Engineering considerations for the application of extremophiles in biotechnology.

Biotechnology may soon take greater advantage of extremophiles--microorganisms that grow in high salt or heavy metal concentrations, or at extremes of temperature, pressure, or pH. These organisms and their cellular components are attractive because they permit process operation over a wider range of conditions than their traditional counterparts. However, extremophiles also present a number of challenges for the development of bioprocesses, such as slow growth, low cell yield, and high shear sensitivity. Difficulties inherent in designing equipment suitable for extreme conditions are also encountered. This review describes both the advantages and disadvantages of extremophiles, as well as the specialized equipment required for their study and application in biotechnology.

Pressure and Temperature Effects on Growth and Methane Production of the Extreme Thermophile Methanococcus jannaschii.

The marine archaebacterium Methanococcus jannaschii was studied at high temperatures and hyperbaric pressures of helium to investigate the effect of pressure on the behavior of a deep-sea thermophile. Methanogenesis and growth (as measured by protein production) at both 86 and 90 degrees C were accelerated by pressure up to 750 atm (1 atm = 101.29kPa), but growth was not observed above 90 degrees C at either 7.8 or 250 atm. However, growth and methanogenesis were uncoupled above 90 degrees C, and the high-temperature limit for methanogenesis was increased by pressure. Substantial methane formation was evident at 98 degrees C and 250 atm, whereas no methane formation was observed at 94 degrees C and 7.8 atm. In contrast, when argon was substituted for helium as the pressurizing gas at 250 atm, no methane was produced at 86 degrees C. Methanogenesis was also suppressed at 86 degrees C and 250 atm when the culture was pressurized with a 4:1 mix of H(2) and CO(2), although limited methanogenesis did occur when the culture was pressurized with H(2).

High-pressure-temperature bioreactor for studying pressure-temperature relationships in bacterial growth and productivity.

Thermophilic organisms offer many potential advantages for biotechnological processes; however, realization of the promise of thermophiles will require extensive research on bacterial thermophily and high-temperature cultivation systems. This article describes a novel bioreactor suitable for precise studies of microbial growth and productivity at temperatures up to 260 degrees C and pressures up to 350 bar. The apparatus is versatile and corrosion resistant, and enables direct sampling of both liquids and gases from a transparent culture vessel without altering the reaction conditions. Gas recirculation through the culture can be controlled through the action of a magnetically driven pump. Initial studies in this bioreactor of Methanococcus jannaschii, an extremely thermophilic methanogen isolated from a deep-sea hydrothermal vent, revealed that increasing the pressure from 7.8 to 100 bar accelerated the production of methane and cellular protein by this archaebacterium at 90 degrees C, and raised the maximum temperature allowing growth from 90 to 92 degrees C. Further increases in pressure had little effect on the growth rate at 90 degrees C.

Double-blind comparison of half-dose and standard-dose flupenthixol decanoate in the maintenance treatment of stabilised out-patients with schizophrenia.

A double-blind controlled trial of 50% dose reduction in maintenance treatment in stable out-patients with low BPRS scores and good social function shows a significantly higher relapse rate in the low-dose group at 12 months (P less than 0.05). After an interval of 24-36 months from dose reduction, 56-76% had experienced a relapse and 76-79% had resumed their former dosage. No clear advantage was shown for the lower dose in either a reduction of side-effects or improved social function, but a reduced prevalence or lower rate of symptom emergence for tardive dyskinesia was suggested.

The discontinuance of maintenance neuroleptic therapy in chronic schizophrenic patients: drug and social consequences.

In a prospective follow-up the outcome of 60 chronic schizophrenic patients who discontinued neuroleptic therapy after remaining stable 12-48 months was compared with controls continuing medication. Not only did the drug-discontinued patients have more relapses (P less than 0.001), but the form of relapse was both more severe and acute, resulting in differences of self-injury (P less than 0.05), anti-social behaviour (P less than 0.01), inpatient admissions (P less than 0.001), and the use of compulsory powers (P less than 0.01). In patients who relapsed, both social and work function was affected adversely for some months. Patients who remained relapse-free without drugs (20%) had a level of work and social function similar to medicated patients. At the end of 18 months the patients who discontinued depot maintenance therapy were found to have been prescribed one-third more neuroleptic drugs than controls, with a possible increase in the risk of long-term tardive dyskinesia.