What price a new cure?

The recent announcement by NICE, the National Institute for Clinical Excellence to deny NHS patients access to the anticancer drug trastuzumab emtansine (called Kadcyla by the manufacturers, Roche) is a result of their cost benefit analysis. It is useful to consider not only the cost of drug discovery, development and clinical trials, but also the price a particular market (or health economy) will stand. The NHS in the UK is facing increasingly tough decisions on how to allocate its annual budget (of just under £100bn), especially when a single drug for a single patient, for one year is just under £100 000: clearly this is why prevention is their byword!  At the same time $800m (approx £480m) is the generally agreed cost of anti-cancer drug development. It is inevitable that some will feel that the NICE decision is harsh, but it has to be seen in the context of other priorities. It also has raises important issues for drug discovery management by the Pharmaceutical sector.

In an earlier Blog I discussed the challenge of making a profit from the sale of

paracetamol, this is the other end of the spectrum. The challenge here is to meet the demands of the UK population whose average lifespan is significantly higher than say that in a developing country (typically by 30 years!) and around 10-15 years more than in the UK when the NHS was established. How might you therefore persuade an investor to back your business plan to develop a new anticancer treatment given the economic climate in the UK and the even greater pressures on healthcare budgets in the majority of the developing countries? It is worth thinking about the cost of typical treatments and the difficulties faced by NICE alongside those facing the drug companies.

For example, a kidney transplant which lasts for about 10 years saves the NHS £24, 000 pa against the comparative cost of renal dialysis. The upfront transplant surgery costs and the post operative care are significantly lower than the annual costs (around £30 000) of renal dialysis. Importantly, this needs to be considered in the context of the 40 000 cases of renal failure diagnosed per year. And that's just one example. The amount spent per capita per year in the UK on health care works out at around £300. Clearly, the system we operate of redistributing tax revenues and National Insurance contributions is under extreme stress, both as a consequence of increasing life expectancy and probably also a result of a long period without a major conflict involving citizens! You will of course be aware of the influence of the last century's two World Wars, which were only separated by 21 years.

On the topic of conflict driven innovation, I am reminded that it is the centenary of the discovery of citrate as an anti clotting agent. A most timely intervention for the start of WWI and the important discoveries made on the biochemistry and physiology of haemoglobin, driven in part by the need to manage the high casualty levels resulting from trench warfare: in particular the valuable practice of blood transfusion. WWII by comparison, presented a major stimulus for antibiotic development on an affordable, large scale in order to combat field infections. Finally, having spent some time working at the Liverpool School of Tropical Medicine, I am still taken aback by the age of some of the drugs used to treat TB and malaria: TB combination therapies were developed 50 years ago and in the case of malaria, quinine based drugs remain in widespread use after nearly 100 years. However, the need for drugs to treat tropical diseases has probably been influenced significantly by our involvement in conflicts in the East illustrating once again that the drivers behind drug development are complex and often surprising! Hopefully, the intensive research efforts to produce artemesin at an affordable price will be successful and the influence of the Bill and Melinda Gates organisation will catalyse further developments.

I wanted to make you think about the economics of drug discovery when you are discussing your business plans. I firmly  believe that taking stock of historical influences and events can be informative. Now you have a think and discussion amongst yourselves about the government's decision to stockpile Tamiflu from around 2006-2010! 

From the hook-and-eye to velcro: does a new invention always displace the previous one?

I was listening to the Book of the Week on Radio 4, B is for Bauhaus, and I was taken with the history of the invention and patenting of the zip or zipper. It reminded me of how human invention and design is reflected in Nature. The hook-and-eye was major step forward in the clothing business, since it allowed a whole range of items to "stay up!". As clothing became increasingly sophisticated and those with sufficient money would buy and wear more and more individual items, the demand for secure fasteners also increased. However, which came first the hook-and-eye or the button. It is clear that ornamental buttons have been around for a couple of thousand years, but buttons and importantly, button holes developed before the hook-and-eye, which surprised me. 


The question I asked myself as the author began discussing the impact of the arrival of the zip fastener in its current form: did it ring the death knell for the button? (Moreover, did velcro seal the fate of the zipper?) Well yes the zipper did for trousers, but not for suit jackets (well not all). But more importantly, this is a story of niche businesses and the adjustments and the accommodations made by society (globally) to make way for a new invention that improves upon one idea in many ways.....but not all. What is the lesson from this story? Well as an undergraduate it was made very clear that all enzymes are proteins. However, in the mid 1980s, it emerged that certain RNA molecules possessed catalytic activity. Did this turn the world of Biochemistry upside down? No, it just made everyone rethink their fundamental assumptions and it became clear that catalytic RNA was not as effective in general terms as protein catalysts, but rather there are some aspects of bio-transformation that are best achieved by RNA enzymes. Moreover, maybe catalytic RNA preceded protein-based enzymes....

Today, you can by a box of hooks and eyes on E Bay just as easily as a box of buttons or zips. You can also expect to find a hook-and-eye in one or two places where you will never find a button or a zip. The point is you may have to adjust your business plan/model in order to survive, but this is where long term business planning and foresight management is important. Other examples would transport: ships, trains, planes....bicycles. They all co-exist and different opportunities exist in different markets. So include some thoughts on long term sustainability and think of examples of coexisting products and examples were an invention has been completely replaced (I immediately think of a product that goes together with a TV). 




And then of course there is velcro, and its biological mimic! 

Poster Preparation Tips

The poster is a tried and tested format for the presentation of scientific data at conferences. It is probably quite a recent development (it has been suggested it was first introduced at European scientific symposia as a means of dealing with language barriers). The earliest references to posters I have come across in the USA go back to the early 1970s. However, today, no scientific meeting would be the same without the animated poster sessions. A poster is often a useful vehicle for PhD students to "exhibit" their work to an audience of scientists, young and old, providing essential experience in communication skills and as a means of simply meeting the community of scientists in your chosen field of research. In recent years, the poster has become a means of enabling students to deliver all kinds of verbal "pitches" and as a focus for discussion as part of the assessment of a module or course.


When planning the design of your own poster, the rules are pretty simple; indeed the conference or class organiser often lays down the size of paper and font etc, in order to manage the display space and poster numbers. Your poster should be readable (from a reasonable standing distance), it should follow a systematic "path" (each text block and image should be in a clear order: use numbers if necessary). It should be appealing, use colour and striking images: I like the use of infographics as pioneered by the newspapers in weather forecasting: see the Economist and newspapers such as the Financial Times for examples. Here, you combine data with explanations in a way that makes the poster person-independent. In other words, when you walk away from your poster, anyone interested can get the"message" without you being there.

The poster session will provide you with the opportunity to "pitch" your ideas to members of staff as well as experienced entrepreneurs, who will be taking part in the evaluation. For the Molecules to Market Poster session, you should think about including the following sections:

1. Company name and names of members (Title)
2. Introduction/Company Mission
3. Description of your product or idea
4. Market and competition
5. Financial model
6. Milestones: from incorporation to exit
7. Why should we invest in you?

The poster size information is made available at the FCP201 Edmodo site (entitled Poster Template). The date and time for the poster session, which will be held in the Council Room on D floor of Firth Court is Wednesday afternoon, 7th May, 2014. There will be prizes for the best posters on display and the best presentation skills.

Faculty Level Molecules to Market Presentations

As promised, some general comments on yesterday's marathon presentation session, in preparation for the M2M "Oscars" next! I think Emma's idea to use a single powerpoint slide format worked incredibly well, allowing time for you to get your ideas across while fostering discussion. We are using the term committees, for the first time, in the  Faculty wide M2M module (FCP201) to identify groups (or teams) prior to settling on a virtual company name. Each committee can access the specific comments on your presentation, by creating an account with Edmodo (which is free) and entering the code that you will shortly receive by email. The group that you will join is called FCP201. I shall give some general comments on the styles, the content and the commercial viabilities, as well as some guidance in respect of the next assessment, namely the poster day.


Company names and logos. I think you will all agree that there were some great names and some that were a little less memorable, but always functional! I would recommend brainstorming the name and make sure its not taken (carry out a domain search). The name usually, but not always reflects the nature of the business: It should roll off the tongue and look good in the logo or on the web site. The logo itself should combine simplicity of design, with impact: it should again be memorable (see right). If someone in your committee has a flair for design, let them create a set of draft ideas and then vote for the one(s) you all like best. I was very impressed with your first attempts and don't think there were too many turkeys!

The Science. First of all, I have to say that you drew on your core knowledge (mostly some aspect of Biology) really well and some committees had developed it much further than I expected. The majority of talks involved the development of new medicines, or had a nutritional theme. I would like you to firm up the Science for your posters. If you are focusing on a molecule, or class of molecule, you must be able to discuss it in detail and you should know the chemistry/biochemistry relating to it/them. I also want you to produce a schematic diagram that connects the science with the application in a clear manner. You should expect to be "grilled" on the science during the poster session. Given the devolution of roles within the committee, it may be useful for one member to take the lead on the Science and feedback to the rest of the team for shaping the communication of the Science to potential investors and customers.

The competition and your USP. We need you to explain the market in which you will operate. Who are your major competitors? Why is your product better than those currently available? What is your unique selling point (or proposition)? I wanted to see more evidence of the market size, the likely selling price and the margins that you are able to forecast. I am aware that the cost of manufacturing is often difficult to estimate and the margins made for example, by Land Rover on the sale of a Range Rover, or Heinz on the sale of a can of baked beans, are closely guarded secrets, but try to de-convolute the cost of production and look at the margins and forecasted sales, in comparison with your own operating costs: not forgetting re-investment in order to make the company sustainable in the long term.

Communicating with investors and clients/customers is a fundamental part of any business. I think the teams were generally inclusive, with a number of the group directly contributing to the presentation, while some of you hung back. As long as everyone contributes to the assessed material this is OK, but we will expect all company members to make some contribution to the post-presentation and general discussions. It is through our assessment of these sessions that we can begin to determine how much you connect with different strands of material and concepts which are covered in independent modules. 

Posters. The final session is scheduled for 7th May where you will use the scientific poster as a vehicle for pitching your business. Several assessors will spend the session quizzing you as a company and a winner will be selected before the end of the day and awarded an appropriate prize. The template to use for the poster will be available via MOLE and the Edmodo site shortly, together with some tips and advice that you may choose to ignore or incorporate into your poster design. However, your poster must conform to the general layout (size and key elements), but you are responsible for ensuring it creates the impact necessary to secure the prize!

Update Feedback is now posted on Edmodo

First presentation session for level 2 undergrads

This is a short post to say two things. Yesterday afternoon was a great event: 13 new business ideas and some very nice Science. But the most rewarding thing from the perspective of the module coordinators was the astonishing level of engagement, considering the large group size. I shall follow up by tomorrow with some comments on all presentations and a general overview, but wanted to congratulated all committees on a resounding success!

Print and be damned!

The column that sits on a spot near St George's Hall and the Walker Gallery/World Museum in Liverpool supports the Duke of Wellington (well a statue of him!). It was nearly 200 years ago when he delivered his now famous challenge to a notorious publisher and blackmailer: "Publish and be damned!" So when I was working through ideas to talk over with George Rule (our resident 3D printer expert) about how we will be introducing 3D printing into the Liverpool Life Sciences UTC laboratory programme, I came across the US Biotech company Organovo. I had been thinking about printing molecular models of proteins, alpha helices, DNA duplexes and even printing lab equipment to facilitate and customize our experimental work. But I hadn't appreciated just how far patents in this area had come on over the last 5 years.   

I have been delivering talks on Biotechnology and Synthetic Biology to a range of groups from schools to University of the third age groups and I have been using the concept of 3D printing to explain the principles of protein synthesis and protein folding in cells (on the ribosome, shown right). The nice thing about biological 3D printing of proteins, is that often (but importantly not always), the sequence of amino acids, self-determines the final 3D structure of the protein; and in less than a second. So as biological 3D printers, ribosomes are pretty smart. However, I am not sure that the term "printing" is a quite right? Printing is defined by the OED as "marking a surface with text, a pattern, a design, or an image". In 3D printing, we are creating an object that is not attached to a surface. I wonder whether 3D publishing might be better, or perhaps molecular sculpting. Then I remembered my conversation with Professor Keith Ridgway at Sheffield's Advanced Manufacturing Centre, where he showed me how he "sprayed" powdered metals and bonded them in a furnace in order to construct 3D objects for jet engines: quite the opposite of traditional sculpting! So for now, printing it is!

Back to Organovo, who are pioneering the use of Bio-printing for the production of tissues for pre-clinical drug screening and ultimately for tissue implantation. So what do they mean by this term? They are taking cells and using their 3D printing technologies to generate an architecture, that mimics that found in tissues. This provides (in their view) a more relevant assay system for drug screening, and also provides a more sophisticated approach to tissue implanting during corrective surgery. Take a look at the videos on their web site and the Economist view (RHS). When I started thinking about the potential not only to make molecular models of bacteriophage, but also the possible printing of virions, I never imagined the technology was so advanced. 

Getting off the starting blocks

I looked through all of the online discussion notes today for the Faculty Module, and two things struck me. The first was that only 50% of the group have used the online chat room resource on MOLE and the other was the level of engagement that those who have participated have shown. I will of course respect the confidentiality of your ideas until they are fully formed, but there are a few things that you may wish to consider. The first relates to the value of your idea and whether it is best to consider patenting.

To file, or not to file? Coca cola kept their recipe secret (well as best they could!) and since the business started more than 20 years ago, in 1886 to be precise, this was clearly a good decision, since their market lead and subsequent revenues, have ensured that they have been able to compete with any alternative providers: last time I looked Coke was selling 10 bottles of coke for every bottle of Pepsi. The same is true of Jelly Babies: a closely guarded secret recipe that has taken many years to copy, but Bassetts of Sheffield company maintained a long enough market lead (founded in 1842!) to become an attractive acquisition by Cadbury-Schweppes in 1989.

Thomas Edison, a prolific filer
of patents, who was
only recently overtaken!

The use of patents to create value in a company is also a successful business option: in 2012 IBM held over 6,000 patents, with the top ten companies being exclusively electronic or ICT related. In 1997, IBM were still top, but with around 1700 patents. The countries filing most patents last year were Japan, China and the USA, with South Korea emerging as a major player. Clearly as the BRIC countries become more mainstream economically and the emerging MINT countries following suit, patenting will become a strong indicator of economic performance. So it is clear that examples exist where secrets (or know how) can be a successful strategy, but so too can patent protection. You will have to decide which route you think will be the best for your business. 

Next I will look at location, which is something one or two committees have discussed in the chat rooms.