The New York Times has a rather chilling account of how radiation overdose in the treatment of some cancer patients caused deadly side effects leading to death. The entire sobering article deserves to be read. In one case a man's tongue was going to be selectively irradiated; instead his whole face received a blast of radiation that led to a horrible, slow death. Scott Jerome-Parks's story makes for very painful reading. In another case, misguided radiation beams literally cut out a hole in a woman's chest that gradually killed her. This was Alexandra Jn-Charles. Both Mr. Jerome Parks and Ms. Jn Charles died within a month of each other in 2007.
And all this mainly because of computer errors that were not detected by human beings, errors that caused the radiation to be overdosed or misdirected. Seems like one of those classic "technology is a double-edged sword" kind of scenarios with the whole system just becoming too complex for human understanding. In one instance, a wedge in a linear accelerator delivering the radiation was supposed to focus the beam in the "in" position. But the computer that used Varian software- the same software that I used in grad school for operating the NMR spectrometer built by the same company- made a mistake and instead pivoted the wedge to the "out" position, removing the radiation shielding. The mistake was not detected 27 times, leading to acute radiation overdoses in the wrong parts of the body. In the case of the man whose tongue was supposed to be treated, an error in the software failed to save the critical settings for the accelerator which would have focused the radiation to the right parts. The computer repeatedly crashed, leading to the collimator beams being left wide open, and nobody noticed this.
The statistics unearthed by the Times are startling. From 2001 to 2009, more than 600 cases of improper radiation treatment were reported. Out of those, 255 were related to an overdose, while 284 were related to the wrong parts of the body being exposed to radiation. Even in its idealized form radiation has side-effects, so one would assume that doctors and technicians would be deathly serious about operating these protocols. These statistics were collected for New York State, which is apparently supposed to have some of the strictest radiation standards in the country.
What is even more shocking is the lack of transparency due to "privacy laws". Names of the culprits have been withheld, and some of them seem to have been let off the hook with a simple reprimand. St. Vincent's hospital and University Hospital of Brooklyn, where the two accidents had happened, were simply fined a thousand dollars by the city of New York. Some doctors who have participated in the treatments refused to talk to the journalists. There also does not seem to be a single agency responsible for these radiation safeguards. On top of it all there seem to be scant ways for patients to pick beforehand which hospital they would like to receive radiation treatment in, since records of mistakes are not available to the public. The whole shebang sounds appalling.
Now I understand that 600 cases in 8 years is probably small potatoes compared to the total number of cases in which radiation has worked successfully. Nonetheless, the factors responsible for the lapses and the horrendous consequences deserve scrutiny (seriously, death due to "computer error" sounds like something out of a bad science fiction horror movie). For something as serious as radiation treatment for cancer, one would assume that the same kinds of safeguards, fail-safe mechanisms and backup checks would be in place as are used in nuclear reactor safety. What boggles my mind is that there exist no fail safe mechanisms which would simply shut down the system when they detect an overdose. It simply seems that shoddy training, computer error, and lack of accountability are dealing out death and enormous physical and psychological suffering to patients and their families.
Field of Science
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Change of address1 year ago in Variety of Life
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Change of address1 year ago in Catalogue of Organisms
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Earth Day: Pogo and our responsibility1 year ago in Doc Madhattan
Go, learn some linear algebra
When I was taking math classes in college I enjoyed topology, differential equations, calculus and combinatorial math, but somehow could not bring myself to drum up enthusiasm for linear algebra.
If I had picked physics as my major (which I almost did), I would not probably have escaped from the clutches of linear algebra while learning quantum mechanics. As it happened I picked chemistry, and most of the quantum chemistry that was served to me after that was sans linear algebra.
On his blog luysii has an excellent set of notes on linear algebra from a QM class that he audited. As I mentioned on his blog, it's interesting how much one can get away with in QC without linear algebra. Thus, take a look at some classic textbooks- Levine, McQuarrie and the classic Pauling and Wilson- and one can go a long way with very little LA. The only things that you are really required to know are eigenvalues and eigenfunctions, but even then the Dirac notation is usually skipped in elementary QC. About the only QC book I know which utilizes large doses of LA is the sophisticated book by Szabo and Ostlund.
Yet LA matters and as luysii demonstrates, there is a generality and elegance to it. There is at least one key LA theorem which is mandatory knowledge in QC. When you are learning about the variational principle (which is used to find approximations to the ground state energy of a system), you derive the so-called secular equation by utilizing a very important LA theorem; that a set of linear homogeneous equations has a non-trivial (non-zero) solution if and only if the determinant of the coefficients is zero. Further on, matrices also come into play in important ways when you are learning about the calculation of transition states, normal modes, and energy minima in molecular mechanics. In the latter exercise you have to calculate the Hessian matrix and then diagonalize this monstrosity (thank god for computer programs).
Perhaps it's not surprising that QC can go a long way without much linear algebra. QC is an application of QM to problems of chemical interest, and the whole reason why the Schrodinger formulation of quantum theory became hugely more popular than the equivalent Heisenberg matrix formulation was that it was more tractable to applications (essentially plug in the correct expression for the potential energy) and couched in the more familiar 19th century language of differential equations. If you wish to know about matrix mechanics take a look at Max Born's excellent book "Atomic Physics"; I had to give up on that particular section.
But even the great Erwin's celebrated paper introducing his equation was titled "Quantization as an Eigenvalue Problem". Maybe it is worth even for a "quantum engineer" (as the late Wolfgang Pauli once somewhat derisively called Enrico Fermi) to learn some linear algebra.
If I had picked physics as my major (which I almost did), I would not probably have escaped from the clutches of linear algebra while learning quantum mechanics. As it happened I picked chemistry, and most of the quantum chemistry that was served to me after that was sans linear algebra.
On his blog luysii has an excellent set of notes on linear algebra from a QM class that he audited. As I mentioned on his blog, it's interesting how much one can get away with in QC without linear algebra. Thus, take a look at some classic textbooks- Levine, McQuarrie and the classic Pauling and Wilson- and one can go a long way with very little LA. The only things that you are really required to know are eigenvalues and eigenfunctions, but even then the Dirac notation is usually skipped in elementary QC. About the only QC book I know which utilizes large doses of LA is the sophisticated book by Szabo and Ostlund.
Yet LA matters and as luysii demonstrates, there is a generality and elegance to it. There is at least one key LA theorem which is mandatory knowledge in QC. When you are learning about the variational principle (which is used to find approximations to the ground state energy of a system), you derive the so-called secular equation by utilizing a very important LA theorem; that a set of linear homogeneous equations has a non-trivial (non-zero) solution if and only if the determinant of the coefficients is zero. Further on, matrices also come into play in important ways when you are learning about the calculation of transition states, normal modes, and energy minima in molecular mechanics. In the latter exercise you have to calculate the Hessian matrix and then diagonalize this monstrosity (thank god for computer programs).
Perhaps it's not surprising that QC can go a long way without much linear algebra. QC is an application of QM to problems of chemical interest, and the whole reason why the Schrodinger formulation of quantum theory became hugely more popular than the equivalent Heisenberg matrix formulation was that it was more tractable to applications (essentially plug in the correct expression for the potential energy) and couched in the more familiar 19th century language of differential equations. If you wish to know about matrix mechanics take a look at Max Born's excellent book "Atomic Physics"; I had to give up on that particular section.
But even the great Erwin's celebrated paper introducing his equation was titled "Quantization as an Eigenvalue Problem". Maybe it is worth even for a "quantum engineer" (as the late Wolfgang Pauli once somewhat derisively called Enrico Fermi) to learn some linear algebra.
How much chemistry can we wring out of the universe?
Chemiotics II (luysii) had a very interesting post on his blog about the number of proteins of a given length that can be constructed from the entire mass of the earth. Comparing the masses of amino acids to the mass of the earth, he demonstrated that all the earth's mass will be pretty much exhausted with all combinations of a protein that's only 41 amino acids long, which is peanuts as far as your typical protein goes. Such calculations have great relevance for the origin of life if we are to understand the design and evolution of biomolecules.
One can ask similar questions about crystals or small organic molecules. For the latter one can similarly show that the number is much more than the number of atoms in the universe. But most naturally occurring organic molecules have a preponderance of certain fragments like benzene rings. Similarly, there are only a certain rather small number of symmetry groups for crystals. Therefore it seems that in reality, we are dealing with modular units which are much smaller in number (although still quite large) rather than the bare individual units which compose proteins/small molecules/crystals. Thus once these modular units evolved, natural selection probably worked on them instead of trying out possible combinations of their individual atoms. Also remember that natural selection can work on a population of individuals- any kind of individuals- if one of them shows even the slightest advantage with respect to replication. In case of sequences of amino acids, such replicative advantages could arise from several features; stability, charge distributions that could serve to protect the sequences from aqueous hydrolysis or attract one sequence to another, or conformational flexibility that could serve to effect flexibility in the functions of the sequence. Any one of these features could serve to "fix" a particular sequence or group of sequences in a pool of sequences.
In case of proteins for instance, one should ponder how many of the many possible sequences considered could be energetically favored. Some sequences that pit bulky or similarly charged amino acids next to each other could be disfavored by steric and electrostatic factors. Also in case of proteins, the conservation of 3D structure relative to sequence must have been a boon for natural selection. For instance, there's an enormous number of sequences that can fold up into alpha helices (although certain amino acids are favored and others are disfavored) or sheets (where amino acid preferences are not as pronounced). Thus one gets the feeling that natural selection could have some flexibility in designing sequences that would fold into energetically favored secondary structural motifs. However this would not work as well for the active sites of enzymes, where very specific amino acids need to be located in very specific positions in order to effect catalysis. But even here, certain amino acids such as histidine and lysine are interchangeable in terms of their acid-base catalysis roles.
A particularly interesting case that comes to my mind is that of amyloid. Once thought to be the province of only proteins like ß-amyloid, it has now been extensively shown (most notably by Christopher Dobson of Cambridge University, for instance see Nature Chemical Biology 5, 15 - 22 2009, doi:10.1038/nchembio.131 ) that virtually any protein can form amyloid under the right conditions. Amyloid may have been evolution's dream, since it could have tremendous flexibility in picking sequences and coercing them to form amyloid-like structures under the right conditions. As work in which I participated demonstrated (Biochemistry, 2008, 47 (38), pp 10018–10026, DOI: 10.1021/bi801081c), the simplest of changes in conditions like temperature and pH are enough to drastically modulate the architecture of amyloid assemblies.
Thus, while there was potentially an infinite pool of possibilities to design proteins from, as evolution proceeded, I think that the funnel of possibilities became narrower and narrower as the units needed to achieve optimum design became more tailored and building-block like. It's a very interesting question to contemplate the details of this matter.
One can ask similar questions about crystals or small organic molecules. For the latter one can similarly show that the number is much more than the number of atoms in the universe. But most naturally occurring organic molecules have a preponderance of certain fragments like benzene rings. Similarly, there are only a certain rather small number of symmetry groups for crystals. Therefore it seems that in reality, we are dealing with modular units which are much smaller in number (although still quite large) rather than the bare individual units which compose proteins/small molecules/crystals. Thus once these modular units evolved, natural selection probably worked on them instead of trying out possible combinations of their individual atoms. Also remember that natural selection can work on a population of individuals- any kind of individuals- if one of them shows even the slightest advantage with respect to replication. In case of sequences of amino acids, such replicative advantages could arise from several features; stability, charge distributions that could serve to protect the sequences from aqueous hydrolysis or attract one sequence to another, or conformational flexibility that could serve to effect flexibility in the functions of the sequence. Any one of these features could serve to "fix" a particular sequence or group of sequences in a pool of sequences.
In case of proteins for instance, one should ponder how many of the many possible sequences considered could be energetically favored. Some sequences that pit bulky or similarly charged amino acids next to each other could be disfavored by steric and electrostatic factors. Also in case of proteins, the conservation of 3D structure relative to sequence must have been a boon for natural selection. For instance, there's an enormous number of sequences that can fold up into alpha helices (although certain amino acids are favored and others are disfavored) or sheets (where amino acid preferences are not as pronounced). Thus one gets the feeling that natural selection could have some flexibility in designing sequences that would fold into energetically favored secondary structural motifs. However this would not work as well for the active sites of enzymes, where very specific amino acids need to be located in very specific positions in order to effect catalysis. But even here, certain amino acids such as histidine and lysine are interchangeable in terms of their acid-base catalysis roles.
A particularly interesting case that comes to my mind is that of amyloid. Once thought to be the province of only proteins like ß-amyloid, it has now been extensively shown (most notably by Christopher Dobson of Cambridge University, for instance see Nature Chemical Biology 5, 15 - 22 2009, doi:10.1038/nchembio.131 ) that virtually any protein can form amyloid under the right conditions. Amyloid may have been evolution's dream, since it could have tremendous flexibility in picking sequences and coercing them to form amyloid-like structures under the right conditions. As work in which I participated demonstrated (Biochemistry, 2008, 47 (38), pp 10018–10026, DOI: 10.1021/bi801081c), the simplest of changes in conditions like temperature and pH are enough to drastically modulate the architecture of amyloid assemblies.
Thus, while there was potentially an infinite pool of possibilities to design proteins from, as evolution proceeded, I think that the funnel of possibilities became narrower and narrower as the units needed to achieve optimum design became more tailored and building-block like. It's a very interesting question to contemplate the details of this matter.
A biochemical parody of Bryan Adams
For some reason when I was in high school Bryan Adams was big, and we used to listen to his songs all the time. These days I find many of his songs too sappy, but I still love some of the melodies and find myself going nostalgically down memory lane when "Summer of '69" or "Everything I Do" or "Cloud Number Nine" wafts on to the air from somewhere.
So yesterday I happened to be looking at a particularly ravishing picture of dihydrofolate reductase (DHFR) and Adams's "Have You Ever Really Loved A Woman" randomly started playing on my iPod and Bam! The two topics meshed together in an ungodly union. So here is my tribute to Bryan Adams with profound apologies...an ode to that perfect protein which we can only covet. The original version is copied first to mitigate the trauma that will follow.
HAVE YOU EVER REALLY LOVED A WOMAN
To really love a woman
To understand her - you gotta know it deep inside
Hear every thought - see every dream
N' give her wings - when she wants to fly
Then when you find yourself lyin' helpless in her arms
You know you really love a woman
When you love a woman you tell her
that she's really wanted
When you love a woman you tell her
that she's the one
she needs somebody to tell her
that it's gonna last forever
So tell me have you ever really
- really really ever loved a woman?
To really love a woman
Let her hold you -
til ya know how she needs to be touched
You've gotta breathe her - really taste her
Til you can feel her in your blood
N' when you can see your unborn children in her eyes
You know you really love a woman
When you love a woman
you tell her that she's really wanted
When you love a woman
you tell her that she's the one
she needs somebody to tell her
that you'll always be together
So tell me have you ever really -
really really ever loved a woman?
You got to give her some faith - hold her tight
A little tenderness - gotta treat her right
She will be there for you, takin' good care of you
Ya really gotta love your woman...
Then when you find yourself lyin' helpless in her arms
You know you really love a woman
When you love a woman you tell her
that she's really wanted
When you love a woman
you tell her that she's the one
she needs somebody to tell her
that it's gonna last forever
So tell me have you ever really
- really really ever loved a woman?
Just tell me have you ever really,
really, really, ever loved a woman? You got to tell me
Just tell me have you ever really,
really, really, ever loved a woman?
HAVE YOU EVER REALLY LOVED A PROTEIN
To really love a protein
To understand her - you gotta know her deep inside
Hear every helix - see every sheet
N' give her energy - when she wants to jiggle
Then when you find yourself staring helpless at her domains
You know you really love a protein
When you love a protein you tell her
that she's really conformationally correct
When you love a protein you tell her
that she's catalytically perfect
she needs somebody to tell her
that her half-life?s gonna last forever
So tell me have you ever really
- really really ever loved a protein?
To really love a protein
Let her hold your high-affinity binders-
til ya know how she needs to be crystallized
You've gotta mass spec her - really sequence her
Til you can feel her atoms in your spectrometer
N' when you can see the unformed hydrogen bonds in her pockets
You know you really love a protein
When you love a protein
you tell her that she's really evolutionarily conserved
When you love a protein you tell her that she's peptidase-digestion preserved
she needs somebody to tell her
that her fold will always hold together
So tell me have you ever really -
really really ever loved a protein?
You got to give her some metal ions - hold her co-factors
A little pH-control - gotta treat her ionization state right
She will be there for you, takin' good care of your ligands
Ya really gotta love your protein...
Then when you find yourself staring helpless at her PDB coordinates
You know you really love a protein
When you love a protein you tell her
that she's really conformationally correct
When you love a protein you tell her
that she's catalytically perfect
she needs somebody to tell her
that her half-life?s gonna last forever
So tell me have you ever really
- really really ever loved a protein?
Just tell me have you ever really,
really, really, ever loved a protein? You got to tell me
Just tell me have you ever really,
really, really, ever loved (that helical, sheety, hydrogen bondalacious) protein?
So yesterday I happened to be looking at a particularly ravishing picture of dihydrofolate reductase (DHFR) and Adams's "Have You Ever Really Loved A Woman" randomly started playing on my iPod and Bam! The two topics meshed together in an ungodly union. So here is my tribute to Bryan Adams with profound apologies...an ode to that perfect protein which we can only covet. The original version is copied first to mitigate the trauma that will follow.
HAVE YOU EVER REALLY LOVED A WOMAN
To really love a woman
To understand her - you gotta know it deep inside
Hear every thought - see every dream
N' give her wings - when she wants to fly
Then when you find yourself lyin' helpless in her arms
You know you really love a woman
When you love a woman you tell her
that she's really wanted
When you love a woman you tell her
that she's the one
she needs somebody to tell her
that it's gonna last forever
So tell me have you ever really
- really really ever loved a woman?
To really love a woman
Let her hold you -
til ya know how she needs to be touched
You've gotta breathe her - really taste her
Til you can feel her in your blood
N' when you can see your unborn children in her eyes
You know you really love a woman
When you love a woman
you tell her that she's really wanted
When you love a woman
you tell her that she's the one
she needs somebody to tell her
that you'll always be together
So tell me have you ever really -
really really ever loved a woman?
You got to give her some faith - hold her tight
A little tenderness - gotta treat her right
She will be there for you, takin' good care of you
Ya really gotta love your woman...
Then when you find yourself lyin' helpless in her arms
You know you really love a woman
When you love a woman you tell her
that she's really wanted
When you love a woman
you tell her that she's the one
she needs somebody to tell her
that it's gonna last forever
So tell me have you ever really
- really really ever loved a woman?
Just tell me have you ever really,
really, really, ever loved a woman? You got to tell me
Just tell me have you ever really,
really, really, ever loved a woman?
HAVE YOU EVER REALLY LOVED A PROTEIN
To really love a protein
To understand her - you gotta know her deep inside
Hear every helix - see every sheet
N' give her energy - when she wants to jiggle
Then when you find yourself staring helpless at her domains
You know you really love a protein
When you love a protein you tell her
that she's really conformationally correct
When you love a protein you tell her
that she's catalytically perfect
she needs somebody to tell her
that her half-life?s gonna last forever
So tell me have you ever really
- really really ever loved a protein?
To really love a protein
Let her hold your high-affinity binders-
til ya know how she needs to be crystallized
You've gotta mass spec her - really sequence her
Til you can feel her atoms in your spectrometer
N' when you can see the unformed hydrogen bonds in her pockets
You know you really love a protein
When you love a protein
you tell her that she's really evolutionarily conserved
When you love a protein you tell her that she's peptidase-digestion preserved
she needs somebody to tell her
that her fold will always hold together
So tell me have you ever really -
really really ever loved a protein?
You got to give her some metal ions - hold her co-factors
A little pH-control - gotta treat her ionization state right
She will be there for you, takin' good care of your ligands
Ya really gotta love your protein...
Then when you find yourself staring helpless at her PDB coordinates
You know you really love a protein
When you love a protein you tell her
that she's really conformationally correct
When you love a protein you tell her
that she's catalytically perfect
she needs somebody to tell her
that her half-life?s gonna last forever
So tell me have you ever really
- really really ever loved a protein?
Just tell me have you ever really,
really, really, ever loved a protein? You got to tell me
Just tell me have you ever really,
really, really, ever loved (that helical, sheety, hydrogen bondalacious) protein?
Almost back
I have been in Tasmania for the last three weeks visiting family, enjoying sunny weather while my home in the northeast faced the wrath of the Norse gods. Back next week for a new year of chemical bloggity bloggings.
Happy New Year
Happy New Year
The price of global warming science is eternal vigilance
John Tierney of the NYT weighs in on the hacked emails and accurately nails it
Listen to Capt. Ramsey, son:
I’ve long thought that the biggest danger in climate research is the temptation for scientists to lose their skepticism and go along with the “consensus” about global warming. That’s partly because it’s easy for everyone to get caught up in “informational cascades”, and partly because there are so many psychic and financial rewards rewards for working on a problem that seems to be a crisis. We all like to think that our work is vitally useful in solving a major social problem — and the more major the problem seems, the more money society is liable to spend on it.We are all subject to the confirmation bias, and I can say from experience that we have to battle it in our research every single day as fallible human beings. But as Tierney says, when the stakes are so incredibly high, when governments and international budgets and debts and the fate of billions is going to be affected by what you say, you better fight the conformation bias ten times as much as usual.
I’m not trying to suggest that climate change isn’t a real threat, or that scientists are deliberately hyping it. But when they look at evidence of the threat, they may be subject to the confirmation bias — seeing trends that accord with their preconceptions and desires. Given the huge stakes in this debate — the trillions of dollars that might be spent to reduce greenhouse emissions — it’s important to keep taking skeptical looks at the data. How open do you think climate scientists are to skeptical views, and to letting outsiders double-check their data and calculations?
Listen to Capt. Ramsey, son:
"Mr. Hunter, we have rules that are not open to interpretation, personal intuition, gut feelings, hairs on the back of your neck, little devils or angels sitting on your shoulders..."
The damning global warming emails; when science becomes the casualty
By now everyone and his grandmother must have heard about the hacked emails of the prestigious University of East Anglia Climate Research Unit (CRU). The emails were sent by leading climate change scientists to each other and seem to express doubts and uncertainty. More importantly they also seem to display some troubling signs of rather dishonest discourse, with scientists trying to hold dangerously unfavorable opinions of journal editors who seem to be open to publishing papers that don't seem to agree with their views, and asking each other to delete emails which might signal doubt.
There is at least one example of bad science revealed in the emails. It seems that one set of data from tree ring proxies did not show the expected rise in temperatures for a particular period and showed a decline. What was done was that just for that period, a different set of data from another method which did show the rise was grafted on to this piece of data. John Tierney of the NYT has the two graphs on his blog. Does this change the general conclusion? Probably not. Is this bad science and enough to justify a flurry of indignant questions in the minds of outsiders? Certainly so. Good science would have meant revealing all the pieces of data including those which showed a decline.
Now what is remarkable (or perhaps not remarkable at all) is the vociferous political- not scientific- reaction that has erupted in blogs all over the internet. I would point readers to my fellow blogger Derek Lowe's succinct summary of the matter. While I am not as skeptical about climate change as he is, it is disconcerting to see how much political, personal and social baggage the whole issue is carrying. Whenever a scientific issue starts carrying so much non-scientific baggage, one can be assured that we are in trouble.
The comments on most blogs range across the spectrum. There are the outright deniers who claim that the emails "disprove global warming"; they don't, and I can't see how any set of personal exchanges could say almost anything definitive about a system as complex as the climate. Phrases like "hide the decline" (in the case of the above tree ring proxy data) and "trick" have been taken out of their technical context to indicate subversion and deception. And then there are the proponents who want to act like nothing has happened. I like George Monbiot's take on it where he says that even if the science of climate change has certainly not come crashing down, the public image of climate change has been dealt a serious blow, and denying this would simply mean burying your head in the sand. After all, we are supposed to be the good guys, the ones who are supposed to honestly admit to our limitations and failings, and we are not doing this. What ramifications this will have for the important Copenhagen climate summit this month is uncertain.
However, the very fact that we have to worry as much about the public image of climate science as the science itself plainly speaks to the degree of politicization of the issue. I think the liability of this entire matter has basically become infinite and I think scientists working in the field are facing an unprecedented dilemma which few scientists have ever faced. Here's the problem; we are dealing with an extremely complex system and it is hardly surprising if the science of this system (which after all is only a hundred years or so old) keeps getting revised, reshuffled and reiterated even if the basics remain intact. That would be perfectly normal for a vast, multidisciplinary field like this. That is the way science works. One finds such revision and vigorous debate even in highly specific and recondite areas like the choice of atomic partial charges in the calculation of intermolecular energies. The climate is orders of magnitude more complicated. If the usual rules of scientific discourse were to be followed, making such debates and disagreements open would not be a problem.
But with an issue that is so exquisitely fraught with political and economic liabilities and where the stakes are so enormously high, I believe that the normal process of scientific debate, discourse and progress has broken down and is being bypassed. Scientists who would otherwise engage in lively debate and disagreements have become extremely loathe to make their doubts public. These scientists fear that they would essentially be condemned by both sides. The right wing extremists would seize upon any honest disclosure of debate as the kick that brings the entire edifice crumbling down. They would predictably try to discredit even reasonable conclusions drawn by climate change scientists. At the same time, left wing extremists would essentially disown such scientists and either declare them an anomaly or more predictably declare them to be political and corporate shills. A scientist who honestly voices his doubts would become a man without a country.
This is of course in addition to the ample scorn that establishment upholders like climate blogger Joe Romm would heap on them. Thus, if you are a scientist working in climate change today, it would be rather difficult for you to make even the normal process of science transparent. Plus, most scientists are genuinely scared that all the momentum they have built over the years would fizzle out if their right wing opponents pounce on their private doubts. Think about it. The Copenhagen summit is going to be held in a month. Scientists have faced enormous obstacles in convincing the public and governments about climate change. Your work has been crowned by grudging acknowledgement even by George W Bush and the Nobel Peace Prize for Al Gore. Would you be ready to throw away all this rightly hard-earned and hard-fought consensus for the sake of a few dissenting opinions? The simple laws of human nature dictate that you probably would not.
In my opinion, that is what seems to have happened with the scientists at the CRU. They have been so afraid of not only expressing their doubts (many of which as noted above would be valid given the science involved) but also entertaining other dissenting opinions that they have unfortunately picked the option of trying to silence open debate in a way that would be unacceptable in science in general. One can understand their motivation, but their actions still seem deplorable.
I think these emails point to a much more serious structural problem in the scientific enterprise of climate change. For good reasons and bad, whether to stand up to political hacks or ironically to defend good science, this enterprise has accumulated so much political baggage that it is now virtually impossible for it to compromise, to change, to maneuver even in the face of cogent reasons. The science of climate change has essentially bound itself into a straitjacket. My prediction is that important decisions about this science will in the future be mainly politically motivated. Public consensus not completely backed by good science will be the driving force for major decisions. The consequences of those decisions, just like the climate, are uncertain. We will have to wait and see.
But as usual, the casualty is ultimately science itself. What was good science and ineffective politics before is becoming effective politics and bad science. Whatever else happens, science never wins when it gets so overtly politicized. And hopefully about this there will be universal consensus.
There is at least one example of bad science revealed in the emails. It seems that one set of data from tree ring proxies did not show the expected rise in temperatures for a particular period and showed a decline. What was done was that just for that period, a different set of data from another method which did show the rise was grafted on to this piece of data. John Tierney of the NYT has the two graphs on his blog. Does this change the general conclusion? Probably not. Is this bad science and enough to justify a flurry of indignant questions in the minds of outsiders? Certainly so. Good science would have meant revealing all the pieces of data including those which showed a decline.
Now what is remarkable (or perhaps not remarkable at all) is the vociferous political- not scientific- reaction that has erupted in blogs all over the internet. I would point readers to my fellow blogger Derek Lowe's succinct summary of the matter. While I am not as skeptical about climate change as he is, it is disconcerting to see how much political, personal and social baggage the whole issue is carrying. Whenever a scientific issue starts carrying so much non-scientific baggage, one can be assured that we are in trouble.
The comments on most blogs range across the spectrum. There are the outright deniers who claim that the emails "disprove global warming"; they don't, and I can't see how any set of personal exchanges could say almost anything definitive about a system as complex as the climate. Phrases like "hide the decline" (in the case of the above tree ring proxy data) and "trick" have been taken out of their technical context to indicate subversion and deception. And then there are the proponents who want to act like nothing has happened. I like George Monbiot's take on it where he says that even if the science of climate change has certainly not come crashing down, the public image of climate change has been dealt a serious blow, and denying this would simply mean burying your head in the sand. After all, we are supposed to be the good guys, the ones who are supposed to honestly admit to our limitations and failings, and we are not doing this. What ramifications this will have for the important Copenhagen climate summit this month is uncertain.
However, the very fact that we have to worry as much about the public image of climate science as the science itself plainly speaks to the degree of politicization of the issue. I think the liability of this entire matter has basically become infinite and I think scientists working in the field are facing an unprecedented dilemma which few scientists have ever faced. Here's the problem; we are dealing with an extremely complex system and it is hardly surprising if the science of this system (which after all is only a hundred years or so old) keeps getting revised, reshuffled and reiterated even if the basics remain intact. That would be perfectly normal for a vast, multidisciplinary field like this. That is the way science works. One finds such revision and vigorous debate even in highly specific and recondite areas like the choice of atomic partial charges in the calculation of intermolecular energies. The climate is orders of magnitude more complicated. If the usual rules of scientific discourse were to be followed, making such debates and disagreements open would not be a problem.
But with an issue that is so exquisitely fraught with political and economic liabilities and where the stakes are so enormously high, I believe that the normal process of scientific debate, discourse and progress has broken down and is being bypassed. Scientists who would otherwise engage in lively debate and disagreements have become extremely loathe to make their doubts public. These scientists fear that they would essentially be condemned by both sides. The right wing extremists would seize upon any honest disclosure of debate as the kick that brings the entire edifice crumbling down. They would predictably try to discredit even reasonable conclusions drawn by climate change scientists. At the same time, left wing extremists would essentially disown such scientists and either declare them an anomaly or more predictably declare them to be political and corporate shills. A scientist who honestly voices his doubts would become a man without a country.
This is of course in addition to the ample scorn that establishment upholders like climate blogger Joe Romm would heap on them. Thus, if you are a scientist working in climate change today, it would be rather difficult for you to make even the normal process of science transparent. Plus, most scientists are genuinely scared that all the momentum they have built over the years would fizzle out if their right wing opponents pounce on their private doubts. Think about it. The Copenhagen summit is going to be held in a month. Scientists have faced enormous obstacles in convincing the public and governments about climate change. Your work has been crowned by grudging acknowledgement even by George W Bush and the Nobel Peace Prize for Al Gore. Would you be ready to throw away all this rightly hard-earned and hard-fought consensus for the sake of a few dissenting opinions? The simple laws of human nature dictate that you probably would not.
In my opinion, that is what seems to have happened with the scientists at the CRU. They have been so afraid of not only expressing their doubts (many of which as noted above would be valid given the science involved) but also entertaining other dissenting opinions that they have unfortunately picked the option of trying to silence open debate in a way that would be unacceptable in science in general. One can understand their motivation, but their actions still seem deplorable.
I think these emails point to a much more serious structural problem in the scientific enterprise of climate change. For good reasons and bad, whether to stand up to political hacks or ironically to defend good science, this enterprise has accumulated so much political baggage that it is now virtually impossible for it to compromise, to change, to maneuver even in the face of cogent reasons. The science of climate change has essentially bound itself into a straitjacket. My prediction is that important decisions about this science will in the future be mainly politically motivated. Public consensus not completely backed by good science will be the driving force for major decisions. The consequences of those decisions, just like the climate, are uncertain. We will have to wait and see.
But as usual, the casualty is ultimately science itself. What was good science and ineffective politics before is becoming effective politics and bad science. Whatever else happens, science never wins when it gets so overtly politicized. And hopefully about this there will be universal consensus.
More model perils; parametrize this
Now here's a very interesting review article that puts some of the pitfalls of models that I have mentioned on these pages in perspective. The article is by Jack Dunitz and his long-time colleague Angelo Gavezzotti. Dunitz is in my opinion one of the finest chemists and technical writers of the last half century and I have learnt a lot from his articles. Two that are on my "top 10" list are his article showing the entropic gain accrued by displacing water molecules in crystals and proteins (a maximum of 2 kcal/mol for strongly bound water) and his paper demonstrating that organic fluorine rarely, if ever, forms hydrogen bonds.In any case, in this article he talks about an area in which he is the world's acknowledged expert; organic crystal structures. Understanding and predicting (the horror!) crystal structures essentially boils down to understanding the forces that makes molecules stick to each other. Dunitz and Gavezzotti describe theoretical and historical attempts to model forces between molecules, and many of their statements about the inherent limitations of modeling these forces rang as loudly in my mind as the bell in Sainte-Mère-Église during the Battle of Normandy.
Dunitz has a lot to say about atom-atom potentials that are the most popular framework for modeling inter and intramolecular interactions. Basically such potentials assume simple functional forms that model the attractive and repulsive interactions between nuclei which are treated as rigid balls. This is also of course the fundamental approximation in molecular mechanics and force fields. The interactions are basically Coulombic interactions (relatively simple to model) and more complicated dispersion interactions which are essentially quantum mechanical in nature. The real and continuing challenge is to model these weak dispersive interactions.
But the problem is fuzzy. As Dunitz says, atom-atom potentials are popular mainly because they are simple in form and easy to calculate. However, they have scant, if any, connection to "reality". This point cannot be stressed enough again. As this blog has noted several times before, we use models because they work, not because they are real. The coefficients in the functional forms of the atom-atom potentials are essentially varied to minimize the potential energy of the system and there are several ways to skin this cat. For instance, atomic point charges are rather arbitrary (and definitely not "real") and can be calculated and assigned by a variety of theoretical approaches. In the end, nobody knows if the final values or even the functional forms have much to do with the real forces inside crystals. It's all a question of parameterization which gives you the answer, and while parameterization may seem like a magic wand which may give you anything that you want, that's precisely the problem with it...that it may give you anything that you want without reproducing the underlying reality. Overfitting is also a constant headache and one of the biggest problems with any modeling in my opinion; whether in chemistry, quantitative finance or atmospheric science. More on that later.
An accurate treatment of intermolecular forces will have to take electron delocalization into consideration. The part which is the hardest to deal with is the part close to the bottom of the famous Van der Waals energy curve, where there is an extremely delicate balance between repulsion and attraction. Naturally one thinks of quantum mechanics to handle such fine details. A host of sophisticated methods have been developed to calculate molecular energies and forces. But those who think QM will take them to heaven may be mistaken; it may in fact take them to hell.
Let's start with the basics. In any QM calculation one uses a certain theoretical framework and a certain basis set to represent atomic and molecular orbitals. One then adds terms to the basis set to improve accuracy. Consider Hartree-Fock theory. As Dunitz says, it is essentially useless for dealing with electron delocalization because it does not take electron correlation into account, no matter how large a basis set you use. More sophisticated methods have names like "Moller-Plesset perturbation theory with second order corrections" (MP2) but these may greatly overestimate the interaction energy, and more importantly the calculations become hideously computer intensive for anything more than the simplest molecules.
True, there are "model systems" like the benzene dimer (which has been productively beaten to death) for which extremely high levels of theory have been developed that approach experimental accuracy within a hairsbreadth. But firstly, model systems are just that, model systems; the benzene dimer is not exactly a molecular arrangement which real life chemists deal with all the time. Secondly, a practical chemist would rather have an accuracy of 1 kcal/mol for a large system than an accuracy of 0.1 kcal/mole for a simple system like the benzene dimer. Thus, while MP2 and other methods may give you unprecedented accuracy for some model systems, they are usually very expensive for most systems of biological interest and not very useful.
DFT still seems to be one of the best techniques around to deal with intermolecular forces. But "classical" DFT suffers from a well-known inability to treat dispersion. "Parameterized DFT" in which an inverse sixth power term is added to the basic equations can work well and promises to be a very useful addition to the theoretical chemist's arsenal. More parameterization though.
And yet, as Dunitz points out, problems remain. Even if one can accurately calculate the interaction energy of the benzene dimer, it is not really possible to know how much of it comes from dispersion and how much of it comes from higher order terms. Atom-atom potentials are happiest calculating interaction energies at large distances, where the Coulomb term is pretty much the only one which survives, but at small interatomic distances which are the distances most of interest for the chemist and the crystallographer, a complex dance between attraction and repulsion, monopoles, dipoles and multipoles and overlapping electron clouds manifests itself. The devil himself would have a hard time calculating interactions in these regions.
The theoretical physicist turned Wall Street quant Emanuel Derman (author of the excellent book ("My Life as a Quant: Reflections on Physics and Finance") says that one of the problems with the financial modelers on Wall Street is that they suffer from "physics envy". Just like in physics, they want to discover three laws that govern 99% of the financial world. More predictably as Derman says, they end up discovering 99 laws that seem to govern 3% of the financial world with varying error margins. I would go a step further and say that even physics is accurate only in the limit of ideal cases and this deviation from absolute accuracy distinctly shows in theoretical chemistry. Just consider that the Schrodinger equation can be solved exactly only for the hydrogen atom, which is where chemistry only begins. Anything more complicated that, and even the most austere physicist cannot help but approximate, parametrize, and constantly struggle with errors and noise. As much as the theoretical physicist would like to tout the platonic purity of his theories, their practical applications would without exception involve much approximation. There is a reason why that pinnacle of twentieth century physics is called the Standard Model.
I would say that computational modelers in virtually every field from finance to climate change to biology and chemistry suffer from what Freeman Dyson has called "technical arrogance". We have made enormous progress in understanding complex systems in the last fifty years and yet when it comes to modeling the stock market, the climate or protein folding, we seem to think that we know it all. But we don't. Far from it. Until we do all we can do is parametrize, and try to avoid the fallacy of equating our models with reality.
That's right Dorothy. Everything is a model. Let's start with the benzene dimer.
Dunitz, J., & Gavezzotti, A. (2009). How molecules stick together in organic crystals: weak intermolecular interactions Chemical Society Reviews, 38 (9) DOI: 10.1039/b822963p
California axes science
From the NYT
As the University of California struggles to absorb its sharpest drop in state financing since the Great Depression, every professor, administrator and clerical worker has been put on furlough amounting to an average pay cut of 8 percent.There was a time when people used to go to Berkeley for the lower tuition. Seems the last refuges of education are gradually eroding away.
In chemistry laboratories that have produced Nobel Prize-winning research, wastebaskets are stuffed to the brim on the new reduced cleaning schedule. Many students are frozen out of required classes as course sections are trimmed.
And on Thursday, to top it all off, the Board of Regents voted to increase undergraduate fees — the equivalent of tuition — by 32 percent next fall, to more than $10,000. The university will cost about three times as much as it did a decade ago, and what was once an educational bargain will be one of the nation’s higher-priced public universities.
What did you say the error was??
I was looking at some experimental data for drug molecules binding to a pharmaceutically relevant protein.
The numbers reported were as percentages of binding relative to a standard which was defined to be 100%. Here's how they looked:
97.3 + - (plus or minus) 68.4
79.4 + - 96.1
59.5 + - 55.3
1.4 + - 2.5
Seriously, how did the reviewers allow this to go through?
The numbers reported were as percentages of binding relative to a standard which was defined to be 100%. Here's how they looked:
97.3 + - (plus or minus) 68.4
79.4 + - 96.1
59.5 + - 55.3
1.4 + - 2.5
Seriously, how did the reviewers allow this to go through?
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