Grand Rounds: Geoffrey Cordell on Medicinal Plants
His main message is a heads up that our current system is not sustainable, our planet is already over capacity, and we are eradicating the species that could sustain us and the peoples who know know about them. His solution is science. It bears on the way I'd like to practice medicine.
Medicinal Plants in a World Out-of-Balance
Geoffrey A Cordell
Natural Products Inc., Evanston, IL
research, speaker, drug discovery, quality control
35 years in natural products
he thinks this presentation will be a new whole picture for us
just traveled to India, Sumatra, Singapore, SE Asia is a favorite destination
distinguished gentleman, came out of retirement because he found his passion
world out of balance--terribly
developed "north" is leading
he wants to talk about the future
lecture overview: perspectives, plants place, WMDs and WMIs, visions for restoring balance
THE GREAT DIVIDE
affluence, global people, rich, surplus resource, cause of climate change, living into old age, technological knowledge, theory-driven research (the US, Europe, the "west", the northern hemisphere)
vs
action-driven research, traditional knowledge, impacts of climate change, resource shortages, young, jobless, local people, poverty
WORLD OUT OF BALANCE
6.94 BILLION people today
10 billion by 2035 or 2037 ish
5.5-6 billion is stable world population
we're past the tipping point
pantropical deforestation
no drugs for existing critical global diseases
new and untreatable global diseases (sars, aids, mrsa,vrsa)
increasing drug resistance (cancer, malaria, tb, aids)
getting Rx drug to market costs 1.2 billion $
drugs too expensive for govts, ins, pts
drugs for N vs S
synthetic drugs not sustainable longterm: aspirin
poor quality control (major issue)
can we provide traditional medicines???
want sustainable drugs
human overconsumption of natural resources-->generational crisis
legacy for descendants is grim
TIME article on why drugs cost so much, 2004, drug discovery process inefficient
7% of IND pass clinical trials
2005: 21 novel drugs
overview of US pharm industry in Chem and Engineering News
pharma innovation gap: investment has increased more than return
GREAT HEALTHCARE DIVIDE
Ghana 110 people/healer, 1MD/21,000
US $2096/year, China $227, Ethiopia $21 on healthcare/year (2007)
Poor 56% of dz 2% of care
1556 new meds in last 30 years, 1.3% for dz prevalent in developing world
drug system regulated here, unregulated in southern hemisphere (WHO study)
PHYTOTHERAPEUTICALS
64% (4.4bn)(guesstimate) of world pop uses plants as primary health care source (WHO number 1984)
$4.41bn on phytotherapeuticals in US in 2005
KILLER DZ
AIDS 3.1m death/yr, 5.5m new
TB 2m deaths, 8m new
Diarrhea 1.9m death, 22.7bn new
Malaria 1m deaths, 300-500 new
Hep B 1m deahts, 10-20 m new
SARS 8,096 on 04/04, 774 deaths
H1N1...
ALKALOIDS
he has studied plenty
Papaver somniferum, (poppy) codeine, morphine--the painkiller, Afghanistan produces 95% of world's opium
Erythroxylum coca, cocaine, anesthetic, submarine built in Bogota, Columbia for smuggling drugs to Mexico
NATURAL PRODS AS WEAPONS of mass incapacitation or intimidation
--these are serious poisons
--myth: natural products are safe
--these are easily available
--tylenol in Chicago approx 1979, most bottles have sealed cover because of what happened, someone put cyanide into bottles and 7 people died
--anthrax laced letters in post 9/11
Coniine (Socrates)
Ergot (on wheat, rye, bread, 11th century 1/3 of pop died, bloodless loss of limbs)
Digitalis
Curare
Amanita mushroom
Teratogens
Botulinum toxins
Staph enterotoxins
Ricin, Abrin (Georgi markov killed with umbrella jab in 1978)
--ricin laced letters send to senate in 2004, leaf 8 lobed
Saxitoxin (red tide)
Trichothecene mycotoxins
REALITY CHECK 2009
pop increasing
technology increasing
killer dz increasing
oil decreasing
biodiversity decreasing
(steroids are semi-synthetic)
forest decreasing, population increasing (chart)
CROSSROADS
need new vision, status quo
Woody Allen quote: our choices as despair and hopelessness vs extinction
Saint Hildegard of Bingen quote, "nature at disposal of humankind, wwork with it"
Millenium Ecosystem Assessment: "the ability of ecosystems to sustain future generations can no longer be taken for granted" (UN 2005)
"If you are on the fifth step and you think you are too high, you will never make it to the sixth step." -Ajahn Chah, A Still Forest Pool (Buddhist monk)
PUBLIC HEALTH DISPARITY WITH RESPECT TO MEDICINAL PLANTS
new drug discovery mostly for developed world
development of traditional medicines very unfocused
evidence lacking for traditional medicines, mostly unregulated
still these medicines are fundamental to basic healthcare for most of world
adulteration of medicine isserioushazard
resource depletion threatens health care for billions
RESPONSIBILITIES FOR NAT PROD SCI IN HEALTH CARE
contribute to drug discovery, standardization, foods, awareness of detrimental products
SUSTAINABLE MEDICINAL AGENTS
organic chems used for 75% of drugs
other industries examining plants as oil source
we needto look at sustainable drug options
indigenous people have always known this
natural product extract are no longer of interest to major pharma co's
too long to isolate
ETHNOMEDICINE
study of indigenous uses of medicinal plants
look at all systems: (native American, Unani, Ayurvda, Chinese, Kampo, Thai, others)
rising pop is main challenge, sustainable only if cultivated
275,000 higher plants, ethnomedical reports for 15,000, 60% never studied
74% of plant-derived Rx products discovered based on original ethnomedical use
tubocurarine used in surgery today, poison arrow toxin
where find info? old books, traditional healers, books, reviews, herbaria notations
market places: ask the sellers
ALKALOIDS
21,120 plant alakloids with 1,872 skeleta
15.6% of known nat prods
46% pf plant-derived pharma
76% of known alkaloids never tested in a single bioassay
collaboration is missing in scientific study
A VISION FOR NATURAL PRODUCTS
must contribute to global health and food
develop nat prods as single or combo drugs
utilize traditional meds
improve detection and isolation of novel bioactive nat prods
enhance natural product structurediversification for drugdiscovery
use vegetables as chemical reagents
using plants for green chemistry
synthetic reagents and solvents are costly, must be shipped, borders are an issue
can we use local plants as enzyme sources?
chirality important in most drugs these days
EXAMPLES OF VEGGIES
aqueous extracts of carrots showed reduction of carbonyl grps in modest yield and enantioselectivity
reduction of ketons and aldehyes with Manihot esculenta (pic looked like ginger)
acetylation of citronellol with an immobilized prep from Manihotescuelenta
sustainable reagent source
TRAD MEDICINE
he's a traveller
Kerman, Iran
Marrakech, Morocco
Santiago, Chile
Cape Town, S Africa
Chengdu, China (pic of lg market)
95% of plants collected in forest
worlds largest exporter of medicinal plants (144,000+ tons)
Medellin, Colombia
India--90% of meds are wildcrafted, 4-10,000 facing extinction locally, regionally, nationally
64/71 of rare plant species in active trade
govt agencies developing farms
Traditional medicines are like coffee--they have to work!
MYTHS
dietary supps are safe
dietary supps are regulated (not true, poor reg world wide, no assessment of ag or efficacy)
NEW COMPLICATING FACTOR IN TRAD MED
activity of med mbdt microbial, parasitic, or pathogenic fungus assoc with plant
VISION FOR PLANT MEDICINE
evaluate literature
scientist and clinician evaluate in field
determine active principles and mechanism
eliminate contaminants, adulterants
standardization (bot, chem, bio) (lot to lot analysis)
stability and safety studies
demonstration of efficacy
sustainable development as a crop
reporting of drug-drug (adverse) effects, events (might be useful)
MOLECULAR TECHNIQUES IN MED PLANT ID
botanical identification and authentication to use DNA based techniques (RAPD-PCR)
"similar" plants mb confused in the field (Piper sp several look same but chem diff)
unrelated plants may have same name
incr tech in bio eval
gene based bioassay targets
potentiate the genes of plant and fungal biosynthesis (GMO-->fast growing systems)
new plant combos
locate the plants, monitor and analyze them, remote sensing?
in field DNA analysis? PCR in the woods?
Sean Connery in Medicine Man
put a lab in a suitcase: this man has a good idea what you need and what the technology is
says it's a software issue, hardware is mostly available, GPS, cameras, etc incr hi tech
solar power, battery pack
TOUGH QUESTIONS
how conserve and preserve bio resources?
implications of climate change?
how "green" is the process?
feedback mechanism to evaluate sustainability of evidence-based effectiveness?
environmental impact of wildcrafting vs cultivation?
labeling of RX and OTC re: envir impact? supps labelled?
role of sci groups?
what is global agenda?
CONCLUSIONS
obligation to future generations
nat prods need higher profile
sustainable supplies needed
need integration to prevent wrong use, terrorism
collaboration essential
Q'S
researching indigenous medicine has risk of taking sustainability away from community
commercial gain may complicate healthcare for community where medicine was found
Medicinal Plants in a World Out-of-Balance
Geoffrey A Cordell
Natural Products Inc., Evanston, IL
research, speaker, drug discovery, quality control
35 years in natural products
he thinks this presentation will be a new whole picture for us
just traveled to India, Sumatra, Singapore, SE Asia is a favorite destination
distinguished gentleman, came out of retirement because he found his passion
world out of balance--terribly
developed "north" is leading
he wants to talk about the future
lecture overview: perspectives, plants place, WMDs and WMIs, visions for restoring balance
THE GREAT DIVIDE
affluence, global people, rich, surplus resource, cause of climate change, living into old age, technological knowledge, theory-driven research (the US, Europe, the "west", the northern hemisphere)
vs
action-driven research, traditional knowledge, impacts of climate change, resource shortages, young, jobless, local people, poverty
WORLD OUT OF BALANCE
6.94 BILLION people today
10 billion by 2035 or 2037 ish
5.5-6 billion is stable world population
we're past the tipping point
pantropical deforestation
no drugs for existing critical global diseases
new and untreatable global diseases (sars, aids, mrsa,vrsa)
increasing drug resistance (cancer, malaria, tb, aids)
getting Rx drug to market costs 1.2 billion $
drugs too expensive for govts, ins, pts
drugs for N vs S
synthetic drugs not sustainable longterm: aspirin
poor quality control (major issue)
can we provide traditional medicines???
want sustainable drugs
human overconsumption of natural resources-->generational crisis
legacy for descendants is grim
TIME article on why drugs cost so much, 2004, drug discovery process inefficient
7% of IND pass clinical trials
2005: 21 novel drugs
overview of US pharm industry in Chem and Engineering News
pharma innovation gap: investment has increased more than return
GREAT HEALTHCARE DIVIDE
Ghana 110 people/healer, 1MD/21,000
US $2096/year, China $227, Ethiopia $21 on healthcare/year (2007)
Poor 56% of dz 2% of care
1556 new meds in last 30 years, 1.3% for dz prevalent in developing world
drug system regulated here, unregulated in southern hemisphere (WHO study)
PHYTOTHERAPEUTICALS
64% (4.4bn)(guesstimate) of world pop uses plants as primary health care source (WHO number 1984)
$4.41bn on phytotherapeuticals in US in 2005
KILLER DZ
AIDS 3.1m death/yr, 5.5m new
TB 2m deaths, 8m new
Diarrhea 1.9m death, 22.7bn new
Malaria 1m deaths, 300-500 new
Hep B 1m deahts, 10-20 m new
SARS 8,096 on 04/04, 774 deaths
H1N1...
ALKALOIDS
he has studied plenty
Papaver somniferum, (poppy) codeine, morphine--the painkiller, Afghanistan produces 95% of world's opium
Erythroxylum coca, cocaine, anesthetic, submarine built in Bogota, Columbia for smuggling drugs to Mexico
NATURAL PRODS AS WEAPONS of mass incapacitation or intimidation
--these are serious poisons
--myth: natural products are safe
--these are easily available
--tylenol in Chicago approx 1979, most bottles have sealed cover because of what happened, someone put cyanide into bottles and 7 people died
--anthrax laced letters in post 9/11
Coniine (Socrates)
Ergot (on wheat, rye, bread, 11th century 1/3 of pop died, bloodless loss of limbs)
Digitalis
Curare
Amanita mushroom
Teratogens
Botulinum toxins
Staph enterotoxins
Ricin, Abrin (Georgi markov killed with umbrella jab in 1978)
--ricin laced letters send to senate in 2004, leaf 8 lobed
Saxitoxin (red tide)
Trichothecene mycotoxins
REALITY CHECK 2009
pop increasing
technology increasing
killer dz increasing
oil decreasing
biodiversity decreasing
(steroids are semi-synthetic)
forest decreasing, population increasing (chart)
CROSSROADS
need new vision, status quo
Woody Allen quote: our choices as despair and hopelessness vs extinction
Saint Hildegard of Bingen quote, "nature at disposal of humankind, wwork with it"
Millenium Ecosystem Assessment: "the ability of ecosystems to sustain future generations can no longer be taken for granted" (UN 2005)
"If you are on the fifth step and you think you are too high, you will never make it to the sixth step." -Ajahn Chah, A Still Forest Pool (Buddhist monk)
PUBLIC HEALTH DISPARITY WITH RESPECT TO MEDICINAL PLANTS
new drug discovery mostly for developed world
development of traditional medicines very unfocused
evidence lacking for traditional medicines, mostly unregulated
still these medicines are fundamental to basic healthcare for most of world
adulteration of medicine isserioushazard
resource depletion threatens health care for billions
RESPONSIBILITIES FOR NAT PROD SCI IN HEALTH CARE
contribute to drug discovery, standardization, foods, awareness of detrimental products
SUSTAINABLE MEDICINAL AGENTS
organic chems used for 75% of drugs
other industries examining plants as oil source
we needto look at sustainable drug options
indigenous people have always known this
natural product extract are no longer of interest to major pharma co's
too long to isolate
ETHNOMEDICINE
study of indigenous uses of medicinal plants
look at all systems: (native American, Unani, Ayurvda, Chinese, Kampo, Thai, others)
rising pop is main challenge, sustainable only if cultivated
275,000 higher plants, ethnomedical reports for 15,000, 60% never studied
74% of plant-derived Rx products discovered based on original ethnomedical use
tubocurarine used in surgery today, poison arrow toxin
where find info? old books, traditional healers, books, reviews, herbaria notations
market places: ask the sellers
ALKALOIDS
21,120 plant alakloids with 1,872 skeleta
15.6% of known nat prods
46% pf plant-derived pharma
76% of known alkaloids never tested in a single bioassay
collaboration is missing in scientific study
A VISION FOR NATURAL PRODUCTS
must contribute to global health and food
develop nat prods as single or combo drugs
utilize traditional meds
improve detection and isolation of novel bioactive nat prods
enhance natural product structurediversification for drugdiscovery
use vegetables as chemical reagents
using plants for green chemistry
synthetic reagents and solvents are costly, must be shipped, borders are an issue
can we use local plants as enzyme sources?
chirality important in most drugs these days
EXAMPLES OF VEGGIES
aqueous extracts of carrots showed reduction of carbonyl grps in modest yield and enantioselectivity
reduction of ketons and aldehyes with Manihot esculenta (pic looked like ginger)
acetylation of citronellol with an immobilized prep from Manihotescuelenta
sustainable reagent source
TRAD MEDICINE
he's a traveller
Kerman, Iran
Marrakech, Morocco
Santiago, Chile
Cape Town, S Africa
Chengdu, China (pic of lg market)
95% of plants collected in forest
worlds largest exporter of medicinal plants (144,000+ tons)
Medellin, Colombia
India--90% of meds are wildcrafted, 4-10,000 facing extinction locally, regionally, nationally
64/71 of rare plant species in active trade
govt agencies developing farms
Traditional medicines are like coffee--they have to work!
MYTHS
dietary supps are safe
dietary supps are regulated (not true, poor reg world wide, no assessment of ag or efficacy)
NEW COMPLICATING FACTOR IN TRAD MED
activity of med mbdt microbial, parasitic, or pathogenic fungus assoc with plant
VISION FOR PLANT MEDICINE
evaluate literature
scientist and clinician evaluate in field
determine active principles and mechanism
eliminate contaminants, adulterants
standardization (bot, chem, bio) (lot to lot analysis)
stability and safety studies
demonstration of efficacy
sustainable development as a crop
reporting of drug-drug (adverse) effects, events (might be useful)
MOLECULAR TECHNIQUES IN MED PLANT ID
botanical identification and authentication to use DNA based techniques (RAPD-PCR)
"similar" plants mb confused in the field (Piper sp several look same but chem diff)
unrelated plants may have same name
incr tech in bio eval
gene based bioassay targets
potentiate the genes of plant and fungal biosynthesis (GMO-->fast growing systems)
new plant combos
locate the plants, monitor and analyze them, remote sensing?
in field DNA analysis? PCR in the woods?
Sean Connery in Medicine Man
put a lab in a suitcase: this man has a good idea what you need and what the technology is
says it's a software issue, hardware is mostly available, GPS, cameras, etc incr hi tech
solar power, battery pack
TOUGH QUESTIONS
how conserve and preserve bio resources?
implications of climate change?
how "green" is the process?
feedback mechanism to evaluate sustainability of evidence-based effectiveness?
environmental impact of wildcrafting vs cultivation?
labeling of RX and OTC re: envir impact? supps labelled?
role of sci groups?
what is global agenda?
CONCLUSIONS
obligation to future generations
nat prods need higher profile
sustainable supplies needed
need integration to prevent wrong use, terrorism
collaboration essential
Q'S
researching indigenous medicine has risk of taking sustainability away from community
commercial gain may complicate healthcare for community where medicine was found