Tag Archives: Genetics

Nude Carp Challenge

This term, I’ve been trialling a new lunch time club – Year 11 Genetics. The idea is to attract the very bright Year 11s who are fascinated by the topic, but who quickly get frustrated with how simplistic and uninteresting the iGCSE examples are. These, after all, include the girls who, last year in Year 10, bred ebony vestigial fruit flies and worked out dihybrid cross ratios from first principle. After that, tall vs short pea plants doesn’t quite cut it!

Except that this is where I started, pushing them to challenge the idea of “gene” for height. Really? How does that work, then? Genes code for proteins. What’s a “tall” protein? How can a gene code for “Tallness”?

So we take it back to basics. Tall plants have grown more than short ones. So what is growth all about? Cell division. So how could a gene possibly be associated with that? A hormone that stimulates cell division, perhaps. Ah! Good thinking. There is a hormone, or plant equivalent, with the wonderful name of Gibberellin. It stimulates stem elongation (pause for brief discussion of “foolish seedlings”). Except that Gibberellin isn’t a protein. There is no gene for Gibberellin….

They barely blink. Well, maybe there’s an enzyme that helps make Gibberellin. Enzymes are proteins. Could there be a gene for that?

Now we’re getting somewhere. But how could there be a “recessive” version of this gene? What’s going on there? A few prompts and they get it: do “recessive” genes simply not work? Are they mutations that don’t code for a working protein? So heterozygous plants grow tall because they have a working gene which can code for a working enzyme which will produce gibberellin and stimulate lots of cell division and “tallness”.

So to understand genetics,  you need to understand what DNA actually does.

They really like this because it has explanatory power. They’re not just matching up letters and traits in some trivial logic problem – they’re understanding the biochemical mechanisms. The following week, there’s more of them.

So this time I get them to review their dihybrid work from last year. And then throw linkage at them. It takes them some time, and there’s lots of brilliantly creative ideas along the way, but they get there. Perhaps these genes are on the same chromosome. So you inherit them together.

So to understand genetics, you also need to know the physical location of genes.

Week 3 and, oh look, the predicted linkage ratios don’t seem to be working out exactly. Where have that small percentage of apparently non-linked individuals come from? And why does that percentage seem to vary, depending on the trait? Crossing over and Morgan’s work on mapping chromosomes gets an airing.

So genetics is even more complicated and extraordinary than you realised!

Week 4 and we’re back to what genes code for. A 9:7 ratio of coloured sweet peas to white sweet peas. Huh? They figure out the principles of metabolic pathways and complementary epistasis.It’s just a pleasure and a privilege to watch them working together, trying out ideas, exlaining things to each other, that glorious lightbulb moment when they “get it”.

I add some points of my own. They like my analogy of a cake. You need ingredients, a mixer and an oven. If both the mixer and the oven work, you can turn the ingredients into batter, and then turn the batter into a cake. But if the oven is broken, all you get is batter. And if the mixer is broken, you can’t even get to the batter – you’re just stuck with the ingredients.

And that brings them nicely to the boil for the Nude Carp Challenge. Here it is:

Nude Carp Challenge

Go on, have a go. You will feel ridiculously pleased with yourself when you figure it out. Will my Year 11s? I’ll find out tomorrow!

A good week

nb: this will the last burble of the academic year 2014-15 – the summer holidays are nigh and I want to think about anything other than teaching for at least 6 weeks. But it’s nice to end the summer term on a high note and I’m going to tell you about my 15 minutes of fame.

It’s been a good week.

I started with the glorious weather last weekend that finally enabled us to dig out the water slide and set our sons loose on it. As you can see, George is very happy.


I bought a £2 scratch card that had a £5 prize.

We took our first honey harvest of the year.

And then there was this.


I won’t bore you with details of the process, other than to say that it was very thorough. But, for the final burble of the academic year 2014-2015, I thought I’d tell you about the lesson the judges from the Society of Biology observed.

Year 13. Gene Therapy.

As always, when originally planning this lesson (it’s been in the files for about 4 years), I try to think how to make the students do all the work. Or, rather, how to engage them, make them think, and ensure effective learning. The idea is very simple. We start by covering the actual principle of gene therapy very quickly. Broken gene = broken protein = disease. Insert working gene = working protein = cure. But I want them to get a much fuller appreciation of what the process might involve.

So I divided them into teams of 4 and asked them to imagine that they were working on the development team at Glaxo-Smithkline – or possibly setting up a Young Enterprise Team, depending on the scale of their ambition. Gene therapy is on the research agenda and they’ve been asked to identify a potential genetic disease for gene therapy development. I give them a list of 6 different genetic diseases and ask them to carry out the research that will enable them to identify the most likely contender for successful gene therapy.

Gene Therapy revised 2015

At this point, it’s very important to clarify the rules. They must NOT go away and enter a search for “Cystic Fibrosis, gene therapy” into Google. They’re researching the disease itself, not gene therapy, and using that information to make their own decisions as to whether it’s worth investing zillions of dollars of development money into. They will need to consider lots of different criteria in order to justify their decision.

Now, if your lesson is being observed as part of deciding the Biology Teacher of the Year award, you obviously want to choose a goodie, and this particular example has always proved popular and successful in the past. It has everything I like in a lesson – challenge, interest, relevance, independent team learning and the chance for me to make a coffee and put my feet up catch up with vital administration. Nonetheless – and this is always a good reason to welcome lesson observation – I went away and updated/tightened up the instructions. In addition, I changed some of my original 6 diseases to include conditions currently being researched.

The girls were suitably and predictably brilliant. The judges were great too. There wasn’t any loitering in the back of the lab, doodling on note pads, they both immediately joined a group so that they could talk to the girls and see what was going on. After about 10 minutes of initial brain- storming they had all established a list of criteria to look for in their disease of choice. It needed to be:

  • common enough to make it commercially viable (and common in the developed world, where it could be afforded)
  • it needed to be a recessive condition so that the introduction of a functioning allele could make a difference
  • the affected gene and its associated protein needed to be known and the mechanism fully understood
  • and there needed to be a plausible way of getting at the affected cells.

At this point, they headed off to the IT rooms (pre-booked) and the judges dutifully trotted after them. I took the chance to make a coffee and put my feet up catch up with vital administration.

40 minutes later they were back.

It’s interesting how they divide the jobs up. One team decided to allocate a disease per person. The other team worked through the diseases in order, but with each person looking for a specific feature of each disease. Either way, it worked.

So, discussion time. Are there any diseases that they’ve managed to eliminate as possibilities?

Haemophilia is always one of the first to go. Why? Well, there’s a perfectly effective treatment so it’s hard to justify the cost. Plus, they add, completely straight faced, it only affects men, so why bother? Ah, the joys of teaching in a girls’ school!

Von Hippel-Lindau disease is also easy to eliminate (always good to include some diseases they haven’t heard of – this one sounds intriguing and adds a layer of interest to the research). It’s a truly horrendous condition, but it affects every single one of the 50,000,000,000,000 cells in the body – utterly impossible to deliver a working gene on that scale. Plus it’s thankfully very rare – so, brutal economic reality intruding, you’d never recover your research costs.

Parkinson’s disease raises interesting debate because it’s not a genetic disease. You don’t inherit it. There’s no obvious gene to correct. It’s caused by a specific set of brain cells dying (cells in an area of the brain called the substantia nigra) that deprive the brain of its ability to make the vital neurotransmitter dopamine. For all these reasons, they dismiss Parkinsons as a possible candidate for gene therapy. They do recognise, however, the vast and increasing market available for a successful treatment.

So, the thoughtful reader might enquire, why did I put Parkinson’s on the list at all? Aha, replies the faithful burbler, because there is a gene therapy for this disease currently being researched by a company called Oxford Biomedica (who are also working on Stargardt disease). They’re obviously chasing the potential billions in revenue, but how would this actually work? The students get there quicker than I thought they might – could you put Dopamine gene(s) into some other brain cells, so the ability to synthesize dopamine is restored?


OK, what about the other options? What did they decide for themselves?

Inevitably, cystic fibrosis is everyone’s favourite. It fulfils all the criteria for potential gene therapy. It’s common, particularly in the developed world. It’s recessive. The relevant protein and its mechanism are well understood. Best of all, the cells are readily accessible – lining the airways of the lungs, they are actually in contact with the outside world, so it’s very easy to deliver your treatment, whatever form it takes, to the very cells that need it.

Which is why, of course, everyone has been chasing cystic fibrosis gene therapy for 20 years or more.

And, as a sobering return to reality, in all that time, and despite the billions spent and the careers of brilliant people dedicated to the research, there is still no gene therapy treatment for any genetic disease.

Thank you very much to everyone who has been following my blog. I hope you’ve found it interesting and, if a biology teacher, useful. I plan to be back in the autumn with more of the same. Have a fantastic summer. I’ll leave you with some photos of the Biological Cakes that the Year 12s have been making. Can you guess what they all are?

IMG_0642 IMG_0643 IMG_0645 IMG_0648 IMG_0649 IMG_0634


A few burbles ago, I mentioned that I’d be reporting back on my Year 10 Biotechnology Club, and how they had fared in their attempts to work out Mendelian laws of inheritance from first principle. I hadn’t seen them for a couple of weeks because of various other commitments, but now I have. And, well, wow.

So, just to recap, this is what they did.

I got in some flies. Fruit flies. This is the place: http://blades-bio.co.uk/

We already use Drosophila in Year 13 to investigate sex linkage, but I thought it would be worth trying them on a talented and motivated bunch of Year 10s to look at basic autosomal inheritance. I was initially just going to get some vestigial winged flies and cross them with wild types, but looking at the catalogue I started to see the possibilities, and ended up ordering vestigial winged males and females, and ebony males and females. Then I got the girls to set up vestigial/ebony crosses.

You can’t really go wrong with this as an activity. It’s just brilliant fun – different, interesting, challenging, in every way.  Knocking out the flies, setting up the little breeding tubes, making sure the unconscious flies don’t get stuck in the blue food goo or get smeared across the sorting paper by heavy handed use of a paintbrush, checking the flies have come round, looking first for larvae and the little tunnels through the food, and then for pupae, and then finally for the alarming clouds of offspring…

But the excitement really starts when they knock them out again and look at the phenotypes.

Remember, these are students who haven’t done any genetics. So there’s no pre-conceived theory or received ideas to help them explain or predict. They just see for themselves, from their own crosses, that ebony bodies and vestigial wings have disappeared. Vanished. Every single one of those first generation flies are 100% wild-type.

It’s the kind of thrill that Mendel himself must have had when the pea dwarfiness disappeared. That’s funny…. what’s going on?

And so they cross the first generation flies. This raises the skill bar considerably, as they have to distinguish males from females based on a tiny little black bristle on their front legs.

Slightly stressful, too, as they don’t give them quite enough ether and are still trying to identify males under the binocular microscopes when the knocked out flies start their little break dances, and then start to escape…. It’s a race to set up the new tubes and fly mortality is high…

But a couple of tubes are successful, which was probably a good thing because there are LOTS of F2 generation offspring to count. The students are brilliant, sharing out the work, and dutifully tallying up the 4 different phenotypes. Because, lo and behold, ebony and vestigial is back. In the rather wonderfully perfect ratios of 95 normal wing, normal body, 34 normal winged ebony body, 24 vestigial winged normal body, and 5 of the fly they’ve not yet seen, those with vestigial wings and ebony bodies.

Go on, I say, work it out.

They’re good. Oh, golly, they’re good. By the end of the session, working together, with absolutely no input from me whatsoever, they report that the expected ratio should be 9:3:3:1

I’ll admit it, I’m shocked. I thought they might get the basic idea of dominant and recessive alleles and how a characteristic could disappear for a generation. I thought they might even figure out the ratio of a simple monohybrid cross. But they’ve only gone and worked out the predicted ratio of a dihybrid cross. And seen that their results closely matches their prediction.

Make your students feel brilliant and they will do brilliant things.

I’m now wondering whether we could roll this out as an investigation for the Year 11s when they actually do genetics in the SoW. Cost is a consideration – virgin females are not cheap – and you’d have to be very tight on health and safety – ether is nasty stuff – but it’s got to be more interesting than pea plants….

Go to run. OCR moderation sample request has just come in…

Strawberry and Coconut genetics

I forget who gave me the idea (I’m afraid I can’t claim it as my own), but if you’re currently extracting DNA from onions with fairy liquid (as my poor, weeping Year 12s used to do), then I’d recommend switching to strawberries and coconut shampoo as I did this year. Smells delicious, looks spectacular DSC_8169 (a little like you’ve liquidised a hamster), and produces prodigious quantities of what they’re happy to accept is DNA (though, truth to tell, most of the white goop is almost certainly pectin).

But onions (cheaper), strawberries (make sure you use coffee filter papers – the goop is too thick to go through standard lab filter paper) or frozen peas (frozen peas, along with onions, are the recommended vegetable of choice for the NCBE), there are ways of telling this story. I saw a teacher recently end the Year 12 Nucleic Acids topic with the DNA extraction exercise, reflecting their belief that practical work is a “just a bit of fun”, tagged on at the end if you’ve got time after the serious business of delivering immaculate notes and diagrams. By then, however, the end product comes as something of an anti-climax because they already know all about it. So what’s the point?DSC_8172

I prefer to do it like this…

Start with the DNA extraction. It’s fun, it’s messy, you can throw in some interesting questions on why you need to use detergent, 60’C water baths, protease and ice cold ethanol, and they end up with great goopy snot-like dribbles of “DNA” – several 1000km of the stuff if you reckon on 1m per cell.

Again, I should stress that if you want a higher percentage of real DNA, then onions or frozen peas are better, but given that we’re not going to sequence/amplify/carry out X-ray crystallography with the extracted material, I’m happy with my strawberries. The key learning point, apart from interpreting the extraction design, is that cells contains loads of this stuff, so it must have some really important function.


OK, so there it is, DNA. What next? Well, there’s obviously loads of it, so it presumably has some importance to cells, but what exactly does it do and how exactly does it do it? They’re motivated to find out more so I send them off to think through some of the classic experiments that identified DNA as the molecule of inheritance.DNA experiments exercise

Next lesson, it’s time to explore the structure. You could just tell them, of course, but why not get them to work out the structure for themselves? I do no more than tell them that nucleic acids are polymers of nucleotides, and sketch the structure of a simplified nucleotide for them. They then do exactly what Watson and Crick did – cut out card models and try to fit them together.DNA model instructions DNA model parts (tip: make sure your sugar/phosphates are on a different colour card to your organic bases). Again, I must cite my sources – this is another of Bill’s typically brilliant creations.


What makes this wonderful to watch is that even if they can remember A-T and C-G from (i)GCSE, they can now see why it has to be that pairing – A to T to 2, C to G to 3 (say it out loud), is my tip for remembering the number of hydrogen bonds.


We then bring all the nucleotides together in a large class molecule…

DSC_8202…and I play them the clip from DNAi where Jim Watson recalls the moment when they saw it  – the morning of February 28th, 1953. I tell them he got a Nobel prize for doing what they’ve just done – if you make your students feel brilliant, then they will do brilliant things.

We go back to the model and discuss it. What can they see? They can see that, to put it together, the two strands have to run anti-parallel. They can see the symmetry that the purine/pyrimidine pairing gives. It’s easy to point out the 3’ 5’ direction. I mention the footnote to the original Nature paper – “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material”

Can they see it as well? Yes they can! That base pairing means each half is a template for the other may be half remembered from (i)GCSE, though not with the clarity provided here. The hydrogen bonds which provide such a ready means of unzipping the molecule are also starkly obvious. Their next homework will be interpreting the design and results of Meselson and Stahls’ beautiful experiment. DNA Replication Meselson Stahl prep Meselson Stahl experiments

And so on. We hang our model from the ceiling and attempt to make it 3D and helical. It comes in very useful when explaining PCR to the Year 13s.

In the next lesson, when I finally give them a simplified diagram to label, DNA basic structure the detail they recall and include is fantastic. Because they figured it all out for themselves while I made a coffee and fed the hamsters.