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“Most proteins that drive disease processes are actually undruggable.”

Cover Image: October 2011 Scientific American Magazine

Recently, PayPal CEO Peter Thiel touched on the decline in cutting edge medical research. In “Outsmarting Cancer: A biologist talks about what makes disease-causing proteins so difficult to target with drugs” (Scientific American, October 14, 2011 online), Francie Diep introduces us to Brent Stockwell at the Howard Hughes Medical Institute, who explains a critical current challenge in cancer treatment:

There really is a crisis now occurring in the pharmaceutical industry. For the past 10 to 15 years the number of new drugs has been declining because it’s becoming harder and harder to create new medicines.

Because many disease-causing proteins are “undruggable,”

Proteins that are considered undruggable don’t have large pockets or cavities inside them and instead are relatively flat on their surfaces. There’s no obvious site for a small molecule, a therapeutic candidate, to interact. Fifteen percent of proteins are considered druggable. … Most proteins that drive disease processes are actually undruggable.

Which is why progress will depend mainly on outsmarting the proteins with new strategies.

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24 Responses to “Most proteins that drive disease processes are actually undruggable.”

  1. if you think about it there’s not many diseases that have an actual medical cure. No degenerative disease has a medical cure….a couple sexually transmitted diseases can be controlled with meds, but that’s about it. Even antibiotics are losing the battle nowdays.

    so basically the medical establishment has been a giant flop. And think of all the trillions of tax dollars they’ve been given! Yet people think so highly of science and medicine!…why??…for wearing white coats and looking important? This whole health care debacle could be eliminated immediately if people started addressing their diseases with organic foods, (such as vegetable juice) as Hippocrates suggested long ago. diseases do not form because of a lack of drugs, bun instead because of a nutritional imbalance that chokes off healthy cell function.

  2. Good point, van.

    We shouldn’t lose sight of the miracles of modern medicine: all around the world, lives are being saved and injuries being healed thanks to the knowledge we have gained from conventional medicine.

    But, at the same time, we should recognise the limits to conventional medicine. Broken bones and flesh wounds are within that limit. Problems that cannot be diagnosed (even just by the doctor(s) you visit) are often beyond those limits.

    A doctor is at his best when he’s helping your body to heal itself. It is the miraculous human body which we ultimately have to be grateful for!

  3. “so basically the medical establishment has been a giant flop”

    Really?

    So why have conditions that used to be the major causes of death in earlier times now virtually vanished? Just consider perinatal mortality, TB and wound infection. A “giant flop”?

  4. It’s doubtful he means that, Elizabeth Liddle. He means that we are approaching a limit with current strategies.

  5. anyone care to give me a list of diseases cured in the past 40 years?

  6. You could start with stomach and duodenal ulcers. You could list millions of people who have survived cancer (my uncle is one) because of modern therapies and millions more who didn’t get it in the first place because science removed all doubt about tobacco smoke being carcinogenic, so they quit smoking.

    You could look at the people who had phantom limb pain, some of whom can now get relief because of new techniques in neurology. You could look at all the people like my father and uncle and my brother who didn’t go blind because doctors know how to limit the damage from glaucoma and macular degeneration (and no, they aren’t caused by not eating your vegetables), the latter partly because of advanced anti-sense RNA-based therapy. You could talk to a friend of mine who used to be have trouble breathing because of bronchiectesis. Now she gets alpha-1 anti-trypsin, and is doing much better. These are just the few things that I happen to know something about.

    But you eat your overpriced organic vegetables which have never been shown to have any more nutrients than the conventional kind, and take your supplements, which may or may not do anything useful. If you are going to take them I would suggest the ones designed by real scientists like Bruce Ames.

    If science is such a failure, why are people living longer and staying healthier than at any time in history? When nearly everyone lived on a farm they probably ate lots of vegetables. They still got influenza and plague and malaria and yellow fever and died, and of course I didn’t even mention all the vaccines, which are probably the biggest success story of all. Oh, and there’s the little matter of smallpox, which killed 300 million people in the 20th century (more than all the wars), before it was completely eradicated from the earth by those oh-so-incompetent scientists. And they’re getting close on polio.

    And then there are things like measles and diphtheria, which were down to being quite rare, but are coming back because of the superstition of “naturalness,” which is motivating people to not vaccinate their children, and motivating well-fed Europeans to block the use of genetically modified crops when we are going to need 50% more food production by 2030. Why? Because it makes them nervous. Yes, we should risk millions starving rather than make them nervous.

    And to whoever “News” is, Van didn’t make any nuanced point. He just said that the medical establishment is a giant flop. Apparently he meant to include science in that. But this is all probably useless. You can lead a quack to science, but you can’t make him think.

  7. I’ll give you some statistics from Hematology, the field closest related to my current work-

    Acute Lymphoblastic Leukemia-fatal to 80% cure
    Chronic Myelogenous Leukemia -75% cure
    Acute Promyelocytic Leukemia-better than 85% remission
    Acute Myeloid Leukemia- 80% remission

    Hodgkin Lymphoma-80% cure after initial treatment
    Non-Hodgkin Lymphoma-doubling in survival rate

    Some other advances:
    Antithrombotic therapy-millions saved
    Easily transported and administered clotting factors for hemophiliacs
    Anemia treated with recombinant Epo

    I’d love to transport some of you who think you can do without modern medicine to, say, 1349.

  8. progress continues in a forward direction with the development of new drugs targetting such things like viral proteases, e.g., telaprevir

    http://hcvdrugs.com/

    of course one of the best strategies for curing disease is the prevention of that disease in the first place so I would add all the vaccine preventable diseases to the list of cures….smallpox is no longer with us on this planet thanks to the efficacy of the cure.

  9. Dr. ReC…..yes, I had forgotten about childhood leukemia as a victory medicine. I’ll tentatively give you that, as well as the hodgkin’s lymphoma…..although I would like to know what your definition of “cure” is, as much of the medical community defines cancer “cure” as no recurrence for 5 years after diagnosis. Therefore your percentages may, in fact, be quite skewed. Besides that, though certainly beneficial to many, I would not consider 80% a “cure,” especially when some of these so-called “cured” have future recurrences or bad health complications from the chemo.

    What’s more, as in the case of Hodgkin lymphoma, natural cures are actually very effective against the disease and do not have the long-term side effects (organ damage, toxicity, heightened alzheimer’s risk, etc) that chemo and radiation bring. In fact, chemo and radiation have killed untold millions of people — far and away more than they’ve helped. The cancer industry, for the most part, is a money-bloated scam.

    http://www.naturalnews.com/028.....umors.html (Cancer reseeds itself after chemo, radiation and surgery)

    Anyway…so you’ve listed 2; childhood leukemias, which have a (probably skewed) 80% cure rate and hodgin’s lymphoma, which may also have a skewed “cure” rate of 80%….and may not even exist at all:

    http://www.naturalnews.com/029.....tives.html

    “According to Dr. John Diamond, M.D., “A study of over 10,000 patients shows clearly that chemo’s supposedly strong track record with Hodgkin’s disease (lymphoma) is actually a lie. Patients who underwent chemo were 14 times more likely to develop leukemia and 6 times more likely to develop cancers of the bones, joints, and soft tissues than those patients who did not undergo chemotherapy.”

    so, Dr, is that about it, as far as you can tell, regarding the successes of medicine over the past 50 years?

  10. I feel really sorry for the child whose parents choose ‘natural’ remedies for leukemia instead of medical treatment. There is a lot of disinformation out there. If you want to listen to a quack with a degree in psychology (no training in cancer), be my guest.

    I’ll go to an oncologist.

    No disease intervention I can think of, except that against smallpox has resulted in 100% cure (no cases, no deaths). People, sadly, still get polio.

    So, I listed the medical advances resulting in dramatic changes in mortality in a single field. I find them substantial. I doubt extending the analysis into other fields will do much to change your mind, given your response.

  11. “Because many disease-causing proteins are “undruggable,”

    Is there a design inference on why they are that way?

  12. organ transplants.

  13. DrREC, “No disease intervention I can think of, except that against smallpox has resulted in 100% cure (no cases, no deaths)”

    Actually a smallpox “cure” was discovered long ago (1800s?) by a doctor who figured out that rubbing cow pox scabs on people somehow immunized them from smallpox. This is a miracle of the immune system. Modern medicine can take no credit for this…….and, smallpox, though it can be prevented, still has no cure.

    As for your other examples of ‘cures,” I noticed you didn’t define exactly what you mean by “cure.” Is childhood leukemia considered a “cure” in your mind if a child dies 6 or 8 years after diagnosis or has the cancer return in his bones 3 years later, only to wither a while before he dies? How many of these types of cases get labelled as a “cure” by the medical profession, who is desperate for victories?

    But hey…I’m not anti-doctor…I acknowledge that the medical establishment does great things sometimes….I just don’t think treating diseases with drugs is one of them.

  14. van,

    Welcome to the Big Tent!

  15. Perhaps part of the reason for the slowing rate of medical breakthroughs, despite oceans of funding, is that much of the low hanging fruit has already been plucked. The unfathomably complexity of life appears to be stumping our smartest ID’ers in many areas. This is surprising, given that life is supposed to have been cobbled together by purposeless natural processes.

    I spoke to a good friend of mine who is a leading UK microbiologist. He warned me that most microbiologists are contemplating a time in the not to distant future when antibiotics will be largely innefective. Some are considering new strategies, such as greatly increased use of vaccination i.e. using the bodies own immune system to prevent, rather than cure disease.

    Another reason for the lack of productivity and cures is that the main concern of most drug companies is to hook desperate addicts into a lifetime of drug dependency. Quick cures would be a financial disaster for them. This behaviour is no worse than we would expect from organisations run for profit, largely by individuals who have lost any sense of personnal accountability / responsibility, and see themselves as the products of a purposeless natural process that didn’t have them in mind.

    James Le Fanu discusses the sharp decline in genuine medical breakthroughs in: ‘The Rise and Fall of Modern Medicine. I haven’t read the book yet, but I believe that he has his own theories about the decreasing returns on our medical investment.

  16. This is surprising, given that life is supposed to have been cobbled together by purposeless natural processes.

    Why is it surprising?

    Manufactured products ten to be repairable, have interchangeable parts and have rather simple straightforward structures. Steve Jobs saod that simple is more difficult than complex.

    What you get with living things is that every one is biochemically unique. Medicines affect every individual differently. The foods that some enjoy kill others.

    Why is that if the important feature, the mind, is somewhere else, and the brain is just a radio? why does every radio have to be completely unique?

  17. Medical Advancement Headline News Front

    Center for Disease Control and Prevention

    Kimberly Lindsey, PhD, (Deputy Director)

    Laboratory Science, Policy and Practice Program Office

    “As Deputy Branch Chief in the Division of HIV/AIDS Prevention, she aligned programmatic resources with strategic planning goals, objectives, and initiatives. As an HIV/AIDS prevention project officer, Dr. Lindsey represented the branch on technical assistance to state and local health departments and other federal agencies and partner organizations.”

    “Dr. Lindsey received her doctoral degree in immunology and molecular pathogenesis from Emory University and her bachelor’s degree in molecular biology from the University of Central Florida.”
    ****************

    Well now I don’t know about you folks, but I certainly feel safer knowing somebody with the qualifications like Kimberley Lindsey is at the helm.

    OH, WAIT JUST A MINUTE!

    ———–

    October 11, 2011 “CDC Official Accused of Child Molesting, Bestiality”

    http://abcnews.go.com/US/cdc-o.....d=14713259

    http://www.myfoxatlanta.com/dp.....1010-pm-pk

    I’m sure she was only conducting Lab experiments for AIDS research and prevention.

    “Dr Kimberley Lindsey is also accused of performing sexual acts with two pets.”

    Oops! Well, maybe not.

    —-

  18. OK. But things are looking pretty good on the oncology front right now, and we’ve only just started looking at the possibilities of “personalised medicine” based on genome analysis. There’s also very promising research on aging.

    There is bound to be a limit, but it looks some way away to me.

    And I still don’t see how what we’ve achieved so far could be described as “a giant flop”. A ceiling is not the same as a flop :)

  19. You know the ironic thing is that most evolutionists years ago were part of the ECO-Environmental Crowd often protesting the evil science and technologies. Now more often than not they are these same former protestors are backing the corrupt Industries as champions and defenders.

  20. My brother-in-law is doing really well from a “mini” bone-marrow transplant that was not possible when he was diagnosed with Chronic Lymphocytic Leukaemia a few years ago.

    The pace of progress in oncology is so extraordinary that even dire prognoses come with the caveat “unless we find a solution before that” and often they do!

    Another friend of mine with malignant melanoma is now looking forward to effective treatment for what would have been virtually a death sentence only a couple of years ago.

  21. Well, we haven’t cured death yet, van, that’s true.

    But life expectancy has lengthened hugely, and the prognosis for once almost certainly terminal conditions in many cases is very positive.

    And don’t forget the diseases that are virtually eradicated through vaccination – polio, smallpox, diphtheria, tetanus etc.

    And sanitation, of course, a direct result of the germ theory of disease.

  22. What?

  23. Van

    “if you think about it there’s not many diseases that have an actual medical cure. No degenerative disease has a medical cure….a couple sexually transmitted diseases can be controlled with meds, but that’s about it.”
    =====

    Well there are many of the well known items that do pop back up from time to time, but you are correct that their is no sure fire cure invented that has put any particular disease out of business for good. Many of the old time diseases which plagued Europe, North America, etc have been under control, but they still have their way of ruling as King in many of the 3rd world countries unfortunately.

    Yet Industrialized Developed countries have their own unique set of problems that the 3rd world don’t experience. Either way, chalk it all up to human error and imperfection. Most of these diseases could be prevented by better cleanliness and hygene. That’s actually a problem globally.

    Other problems are horrible scientific technologies such as GMOs and the plastics industries with their Bisphenol-As, Nonylphenols and numerous other cocktails leaching into the water supply. Especially wildlife have been affected. Industrial farming is yet another problem. Recently in Colorado Cantalopes where found to have listeria, but Listeria doesn’t grow on cantalopes, it comes from industrial feedlots. In fact down the road from that farm is an industrial feedlot. Just like in Mexico with the latest Swineflu scare. Came from an industrial feedlot for hog farming.

    Then there is yet another problem. Greed and Selfishness. The problem with most medical industries is their servicing approach as opposed to actual cures. Cures don’t make money. Regular servicing does. Obscene Profits are a driving force for alot of what gets done and what doesn’t.

    Another problem are people’s attitudes towards health by lifestyle choices. You cannot force people to do the right thing. People want to smoke, but they don’t want Cancer, Emphysema, Heart disease, etc. People want to over drink and party, but they don’t want Cirrhosis of the Liver, driving accidents, etc. People want to fornicate when ever and where ever without judgement, but they don’t want AIDS, syphilis and gonorrhea, broken homes, etc. Some folks want to over eat and not necessarily the best foods, but they don’t want obesity, heart attacks, high blood pressure, etc.

    Again much of what happens to humans is NOT the fault of nature. Nature is simply out of balance and humans are a fault for that.

  24. My My , look what the animal rights folks think.

    “Monkey-Murdering Vivisector Kimberly Lindsey Arrested for Child Molestation and Bestiality!!!
    Posted on October 11, 2011 by Negotiation Is Over
    20tweetsretweet

    Editorial Note: The CDC’s very own Dr. Kimberly Lindsey has been arrested for child molestation and BESTIALITY. The illustrious Dr. Lindsey is a graduate of Emory University and has worked with Emory’s Leonard Howell who addicts monkeys to cocaine at Yerkes. Dr. Lindsey is now the deputy director for lab science policy.”

    http://www.negotiationisover.n.....estiality/

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