In the news
21 Nov 2008
3 February 2007
Virtual human metabolism created
Researchers from the University of California have created a virtual model of human metabolism, containing the full range of biochemical reactions in human cells. The breakthrough is highly significant as it could pave the way for new and better treatments for conditions like high cholesterol, and replace animal experiments. The researchers used information from the human genome to construct a database of 3,300 metabolic reactions which in turn was used to create a network of metabolic processes.
The team hope that the network could be used to see what would happen if a drug was used to target a specific metabolic reaction, such as the synthesis of cholesterol. Or it could be used to predict what would happen if you interfere with a metabolic reaction in a specific type of cell, such as a blood or heart cells. And eventually it could even be used to create an individual network for a person, with the flexibility to adapt to our individual, natural variations – something like a ‘bespoke’ metabolism.
Metabolic reactions in cells include those which convert food sources, such as fats, protein and carbohydrate into energy and to make other molecules used by the body. Problems with metabolism can cause hundreds of human disorders, such as haemolytic anaemia, a condition where red blood cells are broken down too rapidly. To test the computer model, the team ran 288 different simulations, such as the synthesis of hormones, testosterone and oestrogen, and the metabolism of fat from the diet. In all cases the behaviour of the model matched the published performance of human cells in defined conditions.
This breakthrough offers the enormous ethical and scientific advantage of being able to use advanced computer technology to bring together a vast amount of complex information on human metabolism and create virtual models for experimental purposes, instead of animal experiments. Computer models that are constructed from human data avoid problems of species differences, so are likely to produce far more relevant results than animal research; the US researchers have already demonstrated a very high level of accuracy. Sophisticated models like this allow scientists to harmlessly alter various biochemical elements and conduct virtual experiments, instead of experimenting on different species with different metabolic systems such as rats and mice. Rodents are often used in such research, including genetically modified (GM) mice with aspects of their metabolism altered to model human metabolic disorders such as obesity, diabetes and high cholesterol.
The pharmaceutical company Pfizer recently halted a £400million trial of a new cholesterol altering drug (torcetrapib), aimed at preventing heart attacks and strokes, when 82 people on the drug died, compared to 51 in a control group. This drug will undoubtedly have undergone extensive animal testing which, it can only be assumed, did not reveal the potential danger – the results of the clinical trial were called “ both surprising and disappointing ” by Pfizer’s CEO Jeffrey Kindler. An advanced computer model of human metabolism could be the key to developing safe and effective new medicines and avoiding both animal suffering and ‘dead end’ drug trials like this in the future.
Additional sources: BBC News On-line; Times On-line; Reported in Proceedings of the National Academy of Sciences
