The Treaty and democratic government

This is the first of a series of articles exploring current implications of the Treaty of Waitangi for New Zealand governance. Here, the objective is to locate the persistent Māori demand for some form of self government in its democratic context of government by- consent. The argument is that the issues are not conceptually difficult. In particular, fears about ‘sovereignty’ are unwarranted. The current burst of activity in ‘Treaty negotiation’ is not a threat to New Zealand’s democracy, but a sign of its strength – a positive and expected part of the constitutional system. As in any democracy, however, there are legitimate questions about the framework within which such negotiation takes place and its limits

With Respect: Parliamentarians, officials, and judges too

An insider's analysis of the relationship between parliamentarians and public servants. (Judges are there too; it turns out there are more than two parties in the relationship between officials and politicians.) Constitutional issues are covered, but the text focuses more on the pressures on people as they work in different parts of government

Claims to Treaty and other rights: exploring the terms of Crown-Māori negotiation

This article delves further into that broad framework by considering the interplay between law and political negotiation, concepts of relationships between citizen and state, the role of rights in political debate, and the effect of concepts of indigeneity on all of these. The broad conclusion is that current legal and policy debates are constantly testing what is different about the state’s relationship with indigenous people, and when, why and how any difference is relevant. The debate must take place, but it needs to be approached with care as it touches on matters that go to the heart of our traditions of democracy and equality

A Synthetic Antibiotic Scaffold Effective Against Multidrug-Resistant Bacterial Pathogens

The dearth of new medicines effective against antibiotic-resistant bacteria presents a growing global public health concern. For more than five decades, the search for new antibiotics has relied heavily upon the chemical modification of natural products (semi-synthesis), a method ill-equipped to combat rapidly evolving resistance threats. Semi-synthetic modifications are typically of limited scope within polyfunctional antibiotics, usually increase molecular weight, and seldom permit modifications of the underlying scaffold. When properly designed, fully synthetic routes can easily address these shortcomings. Here we report the structure-guided design and component-based synthesis of a rigid oxepanoproline scaffold which, when linked to the aminooctose residue of clindamycin, produces an antibiotic of exceptional potency and spectrum of activity, here named iboxamycin. Iboxamycin is effective in strains expressing Erm and Cfr rRNA methyltransferase enzymes, products of genes that confer resistance to all clinically relevant antibiotics targeting the large ribosomal subunit, namely macrolides, lincosamides, phenicols, oxazolidinones, pleuromutilins, and streptogramins. X-ray crystallographic studies of iboxamycin in complex with the native 70S bacterial ribosome, as well as the Erm-methylated 70S ribosome, uncover the structural basis for this enhanced activity, including an unforeseen and unprecedented displacement of upon antibiotic binding. In mice, iboxamycin is orally bioavailable, safe, and effective in treating bacterial infections, testifying to the capacity for chemical synthesis to provide new antibiotics in an era of rising resistance