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Speaker's Footnotes

Relevant notes and citations provided to TED by Rebecca Brachman.

  • 00:16

    "At the time this picture was taken in the late 1800s, one in seven of all people died from tuberculosis."

    The original presentation of tuberculosis as an infectious disease ("The Etiology of Tuberculosis"). Koch, Robert. Die Atiologie der Tuberkulose. Berliner Kliniscben Wocbenschift, No. IS, April IO, 1882, pages 221-230. First presented at a meeting of the Physiological Society of Berlin, March 24, 1882.

    English
    Original German

    Image reference: Felix Barrias, The Death of Chopin, 1885

  • 00:38

    "it was a highly romanticized disease"

    The romanticization of tuberculosis:
    Fukuda, Mahito. The Romantic Images of Tuberculosis: A Cultural History of a Disease. 

  • 00:55

    "By the 1950s, tuberculosis was instead known to be caused by a highly contagious bacterial infection."

    An in-depth history of tuberculosis:
    Daniel, Thomas M. The history of tuberculosis. Respiratory Medicine. 2006 Nov; 100(11): 1862-1870.

  • 01:40

    "dancing in the halls" / "inappropriately happy"

    Iproniazid was originally derived from rocket fuel left over from WWII. This paper gives an overview of how iproniazid’s antidepressant effects were discovered:

    Sandler M. Monoamine oxidase inhibitors in depression: history and mythology. J Psychopharmacol. 1990 Jan;4(3):136-9.

  • 01:55

    "Accidental discovery is not uncommon in science..."

    A few more accidental discoveries in science: Kevin Loria and Randy Astaiza. 15 Amazing Science Discoveries Inspired By Complete Accidents. Business Insider. Jun. 7, 2014.

    A more critical look at the role of serendipity in psychotropic drug discovery: López-Muñoz F, Baumeister AA, Hawkins MF, Álamo C. The role of serendipity in the discovery of the clinical effects of psychotropic drugs: beyond of the myth. Actas Esp Psiquiatr 2012;40(1):34-42. 

  • 02:15

    "Thankfully, since the 1950s, we've developed some other drugs and we can actually now cure tuberculosis."

    Though tuberculosis is now well managed and has a low incidence rate in the US, there is still a global epidemic. In fact, one-third of the world’s population is infected with tuberculosis: 

    United States CDC Tuberculosis Fact Sheet
    WHO Global Tuberculosis Report 2016

  • 02:45

    "Approximately one out of every four adults in the US suffers from mental illness."

    The exact numbers vary from 1 in 4 to 1 in 5.

  • 03:05

    "Depression has in fact now surpassed HIV/AIDS, malaria, diabetes, and war as the leading cause of disability worldwide."

    How the WHO assesses the Global Burden of Disease

  • 03:30

    The second class of antidepressants was also discovered by accident in the 1950s from an antihistamine drug that made people manic.

    The History of Antidepressant Discovery

    Ramachandraih CT, Subramanyam N, Jurgen Bar K, Baker G, Yeragani VK. Antidepressants: From MAOIs to SSRIs and more. Indian J Psychiatry. 2011 Apr-Jun; 53(2): 180–182. 

  • 04:15

    "They actually listed [euphoria] as an adverse side effect."

    One of the original papers reporting the effects of iproniazid on mood in sanatorium patients. This 1954 report is a fascinating read in which technical findings are interspersed with colorful descriptive passages of individual patient's behavior. For example: "[One] patient became elated, very talkative and hyperactive, and had difficulty staying in bed...he admitted to being unable to sleep but stated that he felt better than he had in years... He also observed that he now was in a position to evaluate the effect of this new drug, which he considered remarkable, and asked for permission to address the other patients on the sanatorium radio to explain its effects to them. Physical and vocal hyperactivity became progressively more marked, to a point where the patient was spending practically all of his time pacing the corridors and lecturing to other patients whenever he found the opportunity..."

    Bloch RG, Dooneief AS, Buchberg AS, Spellman S. The clinical effect of isoniazid and iproniazid in the treatment of pulmonary tuberculosis. Ann Intern Med. 1954 May;40(5):881-900.

  • 04:52

    "Functional fixedness..."

    Read more: these Wiki articles and book give a good overview of functional fixedness and other cognitive biases

    Function Fixedness
    Set
    Cognitive Psychology and Cognitive Neuroscience/Problem Solving from an Evolutionary Perspective

  • 05:44

    "They both have terrible side effects."

    deVerteuil RL, Lehmann HE. Therapeutic Trial of Iproniazid (Marsilid) in Depressed and Apathetic Patients. Can Med Assoc J. 1958 Jan 15; 78(2): 131-133.

    Bloch RG, Dooneief AS, Buchberg AS, Spellman S. The clinical effect of isoniazid and iproniazid in the treatment of pulmonary tuberculosis. Ann Intern Med. 1954 May;40(5):881-900.

    Freeman JW, Mundy GR, Beattie RR, Ryan C. Cardiac Abnormalities in Poisoning with Tricyclic Antidepressants. Br Med J. 1969 Jun 7;2(5657):610-611.

  • 06:15

    "So we developed drugs to more specifically focus on serotonin."

    SSRIs are a classic example of "rational drug design," i.e., designing a drug aimed at a known biological target.

    More about rational drug design: Todd A, Anderson R, Groundwater PW. Rational drug design—identifying and characterizing a target. Pharm J. 2009 Jul 31;283:131.

    Interestingly, after many years of rational design being the gold-standard of drug development, there is now a debate as to whether highly targeted drugs may sometimes be too narrow to treat complex diseases with multiple biological components:

    Hopkins AL, Mason, JS, Overington, JP. Can we rationally design promiscuous drugs? Curr Opin Struct Biol. 2006 Feb;16(1):127-36. Review.

  • 06:40

    "and the SSRIs are better but they still have a lot of side effects."

    Review of the limitations of current antidepressants:
    Robinson, MJ. Antidepressant Psychopharmacology: Current Limitations and Future Directions. Primary Psychiatry. 2003;10(1):43-49.

  • 06:50

    "And that means now, in 2016, we still have no cures for any mood disorders, just drugs that suppress symptoms."

  • 08:19

    "Calypsol"

    Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000 Feb 15;47(4):351-4.

  • 12:05

    "And since it’s been published just last year…"

    Brachman RA, McGowan JC, Perusini JN, Lim SC, Pham TH, Faye C, Gardier AM, Mendez-David I, David DJ, Hen R, Denny CA. Ketamine as a Prophylactic Against Stress-Induced Depressive-like Behavior Biol Psychiatry. 2016 May 1;79(9):776-86. Epub 2015 May 4.

  • 12:22

    "…stress is the initial trigger in 80% of cases of depression."

    Mazure CM. Life stressors as risk factors in depression. Clinical Psychology: Science and Practice 2006;5: 291- 313.

  • 12:45

    "This ability to experience stress without developing a psychiatric disorder is known as "'stress resilience'."

    Technical overview of the neurobiology of resilience:
    Pfau ML, Russo SJ. Peripheral and Central Mechanisms of Stress Resilience. Neurobiol Stress. 2015 Jan 1;1:66-79. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260357/

  • 13:35

    "In immune vaccines..."

    How vaccines work: Understanding How Vaccines Work. CDC. Feb 2013.

    NOVA | Immunity and Vaccines Explained | PBS

  • 13:50

    "…Which is different from our treatments"

    General overview:

    What researchers mean by… primary, secondary, and tertiary prevention. At Work, Issue 80, Spring 2015: Institute for Work and Health, Toronto.

    Technical overview:

    The stages of prevention. AFMC Primer on Population Health.

  • 15:30

    "…the burden of mental illness continues to rise: estimated at $2.5 trillion (annually) in 2010, the global cost is expected to reach $6 trillion in the next 15 years."

    Bloom DE, Cafiero ET, Jané-Llopis E, Abrahams-Gessel S, Bloom,LR, Fathima S, Feigl AB, Gaziano T, Mowafi,M, Pandya A, Prettner K, Rosenberg L, Seligman B, Stein A, & Weinstein C. The Global Economic Burden of Non-Communicable Diseases. Geneva: World Economic Forum (2011).

  • 16:10

    "Ketamine is still used as anesthetic."

    Paper describing some of the many uses of ketamine:

    Kurdi MS, Theerth KA, Deva RS. Ketamine: Current applications in anesthesia, pain, and critical care. Anesth Essays Res. 2014 Sep-Dec; 8(3): 283–290.

  • 16:17

    "It’s on the World Health Organization List of Essential Medicines."

    Recent WHO statement on ketamine: WHO Recommends against International Control of Ketamine. Dec 2015.

  • 17:00

    "Ketamine is already FD approved..."

    The drug approval process:

    Lipsky MS, Sharp LK. From Idea to Market: The Drug Approval Process. Journal of the American Board of Family Medicine. 2001;14(5).

  • 17:28

    "There are no incentives to encourage pharma companies to develop them…"

    The challenge of repurposing generic drugs is also known as "the problem of new uses."

    Read more on the problem of new uses: Benjamin N. Roin. Solving the Problem of New Uses. Mich. St. L. Rev. (forthcoming 2014).

    Read more on the challenges of developing prophylactics:

    Offit PA. Why Are Pharmaceutical Companies Gradually Abandoning Vaccines? Health Affairs. 2005; 24(3): 622–630. 

  • 18:10

    "Only a fool is sure of anything, a wise man keeps on guessing..."

    MacGyver, ABC

  • 18:23

    More on our work:

    In this paper, we show that we can also increase stress resilience by manipulating the immune system:

    Brachman RA, Lehmann ML, Maric D, Herkenham M. Lymphocytes from Chronically Stressed Mice Confer Antidepressant-Like Effects to Naive Mice. J Neurosci. 2015 Jan 28; 35(4): 1530–1538.

    Read more in The Atlantic:

    "Preventing Mental Illness With a Stress Vaccine" Nov 26, 2016

    Listen on NPR/KPCC Radio (AirTalk):

    Could a stress vaccine actually work? Nov 30, 2016