and taillights) of your car to be more visible and decrease the chances of your having a collision. "But headlights consume energy and reduce my gas mileage," you might argue. "I wonder if it's a conspiracy of the oil companies to make me consume more fuel and pad out their profits." Um, sure. "In any case, it's a personal choice. I should be able to drive at night without my headlights if I think the risk is outweighed by the fuel savings. It's not your business to tell me I have to run my lights if I have personal reasons not to use them."

Well, it is your personal risk that is greatest; if you drive without your lights, yours is the car most likely to get hit. But that's not the only risk; you put all the other users of the road at higher risk of colliding with you when you don't use your lights. Hence, we as a society require you to use your lights because it makes us all safer. Nobody complains about these laws; we all realize the communal good in requiring everybody to use their lights at night.

How exactly is refusing to vaccinate different?

The Agency problem

I recently heard an interesting podcast on "memes" and the extent of their similarity to genes. One of the hosts (and many online commentators) had trouble with the idea that memes (units of information transmitted among humans) could replicate themselves - after all, a song or phrase doesn't copy itself, does it? This was contrasted with genes, which we were assured could self-replicate, and thus the meme idea was dismissed. We can choose whether or not to pass along a pithy phrase, so it doesn't have the status that a gene does.

Of course, to anyone who understands genetics, the idea that a gene "self-replicates" is pretty silly. Aside from a few special sequences of RNA (and damn if those aren't interesting) DNA is just a molecular encoding of information - not fundamentally that different from a long string of text. Genes are particular stretches of DNA that code for useful proteins, but they are still just information. It takes a bunch of molecular machinery inside a cell to copy that information (or, for that matter, to convert it in to a protein). While it's true that the individual enzymes that copy, transcribe, and translate the information are produced from genetic information, it takes a collection of genes working in concert to duplicate any of the individual genes. For the gene to become more common in the world, it has to be in an organism that survives and reproduces. Genes replicate, proliferate, and disappear in cells in organisms (even if those organisms are unicellular), and genes can't "do" anything on their own.

So why does everybody just assume genes are doing their thing replicating and proliferating? Well, the fact that Richard Dawkins's groundbreaking book was called "The Selfish Gene" may have something to do with it. Dawkins pointed out that from the point of view of a gene, an organism is a "survival machine." Genes don't really "care" about individual organisms beyond their ability to promulgate genes. To bolster this view, Dawkins (correctly) pointed out that individual organisms (and even species) are incredibly short-lived compared to genes; hemoglobin genes, for example, are something like 500 million years old, and the genes for enzymes like DNA polymerase are presumably as old as DNA-based life itself - which is the only kind we know (and yes, RNA viruses are still DNA-based; they require the use of plenty of proteins from their hosts' DNA to reproduce). Most folks seem to accept some sort of independent drive for genes since Dawkins published the book - hence the idea that they are "self-replicating" - and the way Dawkins pointed out that evolution was not just about the survival and reproduction of organisms was a big step forward in understanding. Nonetheless, the idea that emerged ("it's all about the genes") is just plain mistaken.

The problem here is that we humans are used to the idea of agency. That is, changes come from agents which are capable of action in the world. In human political and social systems, agency is a basic assumption; if something happens, somebody must have done it. It's a great concept for explaining a market or a legislature. In understanding an evolutionary process, however, agency is basically useless, because changes occur at so many levels (gene, organism, population) at the same time that one just can't ascribe evolution to a single agent. Genes don't evolve on their own; neither do organisms. Populations evolve (change genetically over time) only to the degree that individuals in the populations are more or less successful at surviving and reproducing, but the change is at a genetic level (usually described as a change in gene frequencies). So who is the agent?

Really thinking deeply about this is hard when you're raised on agency; hell, even evolutionary biologists use Darwin's term "natural selection," as if some agent ("Nature") was carefully deciding who deserves to survive. That, of course, is not just nonsense, but unnecessary; organisms just survive and reproduce, passing on genes that determine part of the likelihood of survival of those organisms. In that situation, there is no agent that has to "select"; instead, better-surviving libraries of genes emerge in the surviving organisms, period. Evolution is literally the most natural thing to happen to reproducing organisms with some sort of genetic system, no agent required.

Back to memes. We have information (words, phrases, ideas, music) that sits around on its own, but tends to get passed around when you have people talking to each other. We (people) use information, share it, find it helpful, tell our kids. Nobody has to go out and force us all to put "ROFL" in our social media posts, but it works, and it spreads. That's a meme, and it deserves the same sort of respect as a concept in social informatics that a gene does in biochemistry. OK, I made up the phrase "social informatics," but you get the point. Genes and memes spread, or they don't; one is biological evolution, the other social evolution, but in any case, there's no point to trying to find the Agent of Evolution behind it all. In a situation where genes or memes can be copied, it just happens.

The problem with biotech patents

There's a big swirl of confusion today as folks try to make sense of the Supreme Court's decision over the patents claimed by Myriad Genetics for variant sequences of the BRCA genes. What Myriad wanted to do was patent the use of natural sequences of those genes (including naturally occuring variants) to diagnose breast and ovarian cancer risk. The court said that you can't do that; patenting native DNA is not permitted because it is a "product of nature". In other words, you can't just take something natural and claim a patent monopoly on its use. That's clear, and to many folks helpful; Myriad was charging something like $3000 per test (which, to be clear, is a massive profit compared to the actual cost of the laboratory work; Myriad would claim that profit is reward for discovering the connection between the BRCA genes and breast and ovarian cancers). If that were the end of the case, things might be reasonably clear...but of course it isn't.

Myriad also held patents on cDNA sequences derived from the naturally occurring BRCA sequences. That means they had isolated mRNA, the version of the gene that leaves the nucleus and provides the template for making proteins, and had then created a DNA version of that mRNA (that's what we call cDNA). Why would you want to do this? Well, for one, there are stretches of DNA in eukaryotes (basically, everything but bacteria and viruses) which are not used to make protein, and these introns are spliced out of the mRNA before it leaves the nucleus. If, for example, you wanted to make a lot of one of the BRCA proteins, you might put a cDNA copy into a bacterium and use it as a protein factory. You have to have cDNA to do that - the introns would screw up the final protein, because the bacterium would treat them like DNA that is supposed to be translated into protein. This is all pretty routine in a molecular biology laboratory.

The Court held that Myriad is able to patent cDNA sequences made from the BRCA genes. The thinking appears to be that because there is human work and manipulation going on, the cDNAs are no longer naturally-occurring. In a strict sense, the court is correct; there are unlikely to be human cDNAs of the BRCA genes floating around in nature. Most folks who understand biology are shaking their heads, however, as creating a cDNA is hardly an innovative thing; again, it's pretty routine. In fact, to convert mRNA back into cDNA, you use an enzyme (reverse transcriptase) that was isolated from retroviruses. Why? Because retroviruses make cDNA all the time - cDNA made from their own genetic material, which is held in RNA form. Retroviruses need to convert that back to DNA if they are going to get the host they infect to make more retrovirus from that DNA (getting the infected cell to make more copies of a virus is the way viruses reproduce). So making cDNA is routine, and the heavy lifting is done by an enzyme "invented" by retroviruses. Most of us think that through and wonder why the cDNA is patentable when the native DNA was not.

What the Court was trying to do, I think, is distinguish between natural DNA and synthetic DNA. One can easily order up a batch of short DNAs made in any combination of bases you would like; indeed, this is routine in a modern laboratory. The Court would surely like to protect with a patent the researcher who comes up with a completely new DNA sequence that does something cool that is not done in nature. One could also imagine someone combining sections of existing genes in a new way that was useful, and granting that invention a patent. In the first case, the product is a totally new DNA; in the second, it is a new combination of existing DNAs.

The fundamental problem, however, is that most biotech patents rely heavily on information derived from nature. The Myriad DNA patents were about using genetic information from DNA to predict disease. The production of recombinant insulin uses human DNA sequences to make insulin in bacteria; nobody "invented" insulin, but instead invented a way to make it in bacteria using the same DNA information. The Polymerase Chain Reaction, which was successfully patented, relies both on unique human ideas (using a fluctuation of temperature to progress through cycles of DNA duplication) but also on a version of the DNA polymerase enzyme that is stable at 95ºC. The enzyme that could handle that high temperature was not invented; it was isolated from bacteria that live in hot springs, and natural selection did the "inventing." That's what most molecular biology really is - cleverly finding ways to use natural processes to do stuff that doesn't happen outside the lab. We use natural enzymes to duplicate DNA, to cut it in specific places, and to link it back together when we're done. We use bacteria to convert DNA into protein, to store chopped up pieces of a genome, and to replenish our stores of particular DNA sequences. We isolate mRNA from bacteria into which we have cloned the corresponding DNA, then use retroviral enzymes to turn the mRNA back in to cDNA. The heavy lifting in molecular biology relies on agents that are "products of nature." At least for now, the human ingenuity is not in designing new things from scratch, but rather in finding out how to get natural agents to do new, useful things.

This fundamental property of biotech just doesn't play well with patent law. Patents were designed to protect inventors designing new things (from the French dessiner, to draw). Indeed, drawings are traditionally a big part of patent law, and previous examples of a principle that make a patent invalid are called "prior art." Nature, in these cases, is a source of materials, while the form comes from human imagination. Edison did not invent tungsten, but he did draw it in to a filament, enclose it in a vacuum, and run a current through it to produce light from electricity. Patent law is great at protecting Edisons.

In biotech, however, we tend to draw not just material substance, but information from nature; a DNA sequence is nothing, really, but a convenient and durable way of storing information around which living things have built a whole set of processes. Most biotech work is discovery rather than invention, discovery of what is already out there in natural genes or non-coding DNA, or in the times and places in which the information in those genes is turned into protein, or in the ways in which those DNA sequences interact. That doesn't mean that there is not a lot of ingenuity and creativity involved, but the biotech researcher is really partnering with nature, and drawing a line between the ingenuity of natural processes and the ingenuity of researchers manipulating those processes in new ways is not going to be easy. We still need patents to encourage innovative research in biotechnology, but nature holds a heck of a lot of prior art.

Being anti-GMO is like being anti-syringe

With the news this week that transgenic (GMO) wheat plants made it into a farmer's field in Oregon, the whole debate over transgenic crops has reignited. The lapse in containment of an experimental transgenic plant (no GMO wheat has yet been approved by the US Department of Agriculture beyond experimental trials) is not a trivial issue, but the reaction shows a deep misunderstanding of the dangers and benefits of transgenic organisms.

First off, the transgenic trait inserted into the wheat plant was resistance to Roundup (glyphosate), a commonly-used herbicide; indeed, it was the fact that the plants were not killed by an application of the herbicide that alerted the farmer to the problem. The way a plant like wheat is made resistant to this herbicide is by adding a gene from the soil bacterium Agrobacterium to the wheat. The gene codes for an enzyme (EPSPS) which both the bacterium and the plant have; while the plant version is essentially shut down by Roundup, the bacterial version is not as affected by that herbicide.

Knowing that this was the transgenic trait lets us make some reliable predictions about the dangers of this "rogue" transgenic plant. First off, the advantage it has over conventional wheat is resistance to an artificial pesticide, so it is unlikely to have any effect on the plant's ability to survive outside fields sprayed with Roundup. That could be inconvenient for farmers using the herbicide, but there is no reason to suspect the wheat would spread in a system that did not include Roundup (i.e., natural grasslands, organic farms, etc.).

Second, while Japan and South Korea suspended wheat shipments from the US, there is no reason to suspect any health risk, even if this crop somehow infiltrated the US wheat distribution network. First off, the modification is merely substituting versions of an enzyme the plant already makes; there's no reason (and, indeed, no evidence) that any of the glyphosate-resistant crops already in wide use (such as corn and soybeans) have any health effects different from conventional varieties. In other words, there's no reason to expect any actual damage to anyone in this case (although knee-jerk bans like those of wheat importers could certainly do economic damage to wheat farmers). I will grant that one farmer in Oregon has a minor weed problem.

Yet what is the result? A firestorm of generic anti-GMO protest. Perhaps, as this interesting article points out, it's just mentally easier to assume a big conspiracy (led by the profit-seeking Monsanto) than to evaluate the actual risks of the case in front of us. In other words, most folks (and many countries and the EU) are just anti-GMO, period. But that is as clumsy a position as it is possible to take, since what matters is not the technology used to put a trait in an organism, but what that trait actually is.

Perhaps an analogy will help. I'd assert that being broadly anti-GMO is like being anti-syringe. Just as transgenic technologies make it possible to put a much broader pool of genetic traits in plants, syringes allow us to put a huge variety of substances into our bloodstreams. Think of what you can do with a syringe. You could fill it with air, pump that into a vein, and give yourself a heart attack in seconds. You could inject an overdose of heroin and stop breathing - or inject a dose of morphine that made a traumatic injury much less painful. You can inject insulin to enhance your body's signal to your cells to take up glucose from your blood (thus treating diabetes). You can inject a tiny dose of the tetanus toxin so that your immune system prevents you from dying horribly from a Clostridium tetanum infection. You could use poor hygiene and give yourself a nasty infection while injecting a vitamin, or you could inject sterile saline and have absolutely no effect at all. In other words, while the syringe makes many new medical treatments possible, the syringe itself is just a delivery mechanism. What really affects the outcome is what you put in the syringe. One could, of course, decide that the potential risks were too great and spurn syringes entirely, but I think we can agree that such a policy was premature!

Transgenic techniques (that result in GMOs) are much the same. They make new things possible, but in themselves are just a tool. What we need to examine carefully are the traits being put into organisms with those techniques. There is potential to do all kinds of good (see, for example, the recombinant production of insulin), and there is potential to carelessly do a lot of damage if GMOs escape human control (although we hardly need transgenic technology for that - see cane toads or rabbits in Australia, or the gypsy moth in North America). There is every reason to be wary of a company like Monsanto that would like to sell farmers both an herbicide and a license to grow a crop that resists it, just as we should be wary that Apple sells both the iPhone and the apps that make the device functional.  The potential uses of transgenic technologies are so much broader than anything Monsanto has in mind, however, that it would be foolish to dismiss them outright. Imagine how much medicine would be handicapped if the syringe had been abandoned after the wife of its co-inventor overdosed on morphine.