From Bench To Bedside

There's good money to be made, by supplying the sick with the drugs of trade.
that's what it's all about, is'nt it? And the sickest thing about it, is that foreign investors are behind it all.
The entire world wants to bring down the U.S.A. and make it a european style conglomeration.
Corrupting our medical processes and flodding the market with bogus drugs is the real issue.
We so not want medications that have disclaimers about "side effects" that are worse than the ailment being treated.
Smoke pot, you will live loinger.

You've raised an important issue, I'll be addressing it starting with this post: http://samuraiscientist.blogspot.com/2009/07/why-isnt-my-disease-cured-yet-problem.html

I'm so glad I live in New Zealand - Medsafe and Pharmac, while not having much money, will do the clinical testing of a drug for a song. Same's true in Australia. Dear Dr. Stein - and all those true medical workers after improving quality of life - come and put your projects to work in NZ and Australia. US dollars go very far here, and the advantage of working here is that with suitable accreditation is automatically accepted. In addition, once a drug passes Medsafe in NZ and the TGA in Australia, the treatment becomes automatically exportable to the US and Europe, and then to Africa and Asia, where it can do much good.

Just a thought - yours from the Antipodes.

Ms. Begley does make the point of the issue precisely, and it concerns motivation. The motivation of our current health care system is profit. That which cannot be patented cannot be greatly profitable. Therefore, all research goes into methods which can be patented and therefore create returns. This is the essential problem with our current system. I believe strongly in capitalism, and that it has been, and remains, the great driver of human progress, but I also understand that it, like any system, has limitations, and here, we meet one. A truly healthy population is certainly more profitable to every part of our society, with the exception of one, the health care industry. This paradox lies at the root of our inability to rein in the system. Of course another problem with capitalism, one which must be closely followed, is the effect I refer to as 'Economic inertia', that being the disincentive to advance a technology which would render existing and profitable technology obsolete. The funding of scientific research is the other problem, and it is a symptom of the above. To do science, one requires money. There is no money in good science, only in patentable, salable science, which ceases to be science, and becomes simply Research and Development. This is not science, it is an investment. Investments are expected to generate a return.

Hi SoonerNat
If the nautral worlds holds all the cures to our aliments why has any "alternative" treatments cured anything. Furthermore people seem to think because something is natural its safer and better which really isn't true at all.

Case in point - your Niacin idea. Taking pharmacological doses of Niacin (1000-2000mg 2-3 times a day) does have beneficial effects mostly by raising your HDLs (while statins lower your LDLs)

However at that does it has numerous "side effects" including liver toxicity, dyspepsia, hyperglycemia (really bad if you have diabetes), higher levels of blood uric acid (gout) cardiac arrhythmias and birth defects in pregnant women. THese side effects can be quite severe (especially the liver damage potential) and that is why it is recommended to do this only by prescription under a docs supervision.

Most commonly it causes acute dermatological problems skin flushing, and itching.
There has been other "slow" release formulations of Niacin that mitigate the dematological effects however clinical trials have not shown efficacy with these formulations

There are currently clinical trials involving Niacin and Laropiprant. to mitigate the flushing but retain the cholestrol lowering effect. Niacin is often prescribed in concert with Statins which clincial trials have shown boost both the HDL increasing effect of Niacin and LDL lowering of statins then when given individually.

This Niacin example is a microcosm of the academic to clinical science going on- there is a tremendous amout of it. Unfortunately there is alot of ignorance regarding this and Sharon's article does more to reinforce it that inform.

I found it fascinating to see a spotlight on progesterone being used as a treatment, which b/c it isn't easily patentable, funding wasn't available for trials. Yet the week before, in Newsweek, women who advocate the use of bio-identical hormones, and celebrities (Oprah, Suzanne Somers) who do the same, were ridiculed and dismissed in a snarky tone for using compounds which have not been subjected to pharmaceutical trials. These substances are never going to enjoy the trials and studies that man-made compounds do, b/c of the money issue. Instead, pharma will manipulate molecules so that they may patent a drug. Meanwhile, patients lose out b/c possible simple, inexpensive and potentially safer alternatives are not explored because the ROI isn't there.

Ask why we have cholesterol lowering drugs that are expensive and possibly damaging, when my $5 bottle of niacin does it better? Why were women given premarin when bio-identicals do the job without the side effects that premarin caused? The pharm companies that have been able to patent bio-identical hormones have had to patent the delivery system, not the "drug" itself. The world is full of natural plants and substances that probably hold the cure to all of our ailments. But the present system requires them to become something they're not in order to merit trials and make it to the next new thing.

I agree completely that the current scientific research paradigm is not conducive to developing new treatments. However, I disagree with Sharon Begley???s assessment of the system. In presentations, scientific manuscripts, and grants, both PhDs and MDs do their best to tie their research to a disease or physiological process. As mentioned by other commenters, these grants are peer-reviewed and are not directly affected by NIH leadership. Successful grants generally have a solid translational component, and I strongly disagree with the suggestions in the article and by other commenters that basic scientists (namely PhDs) are shooting down promising translational research. While pushing translations research may be the main goal, the need to establish a mechanism or understand pathophysiology is not a trivial concern, for two reasons. First, the bench component of research establishes the molecular targets that can be pursued by the pharmaceutical industry or physicians. Second, by completely understanding a disease, better predictions can be made about long-term effects (or side effects) of a treatment.

Begley???s article also may confuse some people into thinking that the NIH is somehow responsible for the journal in which a scientific article is published. In reality, it has been my experience that people studying a topic will read articles regardless of the journal prestige, and weigh each manuscript on its own merits. While publishing in the top journals is certainly desirable, many people have made solid careers publishing reproducible, creative work in mid-level journals.

Good research requires a variety of backgrounds. PhDs spend years learning not only the complexities of a particular disease or process, but also how to do accurate, significant research. MDs do not have the same formal research training, but their experience in understanding diseases and patients is critical. Both groups are equally committed to helping patients, be it directly or indirectly. Excellent research results when basic and translational researchers work together and value each other???s input - not when divisive statements belittle the contributions or motives of basic scientists.

Sarah Ronnebaum, PhD
University of North Carolina

Sharon, you are - sadly - spot on with your assessment. As is Scott Johnson commenting on the many non-profits who are following the same old model. The Ludwig Institute for Cancer Research (LICR) started sponsoring and funding its own early-phase clinical trials a decade ago because our scientists weren't able to translate promising laboratory discoveries into the clinic under a typical granting model. This necessitated us establishing an infrastructure for clinical trials management; not cheap, but certainly do-able for large universities with an endowment. This practice also necessitated a change to how we review our scientists - authorship becomes less important in LICR academic review (because clinical trials don't often produce papers, and when they do, the author list is huge) and "ability to work in a team" becomes far more important. We can do this because we have the flexibility of funding our own scientific staff. Large universities with endowments, and possibly large non-profits, could also be doing the same thing.

Dr. Sarah L. White, Director of Communications
Ludwig Institute for Cancer Research

I and millions of others who suffer with chronic diseases appreciate Sharon Begley???s clear presentation of the ???Catch 22??? of medical research and its translation to patient treatments. I too hope that the Obama Administration chooses a leader of the NIH who is committed to solving this problem. Unfortunately, the failure of the NIH to make good on its promise to ???reward risk-taking and innovative studies??? is only half the problem. The other half is the hundreds of non-profit disease research organizations that have modeled themselves after the NIH and are failing in the same way to translate basic science in to patient treatments. Putting our hopes in a change of leadership at the NIH needs to be part of a bigger solution that includes revamping an entire system that rewards publishing in scientific journals instead of developing science that will lead to patient treatments.

Scott Johnson, President
Myelin Repair Foundation

Sharon,
I believe ulitimately we must start a discussion on the responsibilites of scientists and the administration for medical progress. At least in my environment funding is often regarded as private sponsorship to promote the career of a brilliant scientist. Even the fact, that patenting is essential to secure further development of a therapeutic concept, is still to often dismissed as being greedy. Thus, we must starting to work from all ends in order to arrive at the appreciation that creating value will require a joint effort. Having said this, the indentification of diverting revenue scenarios between individual must be adressed by innovative models for value creation, which probably constitutes an experiment itself. I realize that some most interesting academemic models foster interactions between departments at one specific institutions, but do not allow interactions with small biotech companies and "competing" acedemic centers. Thus, while the incentive to set up novel organisational measures to support translational research, we tend to create another bureaucracy that might be counterintuitive. My personal view is, that we actually need a radical change in our anatomies for value creating from science, which must actually enable symbiotic interactions with partners that converge in their interest to solve a problem, i.e. find a novel cure for a disease or a test for a particular condition. Obvioulsly these requirements are callenges to the scientist as well as to the technology transfer offices or licencing department at Big-Pharma. However, the real value might be created by organisations that assemble dynamically in a darwinian manner, and this appreciation must allow individual solutions and novel anatomies that ultimately enable translational research. In summary, it we wood loosen up the bureaucracy and decide about funding in a more opportunitic manner, this would already constitute a major step in the right direction. There are wnough researches (MDs and PhDs) that would rather work on a goal then one piece of a puzzle, but creating the approriate environment may not be acchieved by a sole paradigm shift. I have posted a proposal for discussion at www.InnVentis.com and would be most interested in cirtical comments and suggestions.

Sharon,
Thank you once again for speaking out on behalf of clinical investigators who labor hard in patient care and yet fail to see their efforts at funding programs that actually treat human patients--not laboratory animals, not culture dishes--get funded by the NIH. We need to hear your voice over and over again.
And no, Kevin, I do not think you know how "science" works. A grant may fail to earn a fundable score because it was poorly written, true, but very often a clinical grant is reviewed by bench scientists who have no clue what it is like to actually take care of a patient, do not know how to evaluate clinical research, and vote for basic science projects that they think are cutting edge and ingenious, but in fact which are very unlikely to make a damn bit of difference to Joe Taxpayer in his or his children's lifetime. But such grants will give such bench scientists the delusion that they are doing something meaningful. Maybe to their laboratory, maybe to their department, but for humanity....? Well, forget about it. I feel scientists generally lose sight that the H in NIH actually stands for "Health."
Should a clinical investigator actually submit a well-written research proposal that stands a strong chance of actually benefiting real people, based on well-collected preliminary data, the enterprise is just dismissed by a team of bench scientists as not being "innovative" enough. This is all too common, I assure you.
NIH is not done by "peer review." It is done by basic scientists, for the most part, who either are tenured and have the time on their hands, or by new basic scientists just setting out who want to assert themselves and micromanage a project that they do not take the effort to understand. I have seen so much misreading of grant applications (as well as misunderstanding of the mechanisms of grant funding, by reviewers who absolutely do not know the difference between an R03 and an R01) that it is nauseating. This folks is how your taxes are spent!

sharon I think your article is not indicative of actual scientific research.
Translational research funding is one of the biggest growth areas. Having patents is important for academic tenure. Increasingly industry is teaming with academic institutes and researchers in big money big research partnerships. Gates foundation and many other basic research funding agencies require clear paths to take your research to the clinic to even get funding.
Your few examples are not well explained why they weren't developed. I don't see one serious academic quoted in your article though to explain how things actually work. NIH grants are done by peer review not government workers. if that person couldn't get funding it most likely is because his work or grant was not adequately substantiated. Publishing positive clinical results in a top journal or lower journal has nothing to do with bringing a treatment to market getting the money to test it is. The private for profit industry is the realm where that happens not academia. It costs more then 200 million dollars to do full clinical trials for FDA approval. Do you realize that? Most drugs take 5-10 years from laboratory to clinic. Do you realize that? Do you realize that 70% of "promising" compounds that start clinical trials fail due to safety/efficacy issues. Ever since the thalidamide debacle establishment of safe doesage for any possible clinical drug is step one. That alone costs tens of million of dollars, meanwhile. There are literally hundreds if not thousands of compounds in the lab that show promise but you need more substanitation then that to start a multimillion clincal trial Furthermore Bush cut the NIH budget and drove a generation of scientists out of science. THat's a bigger hinderance.
Sharon if you want to write more articles like this in the future please contact me II'd be happy to fill you in on important background info.
Best regards
Kevin

It is interesting to note how health and medicine are intertwined. The presumption is that the NIH and similar medical establishments will somehow figure out how to keep us healthy. As a holistic health practitioner, medical researcher, and author of several books on illness prevention, I feel comfortable stating that you are looking for health in all the wrong places. Just look around. The reason we have a health care crisis is because we have a health crisis. People are getting sicker sooner. The present generation is predicted to have a shorter average lifespan than the previous generation.

We need an Office of Illness Prevention (OIP). Prevention is clearly the answer to the health crisis. In actuality, this country does not have a true health care system, it has a BigPharma-funded illness maintenance system instead, that treats symptoms with a litany of drugs and medical procedures. Even the term "preventive medicine" is an oxymoron. Why would anyone need medicine to stay healthy? There really is no illness prevention industry because there is no money in it - it is an anathema to the medical community, which has the distinction of being the third leading cause of death in the US. I strongly advocate the formation of a totally independent committee to operate the Illness Prevention Office. It must be independent of: the food industry, the industry-controlled FDA/EPA/USDA triangle, Big Pharma, the medical community, the health insurance industry, the Surgeon General, the NIH, and even the herbal and supplement industries. It would conduct government funded university research into areas that have been completely ignored, such as using nature as a paradigm for health (I have personally already funded such research with great results).

There would be an anti-revolving-door policy for OIP scientists as follows: anyone who has worked at one of the blacklisted agencies or industries listed above would not be able to work on any OIP project for at least a year after quitting their other post. All of the research from the OIP would be posted free of charge to the world community, and there would be open dialog and feedback between consumers and the OIP via the web. New professional designations would be created for Illness Prevention Practitioners, most of whom would have science backgrounds, but not necessarily medical degrees. Prevention should be part of a mandatory curriculum taught in every medical school that receives Federal funds (all of them). Ultimately, Illness Prevention would become a worldwide initiative, changing the face of health and health care as we know it. For a description of a program based on Nature to prevent and reverse illness, see my books: ???The Wellness Project???, or ???The Original Diet ??? The Omnivore???s Solution???.

Roy Mankovitz, Director
www.MontecitoWellness.com