A lot of successful drugs are hard to publish in good journal because sometimes the mechanism is not exactly known. Gleevec's first paper was published in cancer research (IF ~8). The compound itself with its target was published in Structures (IF~2). How about dimethyl fumarate for MS? It was published in journal I have never heard of. Just imagine that you tell the editors and reviewers that a glutathione depleting agent is going to work in MS. They will laugh at you. Btw, NIH still funds mostly basic research projects with promise of translational goal. However, if you look at majorities of the grants funded , I will still consider them basic research. For example (my personal opinion), saying siRNA/miRNA will one day be a therapy just not right. Chemists have been working over decades to solve that problem, but charged molecules just bad drug. Maybe we should stop funding those projects that studies miRNA mechanism(s).
This thread tells us that English is better than Chinese when talking about a person's age or status.
T*i
25 楼
要真能筛出药来也行。问题是很多就是找到个correlation 或联系到已知的 pathway 了事。我看它们根本就没想筛药,只是说要筛药。很多人的proposal最后几句话肯定是 "... lead to novel drugs or therapeutic approaches..." 一类的。
It tell funded
【在 A******y 的大作中提到】 : A lot of successful drugs are hard to publish in good journal because : sometimes the mechanism is not exactly known. Gleevec's first paper was : published in cancer research (IF ~8). The compound itself with its target : was published in Structures (IF~2). How about dimethyl fumarate for MS? It : was published in journal I have never heard of. Just imagine that you tell : the editors and reviewers that a glutathione depleting agent is going to : work in MS. They will laugh at you. : Btw, NIH still funds mostly basic research projects with promise of : translational goal. However, if you look at majorities of the grants funded : , I will still consider them basic research. For example (my personal
l*s
26 楼
我倒觉得是印证了黑格尔的“凡存在即合理”
about
【在 B******1 的大作中提到】 : This thread tells us that English is better than Chinese when talking about : a person's age or status.
A*y
27 楼
You can not screen for drug in an R01, because the reviewers will call you are going on a fishing expedition. I think 99% of R01 will have something like "lead to novel drugs or therapeutic approaches." However, NIH only have few study section review grants for drug development and all of them are infamous to give tough scores.
【在 T****i 的大作中提到】 : 要真能筛出药来也行。问题是很多就是找到个correlation 或联系到已知的 pathway : 了事。我看它们根本就没想筛药,只是说要筛药。很多人的proposal最后几句话肯定是 : "... lead to novel drugs or therapeutic approaches..." 一类的。 : : It : tell : funded
r*f
28 楼
晚上没吃好的吧,哈哈哈
【在 s***l 的大作中提到】 : 同汗。。看漏了几个字。
c*r
29 楼
My boss told me on the first class that drug discovery is not rocket science , it's much harder. Many trival things make find a new drug difficult, not just finding a valid drug target.
所以这玩艺还是必须 PhD 和 MD 密切合作才能像样弄出点东西来。纯粹MD主导的也 是浪费钱,到底他们的研究能力和时间都远远低于PhD们。我能想象出来的一个完整 的trans res story是这样的:老年痴呆症,clinical postmortem exam identifi ed plaques -> identified importance of abeta40/42 -> identified mutation s related to gamma /beta cleavages -> deposit of plaques in transgenic m ice -> clinical confirming of protective effect of loss of function of b eta secretase, 暂时这个链条断在这里了。如果有beta secretase inhibitor成功 上市,确实抑制老年痴呆症发病了,那就大功告成了。果如此,那我觉得是很完美 的trans res case了。这中间得消耗至少几百万人年,几百亿美元那,长期消耗战 那。
【在 c********g 的大作中提到】 : 所以这玩艺还是必须 PhD 和 MD 密切合作才能像样弄出点东西来。纯粹MD主导的也 : 是浪费钱,到底他们的研究能力和时间都远远低于PhD们。我能想象出来的一个完整 : 的trans res story是这样的:老年痴呆症,clinical postmortem exam identifi : ed plaques -> identified importance of abeta40/42 -> identified mutation : s related to gamma /beta cleavages -> deposit of plaques in transgenic m : ice -> clinical confirming of protective effect of loss of function of b : eta secretase, 暂时这个链条断在这里了。如果有beta secretase inhibitor成功 : 上市,确实抑制老年痴呆症发病了,那就大功告成了。果如此,那我觉得是很完美 : 的trans res case了。这中间得消耗至少几百万人年,几百亿美元那,长期消耗战 : 那。
c*g
52 楼
放在现在绝对可以。这可是很好的临床/流行病/基础研究来回互动的例子。就差药 厂射门了。
【在 s******y 的大作中提到】 : 那中间那几步也能按照translational research 的规格来申请钱么?
【在 A******y 的大作中提到】 : A lot of successful drugs are hard to publish in good journal because : sometimes the mechanism is not exactly known. Gleevec's first paper was : published in cancer research (IF ~8). The compound itself with its target : was published in Structures (IF~2). How about dimethyl fumarate for MS? It : was published in journal I have never heard of. Just imagine that you tell : the editors and reviewers that a glutathione depleting agent is going to : work in MS. They will laugh at you. : Btw, NIH still funds mostly basic research projects with promise of : translational goal. However, if you look at majorities of the grants funded : , I will still consider them basic research. For example (my personal
Most American MD PhDs don't do research after they graduate. Why? The lifestyle is a lot better and the pay is not much different. MD alone have an edge in applying NIH grant starting with training grant (it is separate from the Ph.D. training grant).
【在 A******y 的大作中提到】 : Most American MD PhDs don't do research after they graduate. Why? The : lifestyle is a lot better and the pay is not much different. MD alone have : an edge in applying NIH grant starting with training grant (it is separate : from the Ph.D. training grant).
s*c
62 楼
那可不一定,我怎么觉得现在做research跟制药相关的越来越多了?大部分的 biomedical research,说一千道一万,最后都要去screen drug candidates,这其实 是一个很好的方向,做机理去研究药物或疾病的分子机制当然很重要,在这个基础上 develop新的therapeutic methods或新的drug screening方法也很重要,比如发现新的 drug target,然后利用某些signaling特征或biochemistry,biophysics特征去做 medium- to high through-screening,或者发现以前的药物的side effects的off target,不管protein还是signaling events,然后设计实验去做counter selection去 modify现有的药或重新筛去发现更specific的candidates,这样虽然可能不能发什么好 paper,但是从NIH拿钱绝对不比发NCS要差。 我觉得这是很好的趋势,纯粹做基础研究去研究机理的要有,但是也应该鼓励多做一些 能够实际上或工业界上或医院里有希望用到的方法或手段或实验,就像做computer science的,大学里很多做basic research的,但是多数还是根据不同的市场需要去 develop具体算法或软件。很多人容易有自己的comfort zone,不太喜欢去跳出来改变 尝试比较新的东西或领域,NIH的方向就是逼迫大家都去多尝试跟clinics或者 pharmaceuticals相关的研究,具体做法且不说是否有效,但是我觉得这个思路还是应 该的。