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Date:

October 9, 2000

Subject:

Spread of Antibiotic Marker Genes; On Higher Standards for

 


Colleagues:

Let me take it seriously for a moment because the spread of antibiotic
resistance is a serious challenge in medicine and agriculture.

It would be of use to have an infectious disease specialist comment on the
frequency of occurrence of NG strains resistant to third generation
cephalosporins. Data on occurrence of drug resistant strains of NG can be
found on the CDC website. For example, it was reported in 1998

(http://www.cdc.gov/nchstp/dstd/Stats_Trends/Stats_and_Trends.htm):

Susceptibility to Spectinomycin
All isolates were susceptible to spectinomycin in 1998. There have been
five spectinomycin-resistant isolates in GISP; their locations and years
were: St. Louis-1988, Honolulu-1989, San Francisco-1989, Long Beach-1990,
and West Palm Beach-1994.

Susceptibility to Ceftriaxone
The distribution of MICs to ceftriaxone in 1988 and 1998 are shown in
Figure 16. Over this period, there has been a subtle shift towards higher
ceftriaxone MICs. In 1998, all isolates were susceptible to ceftriaxone.

The fluoroquinolines are also recommended for treatment NG, although, once
again, a low level of resistant strains have been reported:

The emergence of drug-resistant gonococci has limited the usefulness of
previously recommended penicillin-, ampicillin-, and tetracycline-based
regimens. Coexisting chlamydial infections are sufficiently common to
require simultaneous presumptive treatment (see below). Thus, a single
dose of ceftriaxone 125 mg IM for gonococci plus either doxycycline 100 mg
po bid for 7 days or azithromycin 1 g po once for chlamydia is recommended
as initial therapy for urethral, endocervical, pharyngeal, and rectal
infections. Alternatives to ceftriaxone are a single dose of either
spectinomycin 2 g IM, ciprofloxacin 500 mg po, ofloxacin 400 mg po, or
cefixime 400 mg po. All regimens should be accompanied by azithromycin or
doxycycline to treat possible chlamydial co-infection, except in pregnant
women, for whom erythromycin 500 mg po qid for 7 days can be substituted.
In patients known to harbor penicillin-sensitive gonococci, amoxicillin 3
g po with probenecid 1 g po once may be used instead of ceftriaxone.

(taken From the Merck Index at:
http://www.merck.com/pubs/mmanual/section13/chapter164/164b.htm)

The take home messages are fairly simple here:

1. Strains of antibiotic resistant NG are on the rise and will continue to
rise as long as the disease continues to infect subjects and antibiotics
are used to treat infections.

2. Resistance to spectinomycin has already been described in NG and
elsewhere in the microbial community.

3. Spectinomycin resistance is far more likely to spread from bacteria to
bacteria than from plants to bacteria

4. Spectinomycin is no more the drug of choice than one of several other
antibiotics; which is the drug of choice in a given case is dependent on
the antibiotic sensitivity determined for the infecting strain.

5. One would be well advised to avoid infection in the first place...

And what makes me cry?

The posting on the Sustain webpage referred to above makes the following
statement:

The bacterium responsible for gonorrhoea, Neisseria gonorrhoeae, could
acquire the aad gene from transgenic plant materials during infection of
the mouth and small and large intestine as well as the respiratory tract.
N. gonorrhoeae could also acquire the gene indirectly from other bacteria
in the internal and external environments of animals and human beings,
which can take up the gene from transgenic plant materials. Those other
bacteria can serve as a reservoir for antibiotic resistance genes.

As is well known to many of you:

1. Despite years of intense research designed to evaluate the possibility
of antibiotic resistance gene transfer from plants to bacteria in soil and
animals, gene transfer has not been demonstrated. Notice that the
paragraph above says "could acquire." While lots of things "could" happen,
this is one that nobody has been able to demonstrate. This suggests that
the frequency at which this event occurs, if at all, must be extremely
low.

2. To say something will never happen is also not acceptable. Since
transformation is a plausible mechanism by which such a gene acquisition
"could" take place, let's just suppose that acquisition of spectinomycin
resistance occurred at a very very very low frequency. Of what consequence
would the creation of a few spectinomycin resistant organisms be --and I
emphasize very few because we know from research that the rate is so low
as to have been heretofore undetectable? Essentially of no consequence
because the genie is already out of the bottle. Spectinomycin resistance
is already spreading throughout the world of pathogenic bacteria; the
contribution made by the plant to bacteria mechanism of transfer, if any,
would add negligibly to the problem.

3. The spread of antibiotic resistance relates to the already widespread
distribution of resistance genes in nature that are simply waiting to be
selected for, the relatively rapid mechanisms of gene evolution and
transfer within microbes, and poor stewardship in the use of antibiotics
both in medicine and agriculture. It is a serious problem that should not
be trivialized by the suggestion that markers used in bioengineered plants
will add to the spread of resistance. If anything, this is the one area
where research has been done to evaluate the potential hazards that exists
in order to avoid adding to the problem. The discussion of plant to
bacteria transfer diverts attention from the need to develop new
antibiotics and new and effective strategies for managing use of the both
existing and future antibiotics.

4. The recent (May 2000) WHO/FAO Expert Consultation on Foods for
Biotechnology assessed the rationale that has been applied in evaluation
of the safety of antibiotic resistance markers. The analysis can be found
at:

http://www.fao.org/WAICENT/FAOINFO/ECONOMIC/ESN/gm/biotec-e.htm

My final tear is shed wondering whether the people who write the sort of
posting that we are talking about don't understand the underlying science,
or if they understand it well but choose to post what they do in the hopes
of scaring those who are not as well versed in these complex subjects. As
has been observed many times by AgBioView readers, if we rejected
processes and products on the basis of what "could" happen, we might as
well close of shop on all further human invention for I'm sure that there
is nothing that we set about to do for which some dire consequence cannot
be imagined.

As I noted above, it would be interesting to have a second medical opinion
on the posting and I'm sure that some of you can amplify on my comments on
safety evaluation spelled out above.

Bruce Chassy
=============
Assistant Dean for Biotechnology Outreach, Office of Research College of
Agricultural, Consumer and Environmental Sciences and Executive Associate
Director, Biotechnology Center University of Illinois at Urbana-Champaign
238 NSRC 1101 West Peabody Drive
Urbana, IL 61801 b-chassy@uiuc.edu 217-244-7291

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Subj: Re: Higher standard for biotech
From: "Bob Bowden"

Henry Miller wrote:

"Scientists worldwide agree that adding genes to plants does not make them
less safe either to the environment or for humans to eat."

That is not quite correct. Here is a more accurate version:

Scientists worldwide agree that adding genes to plants does not
necessarily make them less safe either to the environment or for humans to
eat.

This difference is important. Genetic engineering can be "mundane" or
exotic. That is why GE products should be evaluated on a case- by-case
basis. Evaluations of "mundane" products need not be expensive and
burdensome. Greater costs should be incurred when novelty and/or
uncertainty are greater.

Yes, we have a higher standard for GE than for conventional breeding. I
think that is appropriate for a controversial new technology that affects
our food supply. And since it is more precise and high tech, GE should be
able to meet that higher standard. Although I agree with Miller that the
probability of serious mishap is very low, as a consumer, I expect GE
products to be carefully evaluated before release.

Bt toxin is a perfect example. I am willing to eat Bt corn because the EPA
and FDA have reviewed it and found it safe. Even though Monsanto surely
has no interest in harming consumers, it is just as surely biased when
evaluating Bt safety. I want an unbiased, scientific assessment of exotic
technology like Bt before I eat it.

In a previous posting (message #736) Miller assured us that he did not
advocate zero regulation on GE foods. In this recent article he argues:
=93Yet, largely because it creates new governmental responsibilities,
larger bureaucratic empires and bigger budgets, regulatory agencies have
regulated gene-spliced foods in a discriminatory, unnecessarily burdensome
way.=94 He goes on to say, =93=85from a scientific vantage point, federal
regulators have the paradigm exactly backward.=94 It certainly sounds like
he advocates less regulation for GE foods than for conventional crop
improvement. That would be very little regulation indeed.



Bob Bowden
Department of Plant Pathology
Kansas State University
Manhattan, KS 66506-5502
RBOWDEN@PLANTPATH.KSU.EDU
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From: Andrew Apel
Subject: Re: AGBIOVIEW: More response to Craig Sams; Is Organic Food
Really Better?


Colleagues,

This discussion about the meaning of the CDC figures regarding illnesses
from
consuming organic produce has become incredibly tiresome. The CDC figures
are not a
study. The numbers, which merely compile anecdotes, are suggestive, and of
course
the agricultural practices are suggestive, but the fact of the matter is,
no real
study of the risks of consuming organic food have ever been conducted.
Argumentation will solve nothing, folks need to open their wallets to fund
a real
study (and be bold enough to consider being trashed or firebombed), or
just say,
hey, E. coli is all-natural, too.

The CDC is shell-shocked as a result of the backlash from organic
activists, merely
on account of the few figures released. The CDC will not do such a study,
since
there is a tacit agreement among US regulators that there are two
standards in the
US for food: safe and untested.

Industry will not do a study of organic food. The organic industry
certainly will
not, and mainstream agriculture, even after years of bombardment, hasn't
figured
out the basics of self-defense yet.

I say, let it go. Soon, organic food will have its own label, and when
folks start
getting sick from stuff with the organic label (or not), we'll find out.
Biotech is
tested, organic is not, so we have to wonder: who are the guinea pigs, and
in whose
experiment?
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From: Matthew Metz
Subject: O157:H7

Dear Dr. Avery-
In several of your postings to Agbioview you have mentioned the
unfounded assertion by the denegrators of modern agriculture calling it
responsible for the evolution of pathogens such as E. coli O157:H7. Here
is some ammunition for debunking thir false argument:

Reid, SD, et al. Parallel evolution of virulence in pathogenic
Escherichia coli. Nature 406(6 July, 2000):64-67.

In this article the authors present evidence that such pathogens are
likely VERY old. O157:H7 diverging from a common ancestor with our
friendly K-12 strain as long as 4.5 million years ago.

Sock it to 'em.

Matt Metz
UC Berkeley
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Subj: Craig Sams replies to Avery, deGregori, Doug Powell, Don Weeks
From: Craig Sams

Craig Sams writes:
Golly! I was just responding to Dr. John Mottley's request for
information, I had no idea that I was going to excite so much controversy.
Alex Avery, Tom de Gregori, Doug Powell and Don Weeks have all asked for
substantiation of various statements in my submission, so here are some
responses.

Doug Powell's comment of 'bullshit (get it?)' on the presence of E coli in
forage fed cattle is probably answered by the FAO report (OK, I know it's
the United Nations, but they did have a big international conference in
July and are usually pretty conservative in their science). This also
deals with Alex Avery's statement that organic cattle have E coli too.
He's right, but at 1% of the level in intensive cattle. I think that's a
big difference, though, of course, poor hygiene in food handling will
allow even a small amount of E coli to proliferate.

Mary-Howell Martens posted their statement, which I excerpt here:

"1. The US Centre for Disease Control (CDC) identifies the main source for
human infection with E. coli as meat contaminated during slaughter.
Virulent strains of E. coli, such as E. coli 0157:H7, develop in the
digestive tract of cattle, which is mainly fed with starchy grain as
research at Cornell University has demonstrated . Cows mainly fed with hay
generate less than 1 % of the E. coli found in the faeces of grain-fed
animals. It is one of the most important goals of organic farming to keep
the nutrient cycles closed. Therefore, ruminants like cattle and sheep are
fed with diets with a high proportion of grass, silage and hay. It can be
concluded that organic farming potentially reduces the risk of E. coli
infection. "

Don Weeks queried whether there really is greater incidence of food
poisoning. I have written to the CDC for data on this, on their website
they only describe it as 'emergent' and note that it is not under control.
In the UK, reported cases of foodborne illness have risen from 19,000 in
1989 to over 100,000 in 1999. It is estimated that only 1 in 10 cases of
food poisoning are reported.

Here's the CDC comment:

www.cdc.gov/ncidod/dbmd/diseaseinfo/escherichiacoli_t.htm

Incidence
An estimated 73,000 cases occur annually in the
United States. Uncommonly
reported in patients in less industrialized
countries.
Sequelae
Hemolytic uremic syndrome (HUS): Persons with
this illness have kidney failure
and often require dialysis and transfusions.
Some develop chronic kidney failure or
neurologic impairment (e.g., seizures or
blindness). Some have surgery to remove
part of the bowel. Death (estimated 61 fatal
cases annually; 3-5% with HUS die).
Costs
Estimated 2,100 hospitalizations annually in
the United States. The illness is often
misdiagnosed; therefore, expensive and invasive
diagnostic procedures may be
performed. Patients who develop HUS often
require prolonged hospitalization,
dialysis, and long-term follow-up.
Transmission
Major source is ground beef; other sources
include consumption of unpasteurized
milk and juice, sprouts, lettuce, and salami,
and contact with cattle. Waterborne
transmission occurs through swimming in
contaminated lakes, pools, or drinking
inadequately chlorinated water. Organism is
easily transmitted from person to
person and has been difficult to control in
child day-care centers.


www.cdc.gov/ncidod/dbmd/diseaseinfo/escherichiacoli_g.htm

What illness does E. coli O157:H7 cause?

E. coli O157:H7 infection often causes severe bloody diarrhea and
abdominal cramps; sometimes the infection
causes nonbloody diarrhea or no symptoms. Usually little or no fever is
present, and the illness resolves in 5 to
10 days.

In some persons, particularly children under 5 years of age and the
elderly, the infection can also cause a
complication called hemolytic uremic syndrome, in which the red blood
cells are destroyed and the kidneys fail.
About 2%-7% of infections lead to this complication. In the United States,
hemolytic uremic syndrome is the
principal cause of acute kidney failure in children, and most cases of
hemolytic uremic syndrome are caused by
E. coli O157:H7.


What are the long-term consequences of infection?

Persons who only have diarrhea usually recover completely.

About one-third of persons with hemolytic uremic syndrome have abnormal
kidney function many years later,
and a few require long-term dialysis. Another 8% of persons with hemolytic
uremic syndrome have other
lifelong complications, such as high blood pressure, seizures, blindness,
paralysis, and the effects of having part
of their bowel removed. "

About 2-7% of infiections (estimated at 73000 cases per annum, so 2-7%
wold average to 3285 per annum) lead to hemolytic uremic syndrome, and of
these, one third (1093) have abnormal kidney function and 8% (262) have
other lifelong complications.

Tom de Gregori asks various questions.
1. He suggests that unpasteurised apple juice is 'organic' because it is
sold in stores that specialise in organic produce. However, the Odwalla
juice was sold in supermarkets. In any case, pasteurisation and heat
sterilization are commonly used on organic products. There is no culture
that prohibits or frowns on such food safety measures. 2. He asks "Are you
implying that organic beef is beyond all possible contamination?" No of
course not, I am just saying that, if the E coli level (FAO report) is 1%
of the level in grain-fed cattle, then the risk is lower, not non-existent.
3. Tom de Gregori asks a long question about bird droppings and plants
forcing their way up through manure. First, let's remember that
conventional farmers are responsible for 99% of all manure applications
and 100% of all uncomposted manure applications. This is not a relevant
vector for E coli contamination of food. Birds do not normally carry E
coli O157:H7 and I did not suggest that they do. 4. He asks about raw
sprouts. Alfalfa sprouts are a minor source of E coli in the USA. However,
they are not usually organic and it is hygiene failures in the process of
sprouting that has allowed E coli to spread. Chinese restaurants use a
huge tonnage of mung bean sprouts daily, but there are established
hygienic processes for producing them. 5. I don't quite understand the
last part of Tom de Gregori's comments about gangrene and botulism in wild
animals and giardia in water collected from the wild. I have not posted
any comments about wild food, though some of my colleagues get great
pleasure out of shooting grouse and catching trout and then cooking and
eating them. I personally eat wild-caught fish, but do not eat raw fish
sashimi for reasons of parasite avoidance. However, we are beginning to
stray from the issue of E coli and organic food.
6. I didn't look up the Tauxe reference as Alex Avery says that he has
stopped making these comments - allegedly due to pressure from organic
activists, though I suspect that he may have thought the issues through
and decided that he had overestimated the role of manure fertilizer in the
spread of E coli.
7. Tom deGregori ask "do you stop reading when you find something that
challenges your cherished assumptions?" Of course not. I wouldn't be
engaging in this extensive correspondence if my mind was closed. My point
that has caused all this trouble was the statement that Avery's E coli
assumptions were 'statistical manipulations." I was deeply concerned by
his allegations when I first read them, as any responsible food
manufacturer would be, so I investigated and found that they were
ill-founded.

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Subj: Balanced biotech info
From: David Hildebrand

>From: "Tim A. Maull" < Subject: Need help in GMO
debate My name is Tim Maull, and I'm one of the few pro-technology
students at

Midwest Land-Grant Universities Biotech Web Links
Illinois http://www.aces.uiuc.edu/research/biotech/bio-news.htm

Comprehensive biotech education web site Indiana
http://www.agcom.purdue.edu/AgCom/news/backgrd/biotech/more_biotech.html

Comprehensive biotech education web site, Biotech Backgrounder Iowa
http://www.biotech.iastate.edu

Comprehensive web site developed by the Iowa State University's
Biotechnology Outreach Education Center Kansas
http://www.oznet.ksu.edu/pr_biotech/

Comprehensive web site including news and factsheets
Kentucky http://www.ca.uky.edu/BREI

Comprehensive web site addressing biotech issues Michigan
http://www.iia.msu.edu/absp/index.html

Agriculture biotechnology support project resource site Minnesota
http://www.cce.umn.edu/biotech/

Comprehensive web site including publications and bioethics Missouri
http://www.agbioforum.missouri.edu

A magazine devoted to ag biotech economics, crop management, and public
policy Nebraska http://ianrwww.unl.edu/ianr/ardc/bioteched.htm

Comprehensive web site including education, bioethics, biotech footlocker
Ohio http://www.ag.ohio-state.edu/~hocorn/gmosites.htm

List of biotech web sites

Wisconsin http://www.biotech.wisc.edu

Wisconsin biotechnology center: BioTrek

Some additional web links:
USDA: http://www.aphis.usda.gov/biotechnology/
Biomednet: http://www.biomednet.com/hmsbeagle/67/reviews/insitu
Information Systems for Biotechnology (ISB) (VA Tech/USDA):
http://www.nbiap.vt.edu/
US Gov: http://www.usia.gov/topical/global/biotech/ IFT:
http://www.ift.org/resource/pdf_files/gmoback.pdf International Food
Information Council Foundation: http://ificinfo.health.org/
Information Systems for Biotechnology Home page: http://www.isb.vt.edu/

Collection of links:
http://www.isb.vt.edu/othersites/indexlinksdblevel1.cfm
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