Biochemistry at the moment is trying to figure out the method by which proteins – the tiny molecules which make our body work – fold themselves into the precise three dimensional shape they take to carry out their function.
The designs for these proteins are coded with four different bases arranged so that in protein-coding areas, every set of three bases (a codon) specifies a certain amino acid. There is some redundancy, as 64 different codons only need to specify 20 amino acids. There are also start and stop codons, making a perfect two-dimensional engineering spec. Each amino acid has around 20 atoms – some more, some less. To make a protein, they are all welded together in the specified order by a very very fast and accurate factory called the ribosome, of which thousands are contained inside every human cell.
Recently a simulation was carried out to observe the folding tenency of the protein villin, a comparatively manageable collection of 140 amino acids – and it took 200,000 networked PCs in the fold-at-home project, working a total of over one million hours to work out all the animation. This is where physics, chemistry and three-dimensional design considerations merge – it is the most complicated engineering challenge imaginable.
No human being can manage these parameters mentally. The equations governing the forces of attraction and repulsion of the tiny atoms are staggering – they cover pages and pages – and the activities are astonishingly quick. It is quite literally a huge, smooth vertical wall standing in front of the intellect at the moment, whose top is hidden in clouds far above. When you hear “hotly debated topic” and “need for further research” you know some very clever people are struggling, and with good reason: the kind of mind which could understand this complexity in real time – to give you an example, within a cell, proteins can collide with 500,000 other molecules in a single second – would already be a super-mind and unrecognisable as a human being. But attempting it is a tribute to human ingenuity and ambition, and this is indeed what scientists are working towards; to the best of my ability as a layman, here is something of what I learned from reading about their work.
The proteins are pretty solid when they’re assembled: apparently they can be three times more difficult to compress than water, and some of their components are arranged as moving subcomponents – for example, able to make 180 degree flips back and forth – anywhere from 100 times a second to (get ready) 10 million times a second. These proteins are called “enzymes” and act as catalysts – like little sanders wearing down organic material, in the mouth or stomach for example. There are 4,000 known enzyme reactions, all different: the time taken to break some materials down has been calculated at 78 million years without these enzymes – but with them, 18 milliseconds. These are extraordinary tools to have flowing freely in your body.
Papain, an enzyme within the papaya fruit, specifically attacks fibrin, the protective protein found around cancer cells and which also attaches tumours to bones, internal organs etc. Scientists recently discovered papain has a restraining effect on cancer, for obvious reasons; where papaya is commonly eaten, tumour rates are low. The older generations in Thailand, for example, had a low incidence of cancer while younger generations, abandoning traditional diets in favour of western chemically-produced fast “food”, adopt cancer at the standard western rate. The remarkable thing about these enzymes is that each can attract, lock, slice, and eject as many as 30,000 proteins in a second, meaning they behave like highly focused chainsaws. Natural technology is presently far beyond what we can achieve.
These engineering challenges are never as simple as we, eager to trivialise the problem and by extension, the solution, make them out to be. When a well meaning member of an audience asked Richard Dawkins to explain why he did not consider the blood clotting mechanism, an ingenious solution of many co-ordinated stages, to be a complex process, Dawkins erupted, “that is a creationist lie!” In fact, all engineering solutions at this level require co-ordinated solutions, which is why at the moment we can hardlyfigure out how they work. ENCODE results were not universally greeted with acclaim: many evolutionists claimed ENCODE told them nothing of any use, perhaps stinging from the new public perception of “junk DNA”, much touted by Dawkins, to be nonsense after all.
Take the hemoglobin molecule, which has four iron platforms, angled away from each other in an incrementally sprung mechanism, to collect up to four oxygen molecules from the lungs and deliver them to the cells. The obvious solution is to make it easy for oxygen to stick to these little machines. But if this were the case, it would mean that after dropping oxygen molecules off to the body’s cells, another passing hemoglobin could immediately snatch them back again. So the hemoglobin is put together in rather a cunning way: the first oxygen molecule can only attach if it is forced under high pressure, due to the surrounding atomic forces within the alpha and beta chains. But once attached, it starts to open up the hemolgobin’s sprung structure, making the second oxygen molecule much easier to attach. And likewise, the third becomes even quicker to attach, and the fourth, instantaneous.
After dropping the first oxygen molecule off, the shape of the protein changes yet again, and the second, third and fourth oxygen molecules are released even more easily. So in conditions of high oxygen pressure, this fantastic little machine works extremely quickly, but in low pressure – passing by lots of oxygen molecules attached to cells – it doesn’t work at all. Except, with a fantastic dual purpose mechanism it does collect carbon dioxide waste from the cell, under conditions of infitesimally small pressure – scavenging this rubbish wherever it can find it, and taking it back to the lungs for release – to be breathed out. Any other design would be totally useless.
So essential is this process that in cases of carbon monoxide poisoning, the hemoglobin, are saturated with a molecule that is extraordinarily hard to shift, become carboxyhemoglobin – dangerous for cell tissues. Hours are required for them to begin to return to normal function. The need is for continual, perfected and comprehensive engineering solutions at all levels. The hemoglbin are only part of such a solution: the red blood cells are shaped to fold into any corner of the circulatory system, and the lungs must allow the storage of air and the expulsion of waste; the muscles must completely engage the lungs and work by an automated system in sleep. The protective ribs must allow expansion, and the whole system must react to the need for more oxygen, while the air intakes must have reactive mechanisms for dealing with obstructions, mucus mechanisms for grit and particles, and so on. All these mechanisms demand coded proteins and mechanical engineering for their storage in the 2-d DNA. So while on every level we see an essential solution, with protective safeguards built in, we imagine that it arrived by a series of errors!
But the hemoglobin needs to be folded in a precise shape, as you can see – it must have a recepticle for the iron atom, the right electrical charges all around each platform, and the right “spring” hinges to allow each binding operation to nudge the other components into a new state, from which they must return when their job is done.
This machine can’t arrive incrementally: it either works, or the organism dies straight away. Slight variations in hemoglobin exist in the fetus, where oxygen conditions are different, and in various animals. Horse hemoglobin differs from the human type by more amino acids than does the chimpanzee’s, for example, but in all cases the unique design is stable and fixed – and even minuscule changes of a single amino acid, or a single wrong placement, both errors involving perhaps 19 atoms – cause horrific disorders.
Consider the problem: an amino acid is comprised of an average of 19 atoms. A typical protein might have 541 amino acids in the case of hemoglobin, or in one case, titin, the component of muscle tissue, as many as 27,000 all joined together end to end. A string of these amino acids is useless on its own – the string must be folded into a precise shape. The amazing thing is this shape is determined completely by the precise order in which these chains of atoms are joined together. Therefore the DNA, carrying this organised string of instructions, must have all its elements – 3 letters for each amino acid, in exactly the right order. Hemoglobin would need 1,623 letters, and titin, 80,000 plus. This is a requirement for massive precision.
One titin molecule would have about half a million atoms. To imagine this, think of each atom as a grain of sand, and each amino acid as a string of sand beads, totalling about 2cm length. Titin would be more than half a kilometre in length. Now imagine trying to fold that at 2cm intervals to get an exact shape, bearing in mind that each join between any two 2cm strings could fold in many different ways in three dimensions. If anyone thinks this is a random procedure, they do not understand the number of possible ways it can go wrong!
The time required to explore every possible folding possibility, needless to say, would be enormous, and even at a million possibilities per second, longer by far than the entire 14 billion years of the Universe. But how long does such a molecule take to form, inside the chaotic conditions of the cell? A few milliseconds.
Amazingly, if the protein is having trouble forming, perhaps because of unusually chaotic conditions in the cell (a protein can bump into another molecule 500,000 times in one second) there are helper units called chaperonins: these resemble thermos flasks which, if they sense a protein is stuck to another one, or having trouble forming, they open their lid to allow the protein inside, where it can form away from the bustle of the cell. When it’s formed, the thermos flask lid untwists, and the protein is released. Time taken: a few thousandths of a second.
What if Dawkins is right – and it IS all random?
Lots of people have been known to ask Richard Dawkins when he claims all life arises from random mutations, and the Universe lacks an intelligent aspect of any sort: “What if you’re wrong?”
Well, it’s a certainly a good question – but there’s another question nobody has ever yet considered: what if he were right?!
People usually can’t imagine exponential rates of growth. The legend goes of inventor of the game of chess being offered any reward by the Chinese emperor. The man looked at the chess board and said, “there are sixty four squares. All I ask for is a grain of rice for the first square, two for the second, then four for the third and so on, until the board is full.” The emperor thought this a foolish request – he was prepared to give this man anything! But trying to suppress his glee, he ordered his staff to carry it out.
Of course, by the 15th square, there were now nearly 33 thousand grains of rice piled on the board. By the 30th square, the reserves of the emperor’s castle were exhausted. By the 37th square, every farm for miles around had to be raised for their stocks of rice, and by the 50th square, the total would have been 1,125 trillion grains of rice – more rice than existed on the whole planet.
I’m a programmer and I design my own database systems. I confess I do it because it’s so easy – if it were frustratingly difficult I would find something else to do. Well, about twenty years ago I was installing at a new client, when the MD asked if his old address database could be de-duplicated and loaded into mine. I took a look and said, sure. Just then their own head of IT, an excitable Chinese fellow, stepped forward and said, no, he would do it. Are you sure, I asked him – it won’t take me long? No, no, he insisted – it was his job.
He went away and wrote his program and later that day started to run it. There were about 100,000 addresses to check, and each with six fields plus a post code. After some hours it was six pm, and he was looking a bit tense – his system had managed to check only two addresses. I waited until he casually sauntered over. “Explain the logic,” I asked. “Well,” he said, “I just take each line in one address, and compare it to each line of every other address, and if I find a duplicate, I delete that record.” How he became a head of IT I will never understand. “Ok, leave it with me.”
What he had asked this computer to do was, for each address, to take six separate lines of an address, one by one, and compare each with every one of the other lines in all the other addresses. A total of 600,000 other fields – so each address had to make 3.6 million checks, meaning a total of 360 billion disk accesses. I worked out it would have taken more than twenty years to run! That is slow even by Accenture’s standards. I didn’t tell him that, of course. One of the reservations clerks was an intuitive guy who knew nothing about computers but who had somehow seen through this IT wizard, and he pleaded with me to tell him how long the process would have taken – I confess, I did.. I can’t stand professionals who are incompetent.
The problem with big numbers is that they are so hard to imagine, since the brain is used to manageable figures of fives and tens. The digit 1 followed by 80 zeroes is assumed to be quite a large number, because, wow, imagine all those zeros! But there again, zeros are not actual amounts, and 80 isn’t such a big number, so surely 80 of anything can’t be all that large? In fact this number is about how many atoms there are in the Universe!
And as for lengths of time, 3 followed by 9 zeroes sounds trivial. But it’s the number of seconds in one hundred years: let’s say you have another 25 years of life remaining – that’s 788 million seconds – and only about 525 million waking seconds.
Yes, yes, but this is boring. What about those proteins?
A protein with a paltry 30 amino acid components – a level at which it might not even be considered a protein – could have those amino acids ordered in 20 to the power 30 (20 x 20 x 20… thirty times) different ways, only one of which would result by chance in the aminos being in the right order to fold into a perfectly functional device (with four-fold symmetry in the case of hemoglobin). Experimenting at one million different ways per second – all failures – would take 634 million billion years. That’s the age of the Universe, multiplied by 45 million.
A larger molecule like titin would take – and this is going to be a big number – 20 to the power 27000, with no guarantee of success. Who can imagine a number with more than 30 thousand zeros? Just wait – I’ve done some calculations! If it were a random process, how much scrap titin would you have before you had one working molecule?
The calculations are below if you want to read them. But the answer is, after getting only one four hundredth of the way through, the waste molecules – each too small to be seen with the naked eye – tightly packed top to bottom, end to end would fill the visible Universe up – a sphere 14bn light years in diameter. To get a chance of one working titin molecule, using the Richard Dawkins method would be impossible in a finite Universe, and would take pretty well forever in an infinite Universe.
And what kind of powerful natural force could possibly create all these failed attempts? How could the result be an island of highly structured order surrounded by an endless ocean of chaos? There would actually be no room for anything else. And yet there are roughly the same number of hemoglobin in your body as there are stars in the universe – 7 followed by 21 zeroes: each formed in a twinkling of an eye… and they all seem to be working perfectly.
The boring calculations:
The Universe is imagined to be 14bn light years across, so assuming it has a spherical shape for the sake of argument gives a volume of 4/3 * pi * the radius cubed. That works out to 410 billion trillion cubic light years. Now a line one light year long is about 9.46 × 1012 kilometres. So a cubic light year is 836 × 1039 cubic kilometres. On a nano scale, the titin protein is about 950 nanometres (nm) long (one million nm = 1 millimetre.. they are really, really small!) and let’s say 100 nm thick. and 20 nm wide. Incorrectly formed molecules would be a lot longer and a lot thinner, but in terms of mass they’d all be the same. This means in a cubic km you have just over 1 billion molecules end to end, 10 billion vertically and 50 billion side by side. That gives a surprisingly manageable number of titin molecules in one cubic km of 500 with 27 zeroes after it.
So the total number of titin molecules to fill the whole Universe – leaving not a single scrap of space for anything else, would be
500 with 27 zeros after it multiplied by 836 followed by 39 zeros multiplied by 410 followed by 21 zeros.
This number, if anyone is still reading, is just over 171 followed by 482 zeros. But the number of failures required using the Dawkins method would have at least 30,000 zeros. It’s the most absurd number you can imagine, and makes the Universe look like a very, very tightly limited place for random, exponential chaos. I can’t work the figure out exactly because my computer gives up after 190 zeros.. which seems fair enough!
And this is only one protein in the human body. The human body contains around 20,000 different kinds of proteins – each needing to be exactly, specifically, precisely configured and pre-aligned in the DNA before it jumps into life. These are vast impossibilities in a disordered state. There is no room whatever for random chaos in this system, and there never could have been. This intuitive understanding is what gave birth to religion, for an individual to try and find the life most in accordance with a machine whose complexity we can never completely fathom.
Biology is machinery, plain and simple. It requires the gene reading equipment, a renewable fuel source, little motors to crank out the fuel all day every day, seamless error checking methods and duplication equipment, plus you have to pack about two metres of DNA into every one of 100 trillion cells of the body. And the whole thing has to work seamlessly for eighty or ninety years without stopping once. Understand how all this works and you will be looking into the mind of the most superb programmer in the Universe.
Random mutations behind tightly engineered biological machinery? No, definitely not.