Medical Biotechnology :
Prospects, Problems & Solutions
for Bangladesh
Shaikh Mizan
Professor & Head
Department of Biochemistry
Anwer Khan Modern Medical College
Scope of Medical Biotechnology - Overview
The scopes and prospects of MBT
could be summarily classified into:
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Pharmaceutical products
Pharmacogenomics
Biotech diagnostics
Human genome project
Gene therapy
Making improved organism through Genetic
Modification
Regenerative biotechnology
Recombinant DNA Biotechnology typically
produces Protein-based drugs
Insulin and its analogs
Erythropoietin (EPO)
Blood factors (Factor VII)
Growth Factors: Filgrastim
Human Growth Hormone: HGH, Somatotropin, Sermorelin
Cytokines
i) Interleukins (ILs): Interleukin-11 (rhIL-11, Neumega)
ii) Interferons
Enzymes: Adenosine deaminase
Vaccines
Etc.
Production of antibiotics is another big
area of biotechnology
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However, microorganisms are improved through
mutations and chromosomal recombination methods
rather than through molecular biological methods.
Monoclonal Antibodies (mAbs) are produced
through cell culture technology
mAbs are:
i) Specific and have high affinities for certain antigens or cell types
ii) Attack foreign toxins, viruses or cancer cells
iii) Drug delivery to specific targets (e.g. radioisotopes)
iv) Half-life of many "humanized" antibodies is often greater than
one week
Basiliximab/Daclizumab
Herceptin (Trastuzumab)
Zevalin
Immunoassays
Antisense ODNs : small synthetic
oligonucletides, bind to double stranded DNA
to inhibit gene expression
i) Hybridization to coding (sense strand) sequences in a
specific messenger RNA or in duplex DNA (the sense
strand is that which is copied)
ii) The antisense strand is the "uncopied" strand
DNA triplex
RNA interference (RNAi or siRNA)
Target specific mRNAs for degradation, thereby leading to
decreased expression of the corresponding protein. One
interference RNA can remove large numbers of mRNAs.
Ribozymes also can specifically
hydrolyse mRNAs
RNA molecules that assume tertiary structures and
have the ability to catalyze chemical reactions,
making them catalysts.
Target mRNA by synthesizing RNA that
1) contains the sequence to bind specifically with the
mRNA of interest
2) contains a ribozyme to catalyze the hydrolysis of
the targeted mRNA
Biotechnology Products from Genetically
Modified Organisms
Biotech chymosin
Source: Chr. Hansen
 enzyme used to curdle milk products
 gene from yeast
 harvested from GE bacteria
 replaces the calf enzyme
bST (bovine somatotropin)
Source: Rent Mother Nature
 increases milk production
 gene from cow
 protein harvested from GE bacteria
 replaces cow protein originally
harvested from pituitary glands
of slaughtered cows
Many agrobiotech products also has
Implications in human health & disease
Golden Rice
 Increased Vitamin A content
 Transgenes from bacteria and daffidol
 Controversory: large amount needed to
solve problem and is a culture issue!!
Sunflower
 White mold resistance
 Resistance gene from wheat
Source: Minnesota
Microscopy Society
Land Mine Detection
Without this effort,
that is dangerous to our military,
children are maimed.
Land Mine Detection
How biotechnology helps
• Patented transgene added to plants
• When metal from mine is detected
• Plant turns from green to red
Mine detected
Edible Vaccines – A Biopharming Dream
• A pathogen protein gene is cloned
• Gene is inserted into the DNA of plant (potato, banana,
tomato)
•Humans eat the plant
• The body produces antibodies against pathogen protein
• Human are “immunized” against the pathogen
• Examples:
Diarrhea
Hepatitis B
Measles
Insulin drug evolution
Stage 1 Insulin was extracted from the glands of
cows and pigs. (1920s)
Stage 2 Convert pig insulin into human insulin by
removing the one amino acid that distinguishes them
and replacing it with the human version.
Human insulin gene introduced in
microorganisms to produce it
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Stage 3: Insert the human
insulin gene into E. coli and
culture the recombinant
E.coli to produce insulin
(trade name = Humulin®).
Yeast is also used to
produce insulin (trade name
= Novolin®) (1987).
Recombinant DNA technology has also
made it possible to manufacture
slightly-modified forms of human insulin
that work faster (Humalog® and
NovoLog®) or slower (Lantus®) than
regular human insulin.
Biotechnology made it possible to fine
tune natural substances like insulin
Amino Acid Substitutons
A- chain
Position
B- chain Position
Source/
Type
A21
B3
B28
B29
B30
Human
Asn
Asn
Pro
Lys
Thr
Aspart
Asn
Aspartic
acid
Lys
Thr
Lispro
Asn
Lys
Pro
Thr
Glulisine
Asn
Pro
Glu
Thr
Glargine
Gly
Pro
Lys
Thr
Lys
Myristic
acid
Detemir
Lys
B31
And
B32
rapid-acting
Arg
long-acting
Gene Therapy – treats disease by inserting
functional genes to replace defective ones
Gene therapy may be Ex vivo or In vivo
First human gene therapy – SCID
patient in 1990
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SCID is severe combined immunodeficiency
Defect in gene called adenosine deaminase (ADA)
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Produces an enzyme involved in the metabolism of
nucleotide dATP
Accumulation of dATP is toxic to T cells
Without T cells, B cells cannot recognize antigen and
make antibodies
Ex vivo gene therapy successful
Vaccines and Monoclonal Antibodies
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Vaccines and Therapeutic Antibodies
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Cancer vaccines – injected with cancer cell antigens to
stimulate immune system to attack cancer cells
Vaccine for Alzheimer’s disease
Monoclonal Antibodies – purified antibodies that are
very specific for certain molecules
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Cancer cells, arthritis, and Alzheimer’s Disease
Treat addiction to harmful drugs
Monoclonal antibodies could be made very
specific for cancer cells
Biotechnology for Improved Drug Delivery
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Maximize drug effectiveness
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Drug solubility, drug breakdown, drug elimination
Microspheres – tiny particles that can be filled with
drugs
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Made from materials that closely resemble lipids found
in cell membranes
Mist sprayed in the nose to treat lung cancer and other
respiratory illnesses; anticancer drugs; anesthetics for
pain management
Nanotechnology – involves designing, building,
and manipulating structures at nanometer
scale
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Nanotechnologym, Nanobots and Nanomedicine could be
used to
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tmonitor blood pressure, blood oxygen levels, hormone
concentrations
unclog arteries, detect and eliminate cancer cells; smart
drugs that could seek out and target specific cells
Biotechnology can revolutionize drug delivery
Pharmacogenomics – Customizes Medicine
Detecting and Diagnosing Human
Disease Conditions are improved
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Advantages of Molecular Diagnostics
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Improvement in sensitivity
High specificity
Cost less
Faster analysis time
Genetic Diseases could be detected by
examining fetal tissues
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Fetal testing for chromosome abnormalities and defective genes
 Amniocentesis (Test at 16 weeks - karyotype)
 Chorionic villus sampling (Test at 8 to 10 weeks - karyotype)
Even a single nucleotide change in a
gene could be detected
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Allele-Specific Oligonucleotide (ASO) Dot Blot to
detect Sickle Cell Anemia
Computer
aided
detection of
hybridization
on a
microarray
chip could
detect the
specific
genes that
are
expressed in
a cell
Embryonic stem cells are derived from
Blastocysts
Even mature body cells could be reverted
back to embryolike state –
Induced Pluripotent Stem Cells (iPSCs)
Mature body cells that have
been reprogrammed to
change their identities and
revert back to an embryolike
state
Generation of stem cells
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Adult Derived Stem Cells – cell from mature tissue that can be
cultured and differentiated to become any cell type from the organ
of origin
Stem cells could be used for regenerations
of almost any kind of tissue
Potential Applications of Stem Cells
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Using stem cells to make white blood cells is
becoming an effective way to treat leukemia
Stem cells from umbilical cord blood used to treat
sickle cell anemia and other blood deficiencies
Stem cells from fat have been used to form bone
tissue in the human skull
Repair of heart cells
Adult stem cells isolated from brain and used to make
neurons in culture
Regenerated cells may be used to replace
damaged tissues – Tissue Engineering
Cell and Tissue Transplantation
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Fetal tissue grafts
Organ transplantation
Cellular therapeutics
Process
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Design a framework or scaffold
Seed the scaffold with human cells
Bathe in nutrient-rich media
Cells will build layers and assume the shape of the
scaffold
Use of regenerated cells
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Application: Bone regeneration
Bone regeneration animation
Use of regenerated cells
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Application: Blood Vessel regeneration
Use of regenerated cells
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Scaffold Guided Tissue Regeneration
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Creates framework onto which cells
are seeded and bathed in growth
factors
The Potential of Regenerative Medicine
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Tissue Engineering
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Sheets of skin grafts
1990s Dr. Charles Vacanti
revealed a mouse with an
engineered ear growing on its
back
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Seeded with cells from a cow
Just the outer ear without the
inner ear structures that
actually detect sound
Use of Stem cells
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Adult Derived Stem Cells
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Hematopoietic stem cell therapy
Use of Stem cells
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Adult Stem Cell Applications: Heart Disease
Use of Stem cells
Embryonic Stem Cells
 Pluripotent
 Possible transplant rejection
Adult Stem Cells
 Multipotent
 Autologous stem cells
reduce chance of rejection
Cells and Tissue Transplantation could
be possible even between species
Xenotransplantation – transfer between species (pig to human)
 University of Missouri scientists have produced cloned,
knockout pigs that lack a gene called GGTA1 (or 1,3
galactosyltransferase)
 The gene normally codes for a sugar that would be
recognized as foreign by humans
The Human Genome Project Has
Revealed Disease Genes on All
Human Chromosomes
This would most likely make possible
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Advanced diagnosis of genetic diseases long before
menifestation of signs and symptoms
Attempt advanced gene therapy
Intrusion in personal privacy
THE BUSINESS & DEVELOPMENT
OF
BIOTECH RESEARCH & INDUSTRY
Global Biotechnology Industry
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Total biotechnology industry revenues were about
US$ 25 billion in 2000.
Then it was predicted that it would be US$ 50
billion in 2010.
But the reality exceeded the prediction. By 2005
the total revenue exceeded US$ 63 billion mark.
The global volume of biotechnology in 2009 was :
Global biotechnology at a glance in
2005
Financial Prospects of MBT
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About $126 billion worth of branded drugs would
be off-patent in the next 5 years, (from June 2012)
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Medical biotechnology has also got great export
potential for developing countries like
Bangladesh, India, etc.
Off patent generics are great opportunity
for developing nations
India: A Case Study
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800 companies, up to 50 on advanced
biotechnology applications.
The industry was valued at US$ 3.7 billion and is
expected to grow to US$ 6.7 billion by 2010.
The Indian biotech industry is ranked sixth in the
world, and stands third in stem cell research.
In 2009-11 India's biotech witnessed a growth of
17 percent to reach US$ 3 billion in revenues, and
is predicted to reach $10 bn by 2015.
Biopharma contributes 70% of the revenue in the
total biotechnology sector.
India: A Case Study (contd.)
Biopharma leads the way
Composition of Indian Biotech Sector (2004-05)
India: A Case Study (contd.)
The medical biotechnology companies in India can
be divided into three broad categories.
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Smaller companies, e.g., Shantha Biotech and Bharat
Biotech.
Large companies, which have started responding to
biotechnology
The third group are contract research organisations
(CROs). Largely their work comes from TNCs.
The reasons behind India's Growth of
Medical Biotechnology
1. National Planning in India
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India’s Sixth Five Year Plan (1980-85) first cover
biotechnology development
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The apex official agency viz. National Biotechnology
Board (NBTB) was set up in 1982
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In 1986, NBTB graduated to a full-fledged government
department called Department of Biotechnology (DBT).
National Planning in India (contd.)
2. In January 2002, the DBT articulated priority
research areas for government funding in
biotechnology. These areas include
 vaccines based on genomic research for
cholera, malaria, AIDS, rabies and
tuberculosis
 gene therapy for cancer treatment.
 biofertilizers, biopesticides, transgenic crops
The reasons behind (contd.):
Budgetary Allocations for
Biotechnology India
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There are six major agencies responsible for
financing and supporting Biotechnology.
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By 2002 the national government has invested
more than US$ 750 million in biotechnology since
1985.
The reasons behind (contd.):
Infrastructure Development
The DBT has established a huge infrastructure for
research, development and bioinformatics.
 Established 55 centres with state of the art R&D
facilities, linked with databases and networks
around the world.
 DBT has supported 51 courses.
 The DBT has 17 task forces, for recommending
and monitoring. .
 DBT has developed a single window & 150
days for clearing new biotech proposals.
The reasons behind (contd.):
HRD and Training in India
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In the first phase (1984-85), 5 universities for
M.Sc./M.Tech programme in this multi.
Now, DBT is supporting 26 M.Sc. courses in
biotech.
DBT supports about 550 post-graduate students
per year.
DBT also sends at least 22-25 scientists in a for
overseas training each year.
Critique of Indian Reality
Critics accuse the government of
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Supporting research in areas that have already
been perfected in other parts of the world
Conducting unnecessary regulatory reviews of
products already approved in Europe and North
America.
Bureaucracy and lack of transparency.
Does not encourage enough the private-sector
investment in the industry.
SWOT Analysis of Bangladesh
Strengths:
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Rich bio-diversity
Low cost of labor in research, development and
manufacturing
Fairly trained human resource
SWOT Analysis of Bangladesh (contd.)
Weakness
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Lack of motivation on part of the government
Weak connection to the knowledge and
information network
Emigration of the experts to rich countries
Unawareness on part of entrepreneur community
SWOT Analysis of Bangladesh (contd.)
Weakness (contd.)
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Disinterest in investing in R&D by the national
entrepreneurs
Almost total absence of coordination between
research and industry
Poor coordination between national research
institutes
Lack of venture capital
SWOT Analysis of Bangladesh (contd.)
Opportunities
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Fairly large local market
Big export potential
Scopes for contract research
SWOT Analysis of Bangladesh (contd.)
Threats
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Heavy investments by neighboring countries like India
and China
Anti-biotech propaganda, fueled by traditionalism and
western funding
Unfavorable IPR and trade policies imposed by the rich
countries or their representative agencies like World
Bank and IMF.
Some Proposals for the Development
of MBT in Bangladesh
1.
2.
3.
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At least one world class science library with
digital facilities in every divisional city.
Declare MBT as a thrust sector
Integrate interdepartmental Medical
Biotechnology R&D program in medical
colleges and universities.
Utilize above facilities for human resource
development in the field also.
Teaching and research positions must be
made non-transferable.
Some Proposals (contd.)
Teaching and research positions must be
made non-practicing.
7. Prevent brain drain.
8. Provide reasonable material incentives in
terms of non-practicing allowance and
allocations from research projects.
9. Government must take initiative to mediate
communication and integration between
academy and industry.
6.
Some Proposals (contd.)
Establish biotech incubators for technology transfer
& commercialization.
11. Government should allocate special venture capital
fund.
12. The fledgling biotech industry must be protected,
boldly disregarding sinister preaching from the so
called international organizations like IMF, World
Bank, WTO, etc.
13. At the least 5% of the national budget should be
dedicated to total R&D, and 2% to R&D on medical
biotechnology.
10.
Concluding Remarks
The most positive feature of this fledgling
technology and industry are:
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1. It is not as capital intensive as other sectors as
chemical industries, automotive, ship building, etc.
3. Small modular ventures leading to
conglomerates could be taken.
2. In contrast it is more knowledge intensive.
4. The know-how of the state of the art technology
is still within reach of us.
Biotechnology could be a
shining path for industrial and
economic development of
Bangladesh