Life 2.0 – a chance to fix the faulty bits?

dna-crane

Rebuilding DNA with CRISPR. Source: New Yorker, Illustration by Todd St.John

BIG things are happening in genetics, for BigD-ers and for the rest of the world. Scientists have discovered a naturally-occurring, highly accurate gene editor, that can be used to cut and paste or delete genes or parts of genes in DNA. They can use the editor to remove a disease-causing mutation, replace faulty or undesirable parts of a gene or to turn a gene off completely.

What could this mean? Say you’ve inherited a genetic mutation that guarantees you’ll get polycystic kidney disease by the time you reach adulthood. And that it is most likely you will spend the rest of your life on dialysis.

What if the mutant genes that cause polycystic disease, passed down from generation to generation, can be clipped out of your genome entirely and you never pass it on to any of your offspring?

That’s the promise of this new gene editor, called CRISPR, which is basically a genetic-level immunity mechanism that evolved in bacteria to fight off disease.  It was discovered about 30 years ago, but scientist have only now, over the last couple of years, discovered its full potential and are beginning to learn how to use it.

For my part, I’d be happy to line up for a couple of new kidneys, maybe improved eyesight (perhaps from some eagle genes), revitalised muscles and bones, and a couple of other refurbs not really worth mentioning. Not too much to ask.

As you can imagine, many people are beginning to see CRISPR as the most world changing (and challenging) discovery since antibiotics or atomic energy.  It has the potential to enable us to radically change humanity’s genetic code, healthcare, food systems, agriculture and manufacturing – even biological life on Earth itself.

CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, which is just about as lame and forgettable as “BackRub,” a search engine named for its analysis of the web’s “back links”, subsequently renamed Google. I prefer something memorable. New Scientist suggested DNA Legokit or Gene Photoshop, but I prefer something snappy and big picture, like Life 2.0.

Whatever, a CRISPR by any other name will still change the world.

But we are in early days. Currently, most CRISPR work is taking place in labs, cutting and pasting genes in crops (tomatoes, mushrooms, etc), chicken eggs, laboratory mice or organelles (tiny collections of human organ cells, often built using stem cells), to test the outcome of the gene changes.

(One of the most important current organelles to BigD members are those described as mini kidneys, that have hundreds of filtering units and blood vessels and appear to be developing just as kidneys would in an embryo. ” We can look at a little organ from the patient and a little organ from the patient that is only different because we’ve gene-edited to correct a mutation. That’s the best way we can model a disease” said lead Molecular Biologist Professor Melissa Little, of the Murdoch Children’s Research Institute. See the whole story in A kidney in a Dish.)

It will be a few years before CRISPR products move out of the lab and start to deliver on Life 2.0 in the real world.

Which is a good thing, because as a species, we need the time, not just to work out what we can do with it, but to decide what we should do with it.  Changes made to DNA are permanent for every subsequent generation (though there is the option to go back and undo the changes…). None of us is perfect; we all make mistakes.  Are we prepared to risk the consequences, intended and unintended?  Should we? Who decides? Even if every scientist using CRISPR is superbly skilled and motivated only to do good, would that make the technology safe for mankind?

Alas, the world is not run by scientists, but by politicians. aND Every generation has its small percentage of geniuses and psychopaths. Hopefully, the geniuses will move us forward. But what if a new Hitler sets up a lab that moved CRISPR to the dark side? What’s to stop him making and even releasing a pathogen against which ‘inferior races’ or their food crops have no defence?

I am not alone in fearing the dark side.  Jennifer Doudna, Professor of Chemistry and Molecular Biology at Berkeley is working at the forefront of CRISPR development. In a recent edition of the New Yorker, the reporter …asked if she had ever wondered whether the powerful new tool might do more harm than good she looked uncomfortable. “I lie in bed almost every night and ask myself that question,” she said. “When I’m ninety, will I look back and be glad about what we have accomplished with this technology? Or will I wish I’d never discovered how it works?”

Her eyes narrowed, and she lowered her voice almost to a whisper. “I have never said this in public, but it will show you where my psyche is,” she said. “I had a dream recently, and in my dream”—she mentioned the name of a leading scientific researcher—“had come to see me and said, ‘I have somebody very powerful with me who I want you to meet, and I want you to explain to him how this technology functions.’ So I said, Sure, who is it? It was Adolf Hitler. I was really horrified, but I went into a room and there was Hitler. He had a pig face and I could only see him from behind and he was taking notes and he said, ‘I want to understand the uses and implications of this amazing technology.’ I woke up in a cold sweat. And that dream has haunted me from that day. Because suppose somebody like Hitler had access to this—we can only imagine the kind of horrible uses he could put it to.”

The nearest equivalent to this problem that exists now is atomic energy and nuclear weapons. First used in August 1945, it took just under 12 years (July 1953) to establish the International Atomic Energy Agency (IAEA) to promote the peaceful use of nuclear energy, and to inhibit its use for any military purpose. With the odd miss (Fukushima), near misses, and wild cards like North Korea, India, Pakistan, and Iran, it has been successful (so far) in achieving its aims.

Perhaps, with all its shortcomings, we need the same kind of organisation for CRISPR – an International Genetic Manipulation Agency (the IGMA)?  At a minimum, we need to establish and administer safeguards against using CRISPR for the dark side. Perhaps by maintaining a central registry of CRISPR companies, labs and peer-approved projects and a repository of the tools and techniques used to manipulate Earth’s gene pool. Perhaps much more.

And we should start soon before some labs jump the gun: Chinese scientists CRISPR a human for the first time.

Easy to say, harder to do.  But for our future’s sake, I’m happy to wait to live the Life 2.0 dream, rather than rush into the Life 2.0 nightmare.

Update

Safeguard procedures and processes are starting to appear: the US Pentagon’s Defense Advanced Research Projects Agency (DARPA) plans to establish a new genetic safeguard initiative called Safe Genes, to cultivate, among other things, a kind of clean-up crew for engineered genes deemed harmful to or undesirable in an ecosystem.  DARPA researchers are developing responses for accidental or malicious “genetic spills”

Kidney disease: meant-to-be or dumb luck? Part 2 – DNA

DNAOne of the (many) cool and wondrous benefits of being alive in the 21st Century is our ability to look deeply into our own bodies, right down to the very building blocks of life, our DNA, to glimpse our personal program for life.  Another almost-as-amazing benefit is that it costs just $99!

I was keen to check it out to see if my DNA had my kidney failure pre-programmed or if it was just dumb bad luck.

Getting started

I had read quite a bit about 23andMe and had long been keen to see what it had to offer.  So I clicked buy and began my journey. (more…)

Kidney disease: meant-to-be or dumb luck? Part 1 – Chance

gladstone ganderI have often wondered if my kidneys were programmed to fail when I was born, or if they were simply the victim of a rough and tumble world; or maybe a bit of both.

I know, everybody is different, but maybe my case could be useful for others.

I had some kind of blockage that stopped urine from leaving my left kidney, which eventually destroyed it.  It happened when I was 19, full of beans, and in the Navy.  (more…)

MSCs help us Reject Rejection

mesenchymal_stem_cell 2The light of rejection-free, healthy kidney transplants has entered the tunnel, and should arrive at our end in just three to five years.

Last month a senior researcher from the Cell and Tissue Therapies WA at the Royal Perth Hospital (CTTWA) presented a paper to the Renal Society of Australia‘s annual conference that has profound implications for us BigDers.  It detailed their early clinical trial successes in using Mesenchymal Stem Cells (MSCs) to stop kidney transplant rejection and to repair acute kidney injury (among many other medical wonders). (more…)

Every donor kidney a perfect match: no more transplant drugs!

Stem CellsWe all hate rejection.  It hurts us somewhere deep inside.  And those of us who’ve had an organ transplant hate it most of all.  Because the only way to make all that pain go away is by taking a hearty (sometimes heroic) dose of anti-rejection drugs.

Rejection is driven by our body’s immune system, a collection of cells (T cells) that recognise and destroy foreign cells: germs, poisons, other bits that find their way into us. All cells have proteins called antigens on their surface.  As soon as these antigens enter our body, the immune system recognises that they are not from our body and attacks them.

When we receive an organ transplant, our immune system (more…)

Dialysis news flash!

It’s been an interesting news week for BigD-ers, with a major advance in stem cell technology  It wont happen tomorrow, but the potential is now the possible: growing a new kidney from stem cells.   It’s not certain yet whether it will be done inside the body, or in a dish and transplanted when full grown, but if we can hang around a few years…

Just click on the headlines below for more.

Australian scientists grow mini-kidney in lab 

Stem cell mini-kidney in a dish

Plus:

University of Queensland kidney breakthrough a step forward in bio engineering

Dialysis needling: if at first…

 

Buttonholes

Buttonholes!

Josie (not her real name) emailed me recently about a problem she had getting one of her needles in:

 

Hi Greg

I hope you don’t mind me getting in touch. My name is Josie, I live in the UK and started home haemo a few months ago. I have had a problem with my fistula tonight and because it is Friday night here I can’t get hold of any of the nurses from my training unit, and having followed your blog I thought I could seek your advice… as I say, I hope you don’t mind me doing so. (more…)

Dialysis and Fluid Restrictions – Tips and Tricks

This week, a guest post from Ros Ball, Past President and currently Secretary of DATA, the Dialysis and Transplant Association of Victoria (Australia).  You may remember Ros when I wrote about her in June a couple of years ago.  She and her husband Charlie have outfitted their caravan with a dialysis machine and travel where most BigD-ers fear to tread:  the wide open spaces of the outback.  Ros’s get up and go, regardless of the demands of BigD is an inspiration, and puts the rest of us sometime travellers in the shade. (more…)

Dialysis: Back to the future with implantable artificial kidney

Hello and welcome to my first post for the New Year.  I hope you had a good Christmas and celebrated the arrival of 2011 in a style that set the tone for the year ahead.  My New Year was easy-going: we went to see The King’s Speech at the movies on New Year’s Eve, followed by a drive to Falls Creek, Victoria’s biggest alpine resort on New Year’s Day.  We stayed overnight and I was back in time for the BigD the next day.

The King’s Speech was a great movie: fabulous acting by Colin Firth and Geoffrey Rush and an inspiring message about how persistence and courage can win you back your life (a familiar theme, and not just for stammerers). (more…)

“Tinkerer” builds his own Dialysis Machine

At various times, I wish we were a little more advanced with the BigD. I wish for access without needles, wearable artificial kidneys and stem cell therapy to regrow a healthy kidney. I am sure they will arrive, eventually.

But once I get over my impatience, reality sets in and I realise how lucky I am to be alive right now, when dialysis has not only been invented but is the streamlined, readily reproducible treatment I take for granted. And to some extent, the same goes for transplants. Today, no-one expects to die from kidney failure, they just (just?) go on dialysis and line up for a transplant. (more…)