CASTLEGAR NEWS, Thursday, April 28, 1977

. For a charm of powerful trouble,

Like a hell broth boil and bubble
A look at DNA. and all its works,

Genetic engineering: ethics, hazards, safeguards —

* hormone and other

Haunted by the spectre of.a biological:
Hiroshima, selentists invelved in Senitig

havi
unprecedented restraints on b thelr freedom
of inquiry.
‘The research establishments of Canada,
Britain and the U.S. now stipulate strict
precautions to be observed in different

experiments antl ban. certain ex-
periments altogether. Other countries are
scrambling to come up with their own
lelines,
It’s easy to see why.
The techniques scientists have de-
veloped for reprogramming the genetic

STORIES ~
by
TIM PADMORE

"codes that determine the'character of all

living things, from viruses to elephants
and redwood trees, offer great potential
for both good snd evil. Sa Ganstle engineering
Is a classic two-edged

There is the very a rs for. exam-
ple, that a way will be found to program
bacteria to produce insulin, human growth RS

com-

body to pote ‘antibodies effective
against the real toxin.
And at Naa ‘one blologist has already
dluraed into making a berms organ-
m.

A. Chakrabarty of the Gaol Electric
Research and Development Centre at
Schenectady, New York, wanted to make a
bacterium that would convert sewage’
sludge into methane, for_use as a fuel. To
do that he planned to insert into an 1
bacterium = fhe sort. that

an enzym
Cellulate breaks down plant cellulose,
which, belng indigestible by humans, gives
bulk to their feces,
Chakrabarty had successfully Inserted

the cellulase enzyme when he reallzed that
were the bacteria to eatape and spread

Most researchers argue that, given
reasonable precautions, the chances of
disaster are remote. The question, of
course, fs just how remota! should they be

Lay uch
‘The debate has been long and heated.
“It started with an experiment. proposed

plex to synthesize easily. There is not -

from pituitary glands obtained at human
autopaes to treat the people who need it,
and there is fear bese insulin supplies, ob-
tained from the pancreases of anim:

‘pigs and sheep, wi wil fall sh short of the future
needs of diabetic:

But consider what would happen if
bacteria used to produce insulin escaped
and became established in. the intestinal
tract of normal people. An insulin over-
dose is not a pleasant to die: weak-
ness, confusion, vertigo, convulsions,
coma, death.

There is the promise, too, af: voracious
oll-eating bacteria to clean up oll spills
auickly'and cheaply. It would be a matter

of speeding up the metabolism and repro- -
ductive rates of existing bacteria that feed
on hydrocarbons.

Tt would not do. cet cure, if the oil-

's Paul Berg, to
investigate animal cancer viruses by in-
serting thelr genes into bacteria. The story

goes-that Berg’s graduate students, bub- ~

bling ahout the experiment at a conference
at the Cold Spring Harbor

ing at the need to restrict gene-splicing re-
search, as is the World Health Organiza-
tion and the International Council of
Stientific Unions.

‘Chere are ominons notes. too, The
U.S.S,R. has indicated that it does not con-
sider military use of the new techniqu ues to
be banned under the 1971

other genes in, the bacteria start growing '
slower, or they lose the plasmids (carriers
of forelgn genetle material], or something
else goes wrong.” =: *

The worry, of course, is that if an error
oecyrs it may be Irretrievable, once the
organisms are out of the lab and multiply-
ing. That's | the reason for using

warfare treaty; at the same time, how-
"ever, official articles "have condemned
military use and the Russians are sald to
be working on thelr own set of guidelines.

Whether the rules set up in other coun-“

tries will be as strict as those in North
America is another question. For econom-
te, cultural (or milltary) reasons, some
countries may be willing to accept greater
Loa in the hope of reaping greater bene-

University of B.C, mleroblologist Eepert
ured Polish research

ogy, reveals something of his country's

attitude in his remark: ‘We Soviet scien-
tists are not afraid of the future and have
no-fear that some blind, powerful force
will be able to direct scientific investiga-
tions on genetic ring in an evil

enginee!
way. The sombre predictions and near- ~

panic mood in the general and sclentific

- press of capitalist countries seem exagger-
ated.””".

It has to be emphasized that the risks
are entirely, Speculative, to the extent that
remain off

Long Island, found themselves at the
centre of a storm of criticism.

rg reconsidered, and was instrumen-
tlie in, iets declaration in July 1974 of
a types
of gene-splicing one “i a!

Six months later, at Asilomar, Calif.,
they came up with a set of voluntary rules
which have served as a model for compul-
sory ones adopted by granting agencies in
the U.S, and other countries.

Two kinds ot precautions are defined:
physical containment, which means, at the
extreme, lab access only through airlocks,
a separate laboratory air supply, wearing
of surgical gloves, impermeable footwear
and protective clothing; and biological

eaters at
tacked essential oil Soe

Orifa

Sieh means using organ-
- isms unlikely to le the labora-
tory" betta te ‘that“cannot’ live at the

unexpected drug resistance 0 on a disease,
causing organism.

Or if cancer researchers confirmed the
suenicien that human cancers can be trig-

ered by viruses when bacteria‘

_Gulmal cancer virus genes escaped and in-
"fected a city or anation,

Nelther the benefits nor the hazards are
any longer hypothetical.

At the af}

human body, for exam-
Pi, or that requ exoteutin ts. Pe

fine And the accidental. production Aa
ecording to both in-

virulent bacteria is, a
-stinct and experience, extremely unlikely.
Miller: “As soon as you start putting

‘The argrint tes often take ena a theolog!-
cal tone — understandably, since what is
contemplated is the creation of new forms
of life, Califo Institute of
biologist Robert Sinsheimer agonizes over
the breaching of what he believes is a
fundamental blologicel barrier preventing
the exchange’ of genes between bacteria:
and higher organisms, New York blochem-

ist Erwin asks: “Have we the

right to counteract irreversibly the evolu- -
tionary wisdom of millions

of years?” .
Yet, much conventional biology —
breeding of superior: at
tiflelal insert for example - Hs
ally an assault on e
Sidegen too, that evolution has’ ar ial
breached the unbreachable. barrier — re-

searchers recently found a strain of —

naturally-occurring intestinal bacteria
producing human chorionle gona dotropin,
ahormone, presumably as a result of natu-
ral exchange of genetic. material in the
human gut.

Whatever the wisdom of ae the
science of genetic engineering — and the
potential rewards are enormous, from con-
trol of genetic diseases to a second and
greater Green Revolution — it is a fact
that the knowledge is. with: us; as’
ineradicable as a noxious strain of bac!
ria escaped from a laboratory, and we are’
going to have to learn to live with it:

Canada’s far-reaching rules

‘The recentiy-approved Canadian guide-

+ lines are the broadest adopted anywhere,

They cover not only genetic engineering,
but all types of work eith cells and vi-
ruses.

Louls Siminovitch of ‘the University of
Toronto and chairman of the Medical Re-
search Council committee that drafted ‘the
rules said other countries have shown a
keen interest in the extended guidelines.

's @ first:-No one’s attempted it-before
Teven though] people have been working on
= fuimor ieuses for 90 years with hardly any
he said in a telephone con-

re-
mained banned. 38,
‘ “We may be reassured that nothing dan-
gerous will come out of labs that stand to
lose government grants if they break the
rules, but what about other groups?
David Suzuki, geneticist and science

sy Sarat ATL 188 the techniques’... are

Falkow is preparing to test a vaccine
against scours, a form of diarrhea often
fatal to young pigs and cattle. The disease’
bacteria kill by secreting a toxin, produced
in response to a particular gene. :
Falkow’s vaccine is‘produced by sepa-*
rating the toxin gene. snipping away a
‘small piece of it and, re-implanting it so

that the bacterium produces a nearly iden- .

tical, but non-toxic, substance. That sub-
stance is the vaccine: It stimulates the

literature so that any.
second-rate scientist can Fepeat them.
While scientists may observe the guide-
‘lines, what ensures that classified re-
search by the military or industry will fol- _
low them? For itet matter, if nuclear-
blackmail by a rist group is a real
possibility, I din biological, blackmail
. would be even more probable.”

No doubt the restrictions will become
“more comprehensive, It appears certain
the U.S. Congress will pass legislation
making the

Tim Padmore writes
about sclence for The Sun.

‘Eye of newt and toe of frog. : wa

Tt is disturbingly easy to create new
forms of life with genetic engineering. So
easy that a bright high school student with
a centrifuge could make his own bathtub

bug.

Here are the ‘ABC's of the science, as
explained to me by University of B.C. bio-
chemist Michael Smith and smlcrebhetogist
Robert Miller.

‘The key is the structure of DNA, discov.

" ered 24 years ago by Francis Crick and

James Watson. DNA consists of two
twisted-ogether strands, each carrying
endless permutations of four basic atomic
units usually denoted by the first letter of
their chemical names: A, T, G and C,

A sequence like... GITACGAGCT... is

a code that tells a cell how to manufacture
proteins that make it func-

“the speci
tion as a yeast cell, 8 frog liver cell or a

mentale

jal coding is suprisingly simple.
Each tualetoflettis stands forcast the
20 or s6 amino acids from which all pro-

* teins are built. A few hundred

triplets
specify the amino acids in a typical protein.
and a few more serve as and stop
signals; together they. constitute ‘ a ne
gene, :
‘The first step ts te snip out some génes.
That can be done quite precisely wit
help of enzymes.

The next CCGG al Ee
organism with some from another and join
the strands together. Bu how to get the
ends of the test-tubeful of tang mole-
cules together and lined up? The secret is
sticky ends,

on industry
and setting penalties for non-compliance.
At least eight European countries are look-

An. enzyme lke the’ one described
creates pieces of DNA with the strands cut
off unevenly. The strand that sticks out is-
said to be sticky. That's because the bases
have a natural attraction for one another
—A sticks to T and G sticks to'C. The at-
traction is why in the original DNA the
bases in the two strands always match up,
Awith Tand 'G with C.

If the same exzyrie {s used to-eut up
both batches of DNA, the uneven ends of
the DNA fragments will match %, too, and
snap together.

“What’s lett to do is details: uni ip

rid”

with another enzym

_ of plecea that joined up in unwanted ways
Miller savers demonstration of the

method.

ent & splash of cloudy ‘orange re fluid, a
iture with a billion or so Eel “coll hacteria,
tet favorite organism, goes
te
ion.

Soap destroys bacteria by disrupting the
“ membrane that holds them together —
that's one ‘reason {t's a suc leaner, .
When the bugs burst, the DNA is released;
it only. takes a few minutes,

‘Then the opalescent Hquid goes into a
centrifuge. The artificial: gravity in the
centrifuge, 8,000 on ines tormal, drags the

ith plasmids because they
propio coped ancient

The plasmid-loaded quid is skimmed
off, Then over to the lab fridge for a bottle
of snipping enzyme. One drop is enough. A
little heat, and ‘there are a billion snipped
plasmids, waiting expectantly.

. Versation last week,

Despite the progress, Siminovitch is un-
easy. Not because he fears unforeseen haz-
ards. Nor because ne knows that there
remain unregulated potential hazards in
wore bem ¢ done in hospital and industrial

ries and in work involving cancer-

— chemicals and animal experimen-

tion — regulation is coming in those areas,
65 a

"He sald he fears a backlash witH the
public demanding too-drastic curbs and
thereby denying itself great benefits.

He and others recall Albert Nite
saying tha

: mayor of Cambridge, Mass.,

Institute of T
Sciectiat could buill

* doing [a planned genetic-engineering

ring ex-
periment] even though I know it is com-.
pletely safe because I didn't want to be as-
sociated with an experiment which could
be accused of creating: a ‘mystery
disease.’”

Despite their trepidation, at leait five
groups of Canadian scientists are expected
to be doing gene-splicing work within the
next year, Many more will be using some
pier beac ade in other genetic re-

Vern Paetkau, of the University’ of-

at Edmonton, heads one group.

The experiment they plan is typical in its
alms and its hyper-prudent approach.

" Paetkatr wants to insert into bacteria the

5 He will ue the C level of eontalziest,
the middle of a scale ranging from’ A; for
dow hasard, 10 Fy for the highest permitted

To aaa ‘sure he is transplanting’ ‘chat:
wy what he thinks he is, Paetkau is pains:

a

nster; they Se at the thought of

the Harvard botanist who predicts an in-
crease in so-called mystery

Saya University of B.C. microbiologist

Robert Miller: ‘I seriously considered not -

Basically the same things are done with
the donor organism, which can be another

bacterium, a virus, or cells from a higher
plant or animal, to produce a solution con-
taining snipped pieces of alien DNA.“ -

* “Then you simply mix the two solutions

together. and incubate at a low tempera- ”

ture — four to'10 degrees — so the ends
en +

‘The only thing left ts to get the spliced

“DNA back-into bacteria. That’s done. by”

mixing the DNA and the bacteria with a
little calcium hydroaide, which softens the
bacteria’s'‘membranes so the plasmi

the mouse DNA he
med instead o of extracting it from mouse

Tews na taisg te Gani involved
will not only be safer, but in the end the °

-Tesults will be more reliable. os

1

chimeras (named for the mythical crea-

ture having as lion's head and a oa
body) can get into the cells.

- Sclentists have been able to make DNA®

chimeras using genes from viruses, proto-'’ :

zoa, insects, sea urchins, frogs, yea!
mammals and various bacterial speci

Making literal chimeras is another thing.

~— scientists ‘will have first to figure ‘out
how cells of advanced organisms diffe

tale, how they know whither they are des.
to be blood, Brain or liver cells de-':

tined to
, Spite the fact that they all contain identical
genetic information. It’s far off but there is

“ nothing fundamental to bar the achieve:

ment,

It won't be dong in a bathtub, however.

What the bathtub method produces is a

DNA complexes, it is impossible to

pure);
Dosefully do‘elther good pr evil, Miller.

“Bae he semale,
he said, it is still necessary to do ev
they aot oe prevent irresponsible tink
Sng wih te sat ot Ue

GENE-SPUICER MILLER
+++ you can do it In the bathtul

Ke

Oe Oc ak eal a ta

panel NY

Ay

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