Staying Sober about Science

The latest issue of The Hastings Center Report carries an essay of mine, "Staying Sober about Science" (free access after registration), about my thoughts on New Directions: The Ethics of Synthetic Biology and Emerging Technologies (PDF) from The Presidential Commission for the Study of Bioethical Issues.

Here is the first paragraph:

Biology, we are frequently told, is the science of the twenty-first century. Authority informs us that moving genes from one organism to another will provide new drugs, extend both the quantity and quality of life, and feed and fuel the world while reducing water consumption and greenhouse gas emissions. Authority also informs that novel genes will escape from genetically modified crops, thereby leading to herbicide-resistant weeds; that genetically modified crops are an evil privatization of the gene pool that will with certainty lead to the economic ruin of small farmers around the world; and that economic growth derived from biological technologies will cause more harm than good. In other words, we are told that biological technologies will provide benefits and will come with costs--with tales of both costs and benefits occasionally inflated--like every other technology humans have developed and deployed over all of recorded history.

And here are a couple of other selected bits:

Overall, in my opinion, the report is well considered. One must commend President Obama for showing leadership in so rapidly addressing what is seen in some quarters as a highly contentious issue. However, as noted by the commission itself, much of the hubbub is due to hype by both the press and certain parties interested in amplifying the importance of the Venter Institute's accomplishments. Certain scientists want to drive a stake into the heart of vitalism, and perhaps to undermine religious positions concerning the origin of life, while "civil society" groups stoke fears about Frankenstein and want a moratorium on research in synthetic biology. Notably, even when invited to comment by the commission, religious groups had little to say on the matter.

The commission avoided the trap of proscribing from on high the future course of a technology still emerging from the muck. Yet I cannot help the feeling that the report implicitly assumes that the technology can be guided or somehow controlled, as does most of the public discourse on synthetic biology. The broader history of technology, and of its regulation or restriction, suggests that directing its development would be no easy task.8 Often technologies that are encouraged and supported are also stunted, while technologies that face restriction or prohibition become widespread and indispensable.

...The commission's stance favors continued research in synthetic biology precisely because the threats of enormous societal and economic costs are vague and unsubstantiated. Moreover, there are practical implications of continued research that are critical to preparing for future challenges. The commission notes that "undue restriction may not only inhibit the distribution of new benefits, but it may also be counterproductive to security and safety by preventing researchers from developing effective safeguards."12 Continued pursuit of knowledge and capability is critical to our physical and economic security, an argument I have been attempting to inject into the conversation in Washington, D.C., for a decade. The commission firmly embraced a concept woven into the founding fabric of the United States. In the inaugural State of the Union Address in 1790, George Washington told Congress "there is nothing which can better deserve your patronage than the promotion of science and literature. Knowledge is in every country the surest basis of publick happiness."13

The pursuit of knowledge is every bit as important a foundation of the republic as explicit acknowledgment of the unalienable rights of life, liberty, and the pursuit of happiness. Science, literature, art, and technology have played obvious roles in the cultural, economic, and political development of the United States. More broadly, science and engineering are inextricably linked with human progress from a history of living in dirt, disease, and hunger to . . . today. One must of course acknowledge that today's world is imperfect; dirt, disease, and hunger remain part of the human experience. But these ills will always be part of the human experience. Overall, the pursuit of knowledge has vastly improved the human condition. Without scientific inquiry, technological development, and the economic incentive to refine innovations into useful and desirable products, we would still be scrabbling in the dirt, beset by countless diseases, often hungry, slowly losing our teeth.

There's more here.


8. R. Carlson, Biology Is Technology: The Promise, Peril, and New Business of Engineering Life (Cambridge, Mass.: Harvard University Press, 2010).

12. Presidential Commission for the Study of Bioethical Issues, New Directions, 5.

13. G. Washington, "The First State of the Union Address," January 8, 1790,

Myriad's Lawyers Want to Patent the Periodic Table

Interesting arguments today before a Federal Appeals Court concerning the "BRCA 1/2" patents.  Recall first that the U.S. Government has filed an amicus brief supporting the trial judge's ruling that naturally-occurring genes cannot be patented (see "Big Gene Patent (Busting) News???" and "Surprise Outbreak of Common Sense in Washington DC").

The Appellate Court is going to decide whether two genes (BRCA 1 and 2), in which mutations are correlated with breast cancer, can be patented.  Myriad Genetics and its lawyers say yes, the ACLU and several groups representing patients, scientists, and clinicians say no.  So did the trial judge.  The basic argument is about whether a naturally-occurring gene sequence that is used in a diagnostic test can be considered an invention.

Nature's The Great Beyond blog has a bit of reporting from yesterday's proceedings.  There is a passage from the blog post I think is worth exploring a bit further for the way the litigants and the judges are talking about the nature of DNA and the nature of elements such as lithium:

Both the lawyers and the judges repeatedly compared the case to efforts to extract a valuable mineral from the ground.

"Why isn't the ingenuity [that justifies patentability] the process of extracting [the mineral]" rather than in the mineral itself, [Judge Kimberly Moore] asked [defendent's attorney Greg] Castanias. "God made it. Man didn't make it."

Castanias retorted: "What we have here are new tools [that are] the products of molecular biologists. They are not the products of nature. They are not the products of God."

If that's the case, [Judge William Bryson] pushed Castanias, are you saying that isolation of pure lithium is properly an invention?

"Yes," the lawyer replied.

That is extraordinary.  Castanias' assertion is contrary to more than a century of U.S. case law and administrative rulings by the USPTO.  Products of nature are explicitly excluded in laws, rulings, and administrative decisions from coverage by patents.  Castanias wants the Appellate Court to rule that the elements in the periodic table, along with any other naturally-occurring substance, are in fact patentable.

The mind boggles.  Following Castanias' reasoning pure oxygen, pure water, and pure gold could all be patented because some process was employed for purification.  If this sort of argument held sway, you could even patent the moon because you require a human invention to go visit and nab a piece of it.  Yes, yes, I know that other inconvenient case law would get in the way of patenting a celestial body, which really doesn't make any sense anyway.  But that is the point.  The trial judge in this case was actually the first to issue a ruling that patents on naturally-occurring genetic sequences are prohibited by law (see "Big Gene Patent (Busting) News???").

This argument revolves in part around the nature of DNA.  Here is another excerpt from the Nature blog post:

Chris Hansen, a staff attorney with the ACLU, told the judges: "Myriad's entire business is built on the proposal that isolated DNA and [naturally occurring] DNA are identical." They don't write to patients with their test results, saying: "You've got a mutation in your isolated DNA but I have no idea what's going on in your body," he said.

Judge William Bryson countered that the act of isolating DNA involves breaking covalent bonds, thus creating a product that does not exist in nature.

"With respect, your honor, I think not," Hansen replied. "DNA is DNA."

But Greg Castanias, a lawyer with the Jones Day firm in Washington DC who represented the defendants, begged to differ. "Isolated DNA does not exist in nature," and wouldn't exist at all without human ingenuity, he said. The entire biotechnology industry, he added, is built on interpreting existing law to say that DNA isolation is sufficient to show the human invention that is required for a patent.

I found the language quoted to be quite interesting.  The notion that "isolated DNA does not exist in nature" is based on the defendants' definition of "isolated DNA".  Judge Sweet spent three pages of his original decision dealing with Myriad's assertions about "isolated DNA", but it is hard to know from the Nature blog post whether this was part of yesterday's conversation.  Here is Judge Sweet's definition (p. 92 of his decision): "Isolated DNA is therefore construed to refer to a segment of DNA nucleotides existing separate from other cellular components normally associated with native DNA, including proteins and other DNA sequences comprising the remainder of the genome, and includes both DNA originating from a cell as well as DNA synthesized through chemical or heterologous biological means".

This is quite close to Myriad's definition of "isolated DNA", but Judge Sweet still found that because the isolated DNA is the same sequence, and therefore conveys the same information, as the sequence in vivo, it cannot be patented because it is a product of nature.

Incidentally, the definition of isolated DNA given above appears to include DNA that is free in the environment.  Free DNA is found in marine and terrestrial environments.  That DNA can be taken up by other organisms via horizontal gene transfer, which means that free DNA is perfectly funtional.  Here, for example, is an interesting little study looking at the uptake of free DNA by aquatic bacteria.

The point being that humans did not invent DNA that is "separate from other cellular components".  Humans may have invented processes to concentrate and purify DNA, or to extract DNA from complex structures, but that does not mean that isolated DNA is itself a human invention.

Surprise Outbreak of Common Sense in Washington DC

News today that the Justice Department has filed an amicus brief outlining a new position that naturally occurring genes should not be patentable.  The New York Times is reporting that "while the government took the plaintiffs' side on the issue of isolated DNA, it sided with Myriad on patentability of manipulated DNA."  The change in position was evidently prompted by the decision of a federal judge this past spring that certain claims in what are known as the BRCA 1/2 patents should be overturned because those genes are preexisting in nature.  Perhaps Jon Stewart has more influence in DC than we all thought.

I am largely on board with the line taken by the Justice Department.  It is pretty close to my own analysis, as described in my post from last spring: "Big Gene Patent (Busting) News???"  There are, however, a few bits that I am still chewing on, which I will get to later.

First, in broad strokes, the government's brief supports the decision of District Judge Robert Sweet that naturally occurring gene sequences are not patentable, but weighed in against Judge Sweet's analysis that DNA coding for natural genes is not patentable if it has been restructured in an artificial construct but is still the same sequence as occurs in nature.  The most obvious example of the latter is a coding sequence with all introns removed and packed in a plasmid as a cDNA.

Here is the Justice Department's language (the text of the brief is available via the NYT page):

The district court erroneously cast doubt on the patent-eligibility of a broad range of man-made compositions of matter whose value derives from the information-encoding capacity of DNA. Such compositions -- e.g., cDNAs, vectors, recombinant plasmids, and chimeric proteins, as well as countless industrial products, such as vaccines and genetically modified crops, created with the aid of such molecules -- are in every meaningful sense the fruits of human ingenuity and thus qualify as "'human-made inventions'" eligible for patent protection under section 101. (p.9)

...The district court correctly held, however, that genomic DNA that has merely been isolated from the human body, without further alteration or manipulation, is not patent-eligible. (p.10)

...Indeed, the relationship between a naturally occurring nucleotide sequence and the molecule it expresses in a human cell -- that is, the relationship between genotype and phenotype -- is simply a law of nature. (p.10)

Here is the meat:

The chemical structure of native human genes is a product of nature, and it is no less a product of nature when that structure is "isolated" from its natural environment than are cotton fibers that have been separated from cotton seeds or coal that has been extracted from the earth.

The scope of Section 101 is purposefully wide and its threshold is not difficult to cross.  See Bilski, 130 S.Ct. at 3225.  New and useful methods of identifying, isolating, extracting, or using genes and genetic information may be patented (subject to the prohibition against patenting abstract ideas), as may nearly any man-made transformation or manipulation of the raw materials of the genome, such as cDNAs. Thus, the patent laws embrace gene replacement therapies, engineered biologic drugs, methods of modifying the properties of plants or generating biofuels, and similar advanced applications of biotechnology. Crossing the threshold of section 101, however, requires something more than identifying and isolating what has always existed in nature, no matter how difficult or useful that discovery may be. (p.11)

It might seem that the Justice Department gives back a lot of power to those who hold patents on natural genes by including cDNAs (with introns removed) as patentable material.  This would seem to give patent holders a lock on the human proteins those genes encode, because the most common way to make a protein is to use a cDNA (or similar) to express a protein in a host like E. coli or yeast.  So unless people come up with a good way to cause overexpression of human proteins from native genes via mechanisms that chop out the introns -- and some methods like that do exist -- the patent seems to block use of the protein.

But I am not sure that this brief gives any succor to those hoping for patent protection of a genetic diagnostic.  Those diagnostics generally work by using a short sequence of the gene in question as a PCR primer to find (or exclude) particular sequences of clinical interest in a patient's genome.  Those primers generally can be found in regions of DNA not interrupted by an intron, or can include the intron in the primer sequence, which means that the primer can consist of sequences that were preexisting in nature.  Only if the primer has to be composed of a sequence that -- in nature -- is interrupted by an intron but is only found in somebody's edited cDNA library without that intron would a patent protect the diagnostic assay.

A penultimate thought on the brief: I am still pondering whether the Justice Department lawyers, in their extended discussion of DNA as information carrying medium, got their analysis right.  I will have to read the brief again.  And perhaps again after that.

Finally, the brief leaves most of my previous conclusions intact, namely that the biggest impact of Judge Sweet's ruling that natural sequences cannot be patented may be for work in organisms other than humans.  From my post last May:

...the rest of the biotech industry shouldn't be concerned about thisruling, frankly.  They might even celebrate the fact that they now have access, potentially, to a whole bunch more genes that are naturally occurring.  Not just in humans, mind you, but any organism.  This opens up a rather substantial toolbox for anybody interested in using biological technologies derived from viruses, bacteria, plants, etc.  If it holds up over the long run, Judge Sweet's decision should accelerate innovation.  That is definitely a good thing.

Now we wait for what the appellate court has to say.

Big Gene Patent (Busting) News???

Well now, isn't this an interesting development.  As covered by many news outlets (NYT, Wired, Genomeweb), US District Court Judge Robert Sweet has invalidated several US patents, sometimes referred to as the "BRCA1/2 patents", held by the University of Utah and Myriad Genetics.  From Judge Sweet's decision: "Products of nature do not constitute patentable subject matter absent achange that results in the creation of a fundamentally new product."  Judge Sweet's decision is here (PDF) via Genomics Law Report.  Here is the ACLU's take.

Here is a brief summary of what follows: The ruling is remarkable.  Various commentators and reporters remark upon it.  They get confused.  I try to clarify.  Then we get to a truly revolutionary part of the decision: it's about science!  And a little bit about law.  Finally: so what if a few patents are invalidated?

Didn't See That Coming.  But I Can't Complain.

Last month, I noted that I was skeptical that the ACLU and other plaintiffs would be so successful in one go.  So I am surprised, but I am certainly not disappointed.  But I am not surprised, while being somewhat disappointed, that the coverage of the decision is so confused and confusing.  This confusion arises, I suspect, because the wording of Judge Sweet's decision is not entirely straightforward in places, and this has led to analyses that are insufficiently careful.  More on these points below.

DISCLAIMER: Please recall in what follows that I am but a humble physicist by training (oh yes, yes, we're all very humble), not a lawyer.  But I have written some stuff about patents on genes, and at least a few people (some of whom are IP law lawyers) think my analysis doesn't suck a lot.

First, over at Genomics Law Report (GLR), John Conley and Dan Vorhaus have a great analysis with a nice title: "Pigs Fly: Federal Court Invalidates Myriad's Patent Claims".  I won't bother to repeat their discussion.  If you are interested in this issue, please read that post as well as Dan Vorhaus' initial post analyzing the decision.  In particular, the reader might want to attend closely Vorhaus and Conley's observations about the potential for appeals, the likelihood of success in that endeavor, and the applicability of the ruling in other jurisdictions.

The short summary of what's transpired so far in the case is that Judge Sweet has invalidated a small number of claims, in a summary judgement ruling that so far applies only in the Southern District of New York.  Assertions that this is the end of the world for companies that hold gene patents are rather overblown.

There's Too Much Confusion, But Here is Some Relief

But now onto some of the confusing bits alluded to above.  The confusion starts, surprisingly, at GLR.  Here are Conely and Vorhaus:  "In the broader policy debate surrounding gene and biotechnology patents, however, this decision is the latest, unmistakable shot across the bow of gene patent holders, particularly those such as Myriad Genetics that have developed businesses around patent-protected genetic tests supported by exclusive rights in underlying gene patents."  Hummm...  Maybe not so much, actually.  Let me get straight to the point: there is a rather substantial difference between a "gene patent" that claims naturally occurring sequences and one that claims sequences that are not natural. 

Here is one way to think about the issues under discussion: in my one hand, I have a piece of isolated DNA that is identical in sequence to one in your body.  It is the same genetic sequence, so it carries the same information.  Indeed, for it to be useful in a test tube for the purposes of diagnosis, it must have both the same information content and the same function as the sequence in your body.  In fact, it only works as a diagnostic tool because it is the same as what is in your body.  As I noted in my earlier post, this is sort of the opposite of invention, and I have never understood why natural genes can be patented.  (Note: Judge Sweet hits this point quite squarely, but not until p.124 of his ruling.)  In my other hand, I have a piece of isolated DNA that is solely the result of human manipulation -- "human ingenuity" -- consisting of a sequence that does not exist in nature.  Both pieces of DNA are isolated, but they derive from very different sources, and are derived by very different means. Unfortunately, everybody discussing the present decision, including Judge Sweet in the early pages of his decision, seems to be a tad careless about the distinction, which leads many people down a rabbit hole.  (There is an extended discussion of the definition of "isolated DNA" and of the BRCA1/2 genes on p.90-92.)

Here is where it starts: Judge Sweet sets up his decision in the first couple of pages focusing specifically on the BRCA1/2 genes, and slightly more generally on isolated human genes: "Are isolated human genes and the comparison of their sequences patentable?" (p.2)  He continues: "Two complicated areas of science and law are involved: molecular biology and patent law.  The task is to seek the governing principles in each and to determine the essential elements of the claimed biological compositions and processes and their relationships to the laws of nature."

This sounds great.  Judge Sweet is clearly referring specifically to certain human gene sequences named in the patents in question.  Alas, on the next page he switches his language to address the specific assertions of the plaintiffs that ""isolated DNA" containing human BRCA1/2 sequences" are not patentable.  The basic contention here is that because the isolated DNA as described in the patents does the same thing inside the body as outside the body -- it is an information storage medium -- there is no difference between the two forms of DNA and therefore the isolated DNA in question cannot be patented.  Judge Sweet concludes (p.4):

DNA represents the physical embodiment of biological information, distinct in its essential characteristics from any other chemical found in nature. It is concluded that DNA's existence in an 'isolated' form alters neither this fundamental quality as it exists in the body not the information it encodes.  Therefore, the patents at issue directed to "isolated DNA" containing sequences found in nature are unsustainable as a matter of law and are deemed unpatentable subject matter.

The judge thereby switches within a couple of paragraphs very seamlessly from language referring only to human genes to language referring seemingly to all "isolated DNA".  It takes another 100 pages to get to a true clarification, and I'll bet very few people have read that far, or followed all the byways and cross-references (p.100): "...The issue presented by the instant motions with respect to the composition claims is whether or not claims directed to isolated DNA containing naturally-occurring human sequences [emph added] fall within the products nature exception.  ...It is concluded that the composition claims-in-suit are excepted."

In other words, Judge Sweet very specifically ruled that the claims on isolated DNA containing naturally occurring sequences are not valid.  Even more specifically, the ruling only applies to the motion in question by the plaintiffs, namely to invalidate the patents on BRCA1/2 held by Myriad et al.  Judge Sweet pointedly cites Diamond vs. Chakrabarty (p.109) -- a case that affirmed the patentability of "genetically engineered" organisms -- in limiting his ruling to the patentability of naturally occurring genes.  The ruling has no applicability outside that subject matter, and therefore has little applicability to, for example, much of anything that might come out of synthetic biology (unless you are talking about a synthetic DNA version of a naturally occurring gene).  Nor, for that matter, does the ruling have any say about any bit of DNA altered to be different from a natural sequence.  Which means that the ruling has very little to do with most patents on DNA, and therefore has very little to do with most of the industry surrounding those patents -- more on this below.

(Side note, as I read through the decision: Myriad's lawyers didn't do themselves any favors by making generally unpersuasive assertions aimed as broadside attacks against the plaintiffs' arguments.  As noted in my previous post on this case "Whither Genome Patents?", the defendants' assertions that patents serve as necessary incentives for scientific research are complete bunk.  Defense attorney Brian Poissant previously argued that "women would not even know they had BRCA gene if it weren't discovered" under a system that incentivizes patents.  I say again, as calmly as I can, bull pucky.  For example, see the publicly funded Human Genome Project.  See also the fact that BRCA2 was sequenced first in academic labs rather than by Myriad, who somehow managed to patent it anyway.  See also the many  BRCA1/2 assays independently developed in academia, the use of which Myriad repeatedly quashed through cease-and-desist letters, as recounted in detail in the decision.  But here is Judge Sweet himself (p.76): "According to Myriad, its policy and practice has been and still is to allow scientists to conduct research studies on BRCA 1 and BRCA 2 freely, the result of which has been the publication of [over 8600 papers] representing the work of over 18,000 scientists."  (It wasn't clear to me whether Myriad's legal team itself provided these numbers -- but if they did: bad legal tactics, fellas.)  In other words, 18,000 scientists have managed to produce a substantial body of work without any promise whatsoever of remuneration based on a patent for BRCA1/2.  Unless, of course, you count keeping your job through the promise of not being sued by Myriad.)  

It's Science!  And Science Always Wins -- Eventually, But May be Delayed By Appeals.

There is another very interesting angle to Judge Sweet's decision.  Andrew Pollack, writing in the New York Times, suggests that the most revolutionary part of the decision is where Judge Sweet recognizes that DNA carries information.  Pollack quotes Rebecca Eisenberg, a law professor at the University of Michigan: "There isn't a whole lot of doctrinal support" for considering DNA as information rather than as a chemical.  That, for me, is a truly eye opening perspective.  Not because I didn't know about it before -- unfortunately, that view is all too prevalent among IP lawyers -- but rather because it is being defended and suggested as a possible grounds for appeal.  True, it may be precedent, but that does not mean it is good precedent.

Here's the thing: There may not be much "doctrinal support" for considering DNA as information, but there is a rather overwhelming amount of scientific and technical support for considering DNA as information rather than as a chemical, say starting with the vast majority of molecular biology and biochemistry papers published in Science, Nature, Cell, PNAS, and any other relevant journal you can think of.  For all of the last six decades, no less.  Oh, and then all those silly textbooks.  The genetics and molecular biology ones, obviously; not the law textbooks.

Judge Sweet, in my humble opinion, already smacked this one out of the park on p.4: "The facts relating to molecular biology are fundamental to the patents at issue and to the conclusions reached.  Consequently, in the findings which follow, the discussion of molecular biology precedes the facts concerning the development, application, and description of the patents."  (Whoa there!  Science and reason trump the law of man!  Or science and reason trump the law of lawyers?  Damn, now that is a novel legal theory.  And a welcome one.  Don't tell Sen. James Inhofe.) 

Unfortunately, Pollack misses this angle, and promulgates further the confusion that Judge Sweet's ruling spells doom for the biotech industry: "Some biotechnology investors and executives say that lack of patent protection for DNA could diminish investment in the field and remove incentives for companies to develop tests."  Never mind that, as described above, Judge Sweet's ruling applies only to patents on naturally occurring genes, which should ameliorate the concerns of most of the "some biotechnology investors and executives".  It is nonetheless true that diagnostics companies that rely on patents claiming naturally occurring sequences may have to reevaluate their business plans.  (For instance, they may want to be especially careful in issuing cease-and-desist letters, lest the ACLU and company get busy again.)  And it may be true that this small fraction of biotech businesses may have difficulty raising capital -- but time will tell.  If it turns out that development of new diagnostic assays lags as a result of more patents on human genes being invalidated, then we will have something real to talk about.  We might consider developing public policy around alternate incentives.  Until there is a demonstrated concern, however, it isn't clear to me that we should be so concerned about the fate of private investors who gambled on patents whose validity has long been questioned.

What Is The Real Impact Going To Be? 

To reiterate the numbers from my earlier post: of the roughtly 2% of US GDP that is derived from biotech, at a rough guess I would put only 1% of the total (so .01% of US GDP) in the molecular diagnostics category that depends explicitly on excluding other uses of patented human genes.  A few billion dollars a year, in other words, might be at risk.  But somebody is going to do the tests, and Judge Sweet's decision lists a variety of tests that cost about 1/3 of Myriad's; that is, before Myriad shut them down with cease-and-desist letters.  If you eliminate those patents, we might have to come up with some other way to incentivize the development and testing of assays.  Prizes come to mind as a fine thing to try.  They work.  Academics and garagistas will be happy to compete for those prizes, I am sure.

But the rest of the biotech industry shouldn't be concerned about this ruling, frankly.  They might even celebrate the fact that they now have access, potentially, to a whole bunch more genes that are naturally occurring.  Not just in humans, mind you, but any organism.  This opens up a rather substantial toolbox for anybody interested in using biological technologies derived from viruses, bacteria, plants, etc.  If it holds up over the long run, Judge Sweet's decision should accelerate innovation.  That is definitely a good thing.

Good Climate Data, Bad Climate "Data" -- Science Always Wins.

This week brings news of 1) a dramatic improvement in the estimates of how soil carbon content is related to atmospheric carbon concentration and 2) the exposure of some really crappy work on the rate of melting of Himalayan glaciers by the International Panel on Climate Change (IPCC).  The soil carbon work is Good Data, but Bad News if you care about the effects of high atmospheric carbon concentrations, while the Himalayan glacier story is all about terrible peer review and Bad Data (non-existent data, actually), which doesn't help anybody figure out the real story on water supplies in Asia.

First up, a paper from this week's PNAS by Breeker et al at UT Austin, "Atmospheric CO2 concentrations during ancient greenhouse climates were similar to those predicted for A.D. 2100".  Already from the title you can see where this is going.

The problem Breeker and colleagues address is the following: how do you correlate the carbon content of fossil soils with prevailing atmospheric carbon dioxide concentrations?  Well established methods exist for measuring the carbon content of compounds in fossil soil, but less certain were conditions under which chemical reactions produce those particular compounds.  It turns out that model used to infer atmospheric CO2 contained an error.  Breeker determined that the primary compound assayed when determining soil carbon content forms at much lower atmospheric CO2 concentrations than had been assumed.

Prior attempts to correlate soil carbon (and by proxy atmospheric CO2) with greenhouse periods in Earth's climate had concluded that warm periods experienced CO2 concentrations of much greater than ~1000 parts per million (ppm).  Therefore, one might conclude that only when average atmospheric CO2 spiked above this level would we be in danger of experiencing greenhouse gas warming that threatened glaciers.  The correction supplied by Breeker substantially lowers estimates of the average CO2 concentration that is correlated with continental glacial melting.  Eyeballing the main figure in the paper, it looks to me like we could be in real trouble above 450 ppm -- today we are at just shy of 390 ppm and there is no sign we will be slowing down anytime soon, particularly if India and China keep up their pace of development and emissions.

Looking forward to 2100, things get a touch squiffy because Breeker relies on an estimate of CO2 concentrations that come out of model of global economic activity.  So the title of the paper might be a tad alarmist, simply because 2100 is a long way out for any model to be taken too seriously.  But the correction of the paleodata is a big story because at minimum it reduces the uncertainty of atmospheric CO2 levels, and it appears to clarify the connection between CO2 levels and continental glaciation.  More work is needed on the later point, obviously, or this paper would have been on the cover of Science or Nature.

Now on to a serious screw-up at the IPCC.  Elisabeth Rosenthal at the NYT is reporting that "A much-publicized estimate from a United Nations panel about the rapid melting of Himalayan glaciers from climate change is coming under fire as a gross exaggeration."  Here is Andrew Revkin's take on DotEarth, and anyone interested in this story should read through his post.  The comments are worth perusing because some of the contributors actually seem to have additional useful knowledge, though, of course, nut jobs aplenty show up from both sides of the debate over climate change.

In a nutshell, the issue is that the most recent IPCC chapter on glaciers contained a conclusion, advertised as real analysis, that was in fact a speculation by one scientist promulgated through the popular press.  The authors of that section of the IPCC report may have been warned about the unsubstantiated claim.  Contradictory data and analysis seems to have been ignored.

So, to be frank, this is a giant, inexcusable fuck-up.  The IPCC is composed of so many factions and interest groups that this may be a case of simple blundering or of blatant politicization of science.  But here is the beautiful thing about science -- it is self-correcting.  It may take a while, but science always wins.  (See also my post of a couple of years ago, Dispelling a Climate Change Skeptic's "Deception".)  Every newspaper story I have seen about this particular IPCC screw-up notes that it was brought to light by...wait for it...a climate scientist.  It is an excellent public airing of dirty laundry by the community of science.  So while this episode demonstrates that the last official IPCC report on glacial melting in the Himalayas should not be used for any sort of scientific policy recommendation or economic forecast, you can bet that the next report will do a damn fine job on this topic. 

Finally, whether or not the IPCC gets its act together, there are plenty of good data out there on the state of the planet.  Eventually, Science -- with a capital S -- will get the right answer.  The same methodical process that has resulted in computers, airplanes, and non-stick fry pans will inevitably explain what is really going on with our climate.  And if you use computers, fly on airplanes, or eat scrambled eggs then you are implicitly acknowledging, whatever your political or religious persuasion, that you believe in science.  And you better, 'cause science always wins.

Dispelling a Climate Change Skeptic's "Deception"

(Updated: Friday 5 Oct 19:15 PST)

A few weeks ago I heard a presentation from someone (hereafter person "A", to remain anonymous) who claimed that increasing CO2 concentrations won't cause significant global warming.  The highly technical argument sounded extremely implausible to me, but it has taken me a while to sort out the details.  This is worth commenting on because the argument is due to be presented in a high profile book due out next year from a very well known publisher.

I don't fault person A for falling for the "deception", but he could have been more critical given the sources he used to build up his argument.

The anti-warming argument was based on a figure from a non-peer reviewed "paper" available on the web.  The figure, in turn, was generated by a fellow named David Archibald using the "modtran" model server hosted by The University of Chicago.  The modtran model server is run by Professor David Archer , in the Department of Geophysical Sciences, to help his students with coursework.  I wrote to Professor Archer to clarify both the intended use of the model and the interpretation of the data.

The model is evidently reasonably well accepted in its description of infrared radiation adsorption by the atmosphere as a function of CO2 concentration, otherwise known as radiative forcing.  But it turns out that to estimate the resulting warming, you have to multiply the radiative forcing by the 'climate sensitivity parameter', which tells you how the atmosphere and oceans respond to added heat.  The climate sensitivity parameter is actually a distribution of values, and models of climate change are usually evaluated using several different values of the parameter.  David Archibald conveniently chose a value that is 40 times smaller than the most likely value in the distribution used by the IPCC.  The value is in the distribution describing the climate sensitivity parameter, to be sure, but it is way the hell out to the left, and very improbable.  Thus one can very accurately claim that Archibald used the correct radiative forcing numbers but he intentionally chose an estimate of climate sensitivity that nobody else believes is physically likely.

Professor Acher posted to with the title, "My model, used for deception".  He is relatively circumspect, though still damning, in his criticism of Archibald.  The comments that follow his post, however, are ruthless.  It seems I set loose the hounds.

I take the time to write this because I have become more aware of late that many climate change skeptics seem to think that anthropogenic climate change (in particular, warming caused by CO2 emissions) is simply a political ploy with no basis in physical reality.  That kind of thinking denies not just climate change, but virtually all of the science our technological economy is built on.  (I will certainly admit some of the rhetoric surrounding climate change bothers me, and I am not comfortable with the idea of brainwashing children to harass their parents about buying hybrid cars.  See the 29 September WSJ, "Inconvenient Youths", or even the recent The Daily Show segment on absurdly over the top children's books from wingnuts on both the left and the right.)

I could care less at this point about the political side of the argument, and why people do or don't like Al Gore.  Physics is physics.  Science always wins.  Science is self-correcting, and over the long term there ain't no politics about it.  The U.S. was founded based on the enlightenment notions of tolerance and rational decision making.  Alas, those words aren't in the Constitution anywhere, and they are seldom uttered inside the Beltway these days.  But if we don't base our policy decisions on science, then we can just forget the U.S. as a viable economic entity, and thus as an entity capable of being the standard bearer of ideals that make this country worth living in and defending.

Farewell PEAR Lab -- You were always overripe.

News in the last few weeks that the Princeton Engineering Anomalies Research Lab -- the PEAR Lab -- is shutting down.  The PEAR Lab, run by Dr. Robert Jahn, the former Dean of Engineering, was by no means celebrated at Princeton.  I spent four years there in graduate school and only heard of the Lab during my last year, in Malcolm Browne's science writing class no less, rather than during all those many hours in Jadwin Hall.

Phillip Ball had a nice retrospective on the Lab in last week's Nature entitled, "When research goes PEAR-shaped."  Ball quotes Will Happer, a professor in the Princeton Physics Department and a member of JASON as saying, "I don't believe in anything [Jahn] is doing, but I support his right to do it."  That's pretty charitable, actually, compared with many of the things said about the lab.  Nature continues to pile it on this week, with another piece: "The lab that asked the wrong questions," by Lucy Odling-Smee.

This is the crux of what was wrong with the PEAR Lab.  In that science writing class, Malcolm Browne occasionally brought in people to be "interviewed" by the class, and one day we had someone in from the Lab.  (My recollection is that it was Jahn himself.)  Can't say I was impressed.  But data is data, and they certainly may actually have measured something interesting, however unlikely that may be.  There are many things we can't yet explain about the universe, and maybe Jahn was on to something.

What I found unfortunate, even unpleasant, in the way the data was presented was the context.  Jahn was represented to us not just as an expert in aeronautics, but also in a whole host of other fields, including quantum mechanics.  And we were offered a physical theory "explaining" one experiment, supposedly a quantum mechanical theory.  Here's the problem: that theory, by its very nature, is wrong.  It is inconsistent in its conception and structure with all the rest of quantum mechanics.  The folks in the PEAR Lab were definitely asking the wrong questions, in a very deep physical sense, by which I mean that everything about the way they tried to explain the data I saw was contradicted by modern physics in fundamental ways. 

According to Dr. Jahn, a random process seems to be the vital ingredient for anomalous interactions between consciousness and machines -- coins flipping, balls dropping through a forest of pegs, even electronic random number generators -- which is what led him to speculate about connections between his data and a successful theory in which measurements are probabilistic: quantum mechanics.  In some interpretations of quantum mechanics, the observer and the system observed are both part of a larger closed system.  Indeed, Dr. Jahn and his colleagues believe that quantum mechanics may be just a part of a larger theory that includes phenomena studied in the PEAR Lab.  If this is so, then one would expect the structure of the two theories to be similar.

The theory we were told about was purported to explain how an observer could, by thinking "slower" or "faster", change the period of a large pendulum, something like 2 meters in length, if I recall correctly.  A brief refresher on the relevant classical physics: the period of an ideal pendulum is determined only by its length and the strength of the force of gravity, at least in the case when oscillation amplitudes are small, and not by its mass, or the kind of bearing it is suspended from, or any other factor. Though friction will eventually damp a real pendulum by changing its amplitude, not its period.   

The mechanism by which human consciousness might change the period is not easy to imagine.  The human observer states the intention either to increase or decrease the period, and as the pendulum interrupts photodiodes on each swing the time is recorded.  But whereas a quantum mechanical model requires a probability for the observer to intentionally alter, here the observer is actually trying to intentionally change the period.

Before I go on (and on), you must be asking "Why spend so much time on this?"  Why bother to debunk bad science at all?  Because the universe is full of strange and wonderful things, and we don't yet understand them all.  That's what makes life interesting.  Besides, I like thinking about quantum mechanics.  Back to the story.

Dr. Jahn claimed his data is consistent with the the human subject affecting the damping of the pendulum's oscillation.  Microscopically, friction might be changed by heating or cooling the bearings of the pendulum (which could be tested by carefully measuring the temperature of the bearing during an experiment) causing the atoms in the bearing to move around more or less, a phenomena well understood in statistical mechanics -- and in fact a probabilistic effect.  However, since the operator was not trying to influence this probability distribution, it is not clear how his or her binary intention of changing the period of the pendulum was converted into changing the amount of friction.  Or perhaps the observer was changing the length of the pendulum, or the overall strength of gravity, or even the local coupling of the earth's mass to that of the pendulum.  Still no obvious connection to any distribution.

When asking a question of a quantum mechanical system, or a quantum mechanical question in the parlance of physicists, it must be one which can be phrased in terms of what is called an "operator."  Energy, momentum, and position are all operators and as such provide tools for asking quantum mechanical questions.  The energy operator, for instance, would be used to ask about the average energy of the atoms in the bearing.  To find an analogy to the pendulum we must look in quantum mechanics to something called a harmonic oscillator, which can be imagined as a ball rolling back and forth at the bottom a parabolic bowl.  Two operators used in asking questions about such a system are the raising and lowering operators, which as their names suggest change the energy of a particle and its period of oscillation.

So, for the sake of argument, let's give the PEAR Lab a quantum mechanical operator that works on a macroscopic pendulum.  It might be imagined that a human consciousness is utilizing some sort of raising and lowering operator by intending to increase or decrease the period of oscillation of the pendulum.  Yet the data is fit by assuming the friction in the bearing is changing.  It is simply not consistent with the structure of quantum mechanics to ask one valid question and get the answer to a different valid question.  Furthermore, it is hard to imagine how a more general theory, one subsuming quantum mechanics -- oh, what the hell, let's just call it "magic" -- could account for asking a question of the period of the pendulum with an operator belonging to the "magic" theory but get an answer which is the result of asking a question with the well known and well loved energy operator of quantum mechanics and which could only describe the microscopic state of the bearing.  So there.

Then there is that little thing called the Correspondence Principle, proven correct time and time again, which says that quantum mechanics works for small numbers of atoms.  As the number grows, save in very special, very strange circumstances like Bose-Einstein condensates, your theory must reduce to classical physics.  Which brings us back to the classical model that the period of the pendulum depends only on its length.  Nothing about the bearing, nothing about the observer.  Moreover, the pendulum is big, and the human subject is big.  Many, many atoms.  No quantum mechanics.  Wrong question!

Did you follow all that?  Does your head hurt?  Sometimes quantum mechanics does that, I assure you.  But I suppose "magic" could account for your headache, too.  We must allow for that.  Somehow.  See the PEAR Lab.

Sometimes the exploration of something that seems silly results in important insights, and the rest of the time it is important to keep the human participants of science honest.  That's the way science works.  And science always wins.

On Hwang Woo Suk and the Stem Cell Debacle

I've resisted writing about Hwang Woo Suk's fraudulent paper in Science about producing patient specific stem cells.  It just isn't really that big a deal.  A guy who claimed proficiency with chopsticks was directly correlated with producing cutting edge science -- surprise! -- turned out to be not so credible.  He was found out.  Science wins.  Science will always win, eventually.

Yet the affair provides an interesting context for thinking about the tenuous standing of cutting edge science.  Uncovering the fraud is frustrating to those waiting for cures for disease or injury, annoying to those waiting for life extension technologies, and disappointing to almost everyone for whom scientific inquiry is the closest approximation to a pursuit of truth; all true.  But guess what?  Science is a human institution, practiced by humans with all of their faults.  It is simply inevitable that those faults affect scientific results and publications.

But what distinguishes science from other human institutions, notably politics, religion, and business, which have all experienced extraordinary fraud and malfeasance recently in the U.S., is that fundamentally science finds its foundations in the physical world.  The progress of science, and its authority, are tied to what is measurable.  Moreover, those measurements must be repeatable.  That is, a result must be testable and verifiable by others to become accepted.  True, uncovering the Hwang fraud took almost two years, but Hwang's fall was inevitable because the requirement for repeatability means that science is self-correcting.  It happens that the holes in the original Science paper appeared not because of questions emerging from labs trying to repeat the work, but rather from suspicious aspects of the paper itself, such different figures of supposedly different cell lines containing similar images.

The scrutiny of these images and other details of the paper applied by scientists within South Korea, fed by suspicion of the great height to which Hwang aspired, only strengthens the process of science.  We didn't actually have to wait for the results of long and laborious experiments, nor did we have to spend money to repeat Hwang's work.  The fraud fell apart under its own weight.  This is a success.

I, like every other practicing scientist, have to wonder how this episode will affect the public perception of science.  I come to the conclusion that the airing of dirty laundry will only improve the position of science in the long run.  There is no other human institution so ruthless in chopping out the dead wood.  After all, if you are lying or pulling a fast one, the very last thing you want to do is get a bunch of really smart people trying to catch you out, all of whose professional standing improves if they do.

The public perception of all this is complicated slightly by the fact that there is a difference between the science you read in textbooks, and the science reported in journals or on the front page of newspapers and news magazines.  In today's New York Times, Nicholas Wade has a very nice article exploring this issue, prompted by the stem cell fraud:

The contrast between the fallibility of Dr. Hwang's claims and the general solidity of scientific knowledge arises from the existence of two kinds of science - a distinction that is often blurred when new advances are reported first by scientific journals and then by the news media. There is textbook science and frontier science, and the two types carry quite different expiration dates.

Textbook science is material that has stood the test of time and can be largely relied upon. It may include findings made just a few years ago, but which have been reasonably well confirmed by other laboratories.

Science from the frontiers of knowledge, on the other hand, is wild, untamed and often either wrong or irrelevant to future research. A few years after they are published, most scientific papers are never cited again.

I find this latter point the most problematic of the scientific enterprise.  Of the papers with short lifetimes, some are not read or cited because they aren't very good or very interesting, some are only minor improvements on previous work, and some fall by the wayside because they describe dead ends.  In all cases, very little science that gets done, and even less that is finally reported in journals, actually affects the world in a meaningful way.   How can you not feel a bit ambivalent about this?  Isn't this emblematic of some sort of waste, inefficiency, or a Proxmire-attracting, willful misappropriation of funds?  Emphatically not!  This is a cost we must bear as part of the never-ending effort to banish our ignorance and improve the human condition.  At both the institutional and the personal level this cost is intrinsic to science.  Every scientist, and every technologist and inventor, for that matter, has plentiful experience with choosing the wrong path.  Alas, the dominant social structures governing funding decisions and career advancement are based predominantly on the number of papers published, rather than upon their content, which means that often the wrong path, the marginal improvement, and the simply boring result in the lab are gussied up for publication to look far more significant that they really are.

The only real defense against this profusion of craptastic papers is the choice of individuals not to write and publish them.  So I have little hope of progress there.  Enough said about that.

A weaker, but necessary, defense lies in peer review.  In lieu of the sudden popularity of all scientists becoming harsh and discerning critics of our own efforts, we must all keep watch on science as a whole, trying to catch mistakes and fraud before publication.  Yet this process, too, is far from perfect.  Too many anonymous reviewers have political reasons for rejecting papers, and many more just don't do a good job of reading the paper they are judging.  I don't really have a solution to this problem, but I have to wonder if removing anonymity from the review process would clean things up.  Yes, you would have the problem that younger scientists reviewing the work of their elders would be exposed to wrath from above.  But what we have now definitely needs improvement.  Witness the Hwang paper.

Mr. Wade explores the notion of improving the quality of papers through requiring authors to state their contributions to a paper, and by requiring all authors to state their explicit agreement with all conclusions in a paper.  I don't have any problems with the latter, but I can say from personal experience that writing an author contribution statement can be extraordinarily painful, a struggle to carve out sufficient acknowledgments of your own efforts and give perspective on another's efforts, particularly when control of the text lies with someone else.  Still, it's worth a try.  And I support the inclusion of author's contributions for the time being.

Alas, this doesn't help with the review process itself, because it doesn't do anything about biases or laziness of reviewers.  Mr. Wade thus incorrectly suggests that clarifying the author's roles in research has anything to do with the decision-making process during review at a journal.  Nonetheless, save conflation of the review process with writing and attribution, his conclusion is right on the money:

Tightening up the reviewing system may remove some faults but will not erase the inescapable gap between textbook science and frontier science. A more effective protection against being surprised by the likes of Dr. Hwang might be for journalists to recognize that journals like Science and Nature do not, and cannot, publish scientific truths. They publish roughly screened scientific claims, which may or may not turn out to be true.

And thus we must labor on, and through those labors attempt to keep science honest and thereby produce a better world.  Science will always win, eventually.