QDIS Blog

I came across this excellent article in the Oct. issue of Scientific Computing and wanted to make people aware of it.

R&D’s Dirty Little Secret

This article by Robin Y. Smith comments on the elephant in the room for most pharmaceutical companies as well as fine chemicals companies in R&D. The problem is the incomplete and sloppy notebooks. This is the elephant in the room that no one wants to talk about.

He found, based on auditing 10 years of lab notebooks from a top 10 pharmaceutical company, that 15% of the pages had major problems such as being illegible, incomplete, or had some other error meaning the experiment could not be reproduced.

In some of the worst cases, 60% of the pages were deemed not reproducible and this did not count vague phrases such as “worked up in the usual fashion”. If there was ever an area in R&D that could is ripe for improvement, this is it.

Cases of scientists being judged on the number of notebooks filled leading to “dry labbing”. This is where lab notebooks are padded with many planned experiments which are never carried out. Just looking at the number of notebooks filled these scientists appear to be very productive.

I’ve always been frustrated when trying to find info in others lab notebooks. Lack of table of experiments in the front resulting in having to flip through the notebook until you find the right result. Not knowing which of dozens of lab notebooks contains the information you need. Experimental results such as chromatograms or NMR printouts not being in the notebook or even worse, being in another 3 ring notebook that isn’t identified by anything other than a volume number. I have spent too much time trying to find information rather than analyzing and coming up with new experiments.

The problem is at its worst in discovery or med chem groups but I will note that even in most process development groups it is better but still not great.

The article doesn’t comment on stats for use of phrases such as “typical work-up procedure”, “standard procedure”, etc. without referencing some other document or lab notebook page. As a process development chemist, I always found this sort of documentation mind boggling. I had one case were I was repeating a drug discovery process on a small scale to become familiar with the process and at one point encounter a horrible emulsion. I went to the discovery chemist and asked if this is what he saw and if so, what did he do about it. He said yes, he saw that too and he just left it to sit overnight until it separated. This was NOT noted in his lab notebook! Needless to say, this required a lot of work in process development to get a process that would work on even a 22L scale.

The other complaint I have is even when a work-up procedure it listed, most of the time in my experience, the procedure did not list volumes of solvent or aqueous washes used. In another case, it said the organic layer was washed repeatedly with water. I found out that it was washed 15 times with huge amounts of water each time!!! None of that was documented. When I asked the chemist, they said all these washes with that large of volume of water was indeed required to get rid of some inorganic salts. Ends up, using equal volumes and doing 3 washes worked fine.

All of these are huge problems and I do indeed think that electronic notebooks are needed. I’d like to see them used much more widely than they are currently and think this could go a long way towards increasing R&D productivity.

I should point out that the author, Robin Y. Smith is Vice President of Product Strategy at Symyx Technologies and they make software for electronic notebooks.

Technorati Tags: documentation, lab notebooks, R&D productivity

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In getting caught up on reading some trade magazines I recently came across an article that interested me. Regular readers know I have an interest in paleontology and dinosaurs. In Scientific Computing there was a brief mention of a study done by Steve Wang a statistician at Swarthmore College who has calculated that most dinosaurs that ever existed have NOT yet been discovered. He also calculated that 75% of those unknown will be found in the next 60-100 years. This means it will be an exciting time for paleontolgy for the next 100 years.

This was published in the Proc Nat Acad Sci. and here is the abstract. The article is Estimating the diversity of dinosaurs (pdf).

Technorati Tags: dinosaur, paleontology

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This stem cell article appeared in the Washington Post about a week ago and I am just now getting around to commenting on it.

Democrats Plan to Revive Stem Cell Bill - washingtonpost.com:

I really think there are other things I’d like to see at the top of congresses agenda. While I think this is important, I doubt there would be enough votes in congress to override a certain presidential veto. The president has already veto it once and there is no reason whatsoever to expect it not to happen again. However, there could be consideration beyond just getting the bill passed as is common in politics. This may be a way for Democrats to benefit from the debate and ensuing media attention after a second veto and would certainly bring the issue to the forefront for the presidential elections in 2008.

My impression is that the majority of people think there should be funding for such research. It brings to my mind the times when the church and other groups felt that cutting up human bodies to understand the various system such the the respiratory system or the circulatory system was unconscionable and an abomination. I don’t know of anyone today who would say that was wrong given the enormous impact of such knowledge on medicine today.

I truly hope stem cell research can be funded and continued in order to keep the US at the forefront for such research.

Technorati Tags: stem cells

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I always like to see it when a chemist actually gets to lead a major project. Now, Ralf Kaiser a physical chemist at the University of Hawaii will lead a NASA project to study the atmosphere of Titan, one of the moons of Saturn.

Chemist to lead study of Titan’s moon - Yahoo! News

This five year $2.5 million dollar grant from the National Science Foundation will use the NASA infrared telescope located on Mauna Kea on the big island of Hawaii. The hope is that by studying the atmosphere of Titan insight may be gather about earth’s early atmosphere. One of the major issue to be investigated is to see how hydrocarbons in the atmosphere absorb damaging ultraviolet radiation from the sun and preserve some compounds that are may play a role in the early development of molecules essential to life.

The first workshop is scheduled for February of 2007.

Other Resources

• Reaction Dynamics, University of Hawaii at Manoa
• Titanworkshop 2007
• SPACE.com — Titan: A World that Never Grew Up

Technorati Tags: chemist, NASA, space, Titan

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A recent article in Business Week caught my eye. It talks specifically about the biotech industry complaining that too many recent college graduates have little understanding of what was required of them in the real world.

Biotech’s Beef

The main complaint is that they lack some technical skills and have no understanding of the concepts of quality control and regulatory issues. I personally think there are several reasons for this and I’ll discuss each of them below.

Let’s first talk about colleges. There are two major reasons that colleges and universities don’t do a better job at preparing students for jobs in technical fields such as biotech. In regard to technical skills, many colleges do not have the sophisticated equipment needed to train their students. Money is a constant problem and my personal experience is that the equipment in colleges and universities is sometimes decades out of date. This is especially true for expensive equipment. When I was studying as an undergraduate in the early 1980’s, we didn’t even have a working mass spectrometer to use in the advanced analytical lab. We barely had an NMR (60 MHz continuous wave). When I went to graduate studies at a large state university known for its chemistry program, the situation was much better, but still many of the day-to-day instruments such as the gas chromatography equipment was from the 1970’s, although we did have access to high filed FT-NMR.

The second reason that colleges and universities don’t do a better job has to do with make up of those teaching, i.e. the professors. My experience is that many of them have never spent anytime in industry so how can they teach what they don’t know or understand themselves? My personal experience was that in tens years of college, none of the science professors I took a class from or who I knew had ever held a job in industry. They all had graduated, gone on to a post-doc position, and eventually worked in a college or university. It is practically impossible to talk about topics such as the regulatory environment or quality control without any experience in those areas.

In some cases it goes beyond jut not knowing; there are some who seem to have an attitude of contempt for those in industry who may express a desire to teach. Many professors have a certain disdain for industry and those outside their small cliche. As an example, a small community college in my area had an opening for a chemistry professor. I applied and was told that I they had “grave concerns” about my teaching abilities since I hadn’t “taught” for over 14 years. I replied that although I had not taught in a college or university since my graduate school days, I did a lot of teaching in my community, my church, my corporate life and even taught paid training courses in my own consulting business. This didn’t count according to them. They seemed to feel that the lack of teaching experience in the exact environment of a college outweighed the practical, real world experiences I could bring from industry. After several months of not hearing form them, I called and was told they had forgotten about my application and would send me a notice in the mail soon. A couple of days later, I received a very short rejection notice.

All though universities and colleges are to blame for much, some of that blame also lies with biotechs themselves. In many cases, they seem to want fully trained robots that they employ without difficulty. One of the first things cut in down times at companies are the training budgets. Also, there is much talk about employee loyalty and that if they train someone, they will leave for another job before they benefit from the training. This may be true, but, when this is brought up to me, I always ask when was the last time they had a lay-off due to a temporary set back. Invariably within the last 16 months or so they have had some sort of major “restructuring” which included people losing their jobs. Today, companies that complain about employee loyalty but then have lay-offs every time there is a down turn, have no room to complain. To make matters those who have to find other jobs,find upper management at their former company gets rewarded for getting rid of employees?!

Then end result of the short-term short-sightedness of many companies is that the employees are over-worked and pay doesn’t keep up with the increased responsibilities. The motto of corporations today seems to be” do more with less for less”. This means that those workers don’t have the chance to work as an adjunct professor at their local college or university (see my ideas for improving this situation below).

Here are a few of my ideas for improving the situation.

1. Allow industry folks to have a sabbatical to teach in a local college. This could be for just a portion of a semester or quarter; maybe three or four weeks.
2. Industry should encourage colleges to hire adjunct industry faculty (see #1 above). They could earmark money for equipment and then set up a schedule for them to have access to that equipment. At a former university I attended this was done successfully. The company helped purchase a new high-field NMR and in return, they were given one day a week full access to the machine. Then they also did not have to worry about routine maintenance. That was taken care of by the university.
3. Industry needs to set up and effectively run programs to give students industrial experience. This is more than just allowing an intern to flounder for 6 weeks in one of their labs. THere needs to be a culture of showing students what the industry is about if industry is serious about solving this problem.
4. Expose college faculty to industrial positions. Encourage industry to accept professors during their sabbatical to learn about the industry and the various roles needed. This also means industry has to be willing to give this sort of experience to professors.

I am hopeful that the situation can be improved, but it requires more than just talking from both sides. There is a need to implement these sorts of programs in order to keep America competitive in an increasing technological society.

Technorati Tags: science education

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Some recent reports claim that newer more expensive anti-psychotic medications may be no better than older cheaper ones.

• ScienceDaily: Second-generation Antipsychotic Medications Appear To Offer Little Advantage Over Older Drugs
• Newer Schizophrenia Drugs May Be No Better - Yahoo! News

Both these news stories refer to a recent article in the October issue of the Archives of General Psychiatry which showed that after a year, there was no significant difference between those on older medications (118 patients) from those on newer medications (109 patients). iI was based on a quality of life score and after a year the group on the older medications were 53.2 and with the newer medications was 51.3.

Now granted, the number of patients is small but the results seem to indicate that older cheaper medications could be used in some cases. The thing I think that always needs to be kept in mind is that the results vary with individual patients and this is the reason I have reservations about health plans that try to “encourage” patients to use older medications when studies such as this come out. I understand the need to have access to affordable drugs, but i also firmly believe the decision on what to prescribe should be between the patient and their doctor. I understand the need for a preferred formulary, but think that the hurdles put in place up to prevent the use of newer mediations in some cases is detrimental to the patients health. If a patient tries the first generation drug and it either does not work effectively for them or has side effects, then there should be an easy way for them to get access to the second generation drugs. I some cases, the health insurer may refuse to pay for any costs of these newer drugs. While I think paying a larger co-pay is reasonable, not covering the drug at all is not.

Technorati Tags: antipsychotic drugs, schizophrenia

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Drug researcher reports that a new peptide fragment shows activity against influenza A including the H5N1 avian flu in vitro. The fragment is only 20 amino acid residues

New drug provides effective defence against bird flu

The above headline is misleading since the work has only been done in vitro and not in patients. I don’t have access to the actual article so I can’t comment on the amino acid sequence.

The peptide seems to prevent viruses from entering the cell and the survival rate for the animal models was 100%. While this is promising, there have been many cases of drugs showing excellent activity in animal models but never working in humans. It will be interesting to see if this develops and goes beyond the preclinical stage. Since this work comes from the University of Wisconsin-Madison, it would take a deal with a pharmaceutical or biotech company before it moves to the next stage.

Sources

Abstract: INHIBITION OF INFLUENZA VIRUS INFECTION BY A NOVEL ANTIVIRAL PEPTIDE THAT TARGETS VIRAL ATTACHMENT TO CELLS — Jones et al., — The Journal of Virology

Technorati Tags: avian flu, bird flu, antiviral, virology

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One of the topics that the FDA will need to deal with is the whole topic of nanotechnology. It has been a hot topic recently due to an public meeting on this topic recently (Oct. 10, 2006).

United Press International - Health Business - Analysis: FDA comes up short on nanotech:

The above UPI report was released before the FDA meeting mentioned above. This paragraph caught my attention.

Taylor noted that the FDA’s budget would have to be increased by 50 percent to bring it up to its 1996 level. And the agency’s budget for next year won’t improve without action by Congress. President Bush’s 2007 proposed budget will increase the gap between responsibilities and capacity to 56 percent.

Given how important the FDA is (they oversee 25% of the gross national product) and how much work they have to do an increasing budget gap is cause for alarm. Especially in light of the recent rash of problems with spinach and lettuce which seems to indicate that there may not be enough oversight in this area. Add to this trying to keep up with the rapid advances in many areas particularly nanotechnology and you have a recipe for disaster.

There are at least 320 products using nanotechnology already on the market although many of these fall outside the purview of the FDA and about 200 products that would fall under the FDA’s rules are under development.

This is another example of science leading public policy when it comes to cutting edge technologies. I have some experience in this regard when I worked for a company developing polymer based drugs and educating the FDA on how the polymers were characterized. We had to educate some FDA folks as to what the analytical methods were we were using and how the technology worked and why we were using as well as other methods we tried that may not have worked and why they didn’t work.

FDA told to watch nanotech products for risks - Yahoo! News

The above story focuses on the fact that the FDA is ill equipped to deal with nantech products and the possible safety questions. The FDA has created an internal task force to look into nanotech and should have a report out in about nine months (mid-summer 2007). While I applaud them doing this, it seems to be quite late to the party. Nanotechnology has been popular for some time now and many products have been developed based on it. As quick search of Google news archive on nanotechnology shows articles back to March 1991.

A quick search for nanotechnology in Google trends shows searches for it being fairly flat but the really interesting fact to note is that the US does not even appear in the top 10 cities searching for this term. india occupies 6 of the top ten cities

Looking at the trends by country is even more revealing.

Another interesting tidbit is that Iran is number two for searching for the term nanotechnology. The US is down at the number 8 position. I’m not sure what to make of this but it is interesting.

Some other news stories:

• FDA gets mixed advice on nanotechnology
• Experts give FDA advice for regulating nanotechnology
• Nanotechnology: It’s Knocking on FDA’s Door

Other Resources

• FDA web page on Nanotechnology
• FDA nanotechnology - Yahoo! Search Results
• FDA nanotechnology - Google Search

• Yahoo! News Search Results for fda nanotechnology
• FDA nanotechnology - Google News

Technorati Tags: FDA, Google Trends, nanotechnology

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Today seems to be genetic testing day on this blog. Reuters had a report recently on a new genetic test that will likely find great use in oncology.

Test to predict response to chemotherapy drug | Top News | Reuters.com

This is exciting news. Basically, people with lung cancer that express a gene called ERCC1 will likely not respond to cisplatin. For these patients, other chemotherapy should be considered. While not proven yet in large studies, this is interesting and might in the future allow oncologists to select the proper treatment based on genetic testing. Since chemotherapy can have devastating side effects, it is important to get a treatment that has the highest probability of success for a given patient. If you are one of those who would not respond to a given drug, regardless of how effective it is in the given population, you would want to know that before going through a treatment with nasty side effects that won’t work for you. The fact that 75% of people respond doesn’t do you any good if you are in the 25% group. I also think that until recently there seemed to be much more emphasis on finding genes that indicated a person would respond to treatment rather than identifying those who would not respond. I think both are important and in the case of oncology identifying those who would not respond is very important to avoid going through a treatment that causes serious side effects but with no really benefit.

Another example is the HER2 and Herceptin. Women with early breast cancer who have higher levels of HER2 are at significant increase risk of the disease recurring and worst prognosis. However, these very patients respond quite well to treatment with Herceptin. This test is routinely used now for women with breast cancer.

I see this as the future of personalized medicine and not the process of making a specific compound for an individual. Finding out who will and who will not respond to a given treatment will be of tremendous importance to medicine in the 21st century.

Other Sources

• HER2/neu - Wikipedia, the free encyclopedia
• NEJM — HER2 and Responsiveness of Breast Cancer to Adjuvant Chemotherapy
• Adjuvant Trastuzumab: A Milestone in the Treatment of HER-2-Positive Early Breast Cancer — Baselga et al. 11 (Supplement 1): 4 — The Oncologist
• Low ERCC1 Expression Correlates with Prolonged Survival after Cisplatin plus Gemcitabine
• Chemotherapy in Non-Small Cell Lung Cancer — Lord et al. 8 (7): 2286 — Clinical Cancer Research

Search Results

• her2 - Yahoo! Search Results
• her2 - Google Search
• ERCC1 - Google Search
• ERCC1 - Yahoo! Search Results

Technorati Tags: chemotherapy, cisplatin, genetic testing, Herceptin, personalized medicine, trastuzumab

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Lately I’ve been thinking about genetic testing and its proliferation recently, especially those available by mail. A lot of those advertising are paternity related but others cover a wide variety of diseases.

CBS News recently had a good article about this.

Home Genetic Tests For Disease - CBS News

One of the problems with these mail-in testing is that, in the vast majority of cases, there is no counseling involved. What about the situation where a woman has sent in a DNA testing for breast cancer and the results come back that she has the gene in question. What does this mean to her? Does that mean she will definitely develop breast cancer? All of these are sure to be though about and without any access to genetic counseling how are they to get answers. Hopefully, most would turn to their primary care physician but some studies indicate they aren’t informed on what these various genetic testing results mean.

Seems that in some cases, these are like the old snake oil salesmen. They claim to test for all sorts of things but don’t disclose the limitations. There is also the worry of counseling if the results are potentially devastating. THen there is the fact that this industry is largely unregulated.

I think this area will be one that sees a dramatic increase in use in the next few years but like any tool, it needs to be used correctly. I can’t say, based on what I know now, that I think the mail order genetic testing is worth the cost, both monetary and psychological. This is another case where science is far ahead of public policy.

Other Resources

Genetic testing - Wikipedia, the free encyclopedia
DNAPolicy
Talk to Your Doctor or Healthcare Practitioner About Home Genetic Tests

Technorati Tags: genetic testing

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