Morality-Free Stem Cells

Anthony Atala and coworkers at the Institute for Regenerative Medicine at Wake Forest University School of Medicine reported in Nature Biotechnology that they have been able to harvest stem cells from amniotic fluid. The cells, named amniotic fluid-derived stem (AFS) cells, exhibit characteristics between embryonic and adult stem cells. These AFS cells, unlike embryonic stem cells, are readily available; the researchers collected them from backup amniotic fluid samples from amniocentesis, which does not usually harm the fetus or the mother. So far AFS cells have successfully been used to create muscle, bone, fat, blood vessel, nerve and liver cells.

Can anyone object to using these cells on moral grounds? Let's hope not.

Source: EurekAlert, NewScientist

Edit: CNN just posted this story.

The Force in Mitochondria

The Scientist is running an article describing how George Lucas' midichlorians have made the move from Force-wielding microorganisms in the Star Wars galaxy, to the mitochondria of tick ova. While the naming is caused Mental Floss to pick up the story, the existence of a bacterial species living inside mitochondria, which is practically a baterium itself, is unprecendented it would seem. It's not clear if these bacteria destroy mitochondria in order to live in their shells, but Nate Lo, found midichlorians living in every female tick he looked at, regardless of its origin. Oh yea, and George Lucas said it was okay to name the species midichlorians. I wonder what Carolus would think.

Copy Number Variants (and Thanksgiving Dinner)

Scientists at the Wellcome Trust Sanger Institute in Cambridge reported some ground-breaking findings in human genetics yesterday. According to their findings, the human genome varies much more wildly between individuals than previously thought.

Our genome is about 3 billion DNA base pairs long. This sequence of letters (A, C, G, and T) is responsible for everything from the development of a fertilized egg into a fetus, hormonal changes in puberty, and the graying of our hair later in life. DNA accomplishes this dizzying variation of tasks by making proteins - molecular factories that carry out most of the chemistry that takes place in our cells.

For a non-scientific analog, think about a cookbook. Filled with recipes that use wildly different ingredients to accomplish the task of deep-frying a turkey or making creamy mashed potatoes, each of these recipes (the actual instructions on the page) are made up of the same letters of the alphabet. Although we need 26 such letters in English, nature pulls off a language with only four letters. The words in the recipe, like "boil" or "broil" have very similar letters, but their instructions lead to wildly different results.

We assumed, perhaps naively, that each and every human being on the planet had a very similar genome. Everyone had the recipe for a liver, and two kidneys, so what makes us different and unique must be tiny little changes in individual letters. Changing this A to a C, makes my eyes blue and yours brown. You get the idea.

Without sequence data from lots of humans, we couldn't say otherwise, and it seemed like a nice explanation for our uniqueness. It looks like this, in fact, isn't the case. According to the current study, instead of each of us having DNA that is 99.9% identical, that number is closer to 99.5%. This difference is actually significant, but more interesting is the new type of differences that this team of scientists discovered.

Instead of differences in individual letters of our genetic sequence (termed "single-nucleotide polymorphism"), there are a significant number of copy number variable regions. 1,447 of these regions that varied between individuals were found, constituting 12% of the humane genome. The most amazing of these differences is the observation that some people have multiple copies of a certain sequence of DNA.

Let's go back to our cookbook analog to think about this. Imagine that you have to make every recipe in your book today - duplicates included. Your cookbook might have three recipes for pumpkin pie, while mine only has one. With three pies, you'd be better off than me. (Who doesn't like pie?)

It turns out that the number of times a copy of particular sequence of DNA appears in your DNA can have really significant effects. Studies have linked copy number variations to increased risk of HIV infection, and are associated with Parkinson's and Alzheimer's disease.

The paper published yesterday in Nature includes the first map of these variable regions in the human genome. They were only able to detect regions of variation that were around 50,000 base pairs long. With improved methods that could look for smaller regions of variation, the authors guess that they would find many, many more regions of our genetic code that make us unique individuals. Whether these regions are in fact responsible for such terrible diseases as Parkinson's, and if we can start to control them, only time will tell. The current work is certainly the first step.

For additional coverage, see: Reuters, The Independent, Wellcome Trust Press Release, Nature Newsblog, and Slashdot.

The Allure of Scandal: Sames & Sezen Back in the News

Thanks to Chemistry & Engineering News, the Sames/Sezen Scandal is back in the news. Yesterday the following letter from Paul Mengnjoh appeared on their site:

I was disappointed to read that Columbia University chemistry professor Dalibor Sames retracted four more scientific papers (C&EN Online Latest News, June 16). I wonder if this is a trend of a professor and student getting into serious trouble and putting the future of U.S. chemistry, which is the envy of the world, in jeopardy.

I was also surprised to learn that Sames was asked to police himself by trying to redo the experiments, while the student who conducted the experiments had moved on to a German university and was pursuing a doctorate in another subject area. Can someone at ACS explain to us what is really going on here? Should professors supervising graduate students in chemistry be more vigilant in monitoring what is going on in their labs and making sure our chemistry research is not tainted by students who are not careful in recording their findings in lab notebooks? The lab notebooks should be carefully examined before signing off on students' findings so that we don't have the situation that has happened at Columbia. I'm sure other ACS members would also like the answer to the questions I have raised here.

One could argue that the situation is private at this point. The papers have been withdrawn, and that's all we, the public, need to know. It's between Columbia, Sames and Sezen at this point.

I don't think so.

Mengnjoh's letter hits on some important points; please allow me to elaborate. This matter cannot be isolated to the school, the faculty member or the graduate student involved in this situation. The chemistry community must take this grave situation as a warning of what atrocities can occur when the mentor-mentee relationship begins to break down. Assuming that Sezen's results are all but fake, her actions are simply inexcusable. The fact that these lies made it out of the Sames lab are a failure of its leaders, Dalibor, and his group as a whole.

But I'm not writing to shame Bengu or Dalibor. They've certainly been dealt their share.

Let's look at where the system broke down, and what it means for the discipline:

Something drove Bengu to lie the first time. After that she had to keep it going to preserve that first lie (in for a dime, in for a dollar). Pressure from her advisor, her peers, the job market - any or all of these could have made her add her magic to the flask that fateful day. Maybe Sames wasn't paying any attention to what she was doing because it wasn't working. But what about Columbia or chemistry at large? Did Sezen's graduate coursework include a required course in science ethics? What about her undergraduate degree? Did she attend workshops offered by the ACS at a national or local meeting? Does the ACS offer such workshops?

If it was pressure from Sames that drove her to fake these results, what drove him to put undue pressure on his students? Is he just naturally a slave driver? Or was it the ultra-competitive funding situation in the U.S.? Why didn't he look at her primary data? Did he?

These pressures affect more than just Sezen and Sames - they are truths of our world. To ignore this situation as a unique and unrepeatable conflagration of events is immature. This situation is what can result from the system that has been created. There are more graduate students like Bengu, and more faculty members like Dalibor, and if something isn't done to repair the system that allowed this to happen, then it will happen again. How many multi-paper retractions from a prestigious university do you think the general public needs to start doubting the entire field of chemistry?

I wholeheartedly agree with the sentiment put forth by >Paul Mengnjoh in his letter. I hope that he, C&E News, chemists, and the public at large get to know the truth about this unfortunate situation. I also hope that once we have that information that some good can come of it, and that we don't just forget about it once the allure of scandal has passed.

News of this letter was also covered by Paul Bracher.

Update: Bracher wrote a follow-up piece looking into Columbia's misconduct policy.

Splenda is Scary Stuff

Splenda, which comes in those little yellow packages that now reside alongside those red and blue satchels of sugar substitutes at restaurants, has got its fair share of press over the years. There's plenty of opinions on whether this "made from sugar" sugar substitute is safe to eat or not. Some have compared the structure of Splenda (the trade name of sucralose) to DDT, which others compare it to sodium chloride (table salt). You can buy books on how this stuff will kill you, or read about how it was discovered serendipitously by some chemists trying to make better insecticides.

Here's some homework for you: If you know a chemist (preferably an organic chemist, but anyone with a semester or two or organic chemistry will do), show them the structure of sucralose. Ask them if they would eat it. If they don't recognize it as Splenda immediately, I bet they'll give you a disgusted look and say you're crazy. Then tell them what it is. If they are pouring those yellow packages into their lattes, they'll stop. Every single chemist I've run this experiment on has the same reaction: "that stuff can't be good for you." Try it yourself, let me know what responses you get.

Explaining why this molecule is likely not good for you can be a bit complicated, but I'll give it a go. It's those chlorine (Cl) atoms that are so troublesome. First off, the structural comparisons mentioned above are terrible chemical metaphors. There is nothing (aside from it being the same element) at all in common between sucralose and table salt, as FDA Chemist George Pauli would like you to believe. DDT is slightly closer in chemical space to sucralose, but it's still pretty different, and its just irresponsible to try to scare people by making that comparison.

Understanding how those might react in the human body is way beyond the scope of this post, but let me make a much more realistic chemical analogy for you. The potentially harmful portion of Splenda is most like methyl chloride (CH3–Cl). Not in that sucralose is a colorless flammable gas (you knew that), but that methyl chloride and sucralose are both good candidates for substitution reactions. This can lead to the modification of all sorts of molecules in your body, which is hardly ever a good thing.

The short of it is that long-term studies of the effects of eating this miracle sugar have not been done. Splenda's FAQs might suggest otherwise, but I'm skeptical. If the FDA thinks this is chemically similar to NaCl, then we've got some pretty big problems on our hands. Not only does the FDA ultimately decide what is safe for us to eat, but most people don't know enough chemistry to even think twice about their decisions. That's a failure of our schools and our government.

Sezen Follow-up: Coffee & Espresso

Chemistry & Engineering News wrote a follow-up story on the Sames-Sezen retractions today. Although there is not much more in the way of details past what the New York Times wrote yesterday, I cannot resist including this quote from Bengü Sezen regarding the potential irreproducibility of her experiments:

"It is as simple as this: You can not make espresso without coffee beans. Prof. Sames and coworkers claimed in their retractions that they could not reproduce my recipe for espresso. And later (when I asked which brand of coffee beans they used), they stated that they did not have (and never had) coffee beans. Without having coffee beans, how can one try to reproduce the recipe?"

Maybe I don't take my coffee seriously enough, but what happened to apples and oranges? What a terrible metaphor.

The astute reader will also notice that C&E News referred to C-H activation as "a technique commonly used to functionalize hydrocarbons", whereas the New York Times thinks it is "an esoteric field." Common and esoteric - there's the eye of the beholder for you.

For more on this from the blogosphere, check out Paul Bracher's posts: Bypassing the ASAP System II, 3 + 4 = 7 Sames Retractions, New Sames-Sezen Links.

Four more retractions

The New York Times reported today that Dalibor Sames, a Columbia University chemistry professor, has retracted four more papers after the results could not be reproduced in his labs. Back in March, Sames retracted two other papers published in the Journal of the American Chemical Society for the same reason. All of the results in question was performed by a former graduate student in Dalibor's, Bengü Sezen. She, now listed as a PhD student in the Elmar Schiebel's lab at the University of Heidelberg, maintains that her work is reproducible and has been performed by other members of the group. She's confident in her results, in an email to C&E News she wrote:

I am also prepared to perform the reactions under the supervision of professor Sames if I am given a chance.

In the recent New York Times article, Sezen is now calling into question the procedures used to verify her results:

Dr. Sezen said that other members of Dr. Sames's group had not followed detailed procedures for the experiments and that the catalysts needed to shepherd the chemical reactions had not been made.

In for a penny, in for a pound, Bengü (is she really still a Dr. after all this, Columbia?). No one can reproduce this work. Give it up. Accusing other people as being hacks is not the way to go. Pray that you can salvage some of your reputation in your new field and try to stay out of the press, unless of course you cure cancer or something.

Also see: The Chem Blog, and SezenGate 2006 at Tenderbutton.