It’s that time of year when I take some time off for a variety of reasons and tasks – in short, it’s annual leave time. Yes, some much appreciated time off work. Last year I attempted a holiday and nearly died – diseased kidneys, blood poisoning, and internal bleeding – all a result of a kidney stone. What followed was months of illness, as that experience proved a catalyst for an old illness to make a renewed appearance also (Chronic Fatigue Syndrome – CFS). Finally, in the last few weeks, I have been reasonably well and have been working at a frantic pace, trying to make up for lost time.
So now I hope to enjoy these next few weeks, do some traveling (including to the previous destination that I never arrived at due to falling ill on the way), get a bit of personal things done (yeah, including a host of medical stuff) and really, just to relax and have a break – an enjoyable break in fact.
So what does this mean for the Blogs? Well, I was going to continue to post in a haphazard manner over the next three weeks, but have since thought better of it and will not do so. So no new posts for the next three weeks – there may be some still to appear on one of the Blogs that I scheduled in advance, but you won’t hear much from me during this period. So enjoy the break from me, as I enjoy the break from everyday usual life.
Warm Australian waters are home to the box jellyfish (Chironex fleckeri), which is considered to be one of the most venomous animals on the planet.
Box jellyfish stings lead to excruciating pain lasting days, tissue death and scarring at the site of the sting, and with significant exposure, death within minutes. While most jellyfish stings do not lead to death, pain and scarring is quite common.
Despite its potent ability to cause pain and death, to date we’ve had very little understanding of how this deadly venom works. This makes it very difficult to understand how it can cause so much pain – and how to develop medicines to block venom actions.
Published today, our new research has uncovered a potential antidote for box jellyfish venom. By working with humans cells and the gene-editing tool CRISPR, we identified a common, cheap drug that is already on the market and which could be a candidate for treating box jellyfish stings.
Flipping all the switches
This work began in 2012, when we set out to determine what it was about box jellyfish venom molecules that made them so effective in causing pain and damage.
The venom didn’t seem to work through the known pathways that cause cell death. So we used CRISPR genome editing technologies in human cells grown in the laboratory. This let us systematically turn off each gene in the human genome, and test to see which of these is needed for the jellyfish venom to kill the cells.
It’s kind of like flipping all the switches in a house, trying to figure out which one turns off the kitchen lights, but at the whole genome level. We actually didn’t even know if it would be possible to find single genes that when turned off could block the venom action.
But luckily, we were successful. While normal human cells exposed to venom die in the laboratory within five minutes, we identified gene-edited cells that could last for two weeks continually exposed to venom.
Putting the evidence together
Then using new DNA sequencing technologies (that allow us to identify CRISPR guide RNAs targeting specific genes), we identified which human genes had been switched off in our genome editing experiments.
By putting the evidence together, we worked out which genes the box jellyfish venom needs to target in order to kill human cells in the lab.
One we identified is a calcium transporter molecule called ATP2B1, and is present on the surface of cells.
We tested a drug that we know targets this gene. If we added the drug before the venom, we could block cell death, but if we added the drug after the venom, it didn’t have any effect.
So this helped us understand more about how the venom works – and maybe even how it causes pain. We are still looking at this particular pathway in more detail, but at the moment it doesn’t seem promising for a therapy.
Next we looked at the pathways involved in how box jellyfish venom kills cells.
We found four of the top ten genes required for venom action were all part of a pathway that makes cholesterol in cells.
Since cholesterol has been heavily studied over the last 30 years, there are already drugs available that target lots of different steps in cholesterol regulation. We focused on drugs that could bind to cholesterol and remove it quickly, basically acting like a cholesterol sponge.
We found these drugs could completely block the box jelly fish venom’s ability to kill human cells in the lab if added before venom exposure. We also found there is a 15-minute window after venom exposure where if we add this cholesterol sponge, it still blocks venom action.
This was exciting, as the capacity to have effect after the venom means the drug could work as a treatment in the case of being stung by a box jellyfish.
So far our additional studies show that these same drugs can block pain, tissue death and scarring associated with a mouse model of box jellyfish stings.
Moving towards a human treatment
The really cool thing about this work is that the potential box jellyfish antidote we found is in a family of drugs called cyclodextrins. These are known to be safe for us in humans, and are cheap and stable.
So now we are trying to work with the state or national government, or first responders, to see if we can move this venom antidote forward for human use.
As well as developing a topical application at the site of a sting, we also aim to develop this idea as a potential treatment for cardiac injection in the emergency room in the case of very severe box jellyfish sting cases.
Bill Shorten has rebuffed overtures by the Greens leader Richard Di Natale to work closely with a Labor government to promote a strong policy on climate.
Shorten accused the Greens of “trailing their coat and saying, ‘Look at me’”.
“The fact of the matter is that if we get elected we’ll be making decisions in a Labor cabinet and the decisions will be made by members of parliament of the Labor party,” Shorten said, in anticipation of Di Natale’s Wednesday address to the National Press Club.
“What we will do is we will implement the policies we’ve put forward,” Shorten said.
In fact a Labor government, which would be in a minority in the Senate, would probably have to negotiate with the Greens to get its climate policy through the Senate.
After the backlash against the formal Labor-Greens alliance under the Gillard government – in which the two parties worked in conjunction on the carbon pricing scheme – Shorten is anxious to keep maximum distance between the ALP and the minor party.
For its part the government paints Labor and the Greens as “joined at the hip”. Scott Morrison said on Wednesday: “We know who holds the chain – if it’s not the Greens it’s the militant unions”.
In his Press Club appearance Di Natale ran a double line – attacking Labor policies on climate and the environment as inadequate, while stressing the need for co-operation in government.
The Greens were “deeply concerned that Labor has taken a weaker climate policy in 2019 than what they proposed in 2016, which was weaker still than what they took to the 2013 election”.
Di Natale said he was not seeking a formal alliance between the Greens and Labor as in 2010 – rather “we want to work constructively. We want to negotiate”.
He was “not surprised to hear the response from Bill Shorten today […] we hear that time and time again in the lead-up to an election.
“But we need the Greens in the Senate working with the Labor party and other voices to ensure that the policy that’s delivered meets the science and that is up to the challenge of transitioning our economy”.
A Shorten government “will have two pathways open to them after the election, ” he said.
“They can either pursue a climate and energy policy designed to pass through a divided Coalition party room […] or they can negotiate a comprehensive response, based on science, with the Greens.
“My message to Bill Shorten is that you can’t achieve bipartisanship with the Liberals because they can’t even agree among themselves,” he said.
“The decision for Bill Shorten is whether he follows the take-it-or-leave-it approach of Kevin Rudd in 2009, or negotiates with the Greens, just like Julia Gillard did in 2011, to deliver a climate policy that gives future generations a chance”.
Di Natale would not be drawn on what approach the Greens would take if negotiating climate policy with Labor. “The key part of any negotiation is not to conduct it publicly through the media.”
The Greens leader defended his party against criticism over its refusal to support the Rudd government’s scheme, saying Rudd’s policy “would have locked in failure”.
Meanwhile a number of independent MPs and candidates have signed a statement initiated by the Australian Conservation Foundation committing, if elected, to work with each other and other parliamentarians to promote initiatives on climate.
“We recognise that to be a true servant of our communities and our national parliament, we must demonstrate and deliver strong leadership on climate change,” they say.
Among the objectives they commit to are:
opposing the development of the Adani mine
ensuring Kyoto Protocol carryover credits are not used to meet Australia’s 2030 emissions education target
developing a roadmap to power Australia from 100% renewable energy, aiming to achieve at least 50% by 2030
opposing attempts to commit public money to new or existing coal or other fossil fuel operations, including any government underwriting of coal or gas power plants.
Those signing the statement are Andrew Wilkie, member for Clark; Kerryn Phelps, member for Wentworth; Julia Banks, member for Chisholm who is running as an independent candidate in Flinders; Dr Helen Haines, independent candidate for Indi; Zali Steggall, independent candidate for Warringah; Rob Oakeshott, independent candidate for Cowper, and Oliver Yates, independent candidate for Kooyong.