CRISPR Controvery And The Nobel Prize

Not too long ago, the receptor theory of neurotransmission was, well, just a theory. The opponents suggested that chemical transmission was way too slow. There was growing evidence however, that at least some synapses were purely chemical. Julius (Julie) Axelrod and colleagues demonstrated that catecholamines are taken back up after release, and he hypothesized they must be held and released upon demand. For this he won the Nobel prize* with Bernard Katz (who discovered that acetylcholine is released by nerve terminals at the neuromuscular junction) and Ulf von Euler (who demonstrated norepinephrine is a neurotransmitter of sympathetic nervous system and stored in sympathetic nerves). However, the molecular identity of the receptor for these neurotransmitters remained elusive. Several groups were trying desperately to find these receptors with little luck. One of Julie’s former trainees, Solomon Snyder**, used radioactive high affinity opiate antagonists and agonists to try to identify binding sites in the brain. Using opiates was somewhat brilliant because the pharmacological potency of the drugs was well described clinically and could be used to correlate with the in vitro binding data. Eventually he was successful, and the discovery was covered widely (and poorly) by the media as a cure for opiate addiction, which at the time was a huge problem for returning veterans from the Vietnam war. The first author on the publication, Candace Pert, was a graduate student in Sol’s lab. Depending on what account you read, she claimed 100% responsibility for the discovery, and was publicly furious she was not at least co-recipient of the Laskar Award which was given to Sol and two other opiate researchers, Hans Kosterlitz and John Hughes. It is widely believed that this controversy spoiled any chance of this discovery winning the Nobel Prize. One of several accounts of this story is highlighted in the book Apprentice to Genius: The Making Of a Scientific Dynasty.

I can’t help to think that this story mirrors the current debate over who deserves credit for CRISPR. It highlights the ugly underside of politics surrounding science. It would be nice if we were all in this for the pure benefit of mankind. However, sometimes scientists have an agenda to selfishly further their own advancement whether the reward is money or prizes***. It will be interesting to see the long-term consequences of the CRISPR pettiness.

 

* Of a very timely note, after winning the Nobel Prize Julie became quite active in science advocacy. When Nixon announced the “war on cancer” Julie and several other Noble laureates protested publicly and announced that this would significantly set back scientific advancements in the US. Wow, how history repeats itself.

**COI statement: My post-doctoral mentor. I also knew Candace Pert, who has since passed away.

***Axelrod and mentor Bernard Brodie discovered that the popular headache medicine phenacetin was metabolized to acetominophen and this was the active ingredient. Scientific lore muses that Axelrod predicted this on a blackboard prior to doing a single experiment. It never occurred to Axelrod or Brodie to patent this discovery, but McNeil Pharmaceuticals did and marketed it as Tylenol.   Also of note: Axelrod did not get his Ph.D. until many years later (at the insistence of his colleagues).

I Also Owe My Career To Muslim Immigrant Scientists

David Kroll wrote a great piece for Forbes today where he detailed how Muslim scientists played prominently in all stages of his career.

I have had a very similar experience, especially as a faculty member. They were essential contributors to my grants, my papers, and my career advancement. They were kind enough to invite me and the other lab members to Iftar at the local Islamic Center. They invited me into their homes and hearts. I consider them part of my family. It disgusts me to know that they are afraid and no longer feel welcome in this country. As Dr. Kroll suggested, scientists should loudly denounce the downright disgusting and xenophobic/islamophobic rhetoric being discussed in certain political circles, especially by the Republican front-runner Donald Trump. I join him in noting that Muslims are a essential component of the biomedical research community in the United States. In addition to this pragmatic point, I would also note that this is an issue of basic human decency. Discriminating against an entire religion is about as awful and un-American as you can get.

Below is a partial listing of the exceptional science accomplished by Muslim immigrant scientists in my laboratory in just the past five years. I am deeply grateful for all of their contributions, both professional and personal.

 
Borahay MA, Al-Hendy A, Kilic GS, Boehning D. Signaling Pathways in Leiomyoma: Understanding Pathobiology and Implications for Therapy. Mol Med. 2015 Apr 13;21:242-56. doi: 10.2119/molmed.2014.00053. PubMed PMID: 25879625; PubMed Central PMCID: PMC4503645.

 
Borahay MA, Vincent K, Motamedi M, Sbrana E, Kilic GS, Al-Hendy A, Boehning D. Novel effects of simvastatin on uterine fibroid tumors: in vitro and patient-derived xenograft mouse model study. Am J Obstet Gynecol. 2015 Aug;213(2):196.e1-8. doi: 10.1016/j.ajog.2015.03.055. Epub 2015 Mar 31. PubMed PMID: 25840272; PubMed Central PMCID: PMC4519389.

 
Borahay MA, Kilic GS, Yallampalli C, Snyder RR, Hankins GD, Al-Hendy A,
Boehning D. Simvastatin potently induces calcium-dependent apoptosis of human leiomyoma cells. J Biol Chem. 2014 Dec 19;289(51):35075-86. doi: 10.1074/jbc.M114.583575. Epub 2014 Oct 30. PubMed PMID: 25359773; PubMed Central PMCID: PMC4271198.

 
Safren N, El Ayadi A, Chang L, Terrillion CE, Gould TD, Boehning DF, Monteiro MJ. Ubiquilin-1 overexpression increases the lifespan and delays accumulation of Huntingtin aggregates in the R6/2 mouse model of Huntington’s disease. PLoS One. 2014 Jan 27;9(1):e87513. doi: 10.1371/journal.pone.0087513. eCollection 2014.PubMed PMID: 24475300; PubMed Central PMCID: PMC3903676.

 
El Ayadi A, Stieren ES, Barral JM, Boehning D. Ubiquilin-1 and protein qualitycontrol in Alzheimer disease. Prion. 2013 Mar-Apr;7(2):164-9. doi:
10.4161/pri.23711. Epub 2013 Jan 29. PubMed PMID: 23360761; PubMed Central PMCID: PMC3609125.

 
Wang X, Xiong LW, El Ayadi A, Boehning D, Putkey JA. The calmodulin regulator protein, PEP-19, sensitizes ATP-induced Ca2+ release. J Biol Chem. 2013 Jan 18;288(3):2040-8. doi: 10.1074/jbc.M112.411314. Epub 2012 Nov 30. PubMed PMID: 23204517; PubMed Central PMCID: PMC3548510.

 

 

El Ayadi A, Stieren ES, Barral JM, Oberhauser AF, Boehning D. Purification and aggregation of the amyloid precursor protein intracellular domain. J Vis Exp. 2012 Aug 28;(66):e4204. doi: 10.3791/4204. PubMed PMID: 22952038; PubMed Central PMCID: PMC3478677.

 
El Ayadi A, Stieren ES, Barral JM, Boehning D. Ubiquilin-1 regulates amyloid precursor protein maturation and degradation by stimulating K63-linked polyubiquitination of lysine 688. Proc Natl Acad Sci U S A. 2012 Aug 14;109(33):13416-21. doi: 10.1073/pnas.1206786109. Epub 2012 Jul 30. PubMed PMID: 22847417; PubMed Central PMCID: PMC3421158.

 
Stieren ES, El Ayadi A, Xiao Y, Siller E, Landsverk ML, Oberhauser AF, Barral JM, Boehning D. Ubiquilin-1 is a molecular chaperone for the amyloid precursor protein. J Biol Chem. 2011 Oct 14;286(41):35689-98. doi: 10.1074/jbc.M111.243147. Epub 2011 Aug 18. PubMed PMID: 21852239; PubMed Central PMCID: PMC3195644.

 
Stieren E, Werchan WP, El Ayadi A, Li F, Boehning D. FAD mutations in amyloid precursor protein do not directly perturb intracellular calcium homeostasis. PLoS One. 2010 Aug 5;5(8):e11992. doi: 10.1371/journal.pone.0011992. PubMed PMID: 20700539; PubMed Central PMCID: PMC2916833.

Contacting Your Congressional Representative

Update: After a twitter conversation with Benjamin Corb (@bwcorb) from ASBMB, who unlike myself is an expert on science advocacy, the “Don’t” points below are not correct. (Thanks a bunch). He also noted, and I agree, WE NEED MORE SCIENTISTS CONTACTING CONGRESS!! This graph graciously provided by Benjamin Corb/ASBMB could probably take the place of this entire post (click to expand):

CRSlDIxWcAIV-gP

Original Post:

There was an interesting bit on NPR/Houston Public Media this morning regarding contacting your congress person. I can’t find the transcript online, so this is somewhat off the top of my head. Basically, a representative may get 1000’s of emails and 100’s of phone calls a week. That is a lot more than I expected. Most of those emails are discarded (edit: discarded is not correct, they are counted), especially the form letters. This is important since many of the science advocacy groups provide us with web-based form letters to forward to our reps. These simply do not work (edit: are possibly less effective). Additionally, most phone calls fall on deaf ears (edit: again, are possibly less effective). What I found interesting is what does work. First and foremost, a personal and compelling letter send via snail mail is the most likely way for your message to actually make it to your representative’s desk. Second, and I found this even more interesting, is that social media attention directed at the representative is also likely to be noticed by the congressperson’s staff. Finally, and this seems to be a no-brainer, going directly to your representative’s office (either local office or DC) is likely to get the most attention. If you time your visit to the local office while congress is out of session you may actually be able to meet with the representative directly.  So in summary,

Do:

  1. Write an original letter and send it via snail mail to the congressperson’s office.
  2. Visit either the local or DC office of the representative.

Don’t (edit: less effective means of communication):

  1. Sent a form letter, even a modified one.
  2. Phone the congressperson’s office.

Twitter exchange with @bwcorb: