Sunday 26 June 2011

Drug buddies

The pharmaceutical industry is seeking stronger ties with academia in a bid to speed up drug development.

When pharmaceutical company Pfizer announced on 8 June that it is teaming up with eight research institutions in the Boston area to hunt for candidate drugs, the news was cheered from all sides. The governor of Massachusetts, Deval Patrick, praised the US$100-million, five-year deal for the jobs it would bring to the region. Eric Buehrens, interim chief executive of Beth Israel Deaconess Medical Center, one of the academic partners, extolled the benefits to scientific research. Pfizer says that the partnerships will accelerate development of the next generation of drugs.

The agreement is the latest sign of a growing trend in the pharmaceutical industry, which is trying to cut costs and improve efficiency by outsourcing the earliest phases of drug discovery. "All the drug companies are looking for a new model," says Mark Pepys, a professor of medicine at University College London who is collaborating with London-based GlaxoSmithKline (GSK). For academics facing tight research budgets, the deals bring financial benefits — and potentially fraught relationships with the companies and their academic peers.

"My big fear is that we're going to create a polarization within academic centres," says Kenneth Kaitin, director of the Tufts Center for the Study of Drug Development in Boston. "There will be those that partner with industry and in some cases will be looked on more negatively by their academic peers, and those that would never partner with industry because they feel that betrays their academic purity."
Pfizer's partnership is the third agreement it has brokered with institutions since November under a new programme that includes deals with a group of research centres in New York, and an $85-million collaboration with the University of California, San Francisco. Other major pharmaceutical firms, including GSK and AstraZeneca, have also been busy snatching up academic partners .In 2006, AstraZeneca initiated 271 interactions, including collaborations and other agreements, with academia. By 2010, that number had more than doubled to 594.

Discoveries made in academic labs have long fuelled industrial drug development. Greg Wiederrecht, vice-president for external scientific affairs at Merck, readily ticks off the company's drugs that originated in this way. The development of Gardasil, a vaccine against human papillomavirus, began in a lab at the University of Queensland in Australia, for example. RotaTeq, a rotavirus vaccine, was developed with technology from the University of Pennsylvania and the Wistar Institute in Philadelphia. But these relationships are becoming more important as the industry closes its research labs in response to falling profits

Tightening federal budgets are also putting financial strains on academic labs, making industry collaborations more attractive. "Every academic centre is looking at all this money flying around and asking: 'how do we get a piece of this action?'" says Kaitin.

Yet industry's need for secrecy, and its tendency to change its research focus abruptly, can conflict with the more open and stable academic environment. Pepys experienced this first-hand in the 1990s when the Swiss drug-maker Roche abruptly terminated its collaboration with his team. He faced a long and costly battle to retrieve the intellectual-property rights to a compound developed during the project. A little later, Roche agreed to work on the compound with him again, only to prematurely end the collaboration a second time. Once more, Pepys had to fight to continue his work. "It was a very expensive and tedious process that has delayed the drug by about ten years," he says. "And the clock on the patent is ticking."

Nevertheless, Pepys notes that without Roche's help, he would not have been able to develop a compound that, he hopes, will soon be ready for clinical tests in people with Alzheimer's disease. "Nobody except big pharma can make a medicine effectively," he says.

Industry, too, has had its share of frustrations. Shiv Krishnan, a senior director at French drug-maker Sanofi's branch in Bridgewater, New Jersey, notes that Hoechst, a German life-sciences company that Sanofi acquired, paid $70 million in the 1980s to fund research at Massachusetts General Hospital. In the end, however, the firm had little to show for it, Krishnan says. "And why?" he asks. "Because it wasn't collaborative. It was: I'll send you the cheque and you let me know when you have something."
In recent years, industry has taken a more focused and collaborative role in academic research. In its latest agreement, Pfizer says it will set up a lab in Boston that will house about 50 researchers — half of them Pfizer employees, the rest Pfizer-funded postdocs from participating academic labs. The team will work on projects selected by an oversight board comprised of academics and Pfizer executives. The company hopes to develop up to 30 projects from the three agreements, says Anthony Coyle, who is directing the programmes for Pfizer.

Pfizer's programmes are unique in the size of their financial commitments, but not in their pursuit of active collaboration: earlier this year, Sanofi announced similar agreements. Pepys, meanwhile, is working directly with GSK scientists to develop a drug against amyloidosis, a disease caused by a build-up of amyloid protein.

The various deals also aim to smooth over tensions between industry and academia. Duncan Holmes, who heads GSK's Discovery Partnerships with Academia initiative, says that the company will give research partners a year's notice if it chooses to end a collaboration and that, if it that happens, academics would be free to continue with the project. To ease worries about publication restrictions, many agreements stipulate the terms for publication ahead of time. Yet some academics wonder whether the trend towards industry collaboration will harm academic credibility. Some hospitals and universities, including Harvard University, have cracked down on industry relationships after it emerged over the past few years that researchers had received consulting and speaking fees from companies with a vested interest in their research.

Research agreements do not generally raise the same conflict-of-interest alarms as speaking fees, for example, which can be seen as marketing a product for a company, says Eric Campbell, a sociologist at Harvard Medical School in Boston. Also, many institutions vet the language in the contracts, he notes, and industry money is deposited into institutional accounts rather than given directly to investigators.
But Campbell also notes that industry collaborations can restrict or delay publication and lead to a publication bias in favour of a company's product. "You should not in any way accept the notion that these giant institutional agreements are without tremendous danger," he says.


Furthermore, academia's growing appetite for industry funds could tip the balance of power at the negotiating table. "The pressures on a university president are intense," says Howard Brody, a bioethicist at the University of Texas Medical Branch in Galveston. He advocates the creation of an external organization to oversee large-scale collaborations with the drug industry. "We have to remember that institutions have conflicts of interest, just like individuals do," he cautions.

Kaitin, however, says that industry is just as desperate to collaborate, if not more so. "Earnings at these companies are falling through the floor and investors are losing confidence," he says

Nutrient in broccoli and cauliflower kills cancer cells

 Scientists have found that a nutrient present in broccoli, cauliflower and other cruciferous vegetables can selectively target and kill cancer cells while leaving normal prostate cells healthy and unaffected.

Nutrient in broccoli and cauliflower kills cancer cells


The scientists in the Linus Pauling Institute at Oregon State University have shown that sulphoraphane found at fairly high levels in these vegetables is an inhibitor of histone deacetylase, or HDAC enzymes.

HDACs are a family of enzymes that, among other things, affect access to DNA and play a role in whether certain genes are expressed or not, such as tumour suppressor genes.

HDAC inhibition is one of the more promising fields of cancer treatment and is being targeted from both a pharmaceutical and dietary approach, said scientists.

"It's important to demonstrate that sulforaphane is safe if we propose to use it in cancer prevention or therapies," said Emily Ho, associate professor in the OSU Department of Nutrition and Exercise Sciences and the study's lead author.

"Just because a phytochemical or nutrient is found in food doesn't always mean its safe, and a lot can also depend on the form or levels consumed. But this does appear to be a phytochemical that can selectively kill cancer cells, and that's always what you look for in cancer therapies," Ho stated.
The findings were published in Molecular Nutrition and Food Research, a professional journal.

Saturday 25 June 2011

How do I submit a paper to a scientific journal?

Maxine Clarke takes us through the processes involved in submitting a paper to a scientific journal.

Before submitting a paper to a scientific journal, two factors should be kept in mind. The first is the need to ensure that you have a clear, logical message. The second is to present your paper in the correct format for the journal to which you intend to submit the paper.
The first of these is the most important. However careful and beautiful the presentation, a paper will not be published unless it has a clear, sound conclusion (editors of reputable journals will always be happy to advise authors whose scientific conclusions are publishable but who have difficulty in presenting these conclusions in, say, a foreign language).
Before submitting a paper, therefore, be sure that you have something important and publishable to say. To know this, you should discuss your results with others working in the field, both in your own institution and elsewhere.
The best way to do this is to present your results at scientific meetings — if you can get to them. An additional (or alternative) strategy is to join an email list relevant to your field, and use that to obtain feedback about your research plans, and learn about results from others in the field.
Discuss your ideas and proposed paper with people whose work you respect and admire. It may be a good idea to send one or two key scientists a brief summary of your paper, and ask them to send you some informal comments on whether it is worth your while writing a full paper, or if whether you should to do some more work first (and if so, what).
Use the Internet and email if you cannot speak to people directly at meetings. If you can discuss your work by telephone, then do so; but send the recipient a synopsis or draft of your proposed publication first, so that you have something concrete to discuss.
Writing a draft
When you are sure you are ready to write up the paper, prepare a first draft, including the figures, and repeat the consultation process. Ask people at this stage which journal they think would be most appropriate for publication of your work.
Once you feel you have a solid conclusion to present, you need to prepare a final draft of your paper (see "How to write a scientific paper") in the format of the journal to which you intend to submit.
In deciding on the journal, you should bear in mind the advice you have received from others in the field (some of whom may be academic editors of journals and referees themselves, and hence experienced at judging which journal is most appropriate).
You should also be aware of which journals are publishing similar papers to yours, and whether the journal that you have selected has any rules that make it particularly easy — or difficult — for you to submit.
For example, some journals impose page charges (although many do not), which are typically US$50–100 per page but vary greatly. A journal will state its page charges in its instructions to authors. If your institution cannot pay these, you should ask the journal before you submit whether it will waive the charges — many do under such circumstances.
Another factor to bear in mind is that although some journals allow electronic submission via the Internet or by email, others only allow 'hard-copy' submission by post. This may affect your decision about where to submit.
Most journals or their publishers (for example, a scientific society) have websites containing information that will help you to make this decision. Alternatively you may be able to look at the journal of your choice in your library.
Follow the guidelines
Make sure you read thoroughly the journal's editorial policy, guidelines to authors and any other relevant information — for example, which people in your scientific field are on the editorial board — before you submit.
Author information of this type is usually on 'free access' areas of journals' websites, even if the content of the journal is only available to subscribers. But if your library does not subscribe to the journal of your choice and that journal has an online version, it is worth sending the journal an email saying that you are planning to submit a paper, and asking the journal if it will arrange for you to have online access to its contents for a limited time.
This will allow you to look at the level and format of published papers, information that will be helpful when you prepare the final version of your own paper.
Submitting your paper
Once you have read the journal's instructions to authors and prepared your paper, you must submit it according to the journal's instructions.
Different journals have different rules about number of copies of papers to submit, how to prepare figures and tables, whether to include other information supplementary to your paper, whether all the authors have to sign the letter of submission (known as the 'cover letter') or just one, and so on.
When you submit your paper, the cover letter should contain:
·  Your name, address, phone and fax numbers and email address;
·  Alternative contact details if you will be away for any length of time;
·  A brief statement, in a sentence or two, why you think the paper is important and why the journal should publish it (in other words, state the main conclusion of the paper);
·  Names of anyone in the field who has commented on the paper previously particularly if they are individuals of high standing in the field and/or if they are on the editorial board of the journal;
·  Suggestions of a particular person you would like to referee the paper (although you must be confident that the person is independent, in other words does not collaborate with you or have any other reason to be biased in your favour);
·  Details of anyone you would not like to review your paper because you think they would not give an objective assessment; and
·  Any other details you think are relevant.
It is important to keep this cover letter as short as possible, as the editor who will read it probably receives many papers, and will find it easier to assess yours if you can be succinct.
Reacting to a journal's response
When your paper has been submitted, the journal will probably acknowledge receipt. If you do not hear anything from the journal for a couple of weeks, send the editor a short email asking for an acknowledgement of receipt of your paper, a reference number, and the name of the editor who is handling it.
Use this reference number in any subsequent status enquiries. A journal usually provides an email address on its list of staff (known as the 'masthead') that is published in each issue, usually on the front or the back page.
When the journal has assessed your paper (usually with the help of referees, who are independent scientists in the field selected by the journal's editors), the editor will write to you with a decision about publication, and enclosing referees' reports.
Sometimes an editor's letter will be clear, and it is obvious how you should revise your paper for resubmission. If the letter is not clear, write back to the editor (by email) explaining what you do not understand, and ask for an explanation — for example if the referees' comments are difficult to understand, or you are not sure what the editor means in his or her instructions for revising your paper.
What to do if your paper is rejected
If the journal declines to publish your paper, it is a usually a good idea to discuss this decision with a colleague in the field, showing them the reports and editor's letter, before proceeding further. It might be worth appealing the decision, or it might be better to submit your paper to another journal.
If you do decide to appeal the journal's decision, send a letter stating your case, sticking to scientific points (for example, those parts of your conclusions that may have been misunderstood or not appreciated).
Do not send angry or abusive letters, as this will not help your case.

What to do if your paper is accepted
If your paper is accepted for publication, ask the editor immediately, certainly before the paper is published, about the journal's policy on copyright and reprints, and whether there are other conditions of publication.
A journal may provide you with some reprints free of charge if you do not have funds to pay for them. But it is important to ask about this before your paper is published; the journal may not be able to provide free reprints after publication, as they are much more expensive to produce than reprints made at the time of publication of your article.
Alternatively the journal may be prepared to waive its standard copyright restrictions. But you will probably need to ask for such concessions, explaining your circumstances.
When you are given a publication date for your paper, tell your institution so that it can include this information in its annual report or other documents promoting its research.
Finally, remember to thank personally all those who have helped you in preparing the paper, letting them know that it will be published and in which journal.
Maxine Clarke is the executive editor of Nature.