Experimental studies of the mechanism of biological organisation.

One of the most difficult things to understand about living things is their ability to maintain themselves in an active organised state without running down. Physicists expect all systems to be governed by thermodynamics the second law of which states that the disorder, or entropy, of a system will always increase. For a living system this is a sentence of decay, disorder and death and that is the fate of all life. However thermodynamics allows an ordered state to continue provided it is maintained out of equilibrium and a flow of free energy through the system acts to increase the entropy outside of the system. So thermodynamics is compatible with the existence of living things but it does not provide any information on the mechanisms by which living systems organise and maintain themselves.This research programme will provide several experimental tests of a long standing and controversial hypothesis that very long wavelength modes of vibration in the terahertz (THz) region of the electromagnetic spectrum play an important role in the self-organisation of biological systems. THz waves have wavelengths of the order of 300 microns and lie between radio waves and infrared radiation in the electromagnetic spectrum. The idea that THz modes are exploited in mechanisms of biological organisation is appealing since at the temperatures at which living things operate the thermal energy is able to excite waves with energies up to 6 THz. Consequently it is possible that rotational and vibrational modes excited in this frequency range by chemical interactions in living things will have been selected by evolution to play a role in biological organisation. A crucial issue is whether THz modes live long enough to be important in biological activity. The detailed theoretical work is conflicting and the experimental evidence for long-lived THz modes is sparse and controversial. What is needed to resolve this question is experiments. However laboratory sources of THz radiation are weak, with power levels in the micro W to mille W range and these low power levels are the principle reason why it has not been possible to carryout a convincing test of this hypothesis previously. In this programme we will exploit the unique intense THz beamline on the ALICE accelerator at the Daresbury laboratory that is equipped with a tissue culture facility. The beamline has a high peak power, 70 kW, and a low average power 24 mW. The high peak power is delivered in a short pulse of < 1 pico second. The high peak power is important because it enables us to overcome the problem of THz absorption by water. The low average power makes it possible to eliminate thermal effects which can have a major impact on biological systems. Finally some of the experiments could not be done without the ability to maintain the specimens in the tissue culture facility.THz radiation has the potential to influence multiple levels of biological organisation; direct interactions at the molecular level have the potential to affect cell behaviour, which in turn will influence cell-cell interactions thereby affecting the development of the whole organism. We will therefore investigate the role of THz at all three levels of biological organisation by studying:-1) The role of THz modes in biomolecular interactions2) The influence of THz modes on the growth and differentiation of stem cells.3) The influence of THz modes on the normal development of zebra fish embryos. Finally in order to consolidate research collaborations between physical scientists and life scientists in the University of Liverpool we will invite teams from this community to submit proposals for small scale speculative research programmes.

This is a high risk feasibility study to make the first definitive test of the controversial hypothesis that THz modes play an important role in the mechanism of biological organisation. Confirmation of this hypothesis would have direct and major impacts in a wide variety fields. Who will benefit and how will they benefit? Academia: This is described elsewhere. Medicine: A positive outcome of this research would draw attention to the neglected idea formulated by Frhlich that proposed this mechanism to be a key element in the progression of cancer. Given our current understanding of cancer and normal cell behaviour it is apparent that THz radiation could have therapeutic applications in many diseases if the THz modes available at room temperature are involved in cell to cell communication. These speculations suggest new approaches to some of the current problems in health care. However, experimental evidence that THz radiation can affect biological systems is necessary before any these ideas can be accepted. Technology: This programme will establish the communication between accelerator physicists and the research team that is necessary to ensure that the operation of the accelerator and the configuration of the THz beamline be optimised for the delivery of THz radiation to the tissue culture facility. This will be the first time that RAS has been interfaced to an accelerator based source and the proposal will establish the criteria for linking the time structure of the accelerator to the RAS detection system. Industry: The demonstration that THz modes are important in biology coupled with the improved understanding of the operation of an accelerator source of THz could have an impact on the development the THz industry . Commercial companies are already marketing low power instruments that can be used to diagnose skin cancers and that are used in intra-operative analysis of tissue excised in operations. However the current power levels available with laboratory sources are not sufficient to determine the origin of the contrast mechanism in these applications. The THz beamline and tissue culture facility have the potential to resolve this problem and this could lead to the development of low cost portable diagnostic equipment of significantly improved performance. THz also has potential applications in security and the monitoring of industrial processes. However, any wider such developments will depend ultimately upon the determination of safety limits for exposure of human tissues. These early-stage studies can be seen as the essential preliminaries to the wider commercial uptake of THz radiation. What will be done to realise the benefits of the research? The results of the experiments will be published in high impact scientific journals and will be disseminated to :- a) The Liverpool bio-nano group working at the interface between the physical and life sciences that meets monthly. b) The Surface Science of Biologically Important Interfaces (SSBII) UK Network. PW and RLW are members of the SSBII which began as an EPSRC funded Network with the aim of promoting links between surface, biological and medical scientists and which has lead to the creation of a permanent organisation for promoting interdisciplinary conferences in this field. c) The UK Surface Analysis Forum (UKSAF). PW is a consultant to UKSAF which is a group of academic and industrial scientist working on surfaces. The group meets twice a year to discuss the results of scientific research and the development of equipment. It has a strong representation from instrument manufactures. This would be an ideal forum to discuss instrumental developments. d) National and International Conferences. The applicants have a good track record of work in the public understanding of science and have well developed collaborations with industry.