Infectious Disease: What Can Evolution Do For Us? forum: topic
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Back to basics?
Kausik Datta
Monday, 27 October 2008 22:10 UTC
How about the basics of scientific research? Like scientific rigor? What I am about to say is absolutely my personal opinion, based on hearsay and unsupportable anecdotes. But at the end of it, I ask a legitimate question.
From the early to mid ‘90s, a lot of investigators had jumped into the ’HIV bandwagon’ – not only in the US, but in other countries as well. The HIV infected immunocompromised patients were live receptacles for many other infections, then considered ‘opportunistic’, and the focus on HIV research was so expansive and urgent (rightly, of course) that it encompassed easily ‘HIV-associated infections’. Which was fine. But gradually, perhaps, it resulted in the focus getting diluted, and among the first affected was funding. Many investigators found that their otherwise important disease research was in the danger of being under-funded or non-funded unless a link – however tenuous – was made with HIV. When they got the grants, they continued to work in their own existing areas, with just a passing nod to HIV. The big name Pharma companies were pushing money into anti-retrovirals and cocktails, once again, with barely a passing nod to basic HIV research. And then there were the so-called HIV researchers, who knew that their livelihood and continued funding depended upon tenaciously maintaining their link to HIV, and therefore concentrated on diagnostics, therapetics and such like, but less on the basic biology.
Some exciting discoveries did come about during this time through some enterprising investigators. But for myriads of others… Well, here is the hearsay. A friend of mine works in the lab of reputed HIV researcher in big city. When he joined the lab, he found that the research was extremely haphazard with no strictness in record/result keeping, and the scientific standards in that lab were low enough to accept arbitrary results from assays done with no controls if they jived well with the hypothesis, and disregard equally arbitrary results, if they did not, all without any further scrutiny.
Now that is a pretty serious accusation, to my mind, and for want of hardcore evidence, I would not want to make a case of it. But this, taken together with the current status of HIV research (read ‘repeated failures of testable hypotheses’), raises severe doubt in my mind as to the true direction HIV research has taken.
Now the question: Given the amount of money that has been put into it, the time spent and the number of people involved all over the world, why have we not yet been able to demystify HIV? Why have we not found a sure shot cure? Is HIV the bin Laden of the microbial world? Why do we fall back upon the same excuse that the virus mutates rapidly to avoid eradication? I find it unpalatable to accept that all the scientific minds focused on this crucial work still have not made too much sense of it.
Perhaps I am being too harsh. As I said, there have been several exciting discoveries of the mechanisms associated with HIV infection and AIDS. The availability of the multi-drug cocktails has enhanced the life-expectancy of the HIV infected, allowing many of them to lead nearly normal lives. But there is so much more that should have been done, that were not done… yet.
I guess I am just frustrated that mankind seems to be losing the battle with ONE elusive virus, given the unchecked AIDS rampage in Africa, Southeast Asia, and elsewhere. Compounding this outrage are the growing numbers of that evidence-starved, unscientific and frankly crazy gathering called ‘HIV deniers’. If 20-odd years of HIV research cannot provide a definitive knock-out answer to this type of wackaloonery, what will? And when?
Updated 27 October 2008 22:11 UTC
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Virus research is hard.
How many diseases caused by viruses have we eradicated? (One; potentially 2) How many are there in all?
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I agree with Richard – it’s hard. And I think that you are being a little harsh in your assessment: there have been some spectacular gains in the therapies developed against HIV, particularly the antiviral drugs. Alas, none of these is a cure but they do have a big impact on life expectancy.
The downside is that progress towards a vaccine has been agonisingly slow and still appears to be out of reach. I believe this is in part because the pernicious effect of HIV is to infect cells of the immune system that we would hope to stimulate with any vaccine.
And as for your last point:
If 20-odd years of HIV research cannot provide a definitive knock-out answer to this type of wackaloonery, what will?
I’m afraid there is still no cure for human nature… but on the whole that’s a good thing!
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Kausik: you say that what you write is my personal opinion, based on hearsay and unsupportable anecdotes.
Earlier this month, Nature published a web focus on Frontiers in HIV/AIDS. It presents a selection of recent research papers in Nature, a Feature highlighting the expanding HIV epidemic in China, a Review article covering the challenges in vaccine development, and a Commentary calling for better communication and cooperation between vaccinologists, virologists and experts in innate anti-viral immune responses.
Maybe you would like to read that, or some other scientific literature/discussion such as the very good NIH AIDS information website, and formulate some more balanced, contextual suggestions, rather than making “pretty serious accusations that lack hard-core evidence” and various other vague assertions which are in your own words “hearsay”.The “big name Pharma companies” that you denigrate were at the time focusing their efforts on what seemed to be the most productive approach given existing knowledge, and the “cocktails” you belittle are effective, within limtations. If all HIV/AIDS research at the time, instead of just some of it, had focused on basic research, who knows how many more people would have died?
The fact that a disease is complex entity that has no simple “cure” along the magic bullet lines you describe (and which has echoes of a similar conversation here in which Richard Grant and others drew attention to the complexities and frustrations of cancer research) does not mean that there is anything underhand going on.I cannot understand what is motivating your post, frankly.
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So the questions I posed under ‘back to basics’ are indeed drawn from some of the sources Maxine mentions and several others. There seems to be a general view across the research community that a co-ordinated approach is needed that tackles the HIV vaccine research challenge. As a non-expert, it seems to me one of the greatest of these challenges is the quest for a prophylatic vaccine. One would assume that as well as looking at the retrovirus itself, to identify potential vaccine targets, one also needs to gain a deeper understanding of the biology of how HIV (and retroviruses in general) iteract with the human immune system, from infection through to disease manifestation and beyond. Thus my questions aren’t so much about defining a ‘magic bullet’ but more about balancing current post-infection strategies with a basic research approach that may not have any impact on vaccine development for a very long time…
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Richard says:Virus research is hard. How many diseases caused by viruses have we eradicated? (One; potentially 2) How many are there in all?
Richard, forgive me, but your comment brought a smile to my face. A few years back, I came across a video of George W Bush on YouTube, which was made by splicing news footage of the numerous times he had said “being a president is ‘hard work’”; the video ended with a message, ‘Go home, George, take some rest.’
No, but seriously, I do understand that virus research is hard work. I don’t work with viruses (only humble bacteria and fungi), but I have virologist friends who have brought my attention to the complexities, problems and occasional successes in virus research. It is true that we have not been able to eradicate enough viruses, but would you say that they all have the same payload as HIV, even some of the more infectious and dangerous viruses such as HBV/HCV or Ebola? The menace of HIV in terms of life-hours alone should justify the focus on its research.
All I am doing is calling for a greater scrutiny of that research – to honestly evaluate the lacunae as well as the successes, so that a fresh direction may be gained, and efforts, redoubled.
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Stephed says: And I think you are being a little harsh in your assessment.
Stephen, I admitted as much, that I was perhaps being unduly harsh. But I assure you that it is a harshness borne out of frustration, which I think you partly understand – because you recognize that the fruits of the HIV research have been agonizingly slow in coming. I believe I did mention in the penultimate paragraph that there have indeed been some amazing work towards elucidating the mechanisms of the disease, as well as in the therapeutic arena. I applaud that success, but seem to find that woefully inadequate given the magnitude and scope of the problem, and the amount of money, time and efforts that have been put into it.
Come on, how long should a virus be allowed to outwit humanity’s best minds? :)
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I applaud that success, but seem to find that woefully inadequate given the magnitude and scope of the problem, and the amount of money, time and efforts that have been put into it.
This sentiment applies just as much to cancers (see the link in my response above) and to many other biological processes and diseases. The common cold virus, for example, is fiendishly clever and has defeated attempts at a “cure”. Ditto ’flu virus.
I think this discussion would be a more construtive precursor to the Talk Science evening (or in any case) if Kausik could make some specific points instead of casting vague general aspersions on a huge range of efforts that make up a whole field.
The answer to the ‘outwitting viruses’ question is probably that they will live longer than us – along with the insects. ;-)
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Maxine, are you or have you been an HIV researcher? You write with passion in favor of HIV research. I am in favor, too. Please understand that. But I hope that the passion will not cloud your honest appraisal of the situation or influence your ability to accept criticism. Please allow me answer your counterpoints.
…Nature published a web focus on Frontiers in HIV/AIDS… a Feature highlighting the expanding HIV epidemic in China, a Review article covering the challenges in vaccine development, and a Commentary calling for better communication and cooperation between vaccinologists, virologists and experts in innate anti-viral immune responses.
I am glad you mentioned this. Did it have to take more than 20 years of HIV research to realize the need for ‘better communication and cooperation between vaccinologists, virologists and experts in innate anti-viral immune responses’? Don’t you think that the amount of money, time and effort already spent should have ensured this by now?
Yes, I did put in that disclaimer at the beginning, because what I mentioned about the conditions of research in some particular labs was indeed hearsay and unsupportable anecdotes. I am familiar with the positive spiel of NIH on HIV research; I have been to enough Fauci lectures for that, and I applaud this effort wholeheartedly. But what I learnt from the ‘hearsay’ – compounded by my own experience with grants, funding agencies and labs working in HIV research – cast seeds of doubt in my mind that everything was as hunky-dory as it should be.
The “big name Pharma companies” that you denigrate were at the time focusing their efforts on what seemed to be the most productive approach given existing knowledge, and the “cocktails” you belittle are effective, within limtations.
Wow, Maxine, peace! I never denigrated or belittled the efforts of the Pharma companies or the life-saving cocktails that their research produced. Please read the penultimate paragraph of my original post. But surely you are aware of the tremendous amount of money, time and effort that has been spent already (and justifiably so) in HIV research, not just in the US or UK, but all around the world! Wouldn’t you expect a deeper knowledge and better understanding of the basic biology of the virus in 20-odd years, so that we would not have to hide behind terms like ‘existing knowledge’ and ‘within limitations’?
The fact that a disease is complex entity that has no simple “cure” along the magic bullet lines you describe (and which has echoes of a similar conversation here in which Richard Grant and others drew attention to the complexities and frustrations of cancer research) does not mean that there is anything underhand going on.
Please don’t conflate HIV research with cancer research! The biggest challenge facing cancer research today is probably self-non self discrimination and targeted delivery of therapy to the cancerous cells. Am I right in that? HIV is a foreign entity; it is not endogenous to the host body. Do you honestly think the principles behind the research focusing on these two areas are the same?
I did not indicate, nor do I think, that there is anything underhand going on in the field of HIV research per se. What I pointed out, on the other hand, was that the lack of focus on the basic biology of the virus, together with the lack of a close scrutiny of the scientific rigor of the methodologies used in basic HIV research, is what has impeded progress in this field for this long.
HIV research, as you must be aware, more so than many other fields, is not only bench-work, but has a significant emotional and financial component as well. Oftentimes, these components tend to overshadow the scientific component, effectively diminishing critical thinking, good judgment, and sound scientific methods. It happens in other fields of research as well, but for HIV, it is particularly true.
As a scientist, wouldn’t you be wary – in general – of endeavors that lack scientific method, thinking and integrity?
I cannot understand what is motivating your post, frankly.
As I said, simply frustration… at having a single disease entity ravage nations and destroy countless lives, yet the best minds of us not having been able to do anything about it. And the fact that newer challenges are cropping up to compound the misery – not only in form of an evasive virus, but, more significantly perhaps, in form of an infectious idiocy named ‘HIV denialism’ that willfully underestimates the menace of HIV and seeks to belittle the overall field of HIV research. I reiterate my comments from the first post, when I ask that after 20-odd years of HIV research, can we not expect some convincing, illuminating answer that would effectively address these issues? Is our HIV knowledge-base deep enough yet to do that?
Maxine, don’t you think this is a legitimate question?
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OK, I am bowing out of this one after this reply. I want to set a few things straight.
1. I am not conflating cancer research with HIV research. I am saying that these areas, along with many others, reflect complex problems that do not have the magic-bullet solutions that you seem to think should occur after much investment. Indeed, the problems are not only biological: referring to the last paragraph of your post about AIDS in Afrcian and Asian countries: education and religion for example are highly relevant factors in this regard.
2. I have not ever worked in HIV or AIDS research but I am broadly scientifically literate and I have a presonal aversion to arguments that contain innuendo and unsupported, hearsay allegations. I do not think posts containing such material are conducive to constructive debate, because the conversation gets sidetracked into people’s prejudices. I deplore innuendo about some unidentified lab that some unidentified friend claims is having some unidentified poor practices. I think this is irrelevant to this or any other discussion; in my view, remarks such as these should either be withdrawn or substantiated.
3. Your comments about the recent Nature web focus are a case in point. Perhaps you might like to read the articles before being sarcastic about a few words of summary?
4. I do agree that your final question is legitimate. It is a pity that you had to preface it with slurs, which detract from its purpose.
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I guess Maxine will not be reading this further. But since she mentions setting the records straight, I shall add this last post of mine to this thread.
1. education and religion for example are highly relevant factors in this regard.
Absolutely. Only that HIV researchers as such cannot do anything about it. I was trying to point out whatever could be done by the researchers, from exclusively the research angle.
2. I deplore innuendo about some unidentified lab that some unidentified friend claims is having some unidentified poor practices. I think this is irrelevant to this or any other discussion; in my view, remarks such as these should either be withdrawn or substantiated.
Well said. Had this been a court of law, or a scientific journal, or an enquiry committee, I would have indeed kept my mouth shut if I could not present solid evidence to support my claims. However, my understanding was that this was a blog where I could raise a valid concern, and the fact remains that what I gleaned from my friends did indeed alert me to a new angle of the overall problem, related to poor laboratory practices in some labs. I think I have been emphatic enough in my initial disclaimer about the unsubstantiable nature of my observations.
3. Perhaps you might like to read the articles before being sarcastic about a few words of summary?
I am sorry if it came out sarcastic; it was not intended that way. But those phrases have indeed been hackneyed to death, and to be honest, I don’t think that occasional critical retrospection ever hurts any scientific project of merit.
4. I do agree that your final question is legitimate. It is a pity that you had to preface it with slurs, which detract from its purpose.
I am glad you agree with my question. But is there an answer? Can there be? If you perceived any slur, I am sorry about it. I was trying to voice my concern within reason. But thank you for being patient with me.
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