The American biotechnology company Genofix, have come up with a discovery that could save the health services of the world millions of dollars. The process involves injection of a genetically engineered virus into the amniotic fluid of pregnant women. The virus specifically targets the sex organs of the developing male child, and prevents excessive foreskin growth, alleviating the need for costly, time consuming, and painful circumcision.

Scientists at the prestigious Institute for Utterly Unnecessary Medicine (IUUM) have hailed this as a major breakthrough in ridiculous medical intervention. Institute head Erik Watcricksonsky says "this will lead to a fundamental change in pre-natal preventative care in our hospitals". The treatment will be expensive initially, and will necessitate a small increase in insurance premiums for some high risk groups, such as women. But this will be offset by the massive decrease in problems in later life which are caused by poor male hygiene, due to the presence of a foreskin. Richard Fibroblast, Chair of Circumcision at Cambridge University explains that this " . . . could forever rid the human male of the unsightly, unhygienic, emotionally distressing burden of this nasty flap of skin". He continues "like the appendix, this appendage is an evolutionary fossil, going back to the days when our forefathers like Neanderthal man and the chimp risked damaging the tip of their penis through scrapes on rocky outcrops and stinging nettles". The Genofix treatment will also cut back on nasty zip injuries which are costing the NHS millions in expensive anti-biotic treatments and counselling. Junior Minister for productivity Sir John Seaman-Breth, estimates that the average male worker in Britain loses up to an astonishing 5 days work per annum through zip-induced foreskin injury, and high street trouser dealers are breathing a sigh of relief after a series of costly law suits have ripped into their profit margins.

Male circumcision is an ancient and long-standing tradition carried out to this date by many religious groups such as Jews and the Portuguese catholic sect known as the "Calamari Ring". The high profile Archbishop Fromagio (Queso) Nobilo stated in a press conference this morning that "the Calamari Ring will never accept this technology", which threatens the ancient circumcision feast ritual enjoyed by his Church.

It is clear now though that at least in the wealthy countries of the West that the micro-organisms and parasitic beasts which thrive in that cosy, warm, moist male sanctuary will have to find a new home or finally perish. But where can they run to? Professor Fibroblast remarks "this is the proverbial tip of the iceberg for this remarkable technology". Indeed Genofix scientists are developing similar treatments to prevent fingernail and body hair growth, and also to make the gaps between our toes much larger, thus blocking the build up of potentially lethal black stuff. Genofix DNA guru Gene Genie has the last word, "through genetic engineering of the human foetus in utero, a new dawn is beckoning human civilisation, a sanitary germ-free, smell free, clean world. The foreskin will go the way of the dinosaurs, allowing each and every man to finally fulfil his true potential . . . this treatment is the coming of age of genetic engineering technology, and every man will have a penis to be proud of". Way to go Gene!

Who are they?

What are their plans for on-line publishing?

This, the first in a series of brief outlines on commercial publishers, describes recent developments at Reed-Elsevier, a company which, by market value, is the world's largest scientific and academic publisher. An Anglo-Dutch conglomerate, Reed-Elsevier publishes 1200 scientific journals and runs ScienceDirect, an on-line service which maintains the largest electronic database of scientific technical and medical research available. The journals published by the company span the entire bioscience spectrum from biochem et biophysica Acta (BBA) to the Lancet. Recently the company bought both Cell and the Current Biology series.

Reed International own 52% of the Reed-Elsevier group but it is the Dutch component developed by Pierre Vinken in the 1930's (from a century's old company of booksellers) that brought the scientific and academic journals to the partnership formed in 1993. Unfortunately Elsevier proved difficult to absorb and severe tensions in the boardroom (which continued operating, partly in London, partly in Amsterdam) resulted in two chief executives appointed by Reed leaving in quick succession. Then, when the group tried to solve its leadership problems in the autumn of 1997 by merging with Wolters Kluwer (a smaller Dutch rival who would have brought a new chief executive with them), the European Union raised objections (thought to be about monopoly control of the market) and the deal collapsed. The company remained leaderless throughout the following year until another botched attempt to hire a CEO from the US publisher, Simon and Schuster, finally led to Pierre Vinken and some other members of the Dutch contingent leaving the Board. At this point Morris Tabaksblat a former head of Unilever, with the authority that position gives to running Anglo-Dutch enterprises, took over as chairman. He created a single, focused board and began a search for a new chief executive.

Last summer a new CEO, Crispin Davis was finally appointed. He came from Aegis, a small media company where he had been a very successful CEO. Before that he had been with Proctor & Gamble for almost 20 years . He had no experience of publishing, on-line or otherwise, his strengths being in marketing (he introduced Pampers to the UK) and strategic planning.

Following the Reed-Elsevier merger and the struggles in the boardroom there were a series of profit warnings but the company's interest in electronic publishing steadily expanded. When Crispin Davis took over 20% of the revenue in the 26,000-employee company came from on-line activities.

Now, within three months of his appointment, Davis has moved the Elsevier board to London, cut back on jobs, funded increased investment in internet ventures (from £80 to £200 million) and recruited some high profile on-line specialists to his senior management team. At the end of next month he has said he will present a radical, long -term action plan, along with the year-end finances. With such a large market share, and having been able to rely on profit margins from print journals reputed to have been in the region of 40%, the new look Reed-Elsevier is expected to make its presence felt throughout electronic publishing. It can also be expected to take a very firm line with non-profit making challenges from the public sector.

John Armstrong
School of Biological Sciences, University of Sussex

To recognise the arrival of a new medium for communication between biologists, this is intended as a new sort of contribution: not a review or a meeting report, simply a rant about the current status of the field of membrane traffic. Why would anyone wish to rant about membrane traffic? Surely the field is going through a period of spectacular success, amassing new molecules and interactions by the week and progressively colonising neurobiology, development and the study of nearly every process of infection? The colonisations are unarguable and to be celebrated; my concern here is with the first part. What are we doing with all the new molecules and interactions? Can we simply go on collecting them? My contention here is that the field is growing rapidly but without a clear intellectual backbone: to use the flood of new data effectively, we need to convert cell biology into a rigorous and robust physical science. As will be clear from the following, I have only the vaguest idea of how this will be done.

Did membrane traffic ever have a backbone? Let's start with the textbook cartoon: the organelles as fixed, stable boxes connected by arrows (presumably vesicles). There was never any choice in starting with this simplifying assumption: without it the biochemical and genetic approaches which have uncovered so many important molecules would have been impossible. As biochemists and geneticists we are conditioned to think in terms of pathways, so it is natural to think this way about membrane traffic. However, an organelle is not an enzyme. Enzymes by definition are unchanged by the process of catalysis; organelles, in contrast, are the balance of what goes into them, what happens there and what comes out of them. Imagine an enzyme whose properties depended entirely on what reactions it had previously undergone - kineticists would weep. So it should come as no surprise if quite subtle differencesbetween cell types and conditions lead to observations which don't fit in the boxes: the intermediate between ER and Golgi might take on various forms, the point at which biosynthetic traffic to lysosomes meets the endocytic route might appear 'early' or 'late', synaptic vesicles might bud from the cell surface or from endosomes, but the underlying molecular processes may be exactly the same in different cells. A trafficking route is not a metabolic pathway; the flux through it may be determined simply by the amount of 'substrate' rather than the capacity of any one component. The notion that traffic from the ER to the Golgi is the 'rate-limiting step' in the secretory pathway is, incidentally, a good example of the crass misapplication of the enzymatic model.

If the 'box' has reached its limits, with what do we replace it? Do we have to assemble the cell from scratch, building in each molecule and its interactions until we have a giant equation in time and space? Clearly this is not on the horizon. So where else can we go? My suggestion is that we should all imagine ourselves to be chemists or physicists, and ask if we could get away with what we are now doing. What do 'hard' sciences have which we often lack? Well, they have numbers, and they have definitions. What would a chemist make of a band on a gel, showing an interaction between proteins but neither its rate, nor its binding constant, nor even its extent, and then used to explain what happens in the cell? How would a physicist react to micrographs interpreted in terms of organelle-specific patterns which are largely subjective?

New and emerging methods give us an opportunity to progress beyond this level. Single- and multi-coloured GFP fusions offer enormous potential to understand trafficking processes at a much deeper level than before. For example recent work has described not only the rate of transport of GFP fusions through the secretory pathway but the reaction order of individual steps. To a chemist, determining reaction order is an obvious fundamental stage in understanding any process; and yet I have heard established cell biologists dismiss this work as saying nothing new. Likewise, there is huge scope in applying pattern-recognition algorithms and neural nets in the objective analysis of all sorts of light and electron microscopic images. Can one define, for example, a geometric definition of a Golgi complex? Yet I have attended only one presentation of the early stages of such work, which was met with a comment, from a very distinguished cell biologist, that we should be training cell biologists not computers.

The opportunities are there to bootstrap ourselves out of the cartoon world into something resembling a physical science. The rate-limiting step (see above) is probably the extent to which good chemists and physicists are attracted into biology, as it has been for much of the history of the subject. The challenge is admittedly enormous, but if it is not accepted we may soon find ourselves doing the science of the wrong millennium.

Give me an organic vesicle endowed with life and I will give you back the whole of the organised world (Raspail)

Who are they?

What are their plans for on-line publishing?

This, the first in a series of brief outlines on commercial publishers, describes recent developments at Reed-Elsevier, a company which, by market value, is the world's largest scientific and academic publisher. An Anglo-Dutch conglomerate, Reed-Elsevier publishes 1200 scientific journals and runs ScienceDirect, an on-line service which maintains the largest electronic database of scientific technical and medical research available. The journals published by the company span the entire bioscience spectrum from biochem et biophysica Acta (BBA) to the Lancet. Recently the company bought both Cell and the Current Biology series.

Reed International own 52% of the Reed-Elsevier group but it is the Dutch component developed by Pierre Vinken in the 1930's (from a century's old company of booksellers) that brought the scientific and academic journals to the partnership formed in 1993. Unfortunately Elsevier proved difficult to absorb and severe tensions in the boardroom (which continued operating, partly in London, partly in Amsterdam) resulted in two chief executives appointed by Reed leaving in quick succession. Then, when the group tried to solve its leadership problems in the autumn of 1997 by merging with Wolters Kluwer (a smaller Dutch rival who would have brought a new chief executive with them), the European Union raised objections (thought to be about monopoly control of the market) and the deal collapsed. The company remained leaderless throughout the following year until another botched attempt to hire a CEO from the US publisher, Simon and Schuster, finally led to Pierre Vinken and some other members of the Dutch contingent leaving the Board. At this point Morris Tabaksblat a former head of Unilever, with the authority that position gives to running Anglo-Dutch enterprises, took over as chairman. He created a single, focused board and began a search for a new chief executive.

Last summer a new CEO, Crispin Davis was finally appointed. He came from Aegis, a small media company where he had been a very successful CEO. Before that he had been with Proctor & Gamble for almost 20 years . He had no experience of publishing, on-line or otherwise, his strengths being in marketing (he introduced Pampers to the UK) and strategic planning.

Following the Reed-Elsevier merger and the struggles in the boardroom there were a series of profit warnings but the company's interest in electronic publishing steadily expanded. When Crispin Davis took over 20% of the revenue in the 26,000-employee company came from on-line activities.

Now, within three months of his appointment, Davis has moved the Elsevier board to London, cut back on jobs, funded increased investment in internet ventures (from £80 to £200 million) and recruited some high profile on-line specialists to his senior management team. At the end of next month he has said he will present a radical, long -term action plan, along with the year-end finances. With such a large market share, and having been able to rely on profit margins from print journals reputed to have been in the region of 40%, the new look Reed-Elsevier is expected to make its presence felt throughout electronic publishing. It can also be expected to take a very firm line with non-profit making challenges from the public sector.

The last decades of the 20th century saw the media industry struggling for global influences rivalling those of superpower politicians. Developing new means of communication by satellite and digital signals required huge investments but was an essential prerequisite for their products, (which they usually refer to as "content") to be delivered world wide and generate the all important revenues. The intense activity of commercial publishers now developing Internet services is following essentially the same pattern but the cost of on-line transmission compared to print journal distribution is so low that their immediate, up-front requirement is to demonstrate the quality of their saleable content. This is, of course, a marketing challenge, the area publishers best understand. To succeed on the Internet they must persuade their customers, i.e. the research community, that they need to pay for the copyright content that they, the publishers, own. At the moment they are going through the enticement stage where free access is being offered for short intervals provided they obtain your e-mail address. The moment of truth for everyone will come when money needs to change hands.

Because success in exploiting the Internet depends primarily upon quality of content rather than costs of distribution working scientists now find themselves in a position where, they too, can participate directly in the publication process. The bulk of content in the life science literature is, after all, provided by the contributing scientists themselves and it is they, rather than the journalist employees of the commercial publishers, that peer review, and thereby set the essential standards of its quality control. This understanding lies at the heart of any debate over freely accessible electronic archives but it is less generally realised that the exceptional inclusiveness now offered by the Internet also gives the scientific community unparalleled opportunities for increasing the diversity and quality of its literature. Thus, whilst it is inevitable that commercial publishing interests will be strongly represented in the Internet-based scientific publications of the future, life scientists can now ensure that the new literature will also contain initiatives from non-profit making sectors. These initiatives will be distinctive because they need to be justified for one reason only; because they promote good science.

The opposing view, now often being expressed in the existing, traditional channels of the media, is that the Internet represents the freest of free markets so that when the dust settles, all the requirements of the scientific community will have been determined by customer choice. This is a view that refuses to acknowledge that there are substantial areas of scientists' lives and interests which are financially unquantifiable. It is also, in any case, a disingenuous claim in terms of hard economics because it is very difficult to argue that a free market operates in scientific publishing. This is because the libraries of universities and research institutes act as extremely effective buffers between the service providers, the commercial publishers, and their customers, the researchers. Few researchers know (or need to know) the cost of subscribing to their favourite journals and in responding to their demands librarians are in a difficult position when it comes to taking a firm stand with publishers over subscription prices. Recent experience in California suggests that even when institutions group together and begin to operate as consortia publishers retain the upper hand.

In the first half of the last century when science publishing was in the hands of learned societies publishing costs and profits were contained within reasonable limits. But, from the 1950s onwards, as the more aggressive publishing houses discovered that large profit margins could be achieved, this scholarly equilibrium was lost. In recent years the steeply rising costs of print journal subscriptions have raised the spectre that a time might come when cost considerations could deny sections of the scientific community ready access to the best of their published work. Public sector developments in on-line publishing now offer a real possibility that new balances can be struck and it may be possible to remove these concerns completely.

In December the leading publishers of medical and science journals including Reed-Elsevier, Springer, Oxford University Press, Blackwell Science, John Wiley and McMillan launched Crossref a non-profit service that allows researchers free access across the thousands of journals these publishers produce. It is believed that the ability to browse the 3 million articles they contain (with a further half million being added each year) from a single point of access offers real advantages. Stefan von Holtzbring, MD of the Nature publishing group said "It will be a huge benefit to give researchers access to the references across most of articles being published". Floyd Bloom, editor-in-chief of Science was even more enthusiastic saying "This cooperative service creating links among on-line scientific papers should be recognised as a major step forward in gaining access to the recent body of literature, greatly surpassing any other private or government sponsored resource. Scholars everywhere should rejoice". However, if the comparison being made here is with databases like PMC which intends to provide full text versions of published papers rejoicing scholars will be well advised to leave their champagne uncorked. In Crossref each publisher will be setting their own access standards. That is, once an author and the title of a reference is located, further access to abstracts and/or full text will be the point at which the publisher will begin to charge. Levying costs on a payment per article down-loaded or a pay-per-view basis will become their main source of revenue.

At first sight it is hard to imagine bench workers holding current accounts from which they will pay, individually, for a full text article, especially if their libraries continue to subscribe to most of these journals as they do now. If the PMC can offer a wide coverage and is running in parallel there would seem to be even less incentive for using this service.

Recently a journalist asked Internet specialists at Reed-Elsevier about the challenge of free vendors on the Internet. Showing that this was something to which they had given more than a little thought they replied by looking to the long term and posing two questions, "If all the information which is currently for free remains free and increases, then where is the profit going to come from to pay for the endeavour?" and "Where is the incentive for you, as a journalist, to write, or me to manage?". They answered the first of these questions by predicting "Quality must suffer" but then, undaunted, they concluded "There are still many people out there who value trusted sources." This seems to be putting an exceptionally high premium on the abilities of science journalists and managers and making a rather lowly estimation of the contributions made by members of the scientific community who can claim a long and successful history publishing the journals of Learned Societies. It is to be hoped that on-line developments from the public sector will be able to put this and some of the other more altruistic claims made by commercial publishers to the test. Without the unassailable advantages of their printing presses and distribution systems the added value of commercial journalists should now be much easier for all to see.

The different approaches taken in the current debate depends on which side of the Atlantic it is conducted. Surprisingly discussions in Australasia and South America, regions whose geographies suggest they have much to gain from fast, free access to global networks do not seem to have begun in earnest. In the US the NIH approach of Harold Varmus drew heavy fire from several directions but went forward with determination and seems to have succeeded, as far as was practically possible, to keep the debate in the open. Undoubtedly the clarity of vision and sense of purpose which characterised this development was underpinned by the knowledge that the NIH has very considerable power and resource at its disposal.

The European approach, on the other hand, has been cloaked in secrecy. It has been led by the European Molecular Biology Organisation (EMBO) which has sought to recruit other heavyweights on the European scene such as the EU Commission and the European Science Foundation (ESF) to groupings that could speak to the Americans on something like equal terms. As the discussions are proceeding they are being reported piecemeal in the scientific press and most European life scientists find themselves spectating from the sidelines. From that perspective it looks as if a flag of convenience is now being unfurled which claims to cover, not only EMBO (and, most importantly, the EMBO J.), but the whole of European bioscience. This is better than EMBO alone but it is not nearly far enough; a strength of the PMC coverage is that it also extends across biomedicine. It is not easy to understand why the approach of a strongly promoted web site as used for PMC is not being employed for European developments. The absence from the debate of the major European learned societies, some of whom have major publishing interests, and the lack of comment from at least one of the other large federated societies of Europe is also very puzzling.

Many committed Europeans are showing little enthusiasm for the latest EMBO initiatives. They feel that if EMBO, the British Biochemical Society, the Company of Biologists and others that could contribute from the non-commercial sectors in Europe were to be left, (like the journals of the American Cell Biology Society and the American Society for Microbiology), to decide for themselves how to participate directly in the US-based PMC scheme it would not be a catastrophe. This is not, after all, a situation that parallels the debate which surrounded genome sequencing since we are now dealing with information which is already in the public domain. If, when it is up and running, the PMC operates as originally intended, it should hardly matter which side of the Atlantic an editorial board sits.

Within the next few weeks the PMC becomes fully operational. It will offer searchers access to the Medline archive and, where the journal publisher allows, the search can proceed all the way to full text articles. Where the journal publisher restricts access the searcher will be directed to their website. For publishers operating short embargoes transfer to the PMC archive will presumably take place automatically on the date agreed. It will take some time for this arrangement to settle down because the costs and means of paying for down-loaded articles will need to be worked out. Eventually, however, an on-line market will be established and prospective authors should then have to decide if all the costs required by taking the commercial route (restricted access, page charges etc) are worth it.

The most widely available accounts of these European discussions (carrying, inevitably, an appropriate editorial spin) are being retailed by the commercial journals with least to gain from the development of free electronic archives. They are suggesting that EMBO, anxious to have a place at the top table, has now tried to persuade the major commercial publishers to join their consortium. Apparently Elsevier and representatives from Nature have attended the most recent meetings but, it seems, as yet, little progress has been made. To the sans-culottes outside EMBO it seems that these hasty approaches are unlikely to build a consensus of opinion within the European life science community and it is conceivable that they could compromise the best opportunity this community is ever likely to have of obtaining free access to its literature.

Following the recent debate on whether classics should be a compulsory subject in his son's school curriculum a parent received the usual notice from the headmaster saying school fees were about to be increased to £4,000 per anum.

He wrote back to say that while he had always felt he had paid through the nose to keep his son at the school he did not wish to change his method of payment. And, by the way, he would be voting to keep classics compulsory.

Stuart Otway
Final year PhD student
NERC Centre for Population Biology
Imperial College at Silwood Park
Ascot
Berks SL5 7PY

As a final year PhD student, I was recently interviewed by the Times Higher Education Supplement (Goddard, 1999). Asked about my income and training, my initial response was that, yes, it can be hard financially, but the research needs to be done, and although training is informal and often self-driven, one picks up the techniques and skills one needs for a successful career. However, the more I thought about it, the less satisfactory it seemed. Talking to other students revealed a common but usually unspoken sense of frustration and anger. A PhD provides an extensive training in research, culminating in a professional certification. Once qualified, PhD students will conduct and manage research in public and private organisations, may become lecturers, or professors, or perhaps start their own business or consultancy. But what investment is made in training these future experts?

Next year, a PhD student funded by one of the Research Councils will receive £6620. A CASE (Cooperative Awards in Science and Engineering) studentship carries an additional £1350 or more per year, reflecting its value to the partner company, charity or public body. 'But we're not in it for the money' retorts the student, pushing the £10 000+ debt, accumulated over anything up to 8 years of education, further to the back of his/her mind. Unlike other young professionals, most students have no savings, property, or pension plan.

University graduates entering a career in accountancy, management consultancy, architecture or engineering also undertake a 3-year professional training course. It is financed by a company, eager to invest, knowing that these trainees will form its future workforce and management. Why do trainee scientists not receive similar support from the society for which they will work? Many would argue that it is the freedom given to a scientist that enables them to explore beyond the boundaries of knowledge, and that rigid training, contracts and performance evaluations would obstruct progress. But, as scientists we must be professional, and must therefore receive professional training. In the current climate of media exposure, with scientists needing to argue their corner in policy decisions, impacts and risk assessments, and competing for national and international funding, this is more true than ever.

Those embarking on a PhD are certain that they will conduct valuable research and go on to a career in science or its application. Others often see it as a further tier of education, 3 more years of pursuing a hobby before getting a 'real' job, and working for a living. This perception is inevitable - the number of PhD graduates greatly exceeds the available research positions, and many are forced to leave their chosen career with debts and disillusionment. The irony is that the glut of cheap PhD students may substitute for the employment of junior post-docs and research officers. Without a PhD there is little career structure within science but, once qualified, relevant positions are scarce.

In terms of getting science done, PhD students are good value for money. And if many students are expected to leave academia because there are no jobs, there is less incentive to train them beyond what is necessary for their specific research project. The Research Councils' Graduate Schools Programme runs a single training course, held 18 times per year, each for 100 students. It provides valuable insight into teamworking, motivation and management, but it is unsettling that it is aimed almost entirely at showing PhD students how their transferable skills could earn them a lot of money outside academia. Provision of technical and personal development courses is left to the universities, and these differ enormously in what they offer. Even so, most students choose an institution based entirely on the supervisor or research facilities, not on the training programmes offered. This state of affairs will not change until students become more demanding or guidelines and standards are prescribed.

So why do PhD students not complain? They are unlikely to go on strike to protest this lack of training or money. Instead, it becomes another intellectual challenge to overcome. But surely a PhD is about learning how to do great science and proving your ability - not a test of how little money you can survive on, work a full week, and still hold on to your sanity? My mind is my greatest asset, and I'm willing to rent it out to society. However, a brain that is trained to critically analyse and interpret is bound to start pondering the whys and wherefores of working for a society that values it so little. It is no wonder that PhD graduates are tempted to head for the City.

These are not new issues; most were raised at a conference last year (Masood, 1998), but with no effect as yet. The Research Councils must soon decide whether to keep the status quo, or increase the bursary and tuition fees, and therefore cut the number of studentships awarded. Can society afford three or four years of full training when many students are expected to enter work outside the public sector? Shouldn't the money be spread as thinly as possible, to ensure that the maximum amount of science is done?

Two things are clear: a PhD should involve professional training, not just research, and those who achieve this qualification should not be forced to leave science to pay off their debts.

References:

Goddard A (1999) Workhorses of the system. Times Higher Educational Supplement, June 4th, 8 - 9
Masood E. (1998) UK life science students seek better deal. Nature, 395, 315.

Reprinted from " The Biologist, 46, p241, 1999" with permission from the Institute of Biology, Queens Gate, London

The PhD as an international qualification

Postgraduate training courses leading to a PhD are currently under review in several European countries. Some continue to operate single-supervisor schemes; apprenticeship-like arrangements which have not changed much for nearly 50 years. Others are beginning to adopt US-style schemes which provide broadly-based, career development programmes. In the past comparisons between the PhD courses of different countries were difficult because they were based on very different undergraduate systems. Nevertheless, in recent years, it has become evident that prospective PhD students are developing international perspectives of their own and are prepared to make the intellectual and financial leaps required for moving from one country to another. It is no longer uncommon to find some of the very best UK students on programmes in US universities and centres like EMBL and MRC LMB are actively looking to expand their long established, Europe-wide recruitment policies. In the UK recent surveys have found that 10% of all postgraduates in life science now come from abroad and in the British university system as a whole there are close to 30,000 PhD students from overseas.

The many developments in distance learning allowed by the Internet currently underway are expected to promote undergraduate level teaching across international boundaries. This will open up more international opportunities for postgraduates and will, in turn, make the PhD a qualification that needs to meet a generally agreed international standard.

The problems with present day PhD courses

In many countries reviews of postgraduate courses are long overdue. Everyone agrees that skilled life scientists will be in demand in the years ahead but it is evident that few of the existing training schemes are providing the range and depth of skills these people will need. Of equal concern, as indicated by the letter from Stuart Otway, (reprinted above), is the impression that these schemes are unattractive to young people. Given the exciting prospects that lie ahead in Biology and the key role the life sciences are about to play across medicine and industry these schemes ought to be heavily oversubscribed.

What are PhDs for?

Many recent debates have asked the blunt question "Are there too many PhDs?". This question, like much of the training currently available, presumes that most PhDs are intent upon becoming senior academics. Is this really true? And, if it is, should it be?

A recent survey in the US showed that between the mid 1980's and mid 1990's the number of doctorates awarded increased 42% whereas university faculty jobs increased by less than half that rate. In the UK recent figures on permanent positions are even less promising because almost all of the growth in universities which has taken place in recent years has been in short term post doctoral contracts. For young people who regard the PhD as the first step on a ladder that leads to a senior academic position these are depressing projections. For others, and this probably applies to many, if not most, of the people who have begun short term post doctoral contracts in recent years, the hope is that whilst the PhD may not lead to a university professorship, it will be the first step on the road to becoming an established scientist running their own research group. However, this too, is an exceptionally competitive career path on which only the outstanding can expect to succeed.

The inevitable consequence of these traditional views of postgraduate training is that the system is seen to be overproducing; creating a pool of skilled postgraduates from which only a small elite core expects to emerge. Boosted by their recent undergraduate successes, new recruits to PhD courses often seem undeterred by these dis-incentives but once they have established themselves, they become all too aware of the uncertainties that lie ahead. As a result it is not uncommon to find even graduating PhD students with successful thesis work behind them looking for jobs outside science. In modern economies flexibility in the work force is key but no society can afford this kind of reorientation.

The view that there are only one or two ladders worth climbing after a PhD suggests that the courses themselves need to be redesigned. Thus, if, as expected societies with high skill economies will need large numbers of well trained life scientists, a significant proportion of them will need to be trained to PhD level. A recent article by Bruce Alberts, president of the US National Academy, published in the millennium issue of Elsevier Trends Journals considered the general requirement for PhDs and contained the following observation:

"from my perspective we can never have too many PhDs - people who have a deep understanding of science and scientific enquiry and who are excited about science and in touch with at least one of its frontiers. These are the people who are best qualified to communicate the nature of science and to impart scientific abilities to others. They can also spread the values of science - honesty, generosity, a respect for evidence and openness to new ideas - as needed for the world to prosper in the 21st Century. We need people with these abilities to work in many different occupations throughout our societies - not only in schools but also in governments, the media, law and in a large variety of businesses and community organisations."

In life sciences the pervasive value of molecular biology techniques clearly demonstrates that a basic set of laboratory skills needs to be acquired. For experimental scientists this is a prerequisite no different from that expected of any other profession that relies upon a high order of practical expertise, whether surgeons or pilots. It is equally important for PhD students to acquire a fundamental understanding of the scientific method. This takes time, and for most people much more than a three month project, or series of such projects is required. Integral to the training of any qualified scientist is some form of independent commitment requiring experimentation that lasts several years and in which they learn by experience the value of reproducibility and the need to design experiments that ask incisive questions. Finally there are the social skills of laboratory work; the ability to communicate, collaborate and acquire a measure of responsibility for their chosen profession.

Recent developments in the UK

This month the heads of Research Councils and other Government Agencies received a report on PhD training from a UK Life Science Committee (UKLSC) which included representatives of universities, research institutes, a major biomedical research charity and the pharmaceutical industry. The committee concluded (1) PhD courses in the UK were no longer attracting the best undergraduates, (2) recent changes in undergraduate teaching programmes meant that the traditional, 3 year courses which predominate in the UK system was not long enough and (3) employers in industry wanted recruits with a more broadly based education including management training. The committee recommended that the length of training should be extended to 4 years and the stipend increased (obtaining the money by reducing the number of studentships available). To increase the diversity of the training the committee recommended the use of one year postgraduate courses (giving a Masters in Research, M.Res., qualification) as a preliminary to the 3 year PhD. To reflect "the individual needs" of the student they also recommend a new funding system in which University Departments make bids for training grants that would allow them to recruit their own students and tailor their courses accordingly. If accepted these recommendations will make PhD courses in the UK more attractive to students and, having had an extra year before committing themselves to a thesis-based PhD, the student's decision on whether to proceed will be better informed. If a training grant system is introduced it would be a great improvement on the present arrangements which require heads of department and even individual supervisors to solicit student stipends from research councils and charitable foundations independently. Such acquisitive procedures maximise the number of grants each Department can obtain but they work against the development of programmes that consider educational principles from the beginning.

This UKLSC review was the first assessment to have been made for many years and it was, perhaps, inevitable that it would concentrate on the inadequacies of the present system and offer immediate solutions. However, the Committee could have been more courageous if it had taken a longer term view and considered the degree of re-organisation now needed to create a system capable of delivering over the next 20 to 30 years. This, perhaps, is best illustrated by the committee's focus on university Departments for training life scientists. It is generally agreed that developments of molecular biology and molecular genetics within British universities in the 1980Õs and 90Õs would have progressed much more rapidly if they had not been left to develop within independent biomedical departments. In many universities this has been ameliorated to some extent by the creation of biomedical divisions and schools of life science. There remain, however, especially at the postgraduate level, many institutions where individual departments still hold sway. Postgraduate courses in life science need to draw upon expertise and skills from across the full biomedical spectrum. To flourish they need to be supervised by umbrella organisations like graduate schools which can operate unhindered by departmental divisions. It is to be hoped that if training grant schemes are introduced, graduate schools or similar, rather than departments (or single faculties), will be invited to bid for training programme funds.

The recommendation that a preliminary, one year course can provide the added breadth and quality of experience that postgraduate courses now require also bears further discussion. There is no doubt that if all prospective PhD students were to be persuaded to do these courses they would be better placed to decide whether to proceed to a full, thesis-based course. And, if students then leave after an M.Res, their additional practical laboratory experience and management training will obviously make them more useful to prospective employers. But, for students that go on to graduate as PhDs, an additional preliminary year would not, on its own, seem sufficient educational preparation if they are to be regarded as scientists with 20 to 30 year careers ahead of them.

As life science breaks out from the traditional biological disciplines it is evident that it will need a work force that has a broad background understanding of biomedicine. This, for students, like those in the UK, emerging from only 3 years undergraduate education will mean extensive, additional course work at a postgraduate level. For a career life scientist, a continuing education throughout all four years of their PhD courses, with inputs from across the biomedical disciplines and commerce would seem a pre-requisite. This may be what the UKLSC committee had in mind but their report reads as if they expect an M.Res. year to provide all the additional training now required. There is a real danger here because if the committee's recommendations only result in an additional year being added to the existing 3 year programmes it is inevitable that the M.Res. will then be seen primarily as a filter for reducing the numbers of PhDs. More worryingly, the PhD itself will continue to be regarded as only a specialised qualification. Thus, rather than increasing the number of life scientists with a better quality education the report's recommendations could lead to fewer (albeit better paid) PhDs who are still being prepared only for group leader's jobs.

Conclusion

Major developments in postgraduate education for life scientists are inevitable because of the scale of the changes about to take place throughout biomedicine and society in general. For well prepared PhDs there will be a wide variety of careers offering interesting science and a good standard of living. The immediate concern is whether the postgraduate courses we are making available give the breadth and depth of education this preparation requires.

Lisa Jardine
Professor of Renaissance Studies
Queen Mary and Westfield College
University of London

Bewilderment, confusion, panic, stress: such are all emotions we associate with the extraordinary speed at which new information technology and the world-wide web have saturated and transformed our lives. One moment we were browsing in libraries, content to base our most considered thoughts on gems discovered on the open shelves. The next minute we find ourselves driven to search apparently endless on-line data-bases and internet sites with a determination verging on the obsessive, before we can commit ourselves to paper. We are bombarded with unsolicited information via email; bulletin boards and chat rooms offer inviting opportunities to catch up on the latest intellectual gossip. Information overload has set in. The new information-age juggernaut appears to be careering out of control.

We ought to take comfort, however, from the fact that the information revolution which is currently sweeping us all along is the second, not the first such explosion in mass communications. The emergence of the printed book was as staggeringly high-speed a process, in contemporary terms; its impact on life and thought every bit as fundamental and transformative of a whole range of aspects of contemporary life. In 1455, Johannes Gutenberg set up the first recognisably modern printing press in the German town of Mainz. He and his associates developed the metal type, modified the oil-based ink and adapted woodcut presses to take printed pages. The first book off his presses was a Latin Bible (the so-called forty-two-line bible).The impact.of the comparatively low production cost of such a key text in multiple copies had an immediate social and political impact. The prospect of a Bible in the hands of the whole population altered the whole way religious instruction was conceived of and regulated, and paved the way for the Reformation. A little over fifty years later, Martin Luther made virtuoso use of the printing press in disseminating his radical doctrinal polemics in cheap, eye-catching woodcut-illustrated pamphlets (DŸrer became a Lutheran on the strength of them). For eight years after Gutenberg, Mainz was the printing centre of the world-- the Silicon Valley of Renaissance Europe.

The venture capitalists of the fifteenth century -- the merchant bankers who invested in and distributed goods on the international market, from spices to armaments, -- like the internet magnates of today, were quick to spot the business opportunity. For them too it was for decades a lost leader: it is not until the beginning of the sixteenth century, when Aldus Manutius's press in Venice became a beacon for the industry in Europe, that printing went into serious profitability. A number of prominent early printers like Nicolas Jenson went bankrupt along the way. Nevertheless, printing spread with astonishing speed: from Mainz to Strasbourg in 1458, Cologne (1465), Augsburg (1468), Nuremberg (1470), Leipzig (1481), and Vienna (1482). German printers, or their pupils, introduced the 'divine' art to Italy in 1467, Switzerland and Bohemia in 1468, France and the Netherlands in 1470, Spain, England, Hungary and Poland between 1474 and 1476, Denmark and Sweden in 1483. By 1500 the presses had issued about six million books in approximately forty thousand editions: more books, probably, than had been produced in western Europe since civilisation began Printing promised enhanced possibilities for large-scale, reliable data-bases, just as the internet does now. As early as 1471, the great fifteenth-century German astronomer and mathematician Regiomontanus, whose mathematical work Copernicus used to clinch his theory of the heliocentric universe, saw the crucial data-collecting potential of print. With the backing of a local businessman interested in astronomy, he set up a printing press in Nuremberg, mass-producing copies of the mathematical tables and tables of astronomical observations he had collected. Regiomontanus recognised that the printing press was a particularly attractive tool for the mathematician, because data once entered could be reproduced without error. He could reliably produce complex arrays of data, to be circulated world-wide to other specialists who could verify and build upon the figures and measurements. The possibility of the effortless production of multiple copies meant that printed books could disseminate knowledge faster, further and cheaper than ever before. The low price made that knowledge affordable to a wider urban audience, and encouraged them to develop their reading skills. Like the net, the book changed the way people read. For the first time there were multiple, identical copies, so that everyone was effectively reading from the same book. For the first time, as a result, there could be indexes, and tables of contents. The era of cross-referencing had begun -- anticipating the spectacular spread of cross-referencing possibilities currently made available by the on-line search-engine.

The proliferation of email correspondence too has its early print equivalent. International business had always required vigorous exchange of letters between factors at different locations. At the height of the Italian merchant Datini's business activities in the early fifteenth century, he was exchanging around ten thousand hand-written letters a year with those in charge of his outlets in other cities, and his agent in Avignon complained that 'we spend half our time reading letters or answering them'. Epistolary exchange between intellectual scattered around Europe was conducted through the good offices of those plying the commercial trade routes both by land and sea.

With the arrival of the printing press, letters too went into print and volumes of letters became best-selling items. Erasmus's collections of letters -- exchanged with famous and powerful men -- went into many editions, and were read and emulated by educated readers around the globe. Alongside these there was a buoyant market in letter-writing manuals, teaching the art of communicating in epistolary form. The book-trade routes, via which publications could be got from printer to reader, doubled, in their turn, as routes for transmitting the further deluge of letters stimulated by the printed volumes. To the sixteenth-century scholar, the speed at which breakthroughs in knowledge or simply academic gossip could circulate must have seemed as breathtaking, compared to the slow pace of personal travel, as internet chat today. It might be argued that the confessional first-person which we today take as the authentic voice of the individual was coined in the printed letter-exchanges of the sixteenth century. What, then, can we learn generally from the impact of print, that might give us our bearings in today's world of rapid technological change? Here is a good example of the way technical innovation can alter the whole character and ethos of an age. Before the epistolary explosion, we hear little about the innermost thoughts or personal qualms of individuals. Writings of the fifteenth century are studiedly impersonal, allowing us barely a glimpse of the writer behind the pen. After Erasmus and his letter-writing colleagues, however, more introspective, confessional writing comes into vogue. Then as now, the new technology generated an uninformed excitement that was in many ways unrelated to the actual gains (social or intellectual) it offered. In 1542 Historian Johann Sleidan wrote about the printing press as if its arrival marked the beginning of some miracle era of openness: 'As if to offer proof that God had chosen us to accomplish a special mission, there was invented in our land a marvellous and subtle art, the art of printing. Each man became eager for knowledge, not without feeling a sense of amazement at his former blindness'. Those committed to the new industry were convinced they knew where it was all going, and that it was incontestably a force for good. Yet whilst it was true that print made an enormous impact, neither oppression nor ignorance were thereby obliterated.

Perhaps this is the most important lesson to learn from the uncanny parallels between the first and second information revolutions: Neither those most committed to it, nor those deploring its impact from a distance, can have the slightest idea where the revolution will have taken us, a hundred years from now.

Like health-care or public transport, scientific publishing serves its customer base from both public and private sectors. Thrown into disarray by current developments in electronic processing both sectors are now struggling to regain their balance. In the new equilibrium which will soon begin to emerge each believes they will be in control. Currently, most of the running is being made in the US where, against all expectations, the public sector seems to be winning most of the opening skirmishes.

Over the last twelve months the PubMed Central electronic archive maintained by the National Library in Washington D.C. (the NCBI) has begun to provide fast and easy access to full texts of research papers. A core contributor, showing how the system will work, has been the American Society for Cell Biology which arranges for full texts of papers in the Society’s print journal to be accessed within one month of publication. In the last few weeks the PubMed initiative also brought into being a publishing enterprise, BioMed Central, which will publish new electronic journals which, amongst other things, will allow authors to retain copyright. The financing of BioMed Central comes from Current Science, a London based company, and is thus a private rather than the public sector development.

As these initiatives were being promoted from within the NIH, High Wire Press, a not-for-profit organization set up within Stanford University Press, burst on the scene. Set up in 1995 as an electronic printer High Wire is able to give learned societies access to all the electronic sophistication of commercial on-line publishers. Although expensive, High Wire’s service means that any publishing house, however small, can continue with its subscription commitments for conventional printed copy without needing to develop its own expertise in electronic processing. High Wire’s services are so popular with small publishers, both non-profit and commercial, that, during the last year it has signed up no less than 65 publishers and is currently putting out 206 titles on-line. The full texts of these journals (like many in the PubMed archive), are still located on publisher’s websites (and therefore still under their copyright control) but High Wire has recently established a spectacular bridgehead across the copyright barrier by persuading several journals to give free access to the full text papers of their back catalogues. Thus, although it is necessary to wait for a short embargo period (from 18 months for the Journal of Cell Biology to 2 years for J.histochem.Cytochem) High Wire’s free searching facilities can now take you on-line into the full text papers of 62 titles (18 of them going back five years). The importance of this development cannot be over emphasized since it sends a strong signal to commercial publishers that questions whether they can hold their tight control over long term copyrights indefinitely. It is to be hoped that having relinquished this prize to High Wire, Learned Societies will now extend the same courtesies to PubMed Central.

The number of journals that have signed up with High Wire is large compared with those in the PMC ("a handful" scoffed Nature) but their overall coverage is still, of course, fragmentary. Science is included, Nature is not, Cell was but now that it is an Elsevier imprint has been withdrawn. The Company of Biologists, a not-for-profit publisher with publications which include Development, the Journal of Cell Science to the Journal of Experimental Biology is another notable absentee. (but will now be included in July 2001)

Currently the High Wire gateway provides access to 40% of the top 100 journals. Their most recent innovation is to introduce a ‘papers in press’ series for the Journal of Biological Chemistry where original manuscripts are available on-line within 2 hours of reviewer’s acceptance. This makes primary data free world-wide, usually within 10 weeks of submission. And, since it is sent to PubMed, it also becomes searchable via the NCBI crosslinking services within hours. (For more background to High Wire Press and other recent developments see feature article later in this issue).

In recent months, as expected, commercial publishers have also been busy. Elsevier now claims to have the world’s largest electronic archive of full text papers available and is taking out full page advertisements in Nature to promote it. This is not, of course, a free service and it is restricted to the papers in the 1,100 separate journal titles that Elsevier publish (but which now include Cell and the Current Biology titles). The best of those being offered by High Wire are not there. Other publishers (Academic with IDEAL and Springer with LINK) have their own systems and Macmillan (explosively expanding its coverage by introducing new journals like Nature Cell Biology and Nature Immunology) claims to be setting up yet another independent system for its own journals.

Stiching these commercial operations together is CrossRef which now provides a single gateway to 35 commercial publisher websites, thus providing a collective, searchable database containing over 700,000 articles. CrossRef should be fully operational by the end of the year. When asked to consider how it will relate to NCBI developments (since some years ago the government agency built PubRef, a crosslinking service specifically designed for commercial publishers), a commercial publisher said they thought that PubMed had now served its purpose and that, in his view, the best way forward would be for them to join and become assimilated into Crossref.

At the beginning of the year the European initiative in electronic publishing consisted of an EMBO initiative to set up an electronic archive that would be independent but designed to synergise with PubMed Central. The initial meetings called by EMBO encouraged the idea that their development would have a broad content; extending not just across the traditional life sciences but throughout bio-medicine. However, in subsequent EMBO initiated meetings it was evident that the invited participants no longer included representatives of the large biomedical charities (such as the Wellcome Trust) and nor any of the larger European learned societies. Without engaging the interest and, as a consequence, access to financial support from these sources, the EMBO initiative will have to rely upon less predictable revenues (like the EU) and welcome less congenial bedfellows (like commercial publishers) into its enterprise. For the foundation meeting it held in May EMBO drew its participants from the European Molecular Biology Conference (EMBC) which has a wide geographical representation but also included commercial publishers (Stefan von Holtzbrinck from Macmillan/Nature) in its executive committee. The statement of intent put out from this meeting in May seems to propose a scheme designed primarily for molecular biologists working in life science rather than an umbrella organization for European bio-medicine. Sadly there is nothing in their statement of intent to suggest that EMBO’s electronic archives will improve on the access to full text material given by CrossRef or any of the other barrier-protected systems of the commercial publishers.

Perhaps the most exciting proposal in the EMBO initiative is the intention to build their archive developments in association with their centre for bioinformatics in Cambridge (provided funds become available). Clearly, in the post genome phase, structural genomics will be a central interest for molecular biologists and it is here , rather than as a transatlantic partner to PubMed Central, that the EMBO initiative seems likely to make its most distinctive contribution.

The intense activity amongst publishers of the primary scientific literature during the last six months has consolidated the view that electronic publishing will have its first impact on the established print journals and that entirely novel developments like new electronic journals will take much longer. To succeed new journals, especially if they propose to tamper with fundamentals like peer review, will need the scientific community’s approval. Because impact factors and citation indicies now lie at the very core of quality control in Higher Education Institutes and influence everything from career progression to the international ranking of universities, any system that threatens to devalue them (even though they are widely regarded as badly flawed) is unlikely to make more than slow, even glacial, progress.

This real politik assessment is a great frustration to the devotee of open access because it is clear that tools are now available which can put peer reviewed data onto desktop PC’s anywhere in the world within weeks of submission. Cross linked via databases like PubMed these data could be accompanied by reviewer’s comments and authors responses so that the quality of the information which could be available would allow experimenters, regardless of location, to plan and interpret in an environment which is essentially free of data barriers.

Younger scientists will see change to this utopia as inevitable and even those of us who have always enjoyed browsing the stacks it is only the pace and the order with which the transition is managed that now needs to be debated. The best hope must be that a system of open access will develop from the present system of printed journals but that relaxations in copyright controls will allow it to acquire all of the electronic facilities on-line services can now provide. If they wish, the academic community have a strong hand to play in this transition because as authors and reviewers for example they can choose only to patronize journals, such as those of the learned societies, which feed directly into the public sector systems.

Unfortunately recent progress in incorporating electronic processing into the fabric of scientific publishing is also beginning to expose some large holes that need early attention. Currently the most worrying of these is the need for permanent electronic archives in which the entire published literature is tagged for searching. Without them the future generations of experimentalists are likely to behave as if the only scientific literature worth referring to began in the 1990’s. A more detailed background to this problem is given in the box marked ‘Permanent electronic archives, does anyone have a deep enough pocket?’

Most life scientists are public servants and one of the few perks of the job is to be able to take the moral high ground when profit from publishing research findings comes up for debate. The purist’s view is simple, the public pays for academic research and it should remain in the public’s possession when it is published. Indeed, for most academics, research is a continuum from inspiration through experimentation to publication which, as a community, they then quality control by peer review.

The view taken at the opposite end of the spectrum comes from the more buccaneer of the private publishers who regard research papers as marketable content like any other creative product. The senior executives of some of the larger publishing houses see little difference between themselves and their counterparts in the music or film industries where transfer of copyright transfers complete control. The more thoughtful of their colleagues would claim, (copyright controls notwithstanding), that a strong case can be made that says profits are no more than payments for values added. Editing, they would say, is much more than marking manuscripts with a red pencil and in creating and nursing successful journals they would claim to have directly contributed to the many successes life science has enjoyed during the past 40 years. Where, they ask, if it had been left to academics and their learned societies, would the literature of the life sciences now be?

Commercial publishers believe that it needed the teeth of the free market to create high impact journals in the newly emerging areas life science and that the startling quality of the titles that now brighten our library shelves is due largely to them. Mark Twain said of writers that they are either incisors or grinders and scientific publishers would say that it is their talent for knowing the difference that makes them profitable. Lastly, they say, publishing is an extremely competitive industry where the narrow profit margins of the high impact titles have to be spread ever more thinly in order to cross-subsidise the dozens of small circulation titles an expanding life science needs. And, in any case, taking the total cost of biomedical research (the NIH budget for last year was $17, 000, 000, 000) these margins are no more than the drop in the ocean.

Although these well-rehearsed arguments may have been able to justify the print journal system of the last century they are failing to allay fears for the future. In giving an editorial opinion on the controversies surrounding the human genome project the London Independent newspaper identified private vs. public as a defining question of our time. For the exchange of peer reviewed research information the Internet brings all of the answers down firmly on the side of the public. Put simply, if open access on-line is to be fully exploited by the life science community it will run directly counter to the interests of the commercial publishers.

There is no doubt, of course, that in looking for profit making innovations at the leading edge of on-line publishing the big beasts of the commercial jungle will move quickest. And, whilst they will keep a close watch on each other, they do not imagine that the channels through which academics usually direct their energy, (learned societies, university library committees and the like) will pose much of a threat. The Varmus/NIH initiative and High Wire Press could, of course, be a more serious form of competition but if the publishers refuse to participate by holding fast to their copyright controls they can reckon to keep most high profile academics on-side. And, in the US, if they complain loudly enough about big government interfering in the market place they are almost certain to generate a large groundswell of political sympathy.

But they could be wrong. If, in the change from ink to electrons, public sector initiatives give not-for-profit publishers the on-line tools they need, academics will be able to switch their patronage to the public sector without fear of losing the rewards their visibility has given them in the print world. As authors, reviewers or editors they can adjust their allegiances within electronic archives and be sure that its links, key words and the new, impartial citation indicies it is bound to generate, will search them out.

To establish a new order, therefore, life scientists need only ask themselves, when submitting their papers or being asked to review; "What happens to this journal’s profits?"

If, as a result, there is a flood of data into the public sector, they will see the full benefit of open access and, just as important, so will the rest of the world’s life scientists - once they get on-line.

Is this the end of the road for the learned societies?

Until half way through the last century most scientific journals were published by learned societies. Most of these societies included a responsibility for distributing research findings in their statutes and they often invested heavily in order to become independent publishing houses. Their journals generated substantial revenues especially those of European societies with affiliated institutions spread throughout colonial possessions. By the 1960’s, when commercial publishers also began to invest heavily in journal publishing, most societies with journals had come to rely heavily upon their subscription revenues to finance their other activities. Societies that did not own or were only affiliated with a journal were usually financially constrained. Even the American Society for Cell Biology, whose founders had been responsible for the hugely successful venture that was to become The Journal of Cell Biology, had lacked the foresight to retain a controlling interest in its finances. Fortunately the society was able to offset the lack of subsidy from journal revenue by generating substantial alternative revenues from its burgeoning membership and annual meetings. The ASCB now has its own journal (Molecular Biology of the Cell) but wisely derives less than a quarter of its income from this source.

During the second half of the last century the journals of learned societies and those of commercial publishers learned to live alongside each other; the society journals continuing to generate steady revenues (usually supplemented by members reduced, but often captive, journal subscriptions) whilst the commercial publishers surged ahead, moving into new, emerging topic areas and developing almost all of the high impact titles. Early on, most obvious were the successes of Cell and EMBO J. in picking up on applications flowing from recombinant DNA technology and these were reflected in the sluggish development of many of the society-affiliated cell biology journals. By the end of the 1990’s most society journals were, nevertheless, earning their keep but then, suddenly, Biology became an information-rich science; sequenced genomes began to arrive and so did on-line publishing.

For societies which have allowed themselves to depend heavily upon their journal revenues the financial future now looks bleak, profits from print journals seem certain to decline steeply and loyalties to the traditional disciplines within the life science community are fraying. Glum though these prospects are marvellous times lie ahead for life scientists in every almost every other respect; to brighten themselves up societies just need to look again at the mission statements contained in their statutes.

For propagating research information in the age of electronic publishing the authority and expertise that only learned societies can provide will be desperately needed. Most societies own the copyright for all their published literature but if it is to become accessible to electronic cross-referencing it will need to be digitized and tagged. There will undoubtedly be considerable commercial interest in this and Societies will be in a strong position to negotiate how this can be financed without restricting access. In addition to ensuring that the standards of their back catalogues are maintained their editorial boards will also be able insist that that a society’s standards must continue into the digitized future.

There will be other new opportunities which require society stewardship. If, as seems likely, a pattern emerges, in which publications continue to be peer reviewed but the space constraints of the print journal disappear, there will be sustained pressure for supplementary information (down to raw data) to be included with all published papers. This is the most probable route for un-refereed material to find its way into the literature of life science and if, as at present, this material is just left sitting on personal web-sites, the lack of standardization and linkage will render most of it unuseable. Supervised core repositories on society web sites could be used to organize and set the necessary standards for this supplementary information. Systems for other discrete data sets (such as those in PhD theses) might also be considered. By embracing opportunities such as these societies with distinctive characteristics can put a robust stamp (brand image?) on their areas of special expertise which will guarantee long term survival even within the open environment of electronic archives. They could also ensure that their members benefit from the many ways in which the Internet makes interactive groups more cohesive and, at the same time, exploit the reach of the web to explore international rather than national constituencies. These compensations for learning to live without the subscription income from print journals should breath new life into some societies and for others, allow them to extend their influence and best practices into less developed communities.

Conclusion

As the new ice* age descends learned societies will have to adapt but in a knowledge-based environment there can be few species better fitted for survival. Let us hope that the societies we have chosen to belong to realize the cold chill their journal is about to feel signals a new era, not just a fluctuation in the financial weather.

Currently hard copy journals containing published work resides in the multiple archives maintained throughout the world’s universities, national academies and research institutes. Commercial publishers rely on these public institutions for maintaining this collective, citable database but it is only achieved at considerable cost. Existing library budgets are locked into continuing their long-term journal subscriptions and for the many new institutions in higher education set up in Europe through the 1980’s, (developments which continue in the Far East and elsewhere), very large expenditures on back catalogues have been needed. With on-line publishing two questions arise, where will these archives be and who will maintain them?

At present most researchers combine their on-line access to PubMed databases to search for titles and abstracts and then they walk to their libraries to read (and usually photocopy) their full texts in print journals. In institutions with well resourced library services this arrangement works well but, as commercial publishers persuade more libraries to take both print journals and on-line services carrying full text access, it is easy to see how they imagine time with the desk-top PC and its printer will gradually take over from visits to the library. Inevitably, a time will soon come (and with the current rate of progress in electronic publishing, it could be less than five years) when printed versions of journals will be required only for their use as permanent archive libraries. By then the world at large will be on-line and in these circumstances it is hard to imagine institutions with library stacks finding the costs of keeping the printed journal system going solely for this purpose.

An electronic alternative is, of course, available since techniques for scanning, digitizing and tagging are now sufficiently well established for electronic archives to be created which could carry the back catalogues of the entire scientific literature. There is, however, little incentive for the copyright holders of this literature to fund the cost of tagging even the parts they own. (One recent estimate from Stanford suggested that an adequate back catalogue might be in the region of 2 million pages and that this would cost about $9 million to scan and $100 million to tag for searching).

An obvious alternative would be for the commercial and not-for-profit publishers who own these copyrights to relinquish them so that a full text archive funded from public sector or charitable funds could be set up. Initial estimates of back catalogue usage (by measuring cross-linking activity in full text electronic archives) suggests that this philanthropy, (regarded as a ‘turkeys voting for Christmas/Thanksgiving scenario’ by most commercial publishers), may not be as unrealistic as it sounds since most searching activity (more than 90%) takes place within 12 months of an article appearing. Thus, once the full text electronic archives being compiled in the public sector become large enough for useful large searches, private publishers would have little to gain commercially (and risk denying their authors visibility) by withholding their copyright permissions beyond this first year

.

Slow progress in resolving these archiving problems raises the unpalatable prospect of two literatures developing. For many (physiologists and pathologists presented with novel transgenic phenotypes, for example,) the inability to search the literature of the last millennium with a full set of electronic tools will be a great hindrance.

Be not the first by whom the new is tried, Nor yet the last to set the old aside -

Alexander Pope

The previous article in this series on publishers described Elsevier, the largest commercial publisher in science, and since that report, Science Direct, an on-line service that searches all 1,100 of the company’s journals has become fully operational. As expected, this subscription service is state-of-the-art and provides a full text archive in a variety of formats which is accessible to all standard web browsers. High quality services of this kind require very large investments and there are no guarantees that they will always work, let alone be profitable. The penalties for miss-timing this kind of leap into cyberspace have been clear to everyone since 1994 when the American Association for the Advancement of Science failed to launch its first internet venture; for the on-line journal in which they had invested $2,000,000 their buyer would pay only $50,000.

Inevitably, as techniques of electronic processing have progressed, the pressure for old style print journals to incorporate systems in keeping with a readership that now does most of its browsing on-line has continued to grow. Not-for-profit publishers (like Learned Societies, and even National Academies), found these pressures particularly unwelcome when, to everyone’s great relief, the university librarian at Stanford, Michael Keller and his colleagues up at High Wire Press threw them down an escape ladder. Now, not-for-profit publishers are able to take themselves on-line with the confidence of even the most switched-on commercial enterprises.

High Wire Press, so named because its founding members were nervous about the risks involved, was set up in 1995 as part of Stanford University Press. High Wire is an electronic printer, an aggregator rather than a publisher of established journals but as a fast moving innovator in electronic processing it has some outstanding achievements to its credit. This March, for example, in a joint project with the Oxford University Press and which had begun only sixteen months previously, it put all 14 volumes of the Oxford English Dictionary on-line with full search facilities.

The High Wire Press venture was initiated when Robert Simoni, a biologist at Stanford and an associate editor of The Journal of Biological Chemistry (JBC), asked the university library if the journal, which had just become available as a CD-ROM could be distributed electronically to all the PCs on campus. The response from Michael Keller, the Chief Librarian, (who had arrived in 1993 and was a musicologist rather than a scientist) was to propose putting the journal online via the internet and thereby make it available internationally. The American Society of Biochemistry and Molecular Biology (ASBMB), the publisher of the JBC, then gave Keller and his founder member colleagues (Jonathan Sack, Michael Newman, Sandra Senti and Anne Mueller) until the next annual meeting of the society to show what they could do. Within the three months available the JBC was on-line and now, 5 years later, it is the second largest on-line journal in science. It publishes 800 articles each month and puts them out within two hours of reviewers’ acceptance.

Along the way High Wire Press has been at the leading edge of new developments. It has joined with other innovative companies in improving tagging for cross-reference searching and hooked up with international distributors that can provide shortcuts through the global public Internet system. Most recently, to show that they can provide services well beyond those of an electronic printer High Wire have collaborated with Sun Microsystems and established a long term archiving system. This LOCKSS system (Lots Of Copies Keeps Stuff Safe) is a software protocol which allows very large databases to be stored and managed locally, in effect it should provide an electronic equivalent of multiple university libraries. This is an important development because it recognizes that the servers of service providers cannot be considered an alternative to the present system of multiple print journal archives and it should allow the responsibility for preserving and protecting long-term records to be left with university and other institutional librarians.

The performance at High Wire has been achieved without the kind of financial safety net the profit margins of print journals provide commercial publishers (claimed by the publishers to be marginal but estimated at 40% by Forbes Magazine in 1994). Helped along the way with grants from the National Science Foundation and various charitable foundations it has, nevertheless, become almost self-sufficient financially. And, although its services are expensive, it has succeeded in devising business plans which allow smaller publishers to benefit from its services and still gain financially.

This was not at all obvious in the beginning. In the case of the JBC, for example, when the ASBMB signed on with High Wire their main source of revenue came from 4,500 institutions paying an annual subscription of $1,400. 700 of these institutions were taking more than one hard copy subscription so the extra charges for an on-line version needed to set with care: charge the same as the print version for the on-line service and it becomes a third subscription which, inevitably, will be paid for by cancelling the second print version; charge less and the second print versions will be cancelled anyway with a cut the total revenue. The huge volume of good quality material contained in each issue of the JBC nevertheless made the on-line version sufficiently attractive and, as for other journals, an unexpected bonus crept onto the balance sheet; the surprise being the counter intuitive finding that the sales of a hard copy version invariably increase when a parallel on-line version is produced.

Although High Wire Press shares many of the attributes of other new millennium Palo Alto enterprises (including a healthy disregard for government based initiatives) they appear to lack a world conquering hubris. The stated aim of High Wire Press is to re-engineer the way in which scientific information is disseminated so that it is more compatible with the present day requirements of the scientific community. Like many others, they see that the present literature, dominated as it is by print journals tied to the disciplines of the first half of the last century, needs to stitched together by the latest innovations in electronic cross-linking. By exposing new research results to on-line searchers, regardless of their personal interests, these innovations will lift the quality of information exchange throughout the life sciences to new levels. For the academic community High Wire’s intention to share these new technologies with other not-for-profit organizations is a hugely welcome commitment.

Thus unlike the celebrated Mr Kite who performed with Sgt. Pepper’s Band of the 1960’s Mr K and his colleagues at High Wire are not out just to impress with their dazzling displays of electronic acrobatics; their’s is a serious intent. To quote Mr Keller. " For some time I have been concerned about the treatment of scientific information as a commodity. Commercial publishers like Elsevier, Springer, John Wiley and Academic Press are getting rich by getting information from scientists for free and selling it back to the university libraries for large and annually skyrocketing fees. This technology allows us to provide an economically viable alternative, and we have a certain evangelical fervor about it".

There is a concerted PR job being done on the men in white coats to make us think science is fun and funky. It ain't the truth. Science is dull and smelly. This needs to be said for the sake of impressionable schoolchildren who might be gullible enough to consider giving up the oboe in exchange for particle physics. Don't do it, there is a hidden agenda. It's not science that scientists want you to be interested in, it's scientists. Scientists yearn to be loved. They don't want you to want their research, they want you to want their bodies. All their stunted, bifocal lives they've been the dorky ones in the nylon shirts and Cornish pasty shoes who dance by imitating epileptic fits. Scientists grow antibiotics between their toes and change their underpants only when they register on Geiger counters. Scientists start going bald when they are eight and have Hoover bag moustaches when they are twelve. We do need scientists though because when we're finally discovered by aliens we'll need someone to sit next to them at dinner parties. Believe me if you think scientists are dull aliens will be far worse.
A.A. Gill

When I find myself in the company of scientists I feel like a shabby curate who has strayed by mistake into a drawing room full of dukes.
W.H. Auden

Dr Routh the ninteenth century president of Magdalene College Oxford was president for 63 years. A frail little nut of a man he lived until he was a hundred. He was well into his nineties when one of the fellows of the College hanged himself. The other fellows were very worried knowing that they must break the news to Routh but fearful lest the shock would kill him. At length one was deputed to approach him, which he did very nervously; "Mr president, I'm sorry . . . I'm sorry to have to tell you that one of the fellows has committed suicide". "Don't tell me which" said Routh "Let me guess".

Seymour Benzer began mapping the fine structure of the rII phage gene in 1953, i.e. without the benefit of the triplet code. To give people a better idea of what he was finding he collected typographic errors from newspapers. To demonstrate single letter substitutions he used;

" . . . already the doomsday warnings are arriving, the foreboding accounts of a Russian horde that will come sweeping out of the East, like Attila and his nuns".(Boston Globe)

Recently the Washington Post ran a "Style Invitational" asking readers to take any word from the dictionary, alter it by adding, subtracting or changing one letter, then supply a new definition. Some recent winners were:

Sarchasm: The gulf between the author of sarcastic wit and the recipient who doesn't get it.
Reintarnation: Coming back to life as a hillbilly.
Giraffiti: Vandalism spray-painted very high.
Foreploy: Any misrepresentation about yourself for the purpose of obtaining sex.
Inoculatte: To take coffee intravenously when you are running late.
Hipatitis: Terminal coolness.
Osteopornosis: A degenerate disease.
Karmageddon: It's like, when everybody is sending off all these really bad vibes, right? And then, like, the Earth explodes and it's like a serious bummer.
Glibido: All talk and no action.
Dopeler effect: The tendency of stupid ideas to seem smarter when they come at you rapidly.
Intaxication: Euphoria at getting a refund from the taxman, which lasts until you realise it was your money to start with.

Substitutions are easiest (Chromosole, glamerulus, phospholimase, crapt of Lieberkuhn) but all mutations of biological terms (deletions, insertions, inversions or, for the really ambitious, phrases with translocations) with appropriate definitions will be welcome. Book tokens will be awarded for all published contributions.

If the only tool you possess is a hammer it is tempting to treat everything as if it is a nail.

Notice on editor’s door:

The floggings will continue until moral improves

I was so long writing my review that I never got around to reading the book.

Groucho Marx

Nobody ever acquired strength by publishing someone else's weakness.

The New Yorker (22 December 1952)

If the only tool you possess is a hammer it is tempting to treat everything as if it is a nail.

We judge ourselves by what we feel capable of doing, others judge us by what we have already done. Longfellow

When I wrote it only God and I knew what it meant.

Now only God knows.

Robert Browning

The only way to decipher a letter from Lady Cofax is to pin it on the wall and run past it.

I dedicate this book to Mr Winstanley without whose unfailing sympathy and encouragement this book would have been finished in half the time

P. G. Wodehouse

Driving over the Downs in southern England, and thinking of some unimportant problem, I approached a corner in my Lagonda, when, around the corner, driving a battered Austin 1100, came a lady wearing a large flowered hat. I hurriedly pulled over and she missed me by a fraction of an inch.

As we passed she shouted through her open window "pig!".

"Women drivers!" I thought.

Then drove on around the corner, - and hit a pig.

'And were you pleased?' they asked Helen in Hell.

'Pleased?'answered she,'When all Troy's towers fell;

And dead were Priam's sons, and lost his throne?

And such a war was fought as none had known;

And even the Gods took part; and all because

Of me alone!

Pleased?

We received some blotters the other day from the vice-president of a bank. He had sent them to us because we had let drop just the merest hint that we needed them. This clears up an old question which has been stewing and stirring about our mind for many a fiscal period, namely – what do vice presidents of banks do/obviously one of their duties is to be watchful and search out persons needing blotters; and having found such a person, send him some.

He died as he lived - a cyclist.