Collaborative practices for medicinal chemistry research across the big pharma and not-for-profit interface

Drug Discovery Today 2014, article in press
There have been many publications in recent years on the topic of drug discovery collaborations between industry and academic groups. The majority discuss plans and strategies and nothing is ever heard again from the authors with respect to the success of the project or otherwise. This article written by scientists from Astra Zeneca, Medical Research Council Technology and Cancer Research Technology is refreshingly different. It describes a model used by the teams in successful collaborations, highlights the factors which contributed to the success and describes potential improvements which could be considered for future work.

In establishing the working model the authors looked to address key issues which had hampered previous collaborative models. They highlight two key issues as (a) the need for academics to publish work early (largely riven by funding bodies) which has the potential to compromise intellectual property and (b) unbalanced contributions from the parties involved – with industrial groups often acting as coordinators/directors and the academics performing the practical work.

With the issues in mind the groups established collaborative working models from the outset which were actively designed to address these issues and included initiatives which include (a) the initial planning and drafting of research agreement actively involved scientists from each organisation thus addressing conflicting demands at the outset and these agreements contained clear definitions of milestones and ownership of each contributing organisation (b) to create a single project team with members from all the partner organisations which communicates regularly and uses a common language, this overcomes differences in terminology between partner organisations and leads to efficient working (c) the design and use of an electronic data sharing tool to data to be shared in real time across the entire project. The tool contained all of the information necessary to allow team members to rapidly assimilate date and make decisions based on it.

The authors end by suggesting some additional initiatives which could be incorporated in future projects to improve efficiency further still. These suggestions include (a) Further improving face to face communication by considering staff exchanges or secondments and (b) As IT packages were a crucial factor in the success of the projects to ensure that these are set up and all staff trained in their use at the very start of the project, something which the authors could have been set up more efficiently in their experience to date and led to some early problems.
This is an excellent article and any group considering embarking on a collaborative drug discovery exercise is encouraged to read it.

Epigenetics: The sins of the father

In the recent paper in Nature (2014, vol 507, p. 22-24), Virginia Hughes reports the experiments carried out by Dr Dias and Dr Ressler from the University of Atlanta in recent years. They have studied the involvement in inheritance imprints in mice as a result of a fear-based reaction associated to acetophenone. As a result, they found a larger than normal expression of M71 glomeruli receptors in their offspring’s noses. These receptors are encoded by a single gene, known as Olfr151.

This elegant, but still inconclusive cause-effect mechanism approach, brings a possible explanation to a controversial observation back to the 19th century when French biologist Jean-Baptiste Lamark pointed out the pass of acquired traits to future generations. Since then, scientists have observed this phenomenon in plants, animals and even humans.

Although some scientists are still sceptical about the transmitance method, nobody denies the phenomenon. Finding an explanation to this complex problem would involve a deeper study on reproductive biology and to study both mother and father lines over few generations.

The strong suggestion that this heriditary transmission of environmental factors is due to epigenetics, a concept introduced in the 2000’s, where there are some changes in the way that DNA is packed and expressed without altering its sequence, is one of the strong lines of thought, where chemical tags (methylation) on DNA can turn genes on and off.

But even if epigenetics is directly involved in the inheritance, through marks on the material contained in the sperm, the first question to be addressed would be to understand how the effects of environmental/ health legacy get embedded into the animal’s germ cells.

Epigenetics is still unable to explain how this observed phenomenon gets passed down through multiple generations, surviving several rounds of genetic re-programing. Other suggested agents might involve histones (proteins which has been observed that they can be passed down through generations) or short RNA molecules which role would be to latch on DNA and affect further into gene expression.

Scientists are optimistic about finding a cause-effect relationship in the years to come for a phenomenon which has proved elusive for researchers in the past hundred years.