Please circulate widely - Proposed release of transgenic safflower shrouded in s

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Please circulate widely

 

 

Proposed release of transgenic safflower shrouded in secrecy

 

USDA-APHIS conducted an Environmental Assessment (EA) [1] in response to an

application (06-363-103r), received from SemBioSys, Inc to field test a

transgenic safflower (Carthamus tinctorius) line 4438-5A that produces human

pro-insulin. The transgenic safflower was engineered to express an oleosin-human

pro-insulin protein exclusively in its seed. The field site (<1 acre) is located

on

private property in Lincoln County, WA, and will be surrounded on all sides

by a 50 ft fallow strip. The exact location of the site is withheld from the

public; but the application and risk assessment are open for public comment at

http://www.regulations.gov/fdmspublic/component/main until 23 July 2007.

 

Pro-insulin is the precursor to insulin, normally made in the beta cell of

the islets of Langerhans of the human pancreas. The protein is synthesized in

the endoplasmic reticulum (membrane stacks within the cell), where it is folded

and two sulphydryl (-SH) groups are oxidized into a disulphide bond (-S-S-).

It is then transported to the Golgi apparatus (a special organelle) where it is

packaged into secretory vesicles, and processed by a series of proteases into

mature insulin. Mature insulin has 39 less amino acids; 4 are removed

altogether, and the remaining 35 amino acids - the C-peptide - are cut out from

the

middle of the pro-insulin molecule; the two ends segments - the B chain and A

chain - remain connected by the disulphide bond formed earlier [2, 3].

 

A patent application [4] describes the genetic modifications for high

expression of human insulin in plants, including shortening the C-peptide by

four

amino acids.  The APHIS report [1] notes further that the human pro-insulin has

two amino acids removed for stability in plants plus 11 C terminal amino acids

added to ensure retention of the protein in the endoplasmic reticulum of the

plant seed cell. The pro-insulin sequence was fused to the Arabidopsis oleosin

gene, to be exclusively expressed in seeds. Expression of the fused gene was

controlled by the phaseolin promoter and terminator sequences from common bean.

The bean promoter drives seed-specific transcription of the synthetic

pro-insulin.  A selectable marker is regulated by the parsley ubquitin promoter

and

terminator, and was deemed confidential business information even though it is

said to be the most commonly used selectable marker in plants, and had been

used in many previous field trials [1]. Animal feeding tests evaluating the

toxicity of the neither the synthetic pro-insulin nor the marker gene and its

proteins were  included with the EA.

 

Site of release in area with threatened species

 

The area selected for the transgenic safflower field test releases - “

sagebrush steppe†- is dry and dominated by sagebrush. Resident animals

include the

sage grouse, sage sparrows, loggerhead shrikes, and even the once ubiquitous

black-tailed hare or “jackrabbitâ€. According to USAD/APHIS [1], the

threatened

species in the test area also include bald eagle, pygmy rabbits, Columbian

white tailed deer and grey wolf, and the plant species Spalding’s catchfly and

Ladies’ tresses. Pygmy rabbits are the most threatened species, the Columbia

pygmy rabbit feeds mainly on sagebrush and its number may be as low as 30 or

less. There has been limited success in breeding the rabbits in captivity [5,

6].

The pygmy rabbit is likely to feed on the transgenic safflower seeds with

potentially detrimental (even fatal) consequences. The USDA/APHIS report claims

there will be no toxicity from ingesting seeds from the transgenic safflower,

from contact or from inhaling dust and debris [1]. Even if that were true - and

there is evidence ignored by APHIS suggesting that the ingested pro-insulin

from transgenic safflower is active (see below) - the disruption of the habitat

of the pygmy rabbit by human activities and transportation is likely to drive

the threatened animals to extinction. APHIS displays a cavalier disregard for

the threatened species, ignoring studies that do not support their

conclusions.

 

Evidence of potential harm to threatened species ignored

 

There is at least one report showing that transgenic pro-insulin can

effectively reduce blood glucose in rats. Feeding a bracken fungus, Ganoderma

lucium,

modified with a gene for human pro-insulin to diabetic rats reduced their

blood glucose [7]; presumably the modified fungus cell wall and endoplasmic

reticulum prevent rapid degradation of pro-insulin, allowing the transgenic

organism

to deliver insulin to the diabetic animal. Cholera toxin pro-insulin fusion

proteins were produced in lettuce and tobacco plants; and when powdered

transgenic plant preparations were fed to diabetic mice, oral tolerance to

insulin

was produced, preventing the autoimmune degradation of insulin-producing beta

cells in the pancreas [8]. Human insulin produced in Arabidopsis seeds was

activated by exposure to the common digestive enzyme trypsin [9]. The APHIS

report

presumes that human pro-insulin will be degraded too rapidly for it to become

activated when ingested by animals, but the studies cited show that may not

the case. Furthermore, functional argentine peptides were found to enhance

intestinal absorption of insulin such peptides may be encountered commonly in

anti-microbial peptides [10]. Seed debris may produce dust that contains human

pro-insulin, and it is worth noting that inhaled insulin is an available option

for human therapy [11]. The APHIS report dismisses the possibility that inhaled

debris and dust from the transgenic safflower could be active, but provides no

experimental evidence to support that conclusion.

 

APHIS implies that wild animals would not be affected by human insulin [1],

but rabbits were among the animals first used in the discovery of insulin, and

continue to be used as experimental animals in current studies on insulin

action [12]. Furthermore, birds [13] and snakes [14] also respond to human

insulin; and it is probably safe to say that all of the threatened species, and

human

beings are potential victims of the release of food crops modified to produce

human insulin. The APHIS report notes that grain crops surrounding the

transgenic safflower plot will provide a more attractive “free lunch†for

birds and

mammals than the transgenic safflower; that is a fallacious and dangerous

assumption because the ‘free lunch’ will attract both foragers and predators

to

the test site. Furthermore, the fallow strip around the test plot is unlikely

to discourage browsers such as rabbits that feed at night to avoid predators.

 

Safe haven for pharm crops but deadly for humans and wild life

 

Eastern Washington State is rapidly being transformed into a haven for

transgenic crops modified to produce pharmaceuticals. Along with previous

safflower

field test releases, large plantings of humanized barley are being tested. The

exact locations of such tests are not disclosed and people living near the

test sites are unaware of the potential hazards to their health.   The impact

of

such developments on threatened species is also ignored and dismissed by

APHIS.  The APHIS report reads more like a public relations document for the

company rather than an independent critical evaluation of the company proposal.

This is potentially deadly for humans and wildlife, and the agency should be

held

to public account.

 

 

References

 

1. USDA-APHIS Environmental Assessment In response to permit application

(06-363-103r), received from SemBioSys, Inc. for a field-test to produce human

proinsulin (line 4438-5A) in genetically engineered safflower (Carthamus

tinctorius) seeds U.S. Department of Agriculture Animal and Plant Health

Inspection

Service Biotechnology Regulatory Services 06_363103r 06/22/2007 

http://www.regulations.gov/fdmspublic/component/main

 

2. Wikipedia Proinsulin 2007 http://en.wikipedia.org/wiki/Proinsulin

 

3. Davidson, H. Proinsulin processing. Cell Biochemistry and Biophysics 2004

Supplement, 143-57.

 

4. Molony M, Boothe J, Keone R, Nykiforuk C and Van Rooijen.  Method for

production of insulin in plants,  2005 US Patent 2005/0039235A1

 

5. Washington Department of Fish and Wildlife Pygmy Rabbit 1995

 

6. Hays D. Washington Department of Fish and Wildlife Washington Pygmy Rabbit

2003 Recovery Plan Update addendum to 1995 above

 

7. Ni T, Hu Y, Sun L, Chen X, Zhong J, Ma H and Lin Z.  Oral route of

mini-proinsulin-expressing Ganoderma lucidum decreases blood glucose level in

streptozocin-induced diabetic rats. Int J Mol Med. 2007, 20(1), 45-51.

 

8. Ruhlman T, Ahangari R, Devine A, Samsam M and Daniell H.        

Expression of cholera toxin B-proinsulin fusion protein in lettuce and

tobacco chloroplasts--oral administration protects against development of

insulitis

in non-obese diabetic mice.  Plant Biotechnol J. 2007, 5(4), 495-510.

 

9. Nykiforuk CL, Boothe JG, Murray EW, Keon RG, Goren HJ, Markley NA and

Moloney MM. Transgenic expression and recovery of biologically active

recombinant

human insulin from Arabidopsis thaliana seeds. Plant Biotechnol J.

2006,:77-85.

 

10. Morishita M, Kamei N, Ehara J, Isowa K and Takayama K. A novel approach

using functional peptides for efficient intestinal absorption of insulin. J

Control Release 2007, 118(2), 177-84.

 

11. Guevara CA. Inhaled insulin for diabetes mellitus. N Engl J Med. 2007,

356(20):2106-7.

 

12. Barillas R, Friehs I, Cao-Danh H, Martinez JF, del Nido PJ. Inhibition of

glycogen synthase kinase-3beta improves tolerance to ischemia in

hypertrophied hearts. Ann Thorac Surg. 2007, 84(1), 126-33.

 

13. Remage-Healey L and Romero LM. Corticosterone and insulin interact to

regulate glucose and triglyceride levels during stress in a bird. Am J Physiol

Regul Integr Comp Physiol. 2001, 281(3), R994-1003.

 

14. Sidorkiewicz E and  Skoczylas R. Effect of insulin on the blood sugar

level in the grass snake (Natrix natrix L.). Comp Biochem Physiol A. 1974,

48(3),

457-64.