Team:Judd UK/Pages/HP*Gold Integrated

Integrated Human Practices

iGEM interview with Dr Clare Wykes

The global issue of iron deficiency anaemia initially inspired us to embark on our project and we wanted to maintain focus on the real world issue our project could contribute to so we enlisted the input of medical professionals who encounter problems with iron deficiency on a day to day basis. We gave a presentation to a few doctors including a specialist in iron deficiency anaemia before a question and answer session. We then conducted an interview with a consultant at Tunbridge Wells Hospital and have documented the whole transcript of our meeting below.

Questions from the team:

Dr Wykes:

Mateo's question: “How important is studying iron in the blood?” It’s crucial for making blood, without it – I think that’s what you need to bring out in the presentation; iron is essential. You could give some interesting figures, like 5% of the earth’s crust is made of iron, things like that draw the reader in; you’ve got to tell a story and tell why it’s so important.

Mateo's question: “How often do you have to deal with iron-related cases?” I had my clinic this morning; of 18 patients, 2 were iron deficient. The paradox of being a haematologist is that you don't have many dealings with iron deficiency because the causes of it in developed countries are not haematological and there's there’s nothing wrong with your bone marrow; you’re bleeding. So, I think you should paint that story, in developed countries, by far the commonest cause of iron deficiency is bleeding, then dietary, but in developing countries that is different. In the blood films I will look at later, I should think about two or three of those will be iron deficient; patients coming through the door with iron deficiency. You could put a nice picture of iron deficiency; just pretty pictures, make your presentation – because everyone’s is going to have the BioBricks and the more scientific side of it, so you just need to make your presentation stand out. What’s different about yours? That’s what you have to think about. I could provide you with a picture of iron deficiency if you want, that’s fine. I deal with that all the time.

Katie's question: “What are the benefits to a patient of detecting abnormal iron levels are caught early?” Obviously the earlier you pick these things up the better, then you can get on and treat, and investigate.

Moya's question: "What do you think the future direction of haematological research will be and how will this impact on haematological practices within the developed world?" Again, I think what we do in developed countries is very different, and our priorities are very different, and I think the key focus for haematological research in developed countries is next-generation sequencing and personalised treatment, which just isn’t relevant in developing countries; that just couldn’t be even thought of, So, I might have a patient with acute leukaemia, and we’ll send off that patient’s bone marrow up to King’s, and they do a myeloid gene panel, so there are about 20-21 different genes known to be commonly mutated in acute leukaemia, and we look at those, we see which ones they’ve got and potentially (at the moment it’s at clinical trials) but in the future we’ll be able to say “Well they have that, this and that, so we’ll give them this, that and the other” and pick parts of the treatment, so that’s where we’re going with it. So, that’s quite different really from the issues affecting patients in developing countries who wouldn’t even be diagnosed with acute leukaemia, they’d be dead.

Nikita's question: "Do you think that home testing kits [for blood-related diseases] should be handed out for free or should there be a price to pay for a package? That’s a question for politicians to answer really!

What price point do you think is reasonable for such kits both in first and third world countries?" Well, I think that something else to think about, and maybe should be brought into your project is, how do they do it now? What’s good about yours, compared to what there is now. So, what is there now? In a developing country, in the middle of nowhere how would they think about someone having an iron deficiency?


Katie:

You’d probably see the physical effects before thinking about it, and they might be lucky enough to get a blood test?


Dr Wykes:

Clinically, there’s the classic “Are they pale? Do they have pale conjunctiva?” That only really happens if you’re very iron deficient, and there are some other clinical features. Of iron deficiency. So again, pictures of people with iron deficiency? It just makes your presentation look a bit more interesting, that you have pictures of people up, and this is what their blood film looks like, this is why it’s important. I’d put a couple of slides up about the impact that has on people and you said cognitive impact, economic impact, the impact it has on obstetric complications which are increased in women who are iron deficient; that’s what we get twitchy about in this country because they do run into problems. I’d put that up. So, what is there now? Clinically; a screening test and then some oral iron, and see what happens. Is that the safe thing to do? The right thing to do? It makes some sense because you don’t have any other alternative. You could put that in; in many places, there isn’t access to a full blood count, there isn’t access to a ferritin level or other tests we would do for iron deficiency.

There is a haemoglobin colour scale; not for measuring iron, but just for looking at haemoglobin, and by inference, if somebody is anaemic in a developing country, it’ll be because they are iron deficient. So, there’s a colour scale; maybe put that in, that these things are what is available at the moment. The colour scale was released in 2001, by WHO, and they do it on a finger-prick test. Maybe just talk about that.

Oral iron is cheap, and it’s really horrible; gives you constipation, and people don’t really like taking it, in this country we give oral iron, but we are increasingly using intravenous iron –different to developing countries. Ferrous Sulphate you can buy over the counter, that’s about 72p: cheap. However, knowing what you’re dealing with is more helpful. I would include the causes of iron deficiency in the presentation; you’ll get excellent pictures up there; hookworms and the like. You want people to remember this. Everyone will have great science and exciting projects, but you want to spruce it up. You never remember what the boring teachers have said. Price-wise, as cheap as possible. I don’t know how much the haemoglobin colour scale costs. What’s great about your project is that you’ve said as your opening line, “This doesn’t require any medical training to use”, and almost everyone has saliva.

Gabriel's question: "Living in a first world country, we have ample access to medicine and diagnostics. However, third world countries aren't so lucky. How important do you feel projects like ours could be in bridging the development gap between the developing world and the west?" There is a bridging of the development gap in terms of introducing synthetic biology and cutting-edge science into developing countries. There’s also a link between the fact that the more people’s health improves in developed countries, the more stable their economic environment will be.

Alex's question: "What other issues in your field do you think synthetic biology could be useful in solving?" Lots! A lot of research in this country is cancer-based, and in haematology there is a lot of cancer biology, for example, tumour seeking microbes, CAR T cells, which we use to treat patients with leukaemia by changing their T cell receptor with a virus, to attack a particular antigen present on a tumour cell; it’s all interesting and coming into clinical practice, so that’s really exciting. What I love about your project is that it’s just so simple, and that’s what medicine should be about really.

Adam's question: "How much do you think synthetic biology could impact your day to day work?" Well, I’m sure it’ll be different in the future; it’s early days I’d say.

Katie's question: "Would you suggest any improvements to our project for future teams, so that iron testing could be accessible quick and easy for people around the world?” Difficult… What do you think about it? How is it good?


Katie:

I guess the sensitivity could be a bit better.


Dr Wykes:

True, but that’s always going to be difficult when you’re dealing with a 'point of care' kit, it’s very going to be perfect; but you’re not trying to be perfect, you’re trying to be pragmatic.

Katie's question: “Do you think non-invasive iron testing is beneficial for LEDCs?” Non-invasive tests are always useful – everybody wants non-invasive things, don’t they? No one wants a needle stuck in them. It’s not practical either; as you said they haven’t got enough clinically trained staff, no infrastructure there.

What do think are the advantages and disadvantages of using saliva in a home testing kit?" It’s great, because it’s there, and it’s easy to access non-invasively, but as you said, the sensitivity and specificity of it are up for debate.


Jonah:

One of the ideas we had for increasing sensitivity was instead of having a semi-quantitative scale, where we have varying levels of our chromoprotein, we had a range in which a blue one was produced, and another range in which a red one was produced, and a range in which a green one was produced.


Dr Wykes:

Yes, I like that idea, and that’s the same principle the haemoglobin colour card uses actually; as in there’s a blue area and a red area and a green area; something along those lines. I think that would be good.

Alfie's question: "How prevalent is synthetic biology in your field at the moment?" We’ve talked about that a bit already.

Olivia's question: "Where do the biggest challenges lie in implementing a new diagnostic- public opinion, logistics, integrating it into old procedures?" I think when you’re talking about developing and developed countries it’s slightly different, and I think breathing out or people spitting on paper; if it works, and it’s sensible and it’s cheap, and it’s effective, then people will be open to that. People are always reluctant to change, although the cheapness would help.

Jonah's question: "To what extent do you think the concept of a paper-based system could be applied to identifying other issues in haematology?" I think it’s great. Non-invasive, no extra kit, easy. Easily shipped out. When it goes out to the developing countries, you’re suggesting it goes out on a piece of paper?


Jonah & Katie:

Yes, that’s the idea.


Dr Wykes:

Literally, wrapped in cellophane with 100 test sheets in it!


Katie:

Yeah, then the only thing you need to do is rehydrate it.


Jonah:

Which can be done by your saliva itself.


Dr Wykes:

Well, put that in! You have to sell that a bit more, that’s great!

Jonathan's question: "What are your thoughts about our project? What kinds of issues do you think could arise with our model and how would you go about correcting them?" Can we come onto that while we go through the presentation?


Review of presentation

Dr Wykes:

[Introduction to iGem] Are you going to have this slide in your actual presentation?


Jonah:

No, we’re not.


Dr Wykes:

[Team] Good – people love a picture. Get that out there.

[Ideas] So, these are all your previous ideas? Maybe try and divide that out a bit; having a list on a presentation is a bit boring, so maybe divide it into health, etc. Biodegradable chewing gum would be good.


Katie:

Yes, except there’s already biodegradable chewing gum made naturally, called Chicza gum, but our project would have ethical issues with undercutting the farmers who produce it.


Dr Wykes:

That’s another thing you need to think about; I can’t think of any issues, but because it is medicine you need some quality control to ensure that the test does what it is meant to do.

[Our Idea]: I think you need to big this up a bit more, and this is the real selling point; this is a problem in our country and a problem everywhere, and you’re talking about people’s quality of life, and that’s really important.

[Research]: You need to pad this out more; it’s just one paper, and I think you need to talk about it more, and whether there are any other paper-based tests for anything. Just pad out the information about what is currently out there. Are there any other things looking at bodily fluids other than blood, i.e. Urine? Just to think about that. Also faeces – in all seriousness, people start listening when you talk about those two, and you’re going to grab people’s attention. The problem with faeces and urine, in this case, are that because some of the causes of iron deficiency are bleeding, that would skew your results, so that’s not the right thing to do; saliva is a lot more palatable, in every way, but just to show you’ve thought about it. I think then, maybe the next slide, what is currently out there.

[BioBricks and Construct] I’m not going to interfere with this bit, as this is the scientific bit and it’s what you have done, and I think that’s fine. Remember who your audience is though; you’re trying to impress the judges, but I think the judges won’t all be professors of molecular biology though, will they? They can be from a lot of different backgrounds, and you need to have something for everyone in there.

[Lab Work] Good – these are nice (animations) and the pictures are good. I’m not going to dissect your project because I think it’s great. You didn’t mention in your presentation was this bit was (Gel Electrophoresis), and while it’s good to talk about lab work, have you got anything that maybe worked a little better?


Katie:

Yes, we have had some successful lab work.


Dr Wykes:

Okay, that’s good; maybe put that in and take this out, or in a little footnote.


Dr Wykes:

[Human Practices] Yep, these are all good.

I think it’s a really great story, I think it’s a really lovely project; a simple thing, done well, that could change quite a lot of people’s lives. Don’t underestimate that, that’s really important. I think you just need to tell the story a bit more - it’s a good story. How long have you got to present?


Katie:

We have a 20-minute slot, and there’s about 5-7 of us presenting.


Dr Wykes:

When are you leaving?


Katie:

We leave on Thursday 9th.


Dr Wykes:

Okay, if you want to send it to me again, I’d be happy to look at it.


Katie:

Yes, thank you, that would be wonderful.


[Dr Wykes gave us 3 papers on iron deficiency]


Dr Wykes:

You’ve probably seen these, but this one [first one] is for haematologists, it’s from our international annual meeting, and it’s the latest information on iron deficiency. It’s the kind of thing we would read, and it’s a bit dry, but it tells the story well – “anaemia affects more than 2 billion people”, for example. Get those facts out there. This one [third one] has “solving the global problem” and has a bit more about developing countries, so that’s quite good, and it’s from the WHO. I thought these would be quite useful. Is there anything else we haven’t talked about, or that you’re worried about?


Katie:

I can’t think of anything we’ve missed, but thank you so much, it’s always great to have an expert opinion.


Dr Wykes:

Okay, I think it’s a great story, and I think it’s neat, and it has a lot of potential. These sort of bedside, 'point of care' testing ideas are very desirable now. You could mention that even in our country we’re trying to implement more 'point of care' testing; you may come across a hemocue, which is a test for a full blood count by a finger-prick test, and we use those with anaesthetic and for kids in this country. That kind of thing is very attractive for obvious reasons; cost, ease, and one can get an answer straight away, which is very desirable. Answer straight away, here’s your ferrous sulphate, take it away with you. That’s very attractive. Great! Good luck with it.


Katie & Jonah:

Thank you so much for everything.


Dr Wykes:

You’re welcome.


End of interview


Conclusions drawn from Interview

Presentation:

- Interesting images needed to draw epople in to the project and the presentation, ie. hookworms, iron deficiency in the flesh, etc.

- Be aware of the great potential our project has, and try to make to audience aware of it.

- Be aware of the difference in background betweeen audience members, and adapt the presentation and language used accordingly.

- Show a contrast between the technology available in this field currently, and our project.


Lab Work:

- Show the evidence behind or concordant with the research on which we based our lab work.

- Bear in mind that this test is not incredibly sensitive, and adapt our conclusions acordingly in order to find of reliability and precision, without losing functionality.

- Take note of ideas for improving sensitivity or reliability, as these could help future teams to progress in their projects, taking inspiration from that which we thought of doing.


Chemist at YSJ

Whilst presenting at the Young scientist Journal to promote synthetic biology and iGEM to high school students we approached Dr Jon McMaster a Professor of Inorganic Chemistry who showed great interest in our project. Dr McMaster is a Biological Inorganic Chemist with interests in the roles of d-transition metals in biology and he suggested we consider utilising siderophores in our project to limit the Fenton reaction and help us increase the responsiveness of our iron-sensing genes. After the discussion with him, we used his suggestions in our lab-work by using different concentrations of EDTA (another chelator).