Saturday, October 10, 2020

World Mental Health Day: Doctor's Suicides: Maudsley & Lithium!


Atacama where Lithium is extracted  

© Am Ang Zhang 2015

One of my ex-juniors, now retired, called to ask if I have read about another young doctor's suicide. How very sad! If we look back there has been many such suicides and it is sadder that many are very talented people.                   Iris Chang & Nanking: Denial!


Dr. Baldessarini of Harvard:

“Lithium is far from being an ideal medicine, but it’s the best agent we have for reducing the risk of suicide in bipolar disorder,” Dr. Baldessarini says, “and it is our best-established mood-stabilizing treatment.” If patients find they can’t tolerate lithium, the safest option is to reduce the dose as gradually as possible, to give the brain time to adjust. The approach could be lifesaving.

In recent write ups about antidepressants, there is no mention of Lithium. The Cockroach Catcher first worked with one Australian Psychiatrist that worked with Cade and I was, so to speak, very biased towards Lithium. Yes, Lithium has side effects that might be serious. But hang on, you get to live to experience it. Think about it.


"Many psychiatric residents have no or limited experience prescribing lithium, largely a reflection of the enormous focus on the newer drugs in educational programs supported by the pharmaceutical industry."


One might ask why there has been such a shift from Lithium.

Could it be the simplicity of the salt that is causing problems for the younger generation of psychiatrists brought up on various neuro-transmitters?

Could it be the fact that Lithium was discovered in Australia? Look at the time it took for Helicobacter pylori to be accepted.

Some felt it has to do with how little money is to be made from Lithium. After all it is less than one eighth the price of a preferred mood stabilizer that has a serious side effect: liver failure.

 
Perhaps it is in the British History:



First, why a small group from the Maudsley Hospital in the 1960s could, in an almost malicious manner, have sown scholarly confusion about the true effectiveness of lithium. Aubrey Lewis, professor of psychiatry and head of the Maudsley, considered lithium treatment “dangerous nonsense” (). Lewis’s colleague at the Maudsley, Michael Shepherd, one of the pioneers of British psychopharmacology, agreed that lithium was a dubious choice. In his 1968 monograph, Clinical Psychopharmacology, Shepherd said that lithium was toxic in mania and that claims of efficacy for it in preventing depression rested on “dubious scientific methodology” (). Shepherd also scorned “prophylactic lithium” in an article with Barry Blackwell (). Moreover, Shepherd was publicly contemptuous of Schou. He told interviewer David Healy that Schou had put his own brother on it, and that Schou was such a “believer” in lithium that he seemed to think “really there ought to be a national policy in which everybody could get lithium”

Like Covid vaccine now, if developers put brothers or family members on it, we would trust it more.

Quote: In retrospect, “the miracle of lithium was not its treatment of acute mania,” as Dennis Charney at Yale University put it at a 1995 meeting of the Psychopharmacologic Drugs Advisory Committee of the FDA. “Neuroleptics, and even high-dose benzodiazepines, are quite effective for the treatment of acute mania. … The issue is prevention of relapse” (). Indeed, this is the issue, and the mystery is why the FDA has not accepted the prophylaxis of depressive disorder—“bipolar illness,” if one will—as an indication.

With the exception of ECT, lithium is the single most effective treatment in psychiatry. Its side effects are easily manageable, and many patients stay on low-dose lithium for decades. Its benefits, in terms of the relief of mania and the prophylaxis of depression, are incalculable. In assessing the history of lithium, therefore, two questions present themselves:

First, why a small group from the Maudsley Hospital in the 1960s could, in an almost malicious manner, have sown scholarly confusion about the true effectiveness of lithium. Aubrey Lewis, professor of psychiatry and head of the Maudsley, considered lithium treatment “dangerous nonsense” (). Lewis’s colleague at the Maudsley, Michael Shepherd, one of the pioneers of British psychopharmacology, agreed that lithium was a dubious choice. In his 1968 monograph, Clinical Psychopharmacology, Shepherd said that lithium was toxic in mania and that claims of efficacy for it in preventing depression rested on “dubious scientific methodology” (). Shepherd also scorned “prophylactic lithium” in an article with Barry Blackwell (). Moreover, Shepherd was publicly contemptuous of Schou. He told interviewer David Healy that Schou had put his own brother on it, and that Schou was such a “believer” in lithium that he seemed to think “really there ought to be a national policy in which everybody could get lithium” (50, see p. 249). [In a separate interview with Healy, Schou confirmed that the family member was his brother (36, see p. 267)]. Lewis and Shepherd were major figures in the field, and their poorly grounded objections to lithium doubtless steered many practitioners away from a beneficial agent. [Years later, when questioned about this mad campaign against lithium, Shepherd said that English psychiatry did not distinguish between psychogenic and endogenous depression, and if lithium were accepted, “all doctors in England would use it against all types of depression, with the result that many patients not in need of it would only suffer damage from it—therefore lithium must be ravaged with fire and sword” ()].


 Atacama where Lithium is extracted  © Am Ang Zhang 2015

Lithium: The Gift That Keeps on Giving in Psychiatry

Nassir Ghaemi, MD, MPH
June 16, 2017

At the recent American Psychiatric Association annual meeting in San Diego, an update symposium was presented on the topic of "Lithium: Key Issues for Practice." In a session chaired by Dr David Osser, associate professor of psychiatry at Harvard Medical School, presenters reviewed various aspects of the utility of lithium in psychiatry.

Leonardo Tondo, MD, a prominent researcher on lithium and affective illness, who is on the faculty of McLean Hospital/Harvard Medical School and the University of Cagliari, Italy, reviewed studies on lithium's effects for suicide prevention. Ecological studies in this field have found an association between higher amounts of lithium in the drinking water and lower suicide rates.


These "high" amounts of lithium are equivalent to about 1 mg/d of elemental lithium or somewhat more. Conversely, other studies did not find such an association, but tended to look at areas where lithium levels are not high (ie, about 0.5 mg/d of elemental lithium or less). Nonetheless, because these studies are observational, causal relationships cannot be assumed. It is relevant, though, that lithium has been causally associated with lower suicide rates in randomized clinical trials of affective illness, compared with placebo, at standard doses (around 600-1200 mg/d of lithium carbonate).

Many shy away from Lithium not knowing that not prescribing it may actually lead to death by suicide. As such all worries about long term side effects become meaningless. 

Will the new generation of psychiatrists come round to Lithium again? How many talented individuals could have been saved by lithium?

APA Nassir Ghaemi, MD MPH
  • In psychiatry, our most effective drugs are the old drugs: ECT (1930s), lithium (1950s), MAOIs and TCAs (1950s and 1960s) and clozapine (1970s)
    • We haven’t developed a drug that’s more effective than any other drug since the 1970’s
    • All we have developed is safer drugs (less side effects), but not more effective
  • Dose lithium only once a day, at night
  • For patients with bipolar illness, you don’t need a reason to give lithium. You need a reason not to give lithium  (Originally by Dr. Frederick K. Goodwin)



Cade, John Frederick Joseph (1912 - 1980)
Taking lithium himself with no ill effect, John Cade then used it to treat ten patients with chronic or recurrent mania, on whom he found it to have a pronounced calming effect. Cade's remarkably successful results were detailed in his paper, 'Lithium salts in the treatment of psychotic excitement', published in the Medical Journal of Australia (1949). He subsequently found that lithium was also of some value in assisting depressives. His discovery of the efficacy of a cheap, naturally occurring and widely available element in dealing with manic-depressive disorders provided an alternative to the existing therapies of shock treatment or prolonged hospitalization.

In 1985 the American National Institute of Mental Health estimated that Cade's discovery of the efficacy of lithium in the treatment of manic depression had saved the world at least $US 17.5 billion in medical costs.

And many lives too!

I have just received a query from a reader of this blog about Lithium, and I thought it worth me reiterating my views here.      It is no secret that I am a traditionalist who believes that lithium is the drug of choice for Bipolar disorders.
Could Lithium be the Aspirin of Psychiatry? Only time will tell!

Wednesday, October 7, 2020

The Nobel Prize in Chemistry 2020

 


7 October 2020   https://www.nobelprize.org/prizes/chemistry/2020/press-release/

Also: https://www.nobelprize.org/prizes/chemistry/

The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry 2020 to

Emmanuelle Charpentier  www.pscp.tv/w/ckye6DFETEtCZGtiV1hXRUp8MWxEeEx5cEVxalJLbQ3gvbMuVUdCLtZyl1c88KgK2x3D8Fs2rCueROJLPYY7?t=1m33s
Max Planck Unit for the Science of Pathogens, Berlin, Germany

Jennifer A. Doudna
University of California, Berkeley, USA

“for the development of a method for genome editing”

 

Genetic scissors: a tool for rewriting the code of life

Emmanuelle Charpentier and Jennifer A. Doudna have discovered one of gene technology’s sharpest tools: the CRISPR/Cas9 genetic scissors. Using these, researchers can change the DNA of animals, plants and microorganisms with extremely high precision. This technology has had a revolutionary impact on the life sciences, is contributing to new cancer therapies and may make the dream of curing inherited diseases come true.

Researchers need to modify genes in cells if they are to find out about life’s inner workings. This used to be time-consuming, difficult and sometimes impossible work. Using the CRISPR/Cas9 genetic scissors, it is now possible to change the code of life over the course of a few weeks.

“There is enormous power in this genetic tool, which affects us all. It has not only revolutionised basic science, but also resulted in innovative crops and will lead to ground-breaking new medical treatments,” says Claes Gustafsson, chair of the Nobel Committee for Chemistry.

As so often in science, the discovery of these genetic scissors was unexpected. During Emmanuelle Charpentier’s studies of Streptococcus pyogenes, one of the bacteria that cause the most harm to humanity, she discovered a previously unknown molecule, tracrRNA. Her work showed that tracrRNA is part of bacteria’s ancient immune system, CRISPR/Cas, that disarms viruses by cleaving their DNA.

Charpentier published her discovery in 2011. The same year, she initiated a collaboration with Jennifer Doudna, an experienced biochemist with vast knowledge of RNA. Together, they succeeded in recreating the bacteria’s genetic scissors in a test tube and simplifying the scissors’ molecular components so they were easier to use.

In an epoch-making experiment, they then reprogrammed the genetic scissors. In their natural form, the scissors recognise DNA from viruses, but Charpentier and Doudna proved that they could be controlled so that they can cut any DNA molecule at a predetermined site. Where the DNA is cut it is then easy to rewrite the code of life.

Since Charpentier and Doudna discovered the CRISPR/Cas9 genetic scissors in 2012 their use has exploded. This tool has contributed to many important discoveries in basic research, and plant researchers have been able to develop crops that withstand mould, pests and drought. In medicine, clinical trials of new cancer therapies are underway, and the dream of being able to cure inherited diseases is about to come true. These genetic scissors have taken the life sciences into a new epoch and, in many ways, are bringing the greatest benefit to humankind.

 

Illustrations

The illustrations are free to use for non-commercial purposes. Attribute ”© Johan Jarnestad/The Royal Swedish Academy of Sciences”

Illustration: Using the genetic scissors (pdf)
Illustration: Streptococcus’ natural immune system against viruses:CRISPR/Cas9 pdf)
Illustration: CRISPR/Cas9 genetic scissors (pdf)

Read more about this year’s prize

Popular information: Genetic scissors: a tool for rewriting the code of life (pdf)
Scientific Background: A tool for genome editing (pdf)

 

Emmanuelle Charpentier, born 1968 in Juvisy-sur-Orge, France. Ph.D. 1995 from Institut Pasteur, Paris, France. Director of the Max Planck Unit for the Science of Pathogens, Berlin, Germany.

Jennifer A. Doudna, born 1964 in Washington, D.C, USA. Ph.D. 1989 from Harvard Medical School, Boston, USA. Professor at the University of California, Berkeley, USA and Investigator, Howard Hughes Medical Institute.

 




Aug 11, 2013 ... This year's Nobel Prize in Physiology or Medicine goes to Barry Marshall and Robin Warren, who with tenacity and a prepared mind ...
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Oct 9, 2008 ... The three winners of the Nobel Prize for chemistry are (from right) Roger Tsien of the University of California, San Diego; Osamu Shimomura, ...

Tuesday, October 6, 2020

The Nobel Prize in Physics 2020



The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Physics 2020

with one half to

Roger Penrose
University of Oxford, UK

“for the discovery that black hole formation is a robust prediction of the general theory of relativity”

and the other half jointly to

Reinhard Genzel
Max Planck Institute for Extraterrestrial Physics, Garching, Germany and University of California, Berkeley, USA

and

Andrea Ghez
University of California, Los Angeles, USA

“for the discovery of a supermassive compact object at the centre of our galaxy”

 Link: Nobel https://www.nobelprize.org/prizes/physics/2020/penrose/facts/

Black holes and the Milky Way’s darkest secret

Three Laureates share this year’s Nobel Prize in Physics for their discoveries about one of the most exotic phenomena in the universe, the black hole. Roger Penrose showed that the general theory of relativity leads to the formation of black holes. Reinhard Genzel and Andrea Ghez discovered that an invisible and extremely heavy object governs the orbits of stars at the centre of our galaxy. A supermassive black hole is the only currently known explanation.

Roger Penrose used ingenious mathematical methods in his proof that black holes are a direct consequence of Albert Einstein’s general theory of relativity. Einstein did not himself believe that black holes really exist, these super-heavyweight monsters that capture everything that enters them. Nothing can escape, not even light.

In January 1965, ten years after Einstein’s death, Roger Penrose proved that black holes really can form and described them in detail; at their heart, black holes hide a singularity in which all the known laws of nature cease. His groundbreaking article is still regarded as the most important contribution to the general theory of relativity since Einstein.

Reinhard Genzel and Andrea Ghez each lead a group of astronomers that, since the early 1990s, has focused on a region called Sagittarius A* at the centre of our galaxy. The orbits of the brightest stars closest to the middle of the Milky Way have been mapped with increasing precision. The measurements of these two groups agree, with both finding an extremely heavy, invisible object that pulls on the jumble of stars, causing them to rush around at dizzying speeds. Around four million solar masses are packed together in a region no larger than our solar system.

Using the world’s largest telescopes, Genzel and Ghez developed methods to see through the huge clouds of interstellar gas and dust to the centre of the Milky Way. Stretching the limits of technology, they refined new techniques to compensate for distortions caused by the Earth’s atmosphere, building unique instruments and committing themselves to long-term research. Their pioneering work has given us the most convincing evidence yet of a supermassive black hole at the centre of the Milky Way.

“The discoveries of this year’s Laureates have broken new ground in the study of compact and supermassive objects. But these exotic objects still pose many questions that beg for answers and motivate future research. Not only questions about their inner structure, but also questions about how to test our theory of gravity under the extreme conditions in the immediate vicinity of a black hole”, says David Haviland, chair of the Nobel Committee for Physics.

 

Illustrations

The illustrations are free to use for non-commercial purposes. Attribute ”© Johan Jarnestad/The Royal Swedish Academy of Sciences”.

Illustration: Cross section of a black hole (pdf)
Illustration: The Milky Way (pdf)
Illustration: Stars closest to the centre of the Milky Way (pdf)

Read more about this year’s prize

Popular Science Background: Black holes and the Milky Way’s darkest secret (pdf)
Scientific Background: Theoretical foundation for black holes and the supermassive compact object at the galactic centre (pdf)


The Nobel Prize was established in accordance with the will of Swede, Alfred Nobel – inventor of dynamite and holder of more than 350 patents. Awarded annually since 1901, the Nobel Prize is the first annual international award to recognise achievements in Physics, Medicine, Chemistry, Peace and Literature. Nobel Prizes have been awarded to members of Cambridge University for significant advances as diverse as the discovery of the structure of DNA, the development of a national income accounting system, the mastery of an epic and narrative psychological art and the discovery of penicillin.
Affiliates of University of Cambridge have received more Nobel Prizes than those of any other institution.
  • 95 affiliates of the University of Cambridge have been awarded the Nobel Prize since 1904.
  • Affiliates have received Nobel Prizes in every category, 32 in Physics, 26 in Medicine, 22 in Chemistry, ten in Economics, three in Literature and two in Peace.
  • Trinity College has 32 Nobel Laureates, the most of any college at Cambridge.
  • Dorothy Hodgkin is the first woman from Cambridge to have been awarded a Nobel Prize, for her work on the structure of compounds used in fighting anaemia.
  • In 1950, Bertrand Russell became the first person from Cambridge to receive the Nobel Prize in Literature, for his 1946 work, ‘A History of Western Philosophy’.
  • Frederick Sanger, from St John’s and fellow of King’s, is one of only four individuals to have been awarded a Nobel Prize twice. He received the Nobel Prize in Chemistry in 1958 and 1980.


Nobel 2016 in Physics: Gonville & Caius College Cambridge.

2016 David Thouless (Trinity Hall, 1952), Duncan Haldane (Christ’s, 1970) and Michael Kosterlitz (Gonville and Caius, 1962) - Nobel Prize in Physics for theoretical discoveries of topological phase transitions and topological phases of matter

Other Gonville & Caius College Nobel Laureates:

2013 Michael Levitt, Gonville and Caius / Peterhouse Colleges, Nobel Prize in Chemistry, for the development of multiscale models for complex chemical systems

2008 Roger Y. Tsien, Churchill / Caius Colleges: Nobel Prize in Chemistry, for the discovery and development of the green fluorescent protein, GFP
2001 Joseph Stiglitz, Caius College: Prize in Economics, for analyses of markets with asymmetric information
1984 Richard Stone, Caius College and fellow of King's College: Prize in Economics, for developing a national income accounting system
1977 Nevill Mott, Caius / St John's Colleges: Nobel Prize in Physics, for the behaviour of electrons in magnetic solids
1974 Antony Hewish, Caius / Churchill Colleges: Nobel Prize in Physics, for the discovery of pulsars
1972 John Hicks, Caius College: Prize in Economics, for the equilibrium theory
1962 Francis Crick, Caius / Churchill Colleges: Nobel Prize in Medicine, for determining the structure of DNA
1954 Max Born, Caius College: Nobel Prize in Physics, for fundamental research into quantum mechanics
1945 Howard Florey, Caius College: Nobel Prize in Medicine, for the discovery of penicillin
1935 James Chadwick, Caius College: Nobel Prize in Physics, for discovering the neutron
1932 Charles Sherrington, Caius College: Nobel Prize in Medicine, for work on the function of neurons

P.S What is interesting is that in 1972 when I worked at a West London Hospital, the head of Psychiatry was Haldane's father. What an honour!

Aug 11, 2013 ... This year's Nobel Prize in Physiology or Medicine goes to Barry Marshall and Robin Warren, who with tenacity and a prepared mind ...
Jul 26, 2009 ... He was the winner of the Nobel Prize for 2000. In his book In Search Of Memory, he remembered his arrival in New York in 1939 after a year ...


Oct 5, 2015 ... Three scientists from Ireland , Japan and China have won the Nobel prize in medicine for discoveries that helped doctors fight malaria and ...

Oct 9, 2008 ... The three winners of the Nobel Prize for chemistry are (from right) Roger Tsien of the University of California, San Diego; Osamu Shimomura, ...

Mar 3, 2008 ... However, you may be too late to get the Nobel Prize. Rodney Porter in 1972 was awarded the NobelPrize in Medicine for his ground breaking ...