Martina Newell-McGloughlin
Director,
Di t UC S t id Biotech Research
Systemwide Bi t h R h
and Education Program
http://ucbrep.info
What is
Biotechnology?
• Biotechnology is a series of enabling
technologies,
technologies which involves the manipulation of
living organisms or their sub-cellular
components to develop useful
– (insulin)
Products (i i )
– Processes (improved fermentation)
– Services (bioremediation)
• Biotechnology encompasses a wide range of
fields, including th lif i h it
fi ld i l di the life sciences, chemistry,
agriculture, environmental science, medicine,
veterinary medicine, engineering and computer
i
science.
Biotechnology Applications
• Industrial applications: Enzymes, Food, Feedstocks, Fuels,
Microbiological mining, Biosensors
Agriculture
• A i lt
– Plant: Crops, Horticulture, Forestry (Food, Feed and
Fiber), Diagnostics
Animal: M l P lt Fish (F d Ph i
– A i l Mammal, Poultry, Fi h (Food, Pharming, ModelM d l
systems)
• Environment: Low impact alternatives, Pollution
amelioration, Biomass conversion, Detection and analysis
systems
• Medical
– Human: Therapeutics, Diagnostics, Intervention regimens
– Animal: Therapeutics, Diagnostics
• Forensics
– Legal
– Personal
Biotechnology is not new
• 6500 BC Encrusted residue in the shards of a hunter-
gatherer camp unearthed in 1983 by Edinburgh
archaeologist - Neolithic heather beer
• 4000 BC Tigris-Euphrates cradle of civilization -
viticulture established. Babylonia beer a more
popular drink - climate more suited to growing grains
than grapes. In Mesopotamia 40% of cereal
production went into beer production.
• 3000 BC Celts independently discover the art of
Pliny Western
brewing -Pliny the elder notes: “Western nations
intoxicate themselves by means of moistened grain”
• Katz,
Solom Katz anthropologist suggests that these
discoveries led to the transformation from hunting
gathering to agricultural societies about 10,000 year.
• Industrial biotechnology applications have led to
cleaner processes with lower production of wastes
and lower energy consumption
• 90% of the enzymes used in large scale for
commercial applications result from the
exploitation of rDNA methods in the manufacturing
process or for the improvement of the catalysts
themselves.
• Industrial Applications:
– Food: human and animal
– Cleaning
– Textiles
p paper
– Pulp and p p
– Leather and Tanning
– Fuels
– Chemicals
– Metals, minerals and energy.
Following are from “trusted” Sources?
• FAO? World Bank? Ecology Groups?
• FAO: global demand for food 2.5 –3X in
poorest countries by2050 (FAO, Rome).
• 17% of land under cultivation degraded
by human activity from 1945 to 1990. Ag
land shrinks by 20,000 hectares yearly.
(World Bank, 1997)
• Without yield increase land use will
1997 acreage double by 2050
Without t d ti it Chi /I di
• With t greater productivity China/India
will need 4X land area
• Latin America: greatest yield increase
had lower land use (less deforestation)
• High yield “land sparing” better than
“wildlife”-friendly inefficient land use
farming
(Green, Royal Soc. Bird Protection &
African Society Ornithology 2005)
Is Agriculture natural?
8,000 BC Cultivation
19thC Selective Cross breeding
Ea 20th C Cell culture
Md 20th C Somaclonal variation
1930s Embryo rescue
1940s Mutagenesis and selection
1950s
1950 A th culture
Anther lt
1970s Recombinant DNA
1980 Marker assisted selection
1990s ---omics - Bioinformatics
2000s Systems Biology
21st C Epigenetics/RNAi/Paramutation
Adaptive technology/transgenomics
p gy g
Wide Crosses
Tomatoes are members of th
T t b f the
Deadly nightshade family
Lycopersicon
chmielewskii
• High solids = More
sauce: Two L. esculentum
approaches one end:
“Natural” cross with
high solanine “toxic”
wild tomato
• Using antisense,
Back-
switch off existing
g
cross
gene – no
series
introgression of genes
from the toxic plant Tomato Cultivar
Biotech Crops –”process” regulation
Commercialization: 7 to 10 years -at least 9 review stages
• C i li ti t tl t i t
• Biotech crops and foods more thoroughly tested than
conventional varieties ( “assumed” to be safe)- One
1,800
biotech soybean subjected to 1 800 separate analyses
• 23 feeding studies - dairy, beef, poultry, soy/corn equivalent in
composition, digestibility and feeding value to non-GM. Clarke et al
000
2000
• Product description (7 items) - Substantial equivalence with
parent variety - Molecular characterization (17)
• Toxicity studies (as necessary) (5) - Antibiotic resistance marker
genes (4) - Nutritional content (7+)- Allergenicity potential -
Anti-nutritional effects - Protein digestibility
• Environmental aspects (5 items)- Ecological impact (5 items)
Recent studies
Wheat ( Baker 2006), Potato (Catchpole 2005)
Transcriptomic and Metabolomic studies show greater variation between conventional
bred cultivars and even growth locations than between GM and parental variety (except
of course for the intended modification!) - differences between sites were generally
greater than differences between lines
Biotech part of a sustainable future
CO2
Renewable
Resources
Biofuels
Feedstocks
Value Bioremediation
Plants as Factories
Pharmaceuticals/ Industrial products
(Ventria – Rice Lactoferin Lysozyme
Peru 30% Less Diarrhea, Quicker
recovery 3/6 days, 1/3 less recurrence
Quality Traits - ($210B by 2010)
Shelf life –
Improved Nutrition –Improved Functionality
Macro: protein, oils, carbs, fibre
Micro: Vitamins, minerals,
Agronomic Traits – $30B Phytochemicals Antioxidants
Ph t h i l – A ti id t
Biotic/ Abiotic Stress /Yield Remove Antinutrients/allergens/ Toxins
1st Wave 2nd Wave 3rd Wave 4th Wave
Biotech Crop Countries and Mega-Countries (2006)
(James, 2007)
• p
Biotech Crops 2006: 252 M acres ( )
(102 M hts)
• 22 countries (11 LDC) 13% increase over 2005
• 10.3 M farmers up from 8.5 M in 2005
• cotton
90% resource-poor LDC farmers (9.3 M -7.7 M 2005) most BtSource: ISAAA
Retrospective/ prospective 1996- 2006
996 o 006 60X c e se, g es dop o e
– 1996 to 2006 60 increase, highest adoption rate
of any crop technology (James, 2007)
– 10.3 M farmers up 8.5 M 90% resource-poor LDC
billion
– Net economic benefits cumulative $27 billion.
– Pesticide spraying down by 380 M lbs (172 M Kg.)
Environmental footprint of pesticide use by 14%.
– GM reduction in 9.4 billion kg of CO2 emissions in 2004
equivalent removing 5 M cars from the roads. (Brookes 2005)
– Herbicide-Tolerance - increase in no- till: reduction in
erosion, soils much healthier, organic matter, less soil
compaction, fuel use down by 20 gals/acre
– CP papaya saved Hawaii papaya industry (and helped
organic farmers!)
– China BT rice pesticide use down 80% lives saved
– 90% reduction in mycotoxin fungi produce fumonisins
– Blight-resistant potato -UI study concluded for the major
potato-producing regions of the world would be $4.3 B
• Crop production i li it d by salinity on
C d ti is limited b li it
40 % world's irrigated land and on 25
% USA about 1/5 California.
• Blumwald and Zhang genetically
engineered tomato plants that produce
higher levels of a "transport protein.“
• Plants grow and produce fruit even in
irrigation water that is > 50X saltier
than normal. > 1/3 salty as seawater.
Nature Biotech, July 31, 2001
Typed i 10 f
T h
d in 10- font, one human sequence would ld
stretch more than 5,000 miles. Digitally
formatted, can be stored on one CD-ROM.
Biologically encoded, it fits within a single cell.
• Genomics: the analysis of genomes. A genome can be thought of as the
complete set of DNA sequences that codes for the hereditary material that is
passed on from generation to generation. These DNA sequences include all of
g (the
the genes ( functional and p y y)
physical unit of heredity)
• Comparative genomics Info from one organism can have application in another
• Transcriptomics: analysis of all transcripts (expressed genes changes based on
external stimuli – stress- diet – aging = Functional genomics!)
• Proteomics: P
P is h
i Proteome i the set of all expressed proteins for a given organism.
f ll d i f i i
• Metabolomics: analysis of all metabolites produced by organism–can be used
as biological markers
• biology omics
Systems biology, involves the integration of all the “omics” information to
create a whole system view of an entity. By understanding the complete “parts
lists” in a genome, we gain a better understanding of complex biological
systems and how they interact to make a functioning organism.
Nutrigenomics Nutritional Genomics
"Leave your drugs in the chemist's pot if you can heal the patient
food "
with food." (Hippocrates)
• Nutrigenomics Analysis of nutrient regulation of gene expression
• Nutritional Genomics/ Nutrigenetics: Individual response to
nutrients/anti-nutrients.
different nutrients/anti nutrients May change how we prevent and
treat disease and how food is grown and processed?
Nutrigenomics Nutritional Genomics
disease associated
• Monogenic Diseases: 97% “disease-associated” genes
• Phenylketonuria, phenylalanine hydroxylase PHE -> TYR.
Leads to neurological damage and mental retardation.
TYR-supplemented no
PHE restricted TYR supplemented diets -no Aspartame!
• Lactose Intolerance – Juvenile enzyme active in adults
• Fauvism G6PD Deficiency red blood cell enzyme Med
• SNP in haemochromatosis linked gene (HFE) risk for
haemochromatosis,
• A222V MTHFR PM higher intakes of folic acid to lower
serum homocysteine
• Polygenic diseases obesity cancer diabetes and
obesity, cancer, diabetes,
cardiovascular diseases
• Dietary intervention complex and ambitious goal
• Most dietary effect specific interactions on molecular
level, regulation of gene expression directly or
transcription factors
Nancy Fogg-Johnson: “Nutrigenomics” ( correct term should be
Nutrigenetics) will revolutionize health and nutrition – It will inform how
grown, processed,
we prevent and treat disease and how food is grown processed and made made.
Eventually nutrigenomics will be able to discover diets that prevent or
retard the onset of the most serious and widespread of today's killer
diseases, cancer, Alzheimer s.
diseases like cancer as well as degenerative diseases like Alzheimer's
When/if?
• Sitosterolemia (hyperabsorption of sterols hypercholesterolemia risk for
atherosclerosis). Regulation of sterol uptake
• Mice was treated with a lipid metabolism-altering drug
p g g
• DNA microarray used for expression profiling of various tissues.
• Differential display with a control led to the discovery of an unknown gene.
• Computer simulation found that two proteins gene regulated reverse
cells.
transport of dietary sterols out of the apical surface of intestinal cells
• Exploring human gene databases, found a human homologue
• This explained why dietary sterols, which are structurally similar to
cholesterol, are not absorbed in normal individuals.
• By scanning sitosterolemic individuals for this gene, it was found that all of
them had a mutation in this gene responsible for their uncontrolled
hyperabsorption of dietary sterols.
Nutrigenomics Nutritional Genomics
• Nutrigenetics analysis of genetic variations among individuals
with respect to the interaction between diet and disease.
• Individual genetic makeup affects the response to diet and the
susceptibility to diet-related diseases.
• Gene variants associated with differential responses to
nutrients and higher susceptibility to diet-related diseases.
• GOAL: to provide nutritional recommendations for individuals
in what is known as personalized or individualized nutrition.
diet-
• Genetic variations shown to increase the susceptibility to diet
related diseases. Type 2 diabetes mellitus, obesity,
cardiovascular diseases, autoimmune diseases and cancers.
g y p g
• Nutrigenetics aims to study these susceptible genes and
provide dietary interventions for individuals at risk.
• Dutch Famine babies
• Lipomics: lipid profiling
determine fitness susceptibility
Nutrigenomics Nutritional Genomics
sensitivity
• Number of genes regulate lipid metabolism/insulin sensitivity,
thus affect susceptibility to type 2 diabetes mellitus.
• SREBP-1c (sterol response element binding protein) mutations
livers, resistance, T2DM.
led to fatty livers severe insulin resistance T2DM For one
polymorph mRNA highly induced in mice on high fructose
diets. Another PM indicated DM onset in men, but not women
• T2DM: Asian/Hispanic populations insulin resistance rather
than β-cell dysfunction. In African-Americans the opposite.
• Hyperlipidemia: E4 allele in the apolipoprotein E higher LDL
(E1 E2
compared with the other (E1, E2, E3) for same fat intake levels
• ApoA1 women showed increase in HDL with increase in PUFA
compared to G variant taking similar amounts of PUFA.
Haplotype (H K) i l k t i
•H l t hydrolase (LTA4H) risk of
(HapK) in leukotriene A4 h d l i k f
myocardial infarction (MI) European and African Americans. MI
significantly greater in African-Americans HapK. (n6/n3)
Barbecue H t
•B b li ti i t l t dt ti
Heterocyclic aromatic amines acetylated to reactive
metabolites bind DNA - colon cancers. Only NAT2 fast
acetylator PM genotype has higher risk for colon cancer
Caveat Emptor!
C tE t !
Will there be implications for
your insurance if you have a
susceptibility to heart disease?
Will there be implications if you
fail to follow a diet to retard the
onset of symptoms?
• "Nutrigenetic Testing: Tests Purchased from Web Sites Mislead Consumers.“
• Government Accountability Office (GAO) commercial "nutrigenetic" testing
dubious clinical validity of commercial genetic tests, and unethical practices
• Investigators posed as 14 clients used the DNA from just 2 - man (48)-girl
(9mnth). Despite this, the test 'results' were contradictory and warned of risks
p , ,
for various conditions. osteoporosis, heart disease, diabetes and more. Affiliated
companies then offer nutritional supplements to stave off these predicted
sicknesses — but the pills turn out to be little more than multivitamins, offered
with a hefty dose of misleading medical advice. Cost to you a mere $89 to $395!
(Nature, 2006)
Improved Nutritional Content
Many common food crops not perfect for nutritional
requirements of humans or animals.
Proteins
Protein-energy malnutrition (PEM), 1 in 4 children worldwide
70% Asia, 26% Africa, 4% Latin America
• Ratio Lysine/ Methionine: Feed Rations/pollution
• High Lysine maize: C. glutanicum DHDPS (5K/1.5K ppm)
g y g ( pp )
• SRP Nonallergenic Amaranthus Albumin for potato
• High Protein: Cytokinin rescue flower pair kernels fused
single kernel two embryos - high protein/oil low CHO
• Artificial Proteins:
• ASP-1-sweet potato 67% increase protein (EAA 80%)
• MB1 – soybeans
Carbohydrates
• Starch High Amylose (resistant starch) inhibit 2 SBE
• Wheat puroindoline genes in rice better starch/flour
• Low-Stachyose galatose, raffinose: Higher energy-lower
indigestible carbohydrate – sweeter:
Improved Nutritional Content
Fiber – Humans increase
• Polymers, Inulins, Fructo-oligosaccharides (FOS)
• SC Fructans sucrose taste: GI Tract health- fermented
colonic – bifidobacteria (compete pathogenic bacteria)
SC Fatty acid – anticancer/ inhibit HMG-CoAR less LDL
• SC fructans 1-SST Jerusalem artichoke. 90% sucrose
converted "fructan beets“ (Koops, 2000)
• Potato synthesize the full spectrum of inulins from
l b ti h k t
globe artichoke roots
• Lignans: enterodiol/lactone estrogen-dependent cancer
Fib – A i l Decrease
Fiber Animals D
• Brown midrib (COMT)–Decreased lignin increase
digestibility better feed conversion, livestock prefer
(Sorghum)
Improved Nutritional Content
Oils and Fatty acids
• Altering chain length and saturation level
•
• Novel genes to produce unusual fatty acids in oilseed
MUFA: Hi h Ol i A id (L Li l i ) t bl th
• MUFA High Oleic Acid (Low-Linolenic) : more stable than
PUFA heat/ oxidation resistant, little or no postrefining
(hydrogenation): AS oleate desaturase soybean gave
80% oleic acid (23%), ess SF / eat of animals
>80% o e c ac d ( 3%), Less S milk/meat o a as
• Stearate Canola, Shortenings, Cocoa Butter Replacer
• MCT: medical foods, ergogenic aids. Acyl-ACPT canola,
increase in capric (C10) and caprylic (C8)
i i i d li
• High-CLA: Antioxidative effects,-- free radicals heart
disease/cancer
• Omega -3 DHA-EPA “Fish Oil” CV/thrombosis/ Cancer/
Arthritis/ Cognitive/Mental/ premies - Δ6 Desaturase:
Canola precursor SDA 3.6>>ALA in generating EPA
Ω− 6 GLA- 4X Safflower: Neurodegenerative/inflammation
HO • Sitostanol: phytosterol phospholipid Block cholesterol
Sitostanol Cholesterol
Improved Nutritional Content
Micro Vitamins:
Golden rice II β-carotene-Rice (
• AG / )
(70g provide 2/3 RDA)
• Folate increase in rice (pregnancy deficinicies)
• E α−tocopherol γ-TMT; Vit C increase corn DHAR
Minerals Ferritin (bean S protein), Metallothionein (Rice, wheat)
Functional components - effects greater than nutrient value alone
Phytochemicals:
• Carotenoids: Golden Rice, Sweet Potato - (sight, development)
• Lycopene: polyamine Tomato – (reduce LDL prostate cancer)
• Flavanols: Catechins, Flavones: quercetin (less DNA adjuncts)
• Phenolics: resveratrol antioxidant (Sirtuin protection anti-aging)
Anti-nutrients: Trypsin Inhibitors; oxalic acid; furans; Phytate,
Anti nutrients
Bioavailability Phosphate, divalent ions: Phytase (Rice, alfalfa)
Allergens: soy P34 removal; peanut; gluten digestion
Toxins: Glycoalkaloid (potato) AS solanine
• Cyanogenic glucoside (cassava) hydroxynitril lyase
Genomics: Marker assisted selection, generation interval reduction etc.
Transgenics
Agriculture Applications: More efficient production of animal-derived
foods.
- disease resistance
p
- improved p y p growth rate, metabolism,
productivity: improved g
milk/meat quality and composition
Medical Applications
- Produce valuable proteins in milk, blood or urine
- Xenotransplantation
- Disease and developmental models
Clones: Efficiently and truly reproduce the above elites (some hopeful for
Lazarus effect)
Of course the public would never accept genetic engineering of animals!
Large heavily muscled birds with
reduced libido – AI to the rescue
Better Quality “Livestock” Transgenic Coho
Salmon Sockeye GH
grows 6X times
faster converts feed
20% more effectively
reaches maturity ½
time WT
GloFish
EnviroPig Vegetarian milk
Phytase i saliva
Ph t in li (Improved FA)
(I d
HemaTech "knocked out" the prion gene in 12
Lysozyme Goats cloned calves. No disease when brain tissue from
(Also Improved FA) two of the animals exposed to mutant prions
BioSteel (spider silk)
80X tensile strength
of steel in milk of
transgenic BELE
goats. Strength and
flexibility for medical
devices or body y
Willow armor.
Sweetheart (2006) GTC
Helen Sang Roslin (The chick
anti
Biotherapeutics. ATryn, anti-
clotting first drug approved
L d !)
Lady!)
by the European Medicines • 500 flock lentivirus targeted to
Agency (EMEA). Pharming egg white:
G ti i fl
Group anti-inflammatory
t beta-1a
• human interferon beta 1a for
drug in Transgenic rabbits. multiple sclerosis.
• miR24 AntiBody treating
malignant melanoma
Marathon Mouse
Ron Evans et al. genetically engineered an PPAR-delta-
more muscle, less fat and more physical endurance
than littermates (slow twitchers / IIX Fibres).
Mice ran 1,800 meters stayed on the treadmill an hour
longer than controls, which ran 90 minutes and travel
900 M No weight gain on a high fat, high calorie diet
Bring i th Cl ?
B i in the Clones?
Dolly
CC
Millie, Christa, Alexis, Carrel, Dotcom
• Endangered species banked tissue –
• Duplicate valuable “pharm” animals –
Create homogeneous populations
• C t h l ti
of cells, tissues and even organs
for therapeutic transfer
Promethea • Tool to study genome disease, aging and development
Human Biotechnology- Applications
Diagnostics:
M l l tib di N l i A id P b b d
•Monoclonal antibodies, Nucleic Acid Probes, genome-based
Therapeutics:
Drugs
•Drugs
•Vaccines
- Recombinant vaccines
- Recombinant Antigens:
d d
vectored, non-vectored
- DNA Vaccines
•Stem Cells
Gene
•Gene therapy
Genomics:
•Information source for preventative medicine, therapeutics,
diagnostics, gene therapy
Tissue Engineering
Biomaterials, Nanotechnology
Probiotics
Detection of Functional Elements in the Human Genome
Using Comparative Genomics and Evolutionary Models
Nov Seipel’s
Nature Nov. 2004 Adam Seipel s seminal work
applied new computational methods for the
detection of functional elements in the human
g ,
genome, reducing p g genes from an
g protein-coding g
initially estimated 35,000 to only 20,000 to
Adam Siepel
UCSC
25,000.
Humans share a
15% homology with baker’s yeast,
20% homology with Arabidopsis
38% homology with the worm C. elegans
47% h l ith th f it fl
homology with the fruit fly,
63% homology with the mouse,
Functionally interchangeable with their counterpart, model
pathways
organisms genetics for human genes suspected to lie in important pathways.
Piebald Syndrome:
mouse and humans have
hit t h
same white patch on
stomach and forehead
resulting from mutation
in the same (c-kit) gene
Immune system fighting for you……
Minerva
Boor
Herceptin
patient
Herceptin; (Trastuzumab) : Mab treatment for HER2 protein overexpressing
metastatic breast cancer.
Rituxan® (Rituximab): A Mab for the treatment of relapsed or refractory
CD20-+ B-cell non-Hodgkin's lymphoma, cancer of the immune system.
Avastin (Bevacizumab): Humanized Mab VEGF prevents interaction receptors
on the surface of endothelial cells preventing colon cancer angiogenesis.
…and against you
Stem Cells
•. Geron: Phase I clinical trial, for
acute spinal cord injury. Achieved
functional recovery of treated animals
From nanobots to nanorobes
• January 2005: Carlo Montemagno at the
California
University of California, Los Angeles used rat
muscle tissue to power tiny silicon robots, just half
the width of a human hair, a development that
could lead to stimulators that help paralyzed
people breathe and "musclebots" that maintain
spacecraft by plugging holes from
micrometeorites. It was the first demonstration of
muscle tissue being used to propel a
microelectromechanical system.
Leechian logic
• Ditto at GIT has hooked a number of leech neurons up to microprobes.
• neurons.
Did arithmetic with two large leech neurons The researchers joined the
neurons and linked them to PC, sent number signals to each cell. Using
chaos theory, Ditto stimulated the two neurons. From the chatterbox
traffic that followed, the PC extracted the correct answer to an addition
problem.
problem
• This is the first time invertebrate brain cells have used chaos to do
,
arithmetic, let alone communicate the results to humans. Computerp
simulations by Ditto and Sudeshna Sinha in Madras, India, show that
larger clusters of neurons should also be able to do multiplication and
Boolean logic operations, the underlying principle of digital computers.
• Ditto hopes to use his work in developing robotic brains, where the size
of silicon devices will be prohibitive for many years to come.
Bio-computing. Biological Routes to Hybrid Electronic and Magnetic
Nanostructured Materials. Angela Belcher MIT reports in the Jan 9, 2004
issue of Science that she used genetically engineered viruses that are
noninfectious to humans to mass produce tiny materials for next-generation
optical, electronic and magnetic devices. LCDs. computers, Biosensors,
diagnostics, detection, drug delivery
August Estabrook UCSB nano-material assemblies through bio-scaffolding.
Bio-scaffolding DNA, proteins, or a combination of site-specific binding
proteins and DNA duplex structures for the assembly of nano-scale materials.
Able
Potential for these materials as memory devices –Able to generate optical
write-read/ thermal erase memory images by taking advantage of changes in
the nature of energy transfer following thermal fluctuations in the polymer August
assemblies. Estabrook
Cynthia Kenyon,
Wins King Faisal Prize
Elizabeth Blackburn, UCSF
• Cynthia Kenyon, work with C. elegans has demonstrated that
aging is controlled hormonally through the insulin receptor
system
system.
• daf-2 gene Worms live twice as long with good quality of life
• These worms clearly show the rate of aging is not fixed can be
l d A h daf-16, ff i b i hi h
slowed. Another gene, d f 16 affects aging by switching other
genes on or off. Some encode proteins that prevent or repair
damage molecules in the cell.
• Elizabeth Blackburn, UCSF revealed the critical role of
telomeres — segments of DNA that bind both ends of
chromosomes — and could one day explain the secrets of
d i
cancer and aging.
• It may be possible to reset the clock in humans.
Greatest Challenges going forward
Technical
Intellectual Property: PIPRA – Freedom to Operate (FTO)
Liability
Biosafety: LDCs
Acceptance: - countering fear and misinformation
- moral imperative real need v. hypothetical risk