If you have ever worked in a molecular or medical biology research laboratory, chances are one of the first things you learnt was tissue culture (or the microbiology equivalents). Even if you know nothing about biology, you’ve probably heard mentions of “cell culture” on the news, or at the very least heard about the results of studies in tissue culture. If you hear about “cell lines”, you’ve got culture. If you hear about a “laboratory study” showing that your favourite chemical is carcinogenic, you’ve probably got culture. If you hear about new trials on a miracle cancer cure that has been shown to be effective in “preliminary laboratory tests”, you’ve probably got culture. Everything from zombie epidemics to £10,000 animal-free beef is cell culture. Knowing a little bit about what tissue culture is, and what its uses and limitations are, is therefore important when answering such questions as “is my baby’s bottle poisonous?”, “is stem-cell research ethical?” and “is vitamin C an effective cure for colds/cancer/HIV?”

So. What is tissue culture (TC)? It’s when you take specific cells from a multi-cellular animal and grow them in a dish full of nutrients (a mimic of your blood serum). The point of doing this is to create a system on which to experiment which does not require growing and killing lots of individuals — something that is, for some reason, considered unethical. Especially when it’s humans you propose using. Typically, human or other mammalian tissues are used — especially “model organisms” such as mice. You can use healthy or diseased cell lines from all sorts of different organs. Once you’ve grown up a nice batch of cells in your dish, you can see how they respond to your cancer drug, environmental contaminant, or new junk food ingredient. You can see exactly how the behaviour of your cells changes over the minutes, hours and days of exposure; how they recover after the chemical has been flushed away; how your cancer drug works in dozens of different tumours; how your junk food ingredient works in the old and young, male and female, fit and fat; and how your environmental contaminant interacts with other environmental contaminants. It’s great. If you work hard enough, you can know everything you want to know about your chemical within a week. Wipe out cancer and save the world by next Monday. At least, that’s what the animal-rights movement would have you believe. And the tabloid press fall for it daily.

Trouble is, it’s very easy to get superficially interesting answers using TC. Which makes it very easy to convince a journalist that you have important results, but very difficult to convince a scientist. That’s not to say that TC is not important. But everything that we measure in TC is an estimate of what happens in real life situations. It’s a model that uses surrogate measures from which we can develop hypotheses about what happens in reality. A bad analogy is in order, I think. Suppose you are building a car. You want to protect your future drivers from side-on impacts. Very early on in the design process, you have an engineer conduct strength tests on different materials and designs for doors. From this, you can narrow down the field of designs, and make hypotheses about which designs will perform best on the road. But you can not be sure that the strongest material will provide the best protection against injury and death. You would want play with the crash test dummies, before putting the car on the road. And once the car is on the market, you would analyse incidents. Because when the door is attached to the car and put on the road, a huge number of other variables comes into play. And so it is with, er… what was the topic again? Tissue culture.

Cells did not evolve for growth in a dish. They evolved in the context of cooperation with a vast number of other specialist cells in a body. They are not fine-tuned for survival in the absence of skin, an immune system, a digestive system, liver and kidneys. They are not supposed to live like barnacles on plastic. But if you’ve worked with research quality cell lines, you’ll know that it’s surprisingly easy to make them grow in a dish. Feed them every couple of days, and they’ll happily live for many months. Well go and say that to the post-docs and technicians who made it that way. They were up until midnight processing disgusting lumps of freshly excised tumour. They spent months trying out different combinations of nutrients and fungicides in an attempt to make the cells survive longer than a week. They may be easy to grow now, but don’t think there wasn’t any effort involved. Billions of cells died in the process of making those few grow. Under these circumstances, you can hardly expect the cells not have evolved a little. You are introducing them to a vast number of novel mutagens by taking them away from the protection of skin. And putting anything into a new environment is going to mean new selection pressures. When you finally manage to immortalise your cell line, is it because you’ve perfectly adapted the conditions to the cells, or because the cells have adapted to the conditions?

So. There are all sorts of reasons why TC can not be anything more than an approximation of what is happening in real life. A useful approximation, but unreliable in the absence confirmatory evidence from in vivo and population studies. But these are only the intrinsic limitations of TC. When judging the merits of TC based research, you must also take into the account the fact that TC is easily misused and misrepresented, and that charlatans are doing it all the time. TC is a favourite of cargo-cult healers and nutritionists — those who like to keep up a superficial appearance of having a scientific basis for their quackery. Take, for example, the shamen who pedal vitamin C as an HIV/AIDS drug (Patrick Holford, for example) or as a cancer therapy. They will tell you that in TC, vitamin C has been shown to kill tumour cells, or those cells that are infected with HIV. Therefore, the reasoning goes, we should abandon proven therapies, in favour of taking some vitamin supplements. Trouble is, you can chuck a big lump of any chemical in a dish of cells and the cells will die. I could pour a bag of vitamin C into a dish of healthy cells. They will die. Conclusion: those vitamin supplements are deadly poisonous. Except that your cells will never be exposed to a bag of vitamin C, because you have skin, a digestive system, and kidneys. And because people just don’t go around pouring bags of vitamin C down their throats. I could spit in a dish of cells and tell you that spit is a killer. It’s not.

But it’s not just charlatans that abuse TC. Many legitimate scientists bend the rules a little. They may not even be aware that they are doing it. Take the case of Bisphenol A (BPA), something I did a little work on a couple of years ago. BPA is a component of some plastics, notably bottles. It is known to very slowly leach out of the bottles and into your drink. There is a little bit of evidence (mostly from rats) to show that consuming BPA may be harmful. And there are a lot of TC experiments on the chemical. BPA is a xenoestrogen, meaning that it mimics the activity of estrogens. Estrogen, of course, regulates prolactin release, and cell division (particularly in the breasts). We know that BPA mimics estrogens because when we put some in our dish of tumour cells, we see that within seconds the estrogen receptors have been activated, and all the other effects of estrogen follow. There are loads of results to confirm this because there are a lot of experiments into the effect of estrogen (there’s plenty of money in breast cancer research). If you’re doing the experiment anyway, it’s hardly any more effort to look at BPA. And you can pretend that your research has another potential medical application. Since it’s not the primary aim of your research, the journal’s reviewers won’t notice that you’re using it at a thousand times the concentration that you would find it in the body. So even if enough BPA does leach out of your bottle, and even if BPA does do interesting things in the body, a large proportion of the TC studies will be irrelevant to understanding how it does those things, because they look at inappropriately large concentrations and inappropriately small timescales.

So, next time you are flicking through the health pages of the Daily Mail — which I know all of you like to do — engage healthy skepticism when they update the list of miracle cures and carcinogens. Like statistics, tissue culture is incredibly useful — whether you’re searching for the truth, or a convincing lie.

Continue reading at At War With The Motorist…

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This time around, Rubberknickers Pickles is ending The War by lifting restrictions on how much of our town centres can be given over to car parking. The idea is nothing new, of course, but it is assumed that most will have forgotten the previous occasions when it was announced. The “news” is that the paperwork has gone through: the new version of the government’s planning rules are complete.

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In 2000, London’s previous mayor, Ken Livingstone, began the process of fixing forty years of mistakes that had been made in the pursuit of the impossible — the comfortable accommodation of mass motor vehicle use in a dense city centre. He recognised that cities are supposed to be places for people and returned key locations like Trafalgar Square to use as more than mere traffic gyratories.

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I did a double take when quickly scrolling through old phonecam pictures.

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Here’s an interesting one: Genesis chapter 30. If you think Darwin got inheritance wrong, try the Bible.

30:28 And he [Laban] said, Appoint me thy wages, and I will give it.

30:29 And he said unto him, Thou knowest how I have served thee, and how thy cattle was with me.

30:30 For it was little which thou hadst before I came, and it is now increased unto a multitude; and the LORD hath blessed thee since my coming: and now when shall I provide for mine own house also?

30:31 And he said, What shall I give thee? And Jacob said, Thou shalt not give me any thing: if thou wilt do this thing for me, I will again feed and keep thy flock.

30:32 I will pass through all thy flock to day, removing from thence all the speckled and spotted cattle, and all the brown cattle among the sheep, and the spotted and speckled among the goats: and of such shall be my hire.

30:33 So shall my righteousness answer for me in time to come, when it shall come for my hire before thy face: every one that is not speckled and spotted among the goats, and brown among the sheep, that shall be counted stolen with me.

30:34 And Laban said, Behold, I would it might be according to thy word.

30:35 And he removed that day the he goats that were ringstraked and spotted, and all the she goats that were speckled and spotted, and every one that had some white in it, and all the brown among the sheep, and gave them into the hand of his sons.

30:36 And he set three days’ journey betwixt himself and Jacob: and Jacob fed the rest of Laban’s flocks.

30:37 And Jacob took him rods of green poplar, and of the hazel and chesnut tree; and pilled white strakes in them, and made the white appear which was in the rods.

30:38 And he set the rods which he had pilled before the flocks in the gutters in the watering troughs when the flocks came to drink, that they should conceive when they came to drink.

30:39 And the flocks conceived before the rods, and brought forth cattle ringstraked, speckled, and spotted.

30:40 And Jacob did separate the lambs, and set the faces of the flocks toward the ringstraked, and all the brown in the flock of Laban; and he put his own flocks by themselves, and put them not unto Laban’s cattle.

30:41 And it came to pass, whensoever the stronger cattle did conceive, that Jacob laid the rods before the eyes of the cattle in the gutters, that they might conceive among the rods.

30:42 But when the cattle were feeble, he put them not in: so the feebler were Laban’s, and the stronger Jacob’s.

30:43 And the man increased exceedingly, and had much cattle, and maidservants, and menservants, and camels, and asses.

So, I think the deal here is that Jacob makes some pact where he gets to take all of the stripey, speckled, and spotted cows, sheep, and goats, from this other dude Laban’s stock. He does this, leaving Laban with homogeneous flocks of plain individuals. He then attempts fraud by making Laban’s plain individuals mate while looking at stripey things, so that the offspring will be stripey, and Jacob can claim they are his own. And, hey, guys, it totally worked.

It’s not actually at all surprising that the offspring of two plain individuals turn out stripey, speckled, or spotty. That sort of thing is pretty normal. Traits can skip generations and reappear later for a variety of reasons. It could be that one or the other trait is linked to a dominant/recessive gene system; or that they are influenced by complicated combinations of genes, which are shuffled in each generation; or that they are capable of being thrown either way by developmental switches. Indeed, it’s possible even to speculate on reasons why the “feebleness” of cattle might be linked to the tendency to breed true for more traits.

So, assuming that the story has some basis in reality (lets pretend, anyway), Jacob probably just developed a superstition. A convenient myth to explain a mysterious natural phenomenon, while allowing him to believe that he had some influence over that phenomenon. Perhaps he noticed some stripey pattern in the landscape one day, noticed that there was mating going on in the vicinity of the stripes, and then noticed the stripey lambs being born. A meaningless correlation would then appear, superficially, to be a principle of inheritance. From there, the superstition would develop as the believer started counting hits, forgetting misses, and discovering his “ability” to select the stronger more desirable individuals as parents (or post-hoc reasoning that because it has sired a stripey calf, it must be a strong bull).

Alternatively, of course, Goddidit.

As in so many of the things that the Europeans do better than us, the model by which our railways came about is shared with the Americans rather than our continent. When the railways arrived in the middle of the 19th century, most European governments saw the need for their own guidance in planning the railway network, to ensure that it was rational and efficient. But in Britain and America, anybody who could raise the capital could build any railway they liked. Our railway network is the bizarre product of mad Victorian capitalists fighting over real and imaged markets. For the first hundred years, three railways competed for the London-Scotland market — the routes that are now the East and West Coast Main Lines, plus a third, the Midland from St Pancras. Extending the Midland Mainline from Leeds to Settle, the third railway then climbs up the 16 mile long drag to the top of the Yorkshire Dales, the highest point of the mainline network, and down the other side to Carlisle, through 14 tunnels and over 22 viaducts along the way — amongst them the 24 arches of Ribblehead, 100 ft above the boggy valley.

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