Pubdate: Tue, 19 May 2015
Source: New York Times (NY)
Copyright: 2015 The New York Times Company
Contact: http://www.nytimes.com/ref/membercenter/help/lettertoeditor.html
Website: http://www.nytimes.com/
Details: http://www.mapinc.org/media/298
Author: Donald G. McNeil Jr.
Bookmark: http://www.mapinc.org/heroin.htm (Heroin)

MAKINGS OF A NEW HEROIN

All over the world, the heavy heads of opium poppies are nodding 
gracefully in the wind - long stalks dressed in orange or white 
petals topped by a fright wig of stamens. They fill millions of acres 
in Afghanistan, Myanmar, Laos and elsewhere. Their payload - the 
milky opium juice carefully scraped off the seed pods - yields 
morphine, an excellent painkiller easily refined into heroin.

But very soon, perhaps within a year, the poppy will no longer be the 
only way to produce heroin's raw ingredient. It will be possible for 
drug companies, or drug traffickers, to brew it in yeast genetically 
modified to turn sugar into morphine.

Almost all the essential steps had been worked out in the last seven 
years; a final missing one was published Monday in the journal Nature 
Chemical Biology.

"All the elements are in place, but the whole pathway needs to be 
integrated before a one-pot glucose-to-morphine stream is ready to 
roll," said Kenneth A. Oye, a professor of engineering and political 
science at M.I.T.

This rapid progress in synthetic biology has set off a debate about 
how - and whether - to regulate it. Dr. Oye and other experts said 
this week in a commentary in the journal Nature that drug-regulatory 
authorities were ill prepared to control a process that would benefit 
the heroin trade much more than the prescription painkiller industry. 
The world should take steps to head that off, they argue, by locking 
up the bioengineered yeast strains and restricting access to the DNA 
that would let drug cartels reproduce them.

Other biotech experts counter that raising the specter of fermenting 
heroin like beer, jokingly known among insiders as "Brewing Bad," is 
alarmist and that Dr. Oye's proposed solutions are overkill. Although 
making small amounts of morphine will soon be feasible, they say, the 
yeasts are so fragile and the fermentation process so delicate that 
it is not close to producing salable quantities of heroin. 
Restricting DNA stifles all research, they argue, and is destined to 
fail just as restrictions on precursor chemicals have failed to curb 
America's crystal meth epidemic.

A spokesman for the Drug Enforcement Administration said his agency 
"does not perceive an imminent threat" because no modified yeast 
strain is commonly available yet. If that happens, he said, D.E.A. 
laboratories would be able to identify heroin made from it.

An F.B.I. agent who has been following the yeast strains since 2009 
said he was glad that the debate was beginning before the technology 
was ready and before lawmakers moved to restrict it.

"We've learned that the top-down approach doesn't work," said 
Supervisory Special Agent Edward You, who said he coined the "Brewing 
Bad" term and had held workshops for biotech students and companies. 
"We want the people in the field to be the sentinels, to recognize 
when someone is trying to abuse or exploit their work and call the F.B.I."

No scientific team has yet admitted having one strain capable of the 
entire sugar-to-morphine pathway, but several are trying, and the 
Stanford lab of Christina D. Smolke is a leader. She said she 
expected one to be published by next year.

No one in the field thought there should be no regulation, she said, 
but suggestions that home brewers would soon make heroin were 
"inflammatory" because fermenting manipulated yeasts "is a really 
special skill." Implications of research like hers should be calmly 
discussed by experts, she said, and Dr. Oye's commentary "was getting 
people to react in a very freaked-out way."

Robert H. Carlson, the author of "Biology Is Technology," said 
restrictions were doomed to fail just as Prohibition failed to stop 
the home brewing of alcohol.

"DNA synthesis is already a democratic, low-cost technology," he 
said. "If you restrict access, you create a black market."

What is considered one of the last important missing steps, a way to 
efficiently grow a morphine precursor, (S)-reticuline, in brewer's 
yeast, Saccharomyces cerevisiae, was published in Nature Chemical 
Biology on Monday by scientists from the University of California, 
Berkeley, and Canada's Concordia University.

The leader of the Berkeley team, John E. Dueber, said it was not 
trying to make morphine but 2,500 other alkaloids for which 
reticuline is a precursor, some of which might become antibiotics or 
cancer drugs.

Nonetheless, he said, since he realized his research has implications 
for the making of morphine, he sent his draft paper to Dr. Oye, 
suggesting the debate become more public.

One crucial question is whether the technology is of more use to the 
pharmaceutical industry or drug cartels. Dr. Oye argues it is the latter.

Companies are always seeking painkillers that create less addictive 
euphorias or do not paralyze breathing muscles, and having a 
predictable process they could tweak would be useful, but they 
already have a cheap, steady supply of opium from India, Turkey and 
Australia, where poppies are grown legally by licensed farmers.

That chain will be hard to disrupt. Since the 1960s, when it was 
created to convince Turkey to crack down on heroin, the International 
Narcotics Control Board has set quotas. Thousands of small farmers, 
their bankers and equipment suppliers depend on the sales, and they 
have local political clout just as American corn farmers do.

Also, pharmaceutical companies can already synthesize opiates in 
their labs. Fentanyl, a painkiller 100 times as powerful as morphine, 
is synthetic, as is loperamide (Imodium), an antidiarrheal opiate.

Heroin sellers, by contrast, must smuggle raw materials out of 
lawless Afghanistan, Laos, Myanmar and Mexico. Their supply lines are 
disrupted when any local power - from the Taliban to the United 
States Army - cracks down. Brewing near their customers would save 
them many costs: farmers, guards, guns, planes, bribes and so on.

One frightening prospect Dr. Oye raised was how viciously drug 
cartels might react if Americans with bioengineering know-how started 
competing with them. Gunmen from Mexican drug gangs have taken 
control of many secret marijuana fields in American forests.

His commentary suggested several possible steps to prevent misuse of 
the technology. The yeasts could be locked in secure laboratories, 
worked on by screened employees. Sharing them with other scientists 
without government permission could be outlawed.

Their DNA could be put on a watch list, as sequences for anthrax and 
smallpox are, so any attempt to buy them from DNA supply houses would 
raise flags. Chemically silent DNA "watermarks" could be inserted so 
stolen yeasts could be traced. Or the strains could be made "wimpier 
and harder to grow," Dr. Oye said, perhaps by making them require 
nutrients that were kept secret.

Agent You said he did not want to comment on Dr. Oye's suggestions, 
but was glad a threat had been identified by scientists before it was 
a reality, adding, "If this occurred across the board, it would make 
the F.B.I.'s life a heck of a lot easier."
- ---
MAP posted-by: Jay Bergstrom