BISC 005
Biochemistry of Life
Impact of Biotechnology (II)
1
Biotechnology is producing a
scientific revolution.
Recent years have seen an explosion of interest
in biotechnology, the application of genetic
engineering to practical human health problem.
The first and perhaps most obvious commercial application
of genetic engineering was the introduction of gene encoding
clinically important proteins into bacteria.
2
Human insulin: the first commercially produced
genetic engineered product
3
Human insulin: the first commercially produced
genetic engineered product
The human insulin extracted from these bacterial cells, called
recombinant human insulin, can be given to diabetic patient.
4
With similar approach, other medically
important protein is now manufactured.
Bacteria can serve as a low cost “factories” to produce wide
range of useful protein for therapeutic uses.
5
Biotechnology has produced
new and powerful vaccine.
Method
DNA fragment encoding surface
protein of a harmful virus
(as insert)
DNA fragment of
a harmless virus
(as vector)
+
Recombinant viral DNA
infect
Cultured mammalian cells
release
Recombinant virus
(as vaccine)
Recombinant virus has the outside coat of the harmful virus, when injected into body,
the immune system produces antibodies against the coat of recombinant virus.
6
Strategy for constructing a vaccine.
In the future, similar recombinant viruses may be injected into humans to
confer resistance to a wide variety of diseases !
7
Biotechnology is revolutionizing agriculture
It increases yields and resistance to pests, improving nutritional values,
and producing animals or crops with desirable traits.
In 1999, over half of the 72 million acres planted with soybeans in US were
planted with seeds genetically modified to be herbicide resistant,
• so less tillage has been needed, soil erosion lessened
• cultivation of crops become cheaper and more efficient
• the food cost less to get it to your table !
The real promise of agricultural biotechnology is to produce
genetically modified crops with desirable traits that can
directly benefit the consumer !
8
Ti Plasmid: a successful vector for plant cells
Ti plasmid:
• isolated from tumor-inducing bacteria of plant
• able to integrate in the DNA of infected plant cells
9
Regenerate whole plant from cultured cells
By altering the hormonal composition of cultured medium, researchers induced
the cells to grow into embryo, which further grow into whole plant.
Cultured cells from a carrot plant. Roots and shoots of
embryonic plants are already forming.
Researchers can insert gene into Ti plasmid which further put into cultured plant
cells. This Ti plasmid gene become integrated into the DNA of infected plants.
The foreign gene is expressed in the plant tissues, with observable effect on
phenotype.
10
With the Ti Plasmid, we can make
transgenic crop with desirable traits
Herbicide resistance
All four petunia plants were exposed to equal doses
of the herbicide.
Two on top were genetically modified but the two on
the bottom were not.
Crop resistant to herbicide would never have to be weeded !
Use of environmental harmful chemical is lessened.
11
With the Ti Plasmid, we can make
transgenic crop with desirable traits
Insect Resistance
Part of a cotton plant (left) modified for
resistance to attack by worm, as shown
on the unmodified plant (right).
The basic approach is to insert into crop plant a gene encoding proteins that are
harmful to the pests but harmless to other organisms.
• For example, when the tomato hornworm caterpillar ingests this protein, enzymes in the caterpillar’s
stomach convert it into an insect-specific toxin, causing paralysis and death. Because these enzymes
are not found in other animals, the protein is harmless to them.
12
Recent advance: transgenic rice
Problems of natural rice:
• Too little iron.
• Too little vitamin A.
• Too little sulfur for efficient iron absorption. Sulfur is required for iron
uptake, and rice has very little of it.
Worldwide, the two major micronutrient deficiencies are iron, which affects
1.4 billion women (24% of world population), and vitamin A, affecting 40
million children (7% of world population).
The deficiencies are especially severe in developing countries where the
major food is rice.
“A good news to rice eaters: transgenic rice.”
13
Recent advance: transgenic rice
Transgenic rice offers the promise of improving the diets of people in
rice-consuming countries, where iron and vitamin A deficiencies are a
serious problem.
14
Recombinant bovine somatotropin (BST)
BST
• a hormone to stimulate cow’s milk production
• produced by genetic engineering
15
Much controversy exists over BST
BST ingested in milk or meat has no effect on humans, because it is
a protein and is digested in your stomach.
Although BST is functional, harmless and approved by US government,
• BST has met with some public resistance
• some people mistrust any foods produced via genetic engineering
• a generalized fear of gene technology !?
Problems concerning public perception on biotechnology are not uncommon,
which makes an even greater impact on our lives !
16
Even much controversy: Cloning
What is cloning ?
“The difficulty in using transgenic animals to improve livestock is in getting
enough of them. Natural breeding produce offspring too slowly and undo
the engineered desirable traits.”
“One would like to “Xerox” many exact genetic copies of the transgenic stain.”
It is cloning ~~~~~~
In 1997, scientists announced the first successful cloning animals,
“Dolly”,
a sheep grown from a cell taken from an adult sheep.
17
History of Cloning
The ideas of cloning was first suggested in 1938 by German embryologist Spemann,
“Remove the nucleus from an egg cell and put in its place a nucleus from other cell.”
In 1952, the above idea is partly achieved:
“Scientists used very fine tools to suck up nucleus from an frog egg and put
in a nucleus from body cell of another adult frog.”
In 1970, partial success was achieved:
“Scientists inserted nuclei from frog embryo rather than adult tissues. The frog eggs
developed into tadpoles, but died before becoming adults.”
In 1984, scientists succeed in cloning a sheep using a nucleus from a cell of an early
embryo. “So far only early embryo cell seems to be worked.”
However, what we want to do is cloning of an adult animal
from its adult cell, not its embryo !
18
History of Cloning
In 1990s, cell cycle scientist made a key insight,
“Maybe the egg and the donated nucleus need to be
at the same stage at the cell cycle.”
This opens the path to success !
In 1997, scientists removed mammary cells from the udder of a 6-years-old sheep,
and used it to develop a clone sheep which is genetically identical with the same
6-years-old sheep.
The key breakthrough step is to SYNCHRONIZE both mammary cell and egg cell at the
SAME POINT in the CELL CYCLE.
19
Dolly, first successful clone generated
from a differentiated cell
Next slide
Scientists combined a nucleus from a mammary cell and an egg cell (with
its nucleus removed) to successfully clone a sheep.
20
Dolly, first successful clone generated
from a differentiated cell
21
Future of Cloning
It has a major impact on medicine:
• we can easily build a herd of transgenic animals that have human gene
for large scale production of rare hormone
• greatly cheapening the production of expensive drugs
These two mice are genetically identical, but the large one has
one extra gene: the gene encoding human growth hormone.
The gene was added to the mouse’s genome by genetic engineers
and now is a stable part of the mouse’s genetic endowment. We can
extract the human growth hormone from the transgenic mice.
It makes cloning of human possible:
• no reason to believe such an experiment would not work
• but many reasons to question whether it should be done !
22
Stem Cells: replacing damaged
or lost tissues
Embryonic stem cells
• cells from developing embryo
• can develop into any tissue
• give us the ability to restore heart or spinal cord !
Next slide
23
Stem Cells: replacing damaged
or lost tissues
Embryonic stem cells can develop into any body tissues.
Methods for growing the tissues and using it to repair brain, heart and spinal nerves
in adults are being developed.
24
Stem Cells: replacing damaged
or lost tissues
Use of embryonic stem cells
• quite controversial and raising ethical issues
• as the cells are isolated from discarded or aborted embryo
Next to the embryonic is tissue specific
• after embryonic stage, tissue specific stem cells can develop into specific tissue
(after decision is taken, cannot ever produce any other kind of cell)
• it persist even in adult body
• We can use these adult cells rather than embryonic cells !
“Transplanted tissue-specific stem cells may allow us to replace damaged or
lost tissue, offering cures for many disorder that cannot be treated, and do
not present the ethical problems that embryonic stem cells do.”
25
Ethics and Regulations
Are we playing God ?
26
• Is it ethical to create “genetically superior” organisms, including human ?
• Could genetically engineered products administered to plants or animals turn out
to be dangerous for consumers after several generations ?
• What kind of impact on the ecosystem might “improved” crops have ?
27
A closer look on
genetically modified (GM) crops
Is eating GM food dangerous ?
Herbicide resistant soybeans
• herbicide kill the weed by blocking its synthesis of aromatic amino acid
• the gene that confers herbicide resistance does so by enhancing aromatic amino
acid synthesis in crops while humans don’t make any aromatic amino acid anyway
• Is it nutritionally different? No. Same as an “organic” one, just cheaper to produce
Methionine-enriching soybeans
• genes have been added to enhance methionine content
• it is possible that some people may be allergic to the product of the introduced
gene
• screening for allergic problem is now routine, not only GM but all food
No particular dangers are found so far, any more than
allergic response caused by non-GM food.
28
A closer look on
genetically modified (GM) crops
Are GM crops harmful to the environment ?
Monarch butterflies killed by eating pollen from GM corn
• First, it should come as no surprise. GM corn was engineered to contain insect-killing toxin,
which of course kill any insect nearby.
• GM corn does not need to be sprayed with pesticide, while million of insect and birds are killed
by pesticide every year
• pesticide-induced murder of wildlife is far more serious than any possible effect of GM corn on
butterflies
Will pest become resistant to the GM toxins?
• Not nearly as fast as they now become resistant to the far higher levels of pesticides sprayed on crops
The risk to environment seems to be very slight, indeed, in some cases
it lessens the serious environmental damage produced by cultivation or
agricultural pesticides.
29