Sunday 2 May 2010

laws of biology

“Study mathematics like a house on fire” - Charles Darwin

“We all stand on the shoulders of giants” - Isaac Newton

The two famous quotes by the founding fathers of biology and physics illustrate clearly the sad state of biology today. The first one was Darwin’s advice to young Francis Galton, a British polymath, geneticist and statistician, who later gave us some very useful statistical concepts such as correlation, but also some terrible ideas such as eugenics.

The second quote is by Isaac Newton refers to the fact that science should not be a circular or lateral journey but rather a cumulative progress so that each scientist would not have to re-invent the scientific toolbox and results each time they start asking new questions and finding answers to them. Instead, we hope to build on the work and discoveries of those who went before us, while also constantly abstracting, refining and reordering of that components of the scientific framework.

But the lack of mathematics and a slow progress are exactly is the characteristics of modern biology and we are trying to understand its implications below.

Orthologous Gene Groups

Biologists at University of Colorado examined a network of 1600 orthologous gene groups (orthologous genes are related by phylogenetic descent) compiled from 38 genomes, comprising 23,400 genes, for genes that are related by being in the same operon. The colors in the picture above reflect abundance. Orthologous groups that occur in two or three evolutionarily distant species are blue, those that occur in 4-7 species are yellow, those that occur in 8-15 species are orange, while those occurring in 16 or more species are red.

Back to High School

Think back to your high school education. You will probably recall that in physics there were something called Newton’s Laws of Mechanics. If you made it to electromagnetism, you will also recall Maxwell’s Laws, and if you made it to your senior year, perhaps you have a vague image of Einstein’s Laws of Relativity and something called Shroedinger’s equation in quantum physics. Similar soul-searching in chemistry will produce the fundamental laws of thermodynamics and a couple of other successful formalizations such the law kinetics and so forth. All these laws have one thing in common – they can be expressed in simple, mathematical expressions and because of their exceptional, crystal brevity will fit on a piece of napkin.

Now think back to your biology studies. You will only find broad observations, but no laws that were described in mathematics. Statements like evolution is a combination of variation and natural selection, or information flows from DNA to proteins and not vice-versa are not laws, but simply observations. Of course, hey are useful, but in a much more limited way when compared to their counterparts in physics and chemistry, not to mention the theorem-proof framework in mathematics.

The state of affairs in biology today is – for the lack of better word - catastrophic in all of its forms, including molecular biology, biochemistry, cell biology, genomics, proteomics, physiology and bioinformatics, to mention only a few of its innumerable (mostly irrelevant and misguided) sub-branches. There are clearly those who went before us, but for some reason they – perhaps because of excessive excitement over things that unraveled to them or because they missed mathematics classes in high school - never took time to establish a proper highly mathematical scientific framework similar to that created by Newton or Leibniz in physics.

By the way, it should be mentioned up front that the author does not criticize biology and its sub-disciplines from some sort heavily quantitative jock, high-horse attitude. or harbor puerile fascination for esoteric mathematical operator symbols for the sake of it. Nor does he try to flex his mathematical muscles and intimidate biologists who did not study, say, abstract algebra or topology. On the contrary, after completing degree requirements for molecular biology, applied mathematics, and computer science as some would argue (but this is very arguable) at a school that apparently boasts the largest number of Nobel Prize winners in the world that ever studied or taught anywhere (the school is in Boston but I will leave to the reader to guess which of the two), he spent some time in various science departments there, noticed the differences, and sadly concluded that some sciences got it right, and some got it very, very wrong.

Based on what he saw he made up his mind that biology and its graduate programs as they stand today will scare away any intelligent mind having even basic ability for abstraction or clear thought, as opposed to memorization or manual dexterity which seems to be in vogue in modern biology. And so did many of his like-minded friends.

Sadly for biology – and for all of us – those clear minds will probably end up in physics, mathematics, economics (the only social science which has managed to introduce math), or chemistry departments. By the way, many of those minds will be definitely pricing glamorized insurance contracts called derivatives in the financial services sector but that is a topic for a different essay. Let us just say, that this is a very scary thought if we imagine what we would have lost if Einstein or Crick had given in to the temptation of securitizing financial obligations and enjoying merchant yuppie salaries, instead of making fundamental scientific breakthroughs that send tsunamis and earthquakes through their disciplines and took humanities to next century but this is again is a topic for a different essay.


When comparing the genome of two different people, we will see single letter changes called single-nucleotide polymorphisms known as SNPs (pronounced "snips") every few thousand letters. It is in fact these single molecule changes in DNA that make us different. An interesting feature of SNPs is that their ordering has distinct patterns, where sets of consecutive changes are most often found together. There are many methods for looking at this data, so this piece combines several of them into a single visual display.

Biology as Science of YAABA - Yet Another Ad-Hoc Biology Acronym

To be blunt, biology seems to be collapsing under never-ending, diarrhetic data accumulation with almost no sign of abstraction or synthesis. What is worse, the longer we wait, the harder is to find a needle or anything for that matter in the hay stack since this hay stack is now completely out of control and growing to astronomical proportions.

To convince yourself, try browsing through some of the most prestigious peer-reviewed scientific journals today in life sciences such as Nature, Cell and Science. First, you will probably notice that the biology article is many times longer, while at the same time containing less ideas or concepts (if any) than the articles of sister sciences. Also, at a closer look the article resemble at best some sort of strange hybrid between a stream-of-consciousness James Joyce travel journals, Burroughs surreal hallucinatory science fiction, or intentionally ambiguous college freshman humanities papers.

Thus, a typical sentence in a modern biological paper would sound something like the following: “We looked at this, it was green or at least greenish, mixed this and it looked like that. Or maybe not. Who knows, we need to look at again probably. What we saw, we now call it YAABA (Yet Another Ad-Hoc Biology Acronym). For further studies, we need to mix some more acronyms and peek into the microscope. We cannot formulate anything more precise since it is not the manner here, but we have to publish so we threw some stuff out anyway” and so forth.

Such articles make both Mendel and Darwin a couple of hundred years ago seem like real quantitative virtuosos or higher math heavyweights since at least these founding fathers of biology used some form of math like rudimentary additions and subtractions. In contrast, you will be lucky to find even a single rigorous abstraction in modern biology papers, strict and precise formulations which could be then plugged back into the scientific framework so someone else could build on it.

By the way, if you ever showed any of these articles to any of your physicist, chemist or mathematician friends and claimed that these are scientific papers, they would think that either your are pulling some kind of weird joke on them, are heavily medicated or cannot think straight anymore for some other strange reason.

Given that, I am also pretty sure that nobody reads any of the biology articles after the first time they published since who in this time and age has time to plow through this type incoherent, seemingly infinite verbal rambling.

These so-called ‘scientific papers’ remind me in some sense of a highly disturbing music CD that you accidentally accepted from a friend who instead of recording a brief, beautiful piece of melody of five to six minutes, set out to record several hours worth of monotonous, atonal and highly disturbing steel mill noise and who now claims that his recordings are great music (science). Whatever were the reasons of your misguided friend for his strange actions, now even your dog would not listen to this terrible CD. As for you, you would so only under oath, if threatened by gun, Russian mafia, Japanese torture techniques, or something along these lines.

key discoveries in biology made by non-biologists

biologists will not like this but the sad truth is that that many of the most important discoveries of biology in the past century were made actually by non-biologists who took interest in biology. so it seems to me that if it were not for the two physicists who discovered the DNA – Crick and Watson - and the chemist who figured out how to amplify it so it could be actually studied – Mullis – biologists would be still doing what they were doing before that – looking at liquids through a microscope and drawing up shopping lists of things they thought they saw.

I am not trying to imply that biologists would be inherently less intelligent or that this science would attract less intelligent people for some reason (it does repel many intelligent people fond of math as discussed above, however). I can only say that in college I noticed that it does attract many would-be radiologists who consider business and law schools close options to medical school, and treat the entire college career as some sort of bulimic information disorder since the medical profession is designed to teach data retrieval rather than thinking skills. The presence of the conveyer-belt memorize-orgo-go-to-med-school-make-cash types does not really provide for a good learning environment in all biology departments I have seen, but alas, we all have to spend some time with people we find annoying.

Biologists proper, on the other hand, are truly curious about nature and mystified by the unknown but they have a different problem. All biologist or biology graduate students I have met seem to harbor a strange type of artisan masochism which causes them to was pipettes for ours in the labs and invest their time in learning manual skills which will be made useless momentarily by a simple Perkin-Elmer sequencer or other similar machine.

They simply refuse to admit that there are problems and the best they could do is to stop washing pipettes and begin thinking about how to bite the bullet, draw up some decent standards so they could finally make this a proper science and leave behind this eternally entrenched painful nightmare.

sad implications

we should never forget that biology as a study of all living and therefore also our bodies, and such I would argue its discoveries are order of magnitudes more significant than the other sciences. of what value is the inter-stellar travel or better plastics if we drop dead tomorrow, and we all will as it stands now, won’t we? as for space research in particular, i never understood what we are doing in space in the first place since me or anyone i know has gained nothing from it besides science fiction movies. note that i am not saying that we should not pursue space research - these types of arguments are always very dangerous - but only that we should prioritize biology and medical research and take it very, very seriously since it is a little to late to start thinking about when we or our close ones are lying on death bed.

the unfortunate implication of the current gridlock in biology is that the opportunity cost of not straightening things out is invaluable since so many bright minds would not turn away from this intrinsically fascinating science if it had a similar language and framework as other natural sciences do.

Where Do We Go From Here? Or Rather, Where Do We Start?

Biology, biologists and those taking interest in biology – and everybody should since chances are that you, your parents, my parents and I will die of cancer if of nothing else - should start by formalizing a couple of fundamental laws and do that in a mathematical succinct manner, much in the spirit of Newton’s or Maxwell’s laws, or the Laws of Thermodynamics in chemistry. Saying that DNA codes proteins and not the other way around and calling it The Central Dogma is simply not good enough (and even this ‘law’ was formulated by a physicist, Watson). It is a long and painful progress, but at least it is a start and a step in the right direction.

Beyond the linguistic gridlock discussed here, biology has another, deeper problem of focusing on wrong questions, but hopefully that can be fixed with less effort. This more subtle topic will be discussed in a separate article in the future.

Saturday 5 December 2009

Tuesday 2 June 2009

Marketing Estonia to Europe

To Russians: "Estonia. The closest water-operated toilet on the continent"
To Italians: "Estonian women are reserved. They will never hit you"
To Indians: "You will feel right at home. Our cab drivers will try to swindle you as well"
To Swedes: "Europe's least expensive breast implants"
To Africans: "Come and enjoy attention. And not necessarily unpleasant"
To Dutch: "Come and touch a live tree"
To Finns: "Table vodka 9 Euros a liter"
To Americans: ""Estonia is Europe's low-calorie Russia: all the excitement with only half the danger."


***************
Venelastele: "Eesti. Kontinendi lähim veevärgiga kemps."
Itaallastele: "Eesti naised on vaoshoitud. Keegi ei anna sulle vastu kõrvu."
Indialastele: "Tunne end nagu kodus - ka meie taksojuhid petavad."
Rootslastele: "Euroopa odavaimad rinnaimplantaadid."
Aafriklastele: "Tule ja naudi tähelepanu. Mitte tingimata ebameeldivat."
Hollandlastele: "Tule ja puuduta elavat puud."
Soomlastele: "Laua Viin 9 eurot liiter."
Alla 25aastastele meestele: "Maa, kus autosõit on nagu Hollywoodi märulis."
Prantslastele: "Pärast meid teate, mis teie köök väärt on."
Ameeriklastele: "Estonia is Europe's low-calorie Russia: all the excitement with only half the danger."

Friday 29 February 2008

How You Know When You are Dealing with an Estonian

1. You use the word 'normal' if something is ok.
2. When visiting friends abroad you bring along a box of Kalev chocolate.
3. You attended a song festival at least once either as a performer or as a
spectator.
4. You know that going to the sauna is 80% about networking and 20% about
washing
5. You are nationalistic about Skype (it is actually not an Estonian company)
6. 'Kohuke' belongs to your menu
7. You declare your taxes on the internet like all modern people
8. You actually believed for a while that Latvians had 6 toes per foot when
you heard that as a child
9. You are convinced that Estonia is very strategically located
10. You spent at least one midsummer in Saaremaa, Hiiumaa or one of the
smaller islands
11. You can quote films like 'Viimne reliikvia' and 'Siin me oleme'
12. You spit three times around your left shoulder for good luck
13. Words like 'veoauto', 'täieõiguslik' or 'jää-äär' sound perfectly
pronouncable to you
14. You like bold statements, such as this one... [image: Wink]
15. There can never be too much sarcasm
16. You can at times drink hot tea to hot food
17. You are disappointed that Jaan Kross never got the Nobel prize in
literature
18. It would not be suprising for English-speakers to find your namenaughty
(Peep, Tiit, Andres [sounds like undress]) or hippy (Rein, Rain)
19. You have been to Finland
20. You say 'Noh' (sounds like NO) even when you speak English, just to
confuse people
21. You know the lyrics to 'Mutionu' and 'Rongisõit'
22. You would never mistaken Kreisiraadio for a radio station
23. You would agree that wife-carrying is a real sport (at least as long as
Estonians are winning)
24. Your best friend's girlfriend is your English teacher's daughter and
they live next door to your grandparents, who were colleagues with your
advisor, who is friends with your...
25. You think that any beverage below 20% is non-alcoholic
26. You check the thermometer before going out
27. You look in both directions before crossing the road, even if it's a
one-way street
28. You grin very mysteriously when people ask about your national food
29. You teach a non-Estonian speaker the word 'Tänan' before 'Aitäh'
30. You put ketchup inside your pasta (french-cooked gourmet faire la
finemanger pasta) in order to not to get the ketchup-bowl dirty
31. You cheated on your wife/husband at least ten times but you still think
you're in a good marriage.
32. When someone asks you 'where is Estonia?' you quickly reply that it's
located in Northern Europe close to Finland...
33. Your grandmother's 'purse' is an old plastic bag that has been reused
several times
34. Sour cream tastes good with everything
35. A foreigner speaks to you in broken horrible Estonian and you go on
andon about how wonderful their Estonian is compared to 'the Russians''
36. You have ever worn or seen anyone wear 'karupüksid'

Saturday 9 February 2008

Brave New World of XQuery

One could argue that as far as the programming languages go, they are fundamentally the same since they can be mapped to the similar underlying BNF gramar, but one of the more interesting recent additions to this family is QXuery.

If adopted properly, it may do away with 90% redundant code that everyone is writing. The argument is below.

As far programming currently goes (and this has been the state of affairs for past few decades), developers spend their lives transforming data structures among these three layers of different representation of data:

1. persistence tier - relational (RDMBS) -
2. application middle tier - OO (object-oriented) and/or procedural
3. presentation layer - XML in its various forms including XHTML/HTML

Now, in the New Brave World of XQuery you will just deal with XML for the most part - XML in the database, XML in middle tier and XML in presentation layer. No transformations. And the language that ties everything together is XQuery.

There are a couple of important related implementations:

Gexo - http://www.gnu.org/software/qexo/XQuery-Intro.html
BDXML - http://www.sleepycat.com/products/bdbxml.html
XQengine - http://sourceforge.net/projects/xqengine

The W3C Query spec can be found here:

http://www.w3.org/TR/xquery/

As a note of recommendation, I feel one should learn to read W3C specs as well on a regular basis. It’s all you need to keep in touch with evolution of software since most of the fundamental innovations regarding the web have come out of W3C expert groups. For it may be about the only place where top academics and scientists from top vendors meet, sit down and agree on something. For example, SOAP if you remember was the first standard that Sun, Microsoft and IBM actually agreed on.

Saturday 2 December 2006

Cost of Dollar

Recently, I have been noticing that it is becoming cheaper every year to pay back my US college debt since the dollar is now at some 14-year low compared to both EUR and GBP. So from my college loan perspective it is good that I actually waited a bit.

And then noticed this web site called Cost of War set up out of Boston.

Actually, when you come to think of it, this is only the piece financed through taxation, so this doesn't cover the piece financed by Treasury bonds since apparently the actual cost is around
$2 Trillion.


Now, I wonder what is driving down the dollar? Could it be that you have to buy goods to finance the war in dollars and then whoever is selling you the goods needs to (eventually) sell the dollars again in the FX market?

Interestingly enough, it also turns out that the last time the dollar was this low was when we had the 1992 Gulf War.

I don't see many currency pundits making the link though, so I guess I need to start my own hedge fund soon.

Tuesday 24 October 2006

Perfect Repair Systems

What is the source of our aging? Are we similar to inanimate objects around which age via "wear and tear"?

It turns out not. People, like all living things and their cells are self-repairing systems, cars are not. Any molecular biology textbook will describe several repair systems for both DNA and cytoplastic components. Another way of saying this is that cells and people use the energy of the environment (food) for not only movement (as cars do), but also to maintain, with the help of repair systems among
other things, something called cellular homeostasis, or cellular equilibrium roughly speaking. If the repair systems were perfect, which they are not unfortunately, if all the damage and "wear and tear" were repaired perfectly, we could go on living much longer. We are also able to - as anyone could tell you - regenerate parts of our cells in case of wounds. Some lizards can, in fact, generate entire parts of their bodies.

A natural question then arises: "If evolution has developed everything imaginable, why hasn't it developed perfect repair cellular systems?"

To answer the question, consider the following thought experiment. Suppose that several million years ago there was a species of, say, fish that developed a perfect repair systems and as a result couls achieve a lifespan that extended to several hundred or even thousands of years.

If so, why don't we see the species today? Where did it disappear? The answer is that by attaining perfect repair system, the species lost the capacity for mutation and variation and consequently for evolution. It was soon outcompeted by a species which, though mortal on the individual level, carried superior mutations as a species. Evolution presumes variance, selection and mortality. Aging is the cost we pay for evolution and vice versa - extending aging would slow down evolution, and complete immortality the end of evolution.

So if human species developed perfect repair systems, not through evolution, but artificially in a lab (as we have done so much else) would it mean the end of species? Maybe in the long run, say in few thousands years, when we would be outcompeted by apes with superior mutations, but that's not my top concern right now as our clocks are ticking minutes and hours, not in thousands of years.