New Breeding Technologies: Comparing Old and New Ways to Genetically Change Organisms

BIOTECHNOLOGY INDUSTRY ORGANIZATION 1

New Breeding Technologies:Comparing Old and New Ways to Genetically Change Organisms

Adrianne Massey, PhD

Managing Director, Science and Regulatory Affairs

[email protected]


History of Crop Genetic Modification

Understanding the historical development of

crop genetic modification is essential for:

• understanding relative risks

• designing appropriate regulations (hopefully)


Genetic modification of food is not new

Humans have intentionally changed the genetic makeup of all

• Crops we grow

• Livestock we raise

• Microorganisms we use in food processing

“GMO” = all food, except wild fish/game and

wild fruit (e.g., berries)



Crop domestication = Crop genetic modification. Began 10,000 years ago.

Selected seeds from certain plants to be planted for the next year’s crop.

Genetic modification through artificial selection.

[artificial (human) selection vs. natural selection]


Teosinte – wild ancestor of maize

Modern Maize


Historical Development of Maize

Wild, weed relative

Evolution by Artificial Selection

Early humans changed teosinte into maize

by “selecting for” certain traits (genes) and

“selecting against” other traits (genes)


Historical Development of Maize

Of the 59,000 genes in maize, early humans focused on selecting for traits encoded by only 1700 genes.

What do those other 57,300 genes do? Who knows?????



Stage 1. Artificial Selection – work with existing variation

Stage 2: Selective Breeding

Began when we learned how plants reproduce (1660’s)

Controlled which plants reproduced -

Shaped the variation in the population.

Then selected certain seeds for next year’s crop.

femalemale


Selective Breeding Within Same Species

At first……

Same SpeciesShared gene pool

Can exchange genes naturally through

sexual reproduction


Next Step: Selective breeding between different species

Same genusDifferent species

Same species

“Wide Crosses” that would not occur naturally


Selective Breeding Across Species

Some varieties of all major crops came from breeding different species with each other.

Corn Tomato Rice Oat Canola Wheat Soy Potato BarleyBeets Squash Cotton

First fertile, between-species cross in 1700’s“Not natural”


Different genusDifferent species

Next Step: Selective Breeding between different genera

Same genusDifferent species

Same species

Different genusDifferent species


Selective Breeding Across Genera

Bread wheat has beencrossed with at least eleven different species in six different genera.

1890’s - first fertile between-genus cross


A Set of Lab Techniques Made “Wide Crosses” Possible

Bridge species

Chromosome doubling (chemical colchicine)

Embryo rescue

Treat with hormones, immunosuppressants

Protoplast fusion

Anther culture

Diploid tissue culture


“Natural” Plant Breeding (long before genetic engineering)


Genetic Modification through Mutagenesis

What if the existing genetic variation in accessible gene pools is limited?

Plant breeders create new genes in crop plants with mutagens, such as X-rays.

This form of genetic modification is mutagenesis breeding.


Genetic Modification through Mutagenesis

Since the 1930s, plant breeders have used mutagenesis to create new genes in more than 2700 crop varieties that were introduced to the food supply.


Genetic Engineering

The next step in the continuum of genetic modification techniques.

Most like selective breeding because it uses existing genetic variation.

“ Recombinant DNA technology ” - rDNA

Genetic engineering Transgenic crops

Each dot - thousands of genesExcept single gene - disease resistance.

Thousands of genes withUnknown functions

new variety

One gene Known function Inserted into familiar crop variety.

“Genetically Modified” Crops Genetic modification technological continuum

• Selective Breeding -within same species (8000 BC) - between different species* (1700s) - between different genera* (1890s)

• Mutagenesis Breeding* (1930s)

• Genetic Engineering* (1983)

* - “unnatural”


Continuum of technological change characterized by

Improved precision and predictability

Increased dependence on scientific understanding

History of Genetic Modification


Modification Precision Continuum

Selective Breeding thousands of genes unknown function

Mutagenesis totally random unknown number of genes unknown function

Genetic Engineering 1-2 genes

known function


New Plant Breeding Technologies

The trend continues ………..

Increased dependence on scientific understanding




Examples:• Zinc finger nucleases - ZFN (3 types)• Oligonucleotide directed mutagenesis (ODM)• Induced DNA methylation


New Plant Breeding Technologies (NBTs)

Past: Random insertion of new genecisgene (same species) or transgene

Now: Targeted gene insertion (ZNF -3)



Zinc finger nucleases – ZFN-1 and ZFN-2Oligonucleotide directed mutagenesis (ODM)

These technologies allow very precise editing of plant’s existing genetic material (genome) • Single gene deletion• Single nucleotide changes

New genes are not added to crop



Induced DNA methylation

• No change in genome/gene• Change in gene expression


Regulation of NBTs

What does this mean for regulation?

Increased scientific understanding


Breeding ?

or

GE?

Genetic Improvement of Crops

Thousands of genes unknown function

Single gene ofknown function

Breeding

GE

Costs of Regulatory Compliance

$ 0

$15-36 million



Understanding the historical development of

crop genetic modification is essential for:

• understanding relative risks

Seems irrelevant for

• designing appropriate regulations

As we learn more about the molecular biology

of plants, the regulatory system becomes

increasingly burdensome.


1980’s Scientific Consensus on Risks

Risk GE crops = Risks GM crops

Product vs Process Risk Assessment - National Academy of Sciences

- OECD Expert Panel

- Ecological Society America

- American Society Microbiology

- American Medical Association

- Office Technology Assessment (US Congress)

- Environmental Defense Fund

- Audubon Society


Risk and Regulation

Regulatory policy is shaped by:• Science-based risk• Public perception of risk

Science-Based Risk Assessment

“Public” Perception of Risk


Sample of Scientific Community Support

American Council on Science and HealthAmerican Dietetic AssociationAmerican Institute of Biological ScienceAmerican Medical Assoc. Council on Scientific AffairsAmerican Phytopathological SocietyAmerican Society of AgronomyAmerican Society for Cell BiologyAmerican Society for Horticulture scienceAmerican Society for MicrobiologyAmerican Society of Plant BiologistsAmerican Society of Plant PhysiologistsBrazilian Academy of SciencesChinese Academy of SciencesCouncil for AgriScience and TechnologyCrop Science Society of AmericaEntomological Society of AmericaFederation of Animal Scientific SocietiesFood and Agriculture Organization

Genetics Society of AmericaIndian National Science AcademyInstitute of Food Science and TechnologyInstitute of Food TechnologistsInternational Academy of SciencesInternational Society of African ScientistsMexican Academy of Sciences National Academy of Science &

Technology of the PhilippinesNational Academy of Sciences of USANew Zealand Royal CommissionSociety of NematologistsSociety In Vitro BiologyPontifical Academy of SciencesThe Royal Society of LondonThird World Academy of SciencesWeed Society of America


Regulation: A Primer by Dudley and Brito

Number of pages/year in the U.S. Code of Federal Regulations

Executive Orders Callingfor Regulatory Reform

Regulation: A Primer by Dudley and Brito

Health and Environment Regulations

Economic Regulations

USA

Documents

New Breeding Technologies: Comparing Old and New Ways to Genetically Change Organisms