#UCDavis neurosurgeons conducted experimental surgery w/o IRB approval

Not really sure what to say about this other than that this story should be read by many/all who are interested in medical research and/or UC Davis: 2 UC Davis neurosurgeons accused of experimental surgery are banned from human research - Investigations - The Sacramento Bee.

UPDATE 7/23.  Added a summary: Two UC Davis neurosurgeons were treating terminally ill brain cancer patients with an unapproved, experimental treatment that is referred to as "Probiotic Intracranial Therapy for Malignant Glioma".  The treatment involved purposefully infecting patients brains with a bacterium Enterobacter aerogenes apparently because of prior anecdotes and case reports that suggested that patients with these brain cancers who also had brain infections might live longer than those with the cancer but without the infection.  According to the article, there was an investigation at UC Davis into the practices of the surgeons.  It was determined by UC Davis that they did not have IRB approval to carry out the treatments and that there were some other issues with the practice going on.  At the conclusion of the investigation UC Davis wrote a letter to the FDA detailing the case and has banned the two neurosurgeons from performing medical research on humans.  Read the article for much more detail and see the link below.

Many interconnected issues in here involving IRB approval, human experimental treatments and informed consent, UC Davis, and even "probiotics".  Still taking it all in ...  Uggh ...

Other stories posted in the SacBee at the same time:

• Banned UCD doctor is one of UC's highest paid employees
• Other cases
• Confidential letter: UCD outlines doctor's 'serious' offenses (.pdf)

See also

• Surgeon fights UCD with a federal suit - Fighting suspension, he ...
• Northern California Hospital Blog
• Sacramento Bee, The : Board seeking more clout over guest...
• Sacramento Bee, The : Surgeon fights UCD with a federal...
• UC's payroll in 2009 shows spending hike - UC Merced -...
• Top 10 earners list - Compensation at the University of California
• Muizelaar to hold first Julian R. Youmans ... - UC Davis Health System
• Youmans furthers his leadership in neurological surgery | Davis ...
• Best Doctors - Sacramento Magazine - December 2011 ...

Draft post cleanup #4: Gut microbes and cancer

Yet another post in my "draft blog post cleanup" series.  Here is #4:

Interesting article in the Scientist August 1, 2011:
Sharing the Bounty | The Scientist by Michelle Rooks and Wendy Garrett.

It is based on an article from the journal F1000 reports by the same authors.

The article in essence reviews other studies that suggest a possible link between microbes in one's gut and the risk of development of certain cancers.  It is worth a look.

See abstract below:

I am phylogeny obsessed but this is too much to me: phylogeny of cancer subtypes

Just because you have data that could be plugged into a phylogenetic analysis does not mean it makes sense to do so. Case in point - the following paper:

A Differentiation-Based Phylogeny of Cancer Subtypes by Riester M, Stephan-Otto Attolini C, Downey RJ, Singer S, Michor F.

In this paper the authors take gene expression data from various cancer samples/cell lines and then they build phylogenetic trees from the data.  See example below:

Figure 2. A phylogeny of acute myeloid leukemia (AML) subtypes. According to the French-American-British (FAB) classification, AML samples are classified into seven different types according to their level of differentiation (see Table 1). Expression data from 362 AML patients and 7 Myelodysplastic Syndrome (MDS-AML) patients is used to construct a phylogeny of these leukemias. We include expression data of human embryonic stem cells (hESCs), CD34+ cells from bone marrow (CD34 BM) and peripheral blood (CD34 PB), and mononuclear cells from bone marrow (BM) and peripheral blood (PB). The differentiation pathway from hESCs to mononuclear cells from peripheral blood is represented in purple, and the common ancestors of subtypes are shown as pink dots. The bootstrap values of branches are indicated by boxed numbers, representing the percentage of bootstrapping trees containing this branch. The ranking of AML subtypes identified by the phylogenetic algorithm corresponds with the differentiation status indicated by the FAB classification. The M6 subtype, represented by only 10 samples in our dataset, has the least stable branch, leading to lower bootstrap values for those branches where it can alternatively be located.

The pictures are pretty.  They make some sense biologically.  The paper has some very interesting parts and I do not want to suggest that the paper is not useful.  But it makes no sense to me to use a phylogenetic approach to analyze this data.  Phylogenetic methods are about reconstructing history of evolutionary lineages.  They should not be doing that here as far as I can tell since the cancers are from different people with different histories and what they make be looking at is convergent / developmental similarities in the cancer samples.  But they are not looking at history per se.  And thus it is not appropriate to use algorithms that use phylogenetic methods:

It just makes no sense to me to use a phylogenetic method instead of some sort of clustering method in the step where it says "construct tree" in their flow diagram.  Sure phylogenetic methods can make nice pictures.  But they should only be used when the underlying data has a history that is reflected in the model/assumptions of the phylogenetic method.  I could, for example build a phylogeny of cities based on various metrics.  But would that make sense?  Most likely not.  Don't get confused by the fact that similar things group together in the same part of a phylogenetic tree to thinking that that means that a phylogenetic model is right for your data.

I may be obsessed with phylogeny but that obsession applies to applying phylogenetic methods to data with histories that are approximated by the methods being used ...  and this paper seems to not be doing that ...

Hat tip to Eric Lowe, an undergrad in my lab for showing me this paper.

I note - this does not mean that phylogenetic methods cannot be applied to cancer studies.  Case in point - this paper:

Estimation of rearrangement phylogeny for cancer genomes by Greenman CD, Pleasance ED, Newman S, Yang F, Fu B, Nik-Zainal S, Jones D, Lau KW, Carter N, Edwards PA, Futreal PA, Stratton MR, Campbell PJ.

In this paper the authors focus on mutations in cancer cells and they use phylogenetic methods to determine the order in which genomic changes happen in these cancer cells.  This seems to be an excellent use of phylogenetic / phylogenomic methods.

So - lesson of the day - phylogenetic methods should be used on data with a phylogenetic history.  Not so complicated.  But pretty important.

A eureka moment - but not of the good kind

Well, today I had one of those eureka moments that scientists all around the world crave.  You know, where all of a sudden you find out something that causes you to re-evaluate all sorts of aspects of the world you thought you knew.  I have had some of these, here and there before.  Sometimes even about my own work.  More often, when I read a paper or go to a talk that presents some major breakthrough that you just know is going to win a Nobel Prize one day.

I spent part of Thursday talking to some people about this exact type of thing in science.  I was answering some questions from some high school students about why one likes doing research and I said one reason is that such eureka moments can happen (mostly I said science was just fun but also said there are some big discoveries that happen too).

Well, 30 minutes ago this happened to me.  Alas, it was not about science per se.  But more about about how one's assumptions can cloud one's judgement and cuase one to miss what is right in front of you.  You see, I just got back, a few minutes ago, from driving through the pouring rain to get to one of the better restaurants in Davis, Osteria Fasulo, where alas I have never been.  I was going there to have dinner with the amazing, brilliant and fascinating Mina Bissell. Mina is a "Distinguished Scientist" at Lawrence Berkeley National Laboratory and a well known cancer researcher (see a great profile of her by Gina Kolata from the 12/28/09 New York Times here).

Anyway - I have known Mina for many years since I was involved in something called the Defense Science Studies Group (aka DSSG - though be careful when you search the web for this term ...).  Mina gave a seminar here at UC Davis today in the Cancer Center.  And a week or so ago, her host invited me to go to dinner with Mina and I said yes (after my standard delay due to being behind in email all the time).

Alas, I was unable to go to the seminar because it was at 9 AM in Sacramento (about 20 minutes from Davis - most of the UC Davis medical school including the Cancer Center is there) and I had kid duties in the morning.  But I was looking forward all day to having dinner with Mina and to meeting some other cancer researchers at UC Davis who I did not know.  Plus her host had called me Wednesday to make sure I was coming to dinner - she wanted to know because one of the other participants wanted to know how much special wine to bring.  (It was a little weird that she called Wednesday to make sure I was going to dinner Thursday since the message she left me sounded urgent but whatever). It all sounded good - Mina, colleagues I had not yet met, good restaurant I had not been to, fancy wine.

So today at work I left a little early to buy some dinner for my wife and kids who have all been sick - and I dropped it off at home and got ready to go to the dinner.  And then I headed out - through the driving rain to the restaurant nestled within "Village Homes"  in Davis.  I got to the restaurant at just about the meeting time, went in, and ... nobody was there.

The host of the restaurant said there was no reservation for 6:15 but that there was one for 7:30.  But he said - maybe they made a mistake - and he sat me at a table and gave me some sparkling water to drink.  And then I decided to get out my phone to just double check about the dinner.  And that's when I decided to look at Mina's itinerary to see when her last meeting was before dinner so I could guess when they would really arrive.  And that is when I saw it.  Dinner was Wednesday night.  I literally said something I will not print here out loud.  So I missed the dinner.  Turns out they waited for me for a while, tried to call me (they should have sent me email I guess .. or posted something to twitter), and then went ahead without me (I found out about this b/c I called Mina's host to find out if maybe she was still around Davis but she had left at 5 PM).

So I know a long story not really about science.  But here is the reason I am writing it.  I had set myself up for getting the date wrong by a series of assumptions.  I assumed Mina would just come to Davis for the day since she lives 1 hour away in Berkeley.  And since she was talking Thursday, I just assumed the dinner would be Thursday. But alas she came the night before her talk.  All of a sudden - everything made sense in hindsight.  Her host calling me Wednesday and leaving an urgent message about the dinner.  The comment by another one of her hosts that if I could not come to the dinner I could always see her afterwards (I thought he meant go to Berkeley).  And a few other things ... Oh man, what an idiot.  Anyway - I am sure I should not confess to being such a doofus on my blog - but I had planned on writing about Mina when I got back from dinner.  I even brought Rebecca Skloot's amazing "The Immortal Life of Henrietta Lacks" to show Mina, and wanted to know what she thought of the whole HeLa story.  Oh well. Maybe next time.