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Thursday, 14 June, 2001, 17:36 GMT 18:36 UK
Fish in 'suspended animation'

Zebrafish: key to suspended animation
By BBC News Online science editor Dr David Whitehouse

Scientists have induced a state of so-called suspended animation in zebrafish embryos by starving them of oxygen. They say the technique could one day be used in medical treatment.

During the experiment all observable metabolic activity, including heartbeat, ceased in the zebrafish embryos. Afterwards, they returned to normal with no harmful effects on their health or growth.

We can't detect any abnormalities in these fish after they recover

Dr Mark Roth, Fred Hutchinson Cancer Center
This discovery promises to open novel paths of research into suspended animation. It could also lead to new ways to treat cancer and prevent injury caused by insufficient blood supply to organs and tissues.

In addition, the studies may shed light on a problem that perplexes cancer biologists: how oxygen deprivation affects the growth of tumours.

'Normal offspring'

The researchers compared the growth of zebrafish embryos that had been exposed to normal atmospheric conditions with those grown in oxygen-free chambers.

The absence of oxygen caused all observable metabolic activity in the embryos to stop - including a shutdown of the heart, which normally beats 100 times per minute.

The researchers found that 25-hour-old embryos could survive without oxygen for 24 hours and still resume normal development when given oxygen again.

"We can't detect any abnormalities in these fish after they recover,'' says Dr Mark Roth of the Fred Hutchinson Cancer Center in Seattle, US. "They have grown to adulthood, mated and produced normal offspring.''

The research may have profound implications for the understanding of cancer.

Anti-cancer drugs

"We typically think of cancer cells as growing out of control,'' says Dr Roth. "But actually the vast majority of cells in a tumour are in a state of low oxygen tension and are non-proliferating - which is the reason that some tumours don't respond to certain forms of radiation and chemotherapy."

Most anti-cancer drugs work by selectively killing actively dividing cells, meaning that non-dividing tumour cells are immune to treatment.

This new work may help in the understanding of why some cancer cells are in a form of hibernation, and how they may be attacked.

Suspended animation also has a role in the growth of normal cells, Dr Roth says.

"Stem cells - like those that give rise to your skin - are self-renewing and have the capacity to reproduce at certain times in your life,'' he says.

"Some of those cells might be dividing right now, while others withhold their proliferation potential until a later time. Lots of scientists are interested in how cells maintain this state of quiescence and then resume cell division.''

Metabolic shutdown

Zebrafish in the wild have not yet been seen to undergo suspended animation, but the metabolic shutdown induced in the laboratory resembles the reversible state of limbo that has been observed in other organisms.

The next goal is to figure out the molecular pathways that permit this recovery, and why some animals can survive a lack of oxygen while others cannot.

Understanding the mechanisms that control biological quiescence could have dramatic implications for medical care

Dr Mark Roth
Some humans, for unexplained reasons, do manage to survive extreme forms of stress, such as freezing temperatures for an extended amount of time, and manage to recover from a metabolic shutdown.

A potential application of this work could one day include helping people survive life-threatening injuries while in transit to a hospital emergency room.

Bodies or organs held in a state of suspended animation could be repaired and suffer no long-term consequences from extreme stress such as oxygen deprivation.

"Understanding the mechanisms that control biological quiescence could have dramatic implications for medical care, as it could give us an ability to control life processes at the most basic, fundamental level,'' Dr Roth says.

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Zebrafish genome next
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