BACK FROM THE DEAD

How the strange new sci­ence of ‘sus­pended an­i­ma­tion’ will save lives

Reader's Digest Asia Pacific - - Contents - RENE EBERSOLE

The new sci­ence of freez­ing may save your life.

One af­ter­noon in Fe­bru­ary 2011, Kelly Dwyer strapped on snow­shoes and set out to hike a beaver pond trail near her home in Hook­sett, New Hamp­shire, US. Hours later, the 46-year-old teacher hadn’t re­turned home. Her hus­band, David, was wor­ried. Grab­bing his phone and a torch, he told their two daugh­ters he was go­ing to look for Mum. As he made his way to­wards the pond, he called out for Kelly. That’s when he heard the moans.

Run­ning to­wards them, David phoned Laura, 14, and told her to call emer­gency ser­vices. His torch beam soon set­tled on Kelly, sub­merged up to her chest in a hole in the ice. As David clutched her from be­hind to keep her head above wa­ter, Kelly slumped into un­con­scious­ness. By the time res­cue crews ar­rived, her

IM­PROVE­MENTS IN TECH­NOL­OGY MEAN THAT THE ODDS OF COM­ING BACK FROM THE EDGE

ARE GET­TING BET­TER

body tem­per­a­ture was around 20°C. Be­fore she reached the am­bu­lance, her heart stopped. The crews at­tempted CPR – a process doc­tors con­tin­ued for three hours at a hospi­tal nearby. They warmed her frigid body. Noth­ing. Even de­fib­ril­la­tion wouldn’t restart her heart. David as­sumed he’d lost her for good.

But Kelly’s life wasn’t over. A doc­tor rushed her to the nearby Catholic Med­i­cal Cen­ter, where a new team hooked her up to a car­diac by­pass ma­chine that more ag­gres­sively warmed, fil­tered and oxy­genated her blood and rapidly cir­cu­lated it through her body. Fi­nally Kelly’s tem­per­a­ture crept back up. Af­ter she’d spent f ive hours med­i­cally dead, doc­tors turned off the ma­chine and her heart be­gan beat­ing again.

In­cred­i­bly, Kelly Dwyer walked out of the hospi­tal two weeks later with only mi­nor nerve dam­age to her hands.

Bring­ing peo­ple back from the ‘dead’ is not sci­ence fic­tion any more. Typ­i­cally, af­ter just min­utes with­out a heart­beat, brain cells start dy­ing and an ir­re­versible, lethal process is set in mo­tion. But when a per­son be­comes se­verely cold be­fore their heart quits, their me­tab­o­lism slows. The body re­quires so lit­tle oxy­gen that it can re­main in a sus­pended state for hours with­out per­ma­nent cell dam­age.

Thanks to im­prove­ments in tech­nol­ogy (like the car­diac by­pass ma­chine that saved Kelly’s life), the odds are get­ting bet­ter for com­ing back from the edge. They are so good, in fact, that a hand­ful of sci­en­tists and med­i­cal ex­perts are now look­ing for ways to sus­pend life in order to per­form surg­eries with­out the threat of a trauma pa­tient bleed­ing to death, or to pre­vent tis­sue dam­age dur­ing the treat­ment of car­diac events.

The US Depart­ment of De­fense is heav­ily in­volved. In 2010, it launched a US$ 34-mil­lion ini­tia­tive called Bio­chronic­ity. Ninety per cent of war ca­su­al­ties re­sult from bleed­ing out on the bat­tle­field.

“The ques­tion is, can we de­crease the per­son’s de­mand for blood so, for a pe­riod of time, he ac­tu­ally doesn’t

need blood flow­ing,” ex­plains Colonel Matthew Martin, a 49-year-old trauma sur­geon whose re­search is funded through Biochronic­ity. The pur­pose would be mak­ing a wounded sol­dier able to sur­vive longer “so that we can get some­where to treat the in­jury,” says the ac­tive-duty sur­geon.

DR MARK ROTH’S OF­FICE at the vast Fred Hutchin­son Cancer Re­search Cen­ter in Seat­tle, US, is crammed with boxes of news­pa­per clip­pings about peo­ple who came back from the ‘dead’. There is a skier in Nor­way, a tod­dler in Saskatchewan, two fish­er­men who cap­sized in the Gulf of Alaska – all of whom had flat­lined in the freez­ing cold.

“I’ve been a stu­dent of th­ese cases for 20 years,” Dr Roth tells me. At 60, he is widely recog­nised as a pioneer in the pur­suit of us­ing sus­pended an­i­ma­tion in trauma treat­ment.

Hunched over a mi­cro­scope, he in­vited me to take a look at a petri dish bustling with tiny, hours-old ze­bra fish. “Be­cause they’re trans­par­ent, you can see their hearts beat­ing and the blood mov­ing about the tail,” he says. “This is the core of our own an­i­ma­tion – the heart and blood flow. We’re go­ing to take away the oxy­gen and al­ter their an­i­ma­tion.”

Roth be­gan pip­ing ni­tro­gen into a trans­par­ent box con­tain­ing the petri dish. “In time the whole sys­tem in there will be­come straight-up ni­tro­gen, which will get to th­ese crea­tures and turn them off,” he says. “In the morn­ing, we’ll put them back into the room air, and they’ll re­an­i­mate.”

Then he prepped a sim­i­lar ex­per­i­ment. Tak­ing two petri dishes of ne­ma­todes at pre­cisely the same stage of devel­op­ment, he placed one dish in his ni­tro­gen box and left the other on a lab bench. His hypo­­th­e­sis: the gassed worms’ metabol ism should grad­u­ally slow un­til they’re essen­tially sus­pended in time, while their fresh-air sib­lings should keep get­ting big­ger. Be­cause ne­ma­todes

grow quickly, his the­ory would be proved or dis­proved by to­mor­row.

Up un­til the early 2000s Roth’s ex­per­i­ments were con­fined to tiny crea­tures. Then one night he was watch­ing a tele­vi­sion doc­u­men­tary fea­tur­ing a cave in Mex­ico that caused cavers to pass out be­cause of an in­vis­i­ble hy­dro­gen-sul­fide gas.

“If you breathe too much of it, you col­lapse – you ap­pear dead,” says Roth. “But if you’re brought out from the cave, you can be re­an­i­mated with­out harm. I thought: ‘ Wow! I have to get some of this!’”

Af­ter ex­pos­ing mice to 80 parts per mil­lion of that gas at room tem­per­a­ture, he found he could in­duce a sus­pended state that could later be re­versed by re­turn­ing the mice to reg­u­lar air, with no neu­ro­log­i­cal harm. For Roth, it was a break­through. The med­i­cal com­mu­nity im­me­di­ately took no­tice. A $500,000 ‘ge­nius grant’ from a phil­an­thropic foun­da­tion fol­lowed soon af­ter.

Roth has since iden­ti­fied four com­pounds (sul­phur, bromine, io­dine and se­le­nium) that he calls ‘ele­men­tal re­duc­ing agents’, or ERAs. They ex­ist nat­u­rally in small amounts in hu­mans and can slow a body’s oxy­gen use.

Roth wants to de­velop an ERA as an in­jectable drug that can pre­vent tis­sue dam­age that can oc­cur af­ter doc­tors halt a heart at­tack. This hap­pens when nor­mal blood f low re­sumes; the sud­den rush of oxy­gen can per­ma­nently dam­age heart cells, lead­ing to chronic heart dis­ease (the lead­ing cause of death in the world).

Roth’s re­search in pigs shows that if he in­jects an ERA be­fore the block­age is re­moved, it’s pos­si­ble to keep the heart mus­cle from be­ing de­stroyed. Hu­man tri­als on heart-at­tack pa­tients are al­ready un­der­way, and Roth says ERAs could one day be used for a range of med­i­cal con­di­tions, in­clud­ing or­gan and limb trans­plants.

DR SAM TISHERMAN hates the phrase ‘sus­pended an­i­ma­tion’. As di­rec­tor of the Cen­ter for Crit­i­cal Care and Trauma Ed­u­ca­tion at the Univer­sity of Mary­land’s School of Medicine in Bal­ti­more, US, he prefers ‘emer­gency preser­va­tion and re­sus­ci­ta­tion (EPR)’. “We want to pre­serve the per­son long enough to stop the bleed­ing and re­sus­ci­tate him.”

Un­like Roth’s method, Tisherman’s ap­proach is to cool pa­tients into a hypo­ther­mic state, essen­tially in­duc­ing the same state that Kelly Dwyer was in. To do that, he re­places blood in the body with ex­tremely cold sa­line so­lu­tion, quickly re­duc­ing the pa­tient’s core tem­per­a­ture to a frigid 10 to 12°C. If it works, it could be a life­saver.

Rou­tine care for trauma vic­tims with in­juries such as gun­shot wounds typ­i­cally in­volves in­sert­ing a breath­ing tube, and then us­ing in­tra­venous catheters to re­place flu­ids and blood while a sur­geon at­tempts to re­pair the dam­age be­fore the pa­tient’s heart

fails. “It’s a race against time,” Tisherman says. “Only 5 per cent of peo­ple in car­diac ar­rest from trauma sur­vive.”

In­duc­ing a hy­pother­mic state could buy sur­geons as much as an hour to op­er­ate. After­wards, they could re­sume blood flow and grad­u­ally re­warm the pa­tient. Tisherman and his col­leagues have spent more than two decades per­fect­ing their pro­ce­dure in an­i­mals. If hu­man pa­tients fol­low the suc­cess of the an­i­mal stud­ies, their chances of sur­vival could dou­ble.

Col. Matthew Martin, the army sur­geon, was try­ing to achieve the same re­sults as Tisherman – with­out the ex­ten­sive equip­ment that would be im­pos­si­ble to bring to the front lines. That means us­ing chem­i­cals – not cold – to slow the body’s me­tab­o­lism.

“The goal is to cre­ate ‘hip-pocket ther­apy’, ” he says. “A medic could carry a drug in his bag and whip out a sy­ringe for a se­verely in­jured sol­dier, in­ject it and start the process of sus­pended an­i­ma­tion, giv­ing the sol­dier more time to get to a sur­gi­cal fa­cil­ity.”

He and his col­leagues have iden­ti­fied a se­ries of en­zymes known as PI 3-ki­nase, which helps reg­u­late me­tab­o­lism. Af­ter ex­am­in­ing the ef­fects of the drug on pigs, Martin’s early data sug­gests that ad­min­is­ter­ing it at the mo­ment of is­chaemia – when blood flow to the heart be­comes in­ad­e­quate – can slow down the me­tab­o­lism with­out harm­ing the an­i­mal.

MEAN­WHILE, BACK AT Dr Roth’s lab in Seat­tle, he’s like­wise hop­ing the an­swer to stalling time lies within a por­ta­ble, in­jectable drug.

A day af­ter putting his ne­ma­todes to sleep, Roth re­turned to his lab to check on their progress. As ex­pected, the lit­tle worms that spent the night in the ni­tro­gen chamber hadn’t grown but were eas­ily brought back to life when ex­posed to fresh air. At the same time, the ones left out on the ta­ble had grown no­tice­ably larger. Soon they would have ba­bies of their own.

It’s a far cry from sav­ing a hu­man trauma pa­tient. But wit­ness­ing those tiny worms ‘res­ur­rected’, I felt I’d just seen a glimpse of the fu­ture.

Af­ter fall­ing through the ice while snow­shoe­ing, Kelly Dwyer was ‘med­i­cally dead’ for five hours be­fore doc­tors got her heart beat­ing again

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