Nobel prize in medicine – going back to natural products for drugs

Every year there are potentially 1000’s of scientists that could have won the Nobel prize and did not. This year the prize recognizes 3 scientists for their work on parasitic diseases.  William Campbell  and Satoshi Omura won for their work on discovering Avermectin which lead to treatments for River Blindness and Lymphatic Filariasis. Youyou Tu also won for her work on Artemisinin as a treatment for malaria. Although I am sure most of the press reports will miss this obvious link. Both drugs are natural products. Avermectin comes from Streptomyces avermitilis and Artemisinin comes from the sweet wormwood tree. So this points to where drug discovery was focused 30-40 years ago before the use of combinatorial libraries and large high throughput screens was routine. Unlike in recent years, the Nobel committee is not recognizing recent basic science work but drug discovery science from decades ago. One can only wonder if this is a stab at the pharmaceutical industry. Also it is hard to remember the last time this prize was given for drug discovery, let alone anything for parasitic diseases. Maybe the work of Paul Muller and discovery of DDT comes to mind and he won his award in 1948. We all know how that played out and decades later was banned. Before that there was the 1945 award to Alexander Fleming, Ernest Chain and Howard Florey for discovery of Penicillin. Prior to this there was Gerhard Domagk who got his prize in 1939 for discovery of prontosil, an earlier antibiotic. So you can count on your fingers how many scientists have won the Nobel prize in medicine for discovering drugs. Perhaps in 30-40 years they will be giving out the next prize for drug discovery and if so what will it be for, immunotherapy, antibody drug conjugates, gene therapy..Its hard to predict, all I know is by then I will be the average age of some of these recipients now! I just hope we find cures for many of the neglected diseases that continue to kill millions of people before then.



A case for cheaper drug discovery and development

The news has been covering biotech/ pharma for the last few days and it is not a good thing, all because of Turing Pharmaceuticals decision to hike the price of their drug 5000%, which is an old antimalarial called pyrimethamine.  Not surprising the decision was met with an outcry. But looking at the basis for the decision (while I do not condone how it was done) I can see it makes some sense. Sure folks are not going to like it, but then again when there are few or no other options, Turing has total control. The previous owners of the drug could and probably should have raised its price too. What would we rather have the drug pulled from the market altogether? Unfortunately the CEO is taking the heat for the whole pharmaceutical industry as this is just one of many recent price increases. It could have been handled far better in consultation with patient groups and with far better PR. The reality is that to bring a new drug to market for Toxoplasmosis (a parasite) or for that matter virtually any disease would cost $100M’s to $1Bn if we believe the figures and would take at least a decade. If Turing or another company wanted to start now to develop an alternative they would need a significant war chest to do it, which would far exceed the $90M series A financing.

However there are ways to make drug discovery much cheaper and faster. From my own collaborative examples presented recently at a virtual symposium. It can be done and I am not afraid to say it – at least the early part of drug discovery.  Simply using data other people have published, a bit of computer modeling, test a few compounds and find leads that are already approved drugs or old clinical candidates. Yes I have over simplified but the papers should explain in more detail here and here..and for that matter others have published similarly. I think its just time people realized that we have enough data and computer power to do this on our desktop. If Turing are smart they will be doing this already and also going for one of the tropical disease or rare pediatric disease vouchers.

What I do feel needs highlighting in this excitable atmosphere is the real disparity between those rare diseases where there may really only be a handful of patients for a drug or therapy. In that case the company has no choice but to charge a hefty price to recoup costs for their R&D investment. If they are lucky to get a rare disease voucher it may only be a short term fix to offset costs, but what about longterm, will the company still be around, or for that matter the drug? We really need to get debate on this going. This is not a case of generic drugs, its about delivering drugs to a few people that can change their lives.

I think the current furor has done a very valuable service to get us to talk about what is a serious issue. The legacy big pharma’s have really missed the boat, if a Turing or other new upstart can take an asset that big pharma discarded and make money off it then its their problem. The day when a drug company developed treatments for the patient and was an ethical pharmaceutical company sadly left us in the 1960’s. The general public has to wake up and see that it is business. Turing or some other company has to make a profit, because without that there will be no research, however cheaply it can be done. Looking to big pharma for leadership in this situation is not going to work, Turing just led the way and others will follow.



Mistakes in manuscript reviewing 101: how to cloak your identity

A recent example got me thinking more about how anonymous reviewers could do a far better job of being well, “anonymous”. One such reviewer happened to request the mention of some specific type of molecular descriptor property. The lead author on the manuscript with very minimal effort was able to identify the lab that most likely reviewed the manuscript. It also appeared they likely had a conflict of interest and probably should not have reviewed in the first place (possibly a topic for another post). I have also heard of colleagues who are fond of Googling phrases from reviews that other scientists likely use frequently in their own papers, and using that as a way to identify reviewers.

So the bottom line is, if we have to continue to have anonymous reviewers , they might want to disguise their efforts in some way, otherwise they should just openly review.  Here are some quick tips to do a better job of cloaking your identity:

  1. Do not continue to insist the authors add references to your papers – a sure give away, at least add as many references from other groups. If you really want to send the authors off the scent, just refer to papers from many different labs.
  2. If you have a habit of using an unusual word or phrase every time you write a paper, do not use it in your review. Better still, if you have picked out phrases other authors seem to use frequently, throw them into your review.
  3. Do not make reference to a technology only you have published on. Perhaps it would be better if appropriate to reference technologies from several different labs if these are missing.
  4. If the authors credit you or reference your work do not go easy on them and thank them. To disguise your review perhaps request removal of your reference/s and replace with a different labs.
  5. If you have met the authors in the past you may not want to pepper your review with comments you have already relayed in person, clearly the author was not listening to you the first time. However if you overheard someone else ask questions of the author at a meeting, perhaps you could reuse those.

I take no responsibility for the efficacy of the above 5 approaches.

While I am on the case of reviewers here is an extra bonus. Over the years of publishing one sees just about every “reviewer type” there is. Here are 12 examples (I could come up with more over beers I am sure), apologies if you recognize yourself in this list, there is a bit of truth hidden behind the cheekiness:

  1. “Fast and Furious rejection” – clearly this person is far too self important to bother with your manuscript, short review, barely any feedback other than Reject!
  2. “Long Winded” – multiple pages of comments to get their opinion across on all kinds of relatively minor issues. Clearly you will spend days responding to this reviewer, and they will love your attention, stroke their ego please.
  3. “Needs citations”- reviewer clearly lives on PubMed or is a librarian,  suggests multiple papers to add.
  4. “Because the authors have never published in field they have zero to contribute” – you have to be a member of the old boys club or you do not get to publish in “their journal”. This person is the gatekeeper, you stand no chance.
  5. “Their idea is so simple it cannot be meaningful” – reviewer clearly not open to any new ideas that bring their field out of the rut its been in since 1970. Your chances of rebutting are hopeless, give up.
  6. “Luddite” – technology hater, just wants chemists to deal with molecules and not new-fangled computers, let alone anything mobile. What was the Editor thinking suggesting this person?
  7. “Major changes, minor comments” -reviewer proposes a Major change is needed but provides one line critique. A close relative of #1 but kinder.
  8. “Reviewer AWOL” – Makes you wonder when you get reviews from Reviewer #1 and Reviewer #3 what ever happened to Reviewer #2? Did they just forget to respond or was review so bad?
  9. “Professional editorial triage” – this seems to happen mostly with Nature or Science type journals, some minion rejects your work because well you are not part of their club. Occasionally it goes out to an editorial member for one peer “review” before rejection to justify their fair and balanced process. Review is usually one sentence if lucky – get used to it.
  10. “The protector” -this reviewer really has a major issue with exposing your ideas to the “unprepared medicinal chemist/ scientist” because heck they would have to think.
  11. “Anti-commercial / all companies are bad” – this reviewer is strongly opposed to reviewing anything from a company and frequently uses phrases like ” X is a scientific journal and not a platform to announce software tools”. If that truly is the case then how come the journal publishes software tools from academics that have close connections to the companies that license their tools from their university. Something seriously conflicted here.
  12. “This is not science” – because only the reviewer “knows” what true science is. You do not stand a chance with this reviewer, always wakes up on the wrong side of the bed.

I could go on, but perhaps there is something more important to take away here from my mixed bag based on experiences over the years. Increasingly we are all asked to review articles for journals. Speaking as an editorial board member, if you do not have the time or the interest, just decline. It saves everyone time. Please provide feedback to reviewers and not some personal stance. If you have a conflict of interest with an author just decline the review request. If you are some sort of psycho stalker-reviewer of the author then you need help. Get a life.



C&EN’s Advances in Drug Discovery and Development

VirtualSymposium15Twitter440x220v2Next Thursday at 10am EST I will be giving a virtual seminar at this virtual symposium – you can find out more and see all the other speakers too.

This is a first for me – So I hope for some interaction via Twitter #CENSYM15

Slides are done, now I just have to prepare what I am going to say – My talk is titled ” Open science for rare and neglected diseases” – without giving too much away it will highlight many of the recent collaborations .. and goes beyond just “open” science.. Hope you will join me!


I will make slides available on slideshare and F1000Research afterwards.




Raising awareness for Sanfilippo Syndrome IIIC and IIID – could Microsoft help us find our patients?

1 slide flyer for SF v4Previously I had written about the need to find patients for Sanfilippo Syndrome IIIC and IIID to join a registry and take part in a Natural History Study. In fact I keep writing about it in as many places as I can. In addition we are actively working with academics to develop treatments so it would be very useful to find as many patients as we can.I am sure thousands of other rare diseases are in the same boat.

In between recent grant writing spells, I took a little diversion to create a graphic to try to visually present this. This is now on slideshare so anyone can take it and use in their own presentations. It is also on the website for Phoenix Nest alongside lots more info on Sanfilippo syndrome. I am pretty sure there are other places we will put the graphic up on. The families are gratefully acknowledged for providing the photo as well as all the foundations globally and friends who live with the disease 24/7.

In addition we are try to raise awareness in new places – but here is a new one…MICROSOFT of all places- Jonah’s Just Begun is trying to win $50k from an online Twitter challenge which would be enough to fund a postdoc to do more work on the disease.

Cut and paste this line into a tweet!
@JJB4CURE we help save children suffering from Sanfilippo ‪#‎upgradeyourWORLDusa‬ ‪#‎vote‬ #MPSIII

-Do it everyday on all your social media platforms until September 23rd.
Of course it does get you thinking, billions of people on the planet use Microsoft products everyday, what if rare disease foundations could leverage their reach to find patients..or just raise awareness of rare diseases in general. One it would be very nice of them :) and two one would have to think how to actually do it other than sending everyone connected to the internet a little message, in stead of the usual software update. Lets put it this way my daily reminder to upgrade to windows 10 is ever present.
If there are any new patients / families who are reading this please get in touch. Either by sharing a mnessage or dropping a message to Jonah’s Just Begun or Phoenix Nest.
I would love to hear any novel ideas of how to find patients for rare diseases, what works and what does not?
Now back to the research!


ACS 2015, chemistry talks, posters and Tattoo!

I am just back from a very busy trip to Boston for the ACS. It was great to meet up with many people I see only rarely, at these meetings as well as meet new people including one with a molecule tattoo that got a lot of interest on Twitter .

I gave 5 talks on a diverse array of topics from Chagas disease to big data,  including one in the #CINF Careers session organized by Rachelle Bienstock. I have posted these on F1000Research in addition I gave 2 posters and these are also on F1000Research. (As of 21st Aug I have them on Slideshare too)

So a big thanks to all the chairs of sessions and those in the audience for asking great questions and stimulating lots of thoughts on further experiements etc. It was also an honor to be part of the very first JC-Bradley session Chaired by Antony Williams and Andrew Lang on data openness. I tried my best to formulate the complete soup to nuts history of my involvement in the Ebola story that is still in process.  This meeting also marked the first time I attended the small chemical business sessions and I was pleasantly surprised and inspired! I made some great contacts and had chance to chat with entrepreneurs including Dr’s Harry Mandeville and George Whitesides who had started a drug company (GelTex) in the 90s and sold it for $1.3bn to Genzyme.

OK now back to the task of working on grants to see if we can put all this productivity into funding some more research. Back on the treadmill.


A needle in a haystack

A busy day before going to the ACS. We have put a couple of similar posts (here and here) out in an attempt to try to identify some Sanfilippo type D (MPS IIID) patients or at the very least to get their families to register in the registry .

This is like finding a needle in a haystack. Looking through the literature there are so few case reports and certainly nothing recently, which calls out for an update. If you are reading this and know of any, please point them our way and we can let them know there is work ongoing to develop an enzyme replacement.

I would certainly welcome any ideas of how we could find these families.



My updated schedule for the ACS Boston meeting

Well next week it is the ACS in Boston and of course I leave it to the week before to pull everything together. I initially put up here my listing of abstracts titles etc back in May. This has now been updated a bit to include additional talk and poster showings as well as times and locations. I am looking forward to the careers panel on Sunday morning, that is a new one for me. I will also be giving a talk at the Broad on Tue morning  hosted by Patrick McCarren on the Tuberculosis work also, so its going to be a bit busy! I hope to see you there.
Sunday Am
Careers in Chemical Information and Cheminformatics
Panel Discussion & Brunch
9:00 to 11:00 AM, Boston Convention Center, Room 52AB

PAPER ID: 2246123
PAPER TITLE: Applying cheminformatics and bioinformatics approaches to neglected tropical disease big data (final paper number: CINF 10)

DIVISION: Division of Chemical Information
SESSION: The Growing Impact of Big Data in the World of Chemical Information
SESSION TIME: 8:30 AM – 11:50 AM

DAY & TIME OF PRESENTATION: Sunday, August, 16, 2015 from 10:05 AM – 10:30 AM
ROOM & LOCATION: Room 104B – Boston Convention & Exhibition Center

PAPER ID: 2248989
PAPER TITLE: Starting small companies focused on rare diseases (final paper number: SCHB 4)

DIVISION: Division of Small Chemical Businesses
SESSION: Entrepreneurs’ Poster Session
SESSION TIME: 11:00 AM – 1:00 PM

DAY & TIME OF PRESENTATION: Sunday, August, 16, 2015, 11:00 AM – 1:00 PM
ROOM & LOCATION: Galleria – Westin Boston Waterfront

PAPER ID: 2249028
PAPER TITLE: Development and sharing of ADME/Tox and drug discovery machine learning models (final paper number: COMP 104)

DIVISION: Division of Computers in Chemistry
SESSION: Emerging Technologies in Computational Chemistry
SESSION TIME: 8:30 AM – 11:45 AM

DAY & TIME OF PRESENTATION: Monday, August, 17, 2015 from 9:00 AM – 9:30 AM
ROOM & LOCATION: Room 157C – Boston Convention & Exhibition Center

PAPER ID: 2248973
PAPER TITLE: Making it open: Putting cheminformatics to use against the Ebola virus (final paper number: CINF 79)

DIVISION: Division of Chemical Information
SESSION: The Growing Impact of Openness in Chemistry: A Symposium in Honor of JC Bradley
SESSION TIME: 1:00 PM – 5:50 PM

DAY & TIME OF PRESENTATION: Monday, August, 17, 2015 from 1:25 PM – 1:45 PM
ROOM & LOCATION: Room 103 – Boston Convention & Exhibition Center

PAPER ID: 2248989
PAPER TITLE: “Starting small companies focused on rare diseases”
DIVISION: SCHB: Division of Small Chemical Businesses
SESSION TIME: August 17, 2015 from 8:00 PM to 10:00 PM

DAY & TIME OF PRESENTATION: August 17, 2015 from 8:00 PM to 10:00 PM
ROOM & LOCATION: Hall C (Boston Convention & Exhibition Center)

PAPER ID: 2248999
PAPER TITLE: Mobile apps for transporter drug-drug interaction prediction: A tool of the future, now (final paper number: TOXI 48)

DIVISION: Division of Chemical Toxicology
SESSION: General Poster Session
SESSION TIME: 6:30 PM – 8:00 PM

DAY & TIME OF PRESENTATION: Tuesday, August, 18, 2015, 6:30 PM – 8:00 PM
ROOM & LOCATION: Grand Blrm A – Westin Boston Waterfront

PAPER ID: 2248982
PAPER TITLE: Mining big datasets to create and validate machine learning models (final paper number: CINF 159)

DIVISION: Division of Chemical Information
SESSION: Computational Toxicology: From QSAR Models to Adverse Outcome Pathways
SESSION TIME: 1:30 PM – 5:10 PM

DAY & TIME OF PRESENTATION: Wednesday, August, 19, 2015 from 2:35 PM – 2:55 PM
ROOM & LOCATION: Room 103 – Boston Convention & Exhibition Center


My experience of submitting another manuscript to PLOSONE

Its been several years since I last submitted to PLOSONE . Since then we embarked on a Phase II grant working on tuberculosis and after much work by many labs at Rutgers and SRI we are now submitting the work today. So we decided to give PLOSONE a second chance. In the interim I have published in PLOS Computational Biology and PLOS Neglected Tropical Diseases.

So one of the challenges of having a large collaboration is the number of co-authors, this one has 13. Using Editorial Manager just adding author details alone took nearly 1h. They do not make it easy to enter addresses for people from the same group either. Then there are the picky figure resolution and image file formats to deal with that create hours of work for the non graphic designers out there. After trying to get images of the right resolution and size  etc. I have probably re-uploaded at least 10 times, waiting to read the figure quality report only to see the word fail. I have become far too familiar with a graphics program called GIMP and the removal of the “alpha channel”. Frankly I do not want to be spending my time working as a graphic artist just to publish in PLOS, I am beyond tired of their requirements. Compared to other journals like ACS, Springer, F1000Reports etc, submitting to PLOS ones are time consuming in my opinion. After spending 5.5hrs working to submit the manuscript, 4 figures and 5 supplemental files, I am wondering why anyone would want to do this again. Lets see how it does in review.



Wearing many hats

I wear a few different hats and yesterday I was CEO, working on the commercialization plan for a phase II grant for a rare disease. To this point the big selling point was getting a Rare Pediatric Disease Priority Review Voucher but this is a challenge because its unclear if there will be more of these in the future. This lead me to write a post for the good people at Rare Disease Report (any fees will be donated to rare disease foundations).

Today is another day and I am wearing another hat, working on grants for a different company with different challenges.

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