The perfect article, no changes after you finished writing it, nothing that hasn’t been explained by the paper, nothing the reviewers can talk about except..Well Done!

I certainly don’t know anyone who hasn’t had to make a few changes to the paper after peer-review. I haven’t reviewed many articles, but it seems to me that there is a certain amount of pressure on peer reviewers to search for holes in the paper.I remember a Prof. once reviewing a paper for a high impact journal saying, “Its for …, can’t allow it to get in that easily”, almost as if the better the journal the harder the reviewers must work to find reasons for change in the paper.

Obviously, it is a vicious cycle to which I have become a party. I hope over my career that I can change my mindset to the point where I ask myself,” are there large flaws in the paper? Have they forgotten an experiment or a result that needs to be done to change the hypothesis? Have they forgotten to explain a result? Are there any methods issues”. If not, fine. no changes. perfect!

Of course, I might be completely wrong about this and there are researchers and scientists who never rarely need to make changes. If so, please let me know if you have a job vacancy!

I’m sure my apprehension stems from being a novice at this, but I can’t seem to think that my reaction is a little bit schoolboyish waiting for the final examination results. I have tried hard to distract myself – had a couple of reports to write, a project proposal to submit and a presentation to make, but just can’t seem to focus on anything for too long.

Its going to be even worse if I get rejected because it will just mean agonisingly reformatting the paper for another month to send to another journal..and so on.

I often wish there was a central site for all article submissions and people can submit an article with their first and second preference for journals. After that, any journal is allowed to bid for the paper within a span of time and the authors must accept one within that time period. This at least means that authors receive decisions from journal editors about sending the article for peer review quickly without reformatting the paper incessantly. The problem lies in the peer review process which often takes long and allows articles to be rejected at that stage. I haven’t got any ideas for that..any takers?

The vaccine vials that are implicated in the deaths were from the same batch of vaccine manufactured by Indian Immunologicals Ltd., a subsidiary of a national organisation. The company’s press release seeks to absolve itself of any manufacture or production fault. They argue and rightly so that it is unlikely for a batch of 2,50,000 doses to have been faulty and only caused 4 deaths all of whom were administered the vaccine from the same vial.

The health workers and their unions are equally quick to discount any mistake being made at their end. One report suggests that the vaccine diluent used by the nurse administering the vaccine might have been from a different company, albeit the same composition (sterile water).

The central government enquiry into the incident has yet to produce a report as it is awaiting lab results, but has cleared the cold chain and contaminated syringes as the cause.

Either way, the net result of this has been a ban on measles vaccination across the country. An indirect effect of this crisis is the slow down on the polio vaccination drive. I suspect the latter is more likely to be causing the government sleepless nights and will be the driving force behind the government’s action.

The Indian government has attached a disproportionate importance to polio rather than measles. The political incentive(both domestic and international) for eradicating polio seem to over weigh the individual health benefits from measles vaccination. India has very poor measles vaccination coverage (53%) and has a high incidence of measles cases, but despite these damning statistics the government has not pushed measles vaccination strongly enough.

My fear lies in the possibility of a cover-up investigation. Investigation into the probable causes of these deaths, causes of the vaccination failure and side-effects, detailed investigation into the manufacturing unit must be conducted in a truly transparent manner to re-build confidence in the vaccination programs. The alternative might set India back ten years and nullify the great progress that has been made in preventing diseases by vaccination.

It seems like its the biggest difference between lab research and field research. I remember during my lab years, that I would never trust the results of a single experiment. I had to go back and re-do it to make sure I was absolutely correct. Well, I can’t do that with human subjects and its freaking me out.

This of course, isn’t entirely true. If you work with Non-human primates, they are even more precious than humans, so my rant isn’t entirely accurate. Also, if you work with one of those rare genetically modified specially bred species of lab animal then you really don’t want to mess it all up , but by and large mistakes happen and you can repeat the experiment. In fact, its one way in which science distinguishes itself from social science. Repeatability, reproducibility…

I always whined about how if you did work with human cells, subjects your results would always get published even if they were rubbish but with animal work (especially mouse stuff) you really had to find something interesting and new. It always bugged, but I understand now.

anyway, I better get back to the real world and finish deciding what controls to use in my “human experiment”.

As important as the failure of this clinical trial might seem to those interested in HIV vaccines, I agree with Cohen’s suggestion that this might be the beginning of the end for the novel and interesting concept of T cell inducing vaccines. No vaccine used currently in mass immunization programmes attempts to induce T cells, they all act by stimulating antibodies which prevent infection.

As an ex T-cell vaccine man myself, I have grown fond of the idea of developing vaccines which work by this alternative immune mechanism. While this field is still in its infancy and is slowly becoming more popular, I remember going to conferences where the idea of T cell vaccines has often been scoffed at by immunologists.

In my opinion, there are three main arguments against T cell vaccines. One, that in complex organisms like Plasmodium (causing malaria), Leishmania, Mycobacteria( causing tuberculosis) and HIV it will be difficult to find a single molecule that can be targeted to induce protection. Second, the diversity of Human Leukocyte Antigen (HLA), which are surface molecules that present foreign substances to induce T cells, might require finding a single microbial target common to all main HLA subtypes. Lastly, we do not know enough about how to induce a strong T cell memory response in the human population and therefore a lot of the protection afforded by T cell vaccines might be fleeting.

This failed clinical trial might sound the death knell for T cell vaccines in HIV, although I believe that unless further clinical trials are undertaken and also fail, it would be hasty for us to leave this avenue unexplored. The larger problem might be the use of this trial as evidence for mounting skepticism against T cell inducing vaccines and this might lead to funding for vaccine research in this area becoming tighter.

We should probably take a page out of the history of polio vaccine development and not get too bummed out. In 1934, a trial of a killed polio vaccine had to be stopped because participants were getting polio due to vaccination and the scientific community gave up hope to find a vaccine against polio. Funding decreased and the field remained dormant for many years after that incident until Jonas Salk came along to produce his famous vaccine. I am sure that the fight against HIV is not going to slow down, but I can only hope that it is not time for T cells vaccines to go into hibernation.

There are many who blame the growing numbers of International Medical Graduates (IMG) for robbing home graduates of their duly entitled jobs. This week’s BMJ has a debate on the issue authored by two senior consultants who completed their undergraduate training outside the UK.

Dr. Edward Byrne, dean of biomedical training at UCL argues that training posts must go to UK graduates irrespective of merit and only in the event of a shortage (which did not happen this year) should other candidates be asked to fill these posts. Read the full article here. In response, Dr.Edwin Borman refutes this suggestion in the belief that restricting access would damage the future of the profession. Read his commentary here.

The most interesting article in this journal this week, perhaps published either because it reflects the sentiments of many UK graduates and citizens or because of its controversial direction is written by Graham Winyard, retired postgraduate dean of the Hull-York medical school.
The article condones the MTAS system and blames the British government for lacking a comprehensive and firm anti-migration policy for doctors. His suggestion would almost stop any IMG from going to the UK.

”The most obvious action would be to suspend the skilled migrant programme as it applies to doctors and establish a two stage recruitment process similar to that used in other countries,whereby overseas applications are considered after those of domestic graduates (which in our case would have to include Europe).”

I am utterly shocked that UK medical professionals are willing to insulate themselves from the world’s medical community. There is no doubt that jobs are scarce and a combination of expanding medical schools, influx of IMG’s, poor workforce planning and a non-functional computerised selection process has only highlighted the problem. However, the answer cannot be to cocoon yourself but rather to learn from other systems that have similar issues.

How would you expect to advance if you breed practices and knowledge incestuously? A closed,non-competitive system is bound to stagnate if not driven by a need to excel in a global setting. I can only presume that Dr. Winyard foresees and is content to herald the death of meritocracy (as little as it remains in the UK medical system today) and a multicultural NHS workforce in the near future if the government follows his suggestion.

On a personal note, I love the UK and foresaw myself as a medical professional in the NHS, but I am glad that I walked away from them this year. Although I did not predict such a catastrophe, I was convinced that IMG’s would find it hard to work through the system to reach consultant positions. The prevailing antagonism towards IMG’s from senior consultants, who are part of the selection panels, will only make it harder to find good training positions in the NHS in the near future. I would advise IMG’s to look elsewhere for opportunities for the next couple of years

Its a strange field – vaccines. You have a lot of literature on basic science and development and you have tons of literature on vaccine safety, policy and ethics. Yet, there is very little general literature on vaccine trials themselves. How to conduct a good trial, important issues to address, stuff like that is never addressed. I wonder if its because it is pretty obvious to everyone.

In cases you are interested,the best sources for the history of medicine are either the Wellcome Trust Library or the National Library of Medicine history of medicine archives. There are other specialised websites like the James Lind library covering the history of clinical trials or the Edward Jenner Museum website.

I needed a break from benchwork,perhaps because my initial training as a physician in India equipped me poorly to deal with the compulsive,isolated and topsy-turvy world of lab research. So now, I am enjoying the Californian sunshine, Napa valley wines and occasional classroom lecture.

What is my blog going to be about? I don’t know, but I can definitely tell you its going to be eclectic. I am interested in vaccines and vaccinology (whatever that might mean) and I suspect most of my posts might harp on vaccine news overheard in talks, conferences or just the published word. I might just moan a little bit now and then about my experiences in a classroom and attending lectures after working for four years in a lab. But, the truth is that you might just have to wait and watch!!

On a personal note, just finished a terrible exam in epidemiology and am avoiding doing statistics homework by blogging.