One Man’s Quest to Hack His Own Genes(technologyreview.com)
technologyreview.com
One Man’s Quest to Hack His Own Genes
https://www.technologyreview.com/s/603217/one-mans-quest-to-hack-his-own-genes/
22 comments
As I've been saying for the past couple of years, gene therapies are straightforward enough and cheap enough to carry out that people are doing it, usually quietly, but it is happening. You only have to be connected enough to know a biotechnologist or two with the right skills, as the example here shows. The stage of the adventurous and the self-experimenters is an important part of the development of any new medical technology, helping to overcome institutional reluctance while gathering initial data on how best to approach such treatments in practice. The next part of the process, something that does requires much greater funding and participation from the research and development community, will happen over the next few years; it involves making the therapies more robust, the outcomes more reliable, and assembling the suite of tools and clinics needed for those tasks. That is certainly the goal of BioViva, and as they move forward, others will join them.
There is more than enough evidence for the potential utility of enhancement gene therapies based on producing greater muscle growth and improved metabolism via increased follistatin or myostatin knockout, ranging from numerous animal studies to existing natural human and animal mutants to myostatin antibody trials. There is also considerable interest in telomerase gene therapies, though I'd like to wait for more data on that front before diving in myself, given the potential cancer risk. Once these initial approaches are out there, available, and the methodologies of gene therapy have progressed to the point at which there is reliably comprehensive cell coverage - especially in stem cells, as that will determine how lasting the effect is - then a score of other genes bear further investigation and consideration as targets for enhancement therapies.
While I applaud those who set out to undergo gene therapy today, as their work is necessary to move matters along in this age of overabundant caution and oppressive regulation of every activity, I can't say as I think the fellow here made a good choice of gene. This has the look of a more sophisticated form of the hormone therapies practiced over the past few decades, approaches that really don't have a good impact on aging, and outside of correcting deficiencies are not something that should benefit or is expected to benefit someone in normal health for their age. Increased growth hormone, if anything, is exactly the opposite of what animal and human studies suggest is good for longevity.
There is more than enough evidence for the potential utility of enhancement gene therapies based on producing greater muscle growth and improved metabolism via increased follistatin or myostatin knockout, ranging from numerous animal studies to existing natural human and animal mutants to myostatin antibody trials. There is also considerable interest in telomerase gene therapies, though I'd like to wait for more data on that front before diving in myself, given the potential cancer risk. Once these initial approaches are out there, available, and the methodologies of gene therapy have progressed to the point at which there is reliably comprehensive cell coverage - especially in stem cells, as that will determine how lasting the effect is - then a score of other genes bear further investigation and consideration as targets for enhancement therapies.
While I applaud those who set out to undergo gene therapy today, as their work is necessary to move matters along in this age of overabundant caution and oppressive regulation of every activity, I can't say as I think the fellow here made a good choice of gene. This has the look of a more sophisticated form of the hormone therapies practiced over the past few decades, approaches that really don't have a good impact on aging, and outside of correcting deficiencies are not something that should benefit or is expected to benefit someone in normal health for their age. Increased growth hormone, if anything, is exactly the opposite of what animal and human studies suggest is good for longevity.
He's not 'hacking his own genes' though, is he? There's no modification of his germ cells, nor is there stable incorporation of the exogenous material into the genome of the affected cells - more just transient expression of the protein he's interested in.
Giving the extraordinary complexity of the ageing process, with the interplay between multiple genes, each with multiple splice variants and post-translation modifications, and whose expression is modulated by both genetic and epigenetic factors, the chance of success with this approach is minimal.
Giving the extraordinary complexity of the ageing process, with the interplay between multiple genes, each with multiple splice variants and post-translation modifications, and whose expression is modulated by both genetic and epigenetic factors, the chance of success with this approach is minimal.
It's an interesting first step to hacking one's own genes, though. It makes me wonder if it would be possible to transfect human skin cells in situ with a plasmid containing a gene for a fluorescent protein. If possible, it would be the nerdiest of nerd tattoos.
Am I the only one to foresee that such changes can do way more harm than good?
As comments went on a previous post on a similar topic: Genetic changes are a lot like assembler software changes.
The best part? In living things there's very little documentation, based on "poor" reverse engineering (as we know little about it).
As comments went on a previous post on a similar topic: Genetic changes are a lot like assembler software changes.
The best part? In living things there's very little documentation, based on "poor" reverse engineering (as we know little about it).
I agree - we're a long long way off being able to accurately predict the impacts of genetic changes, particularly given effects like pleiotrophy.
We still don't even really understand why a tiny worm with around 1000 cells (C. elegans) has roughly the same number of genes as a human being. Sure, at the cellular level, the complexity of the two organisms is much the same, but at the macro level, it's not even close. Obviously all the information to build the organism is in the germ cells, but discrete genes are just a part of the equation.
In my opinion, as someone why tries to work this stuff out for a living, we are many years away from grasping how it all fits together. Until then, I'd be wary of modifying myself except in the most dire of circumstances.
We still don't even really understand why a tiny worm with around 1000 cells (C. elegans) has roughly the same number of genes as a human being. Sure, at the cellular level, the complexity of the two organisms is much the same, but at the macro level, it's not even close. Obviously all the information to build the organism is in the germ cells, but discrete genes are just a part of the equation.
In my opinion, as someone why tries to work this stuff out for a living, we are many years away from grasping how it all fits together. Until then, I'd be wary of modifying myself except in the most dire of circumstances.
We don't really understand how most of the treatments we have work. We have data, we have in many cases some ideas, but we don't know.
Take Psoriasis as an example, doctors are still prescribing coal tar based treatments. I guess they are ~100 years old. They don't work very well, and people don't really know why they should work at all.
Pretty much all Psoriasis treatments are like this, even the more recent ones. They interfere with some pathway related to the immune system... but we don't really understand why they work.
So we don't really understand "how it all fits together" for current treatments. It's still reasonable to use them if they are relatively safe, and work. Same is true of gene therapies.
Mostly we figure out that things work/are safe through experimentation. Not through totally understanding the system.
Take Psoriasis as an example, doctors are still prescribing coal tar based treatments. I guess they are ~100 years old. They don't work very well, and people don't really know why they should work at all.
Pretty much all Psoriasis treatments are like this, even the more recent ones. They interfere with some pathway related to the immune system... but we don't really understand why they work.
So we don't really understand "how it all fits together" for current treatments. It's still reasonable to use them if they are relatively safe, and work. Same is true of gene therapies.
Mostly we figure out that things work/are safe through experimentation. Not through totally understanding the system.
Realistically, what harm can the experiments described in the article do to the general population?
It's so hard to do anything, even design diagnostic tests, that requires FDA approval that personally I'd avoid any startup that had that on their route to revenue.
It's kind of a shame, and countries where it's easier to develop new treatments and tests are likely to take the lead.
It's so hard to do anything, even design diagnostic tests, that requires FDA approval that personally I'd avoid any startup that had that on their route to revenue.
It's kind of a shame, and countries where it's easier to develop new treatments and tests are likely to take the lead.
I disagree about the revenue concerns.
Many new ideas for medical technologies are founded on academic work that is often fraudulent. When I hear that a startup is going to start the ball rolling on FDA approval, that often means that the technology is more likely to work.
Many new ideas for medical technologies are founded on academic work that is often fraudulent. When I hear that a startup is going to start the ball rolling on FDA approval, that often means that the technology is more likely to work.
First of all, I'm not a biologist but a software consultant and have worked in several software companies as level 3 support.
My personal experience on tiny and sometimes unrelated changes having a catastrophic impact: software configuration changes, new hardware, other softwares bug, antivirus rules and updates, etc.
These points can be roughly related to a living being: psychological/environmental/habit changes, transplant/implant, organ failure/traumatism, immune system false positive (e.g. alergies?), ...
I'm not against the idea gene manipulation, just saying that his doings are very marginal and must not be praised.
If labs have been relying on white mice and drosophilae it's for some good reasons:
Common sense (how many people died because of charlatanism?), ethics and Human Rights.
What is at stakes here can lead either to a nobel price (I sincerely hope for him) or a darwin award (thanks to the ignorance of such red flags).
My personal experience on tiny and sometimes unrelated changes having a catastrophic impact: software configuration changes, new hardware, other softwares bug, antivirus rules and updates, etc.
These points can be roughly related to a living being: psychological/environmental/habit changes, transplant/implant, organ failure/traumatism, immune system false positive (e.g. alergies?), ...
I'm not against the idea gene manipulation, just saying that his doings are very marginal and must not be praised.
If labs have been relying on white mice and drosophilae it's for some good reasons:
Common sense (how many people died because of charlatanism?), ethics and Human Rights.
What is at stakes here can lead either to a nobel price (I sincerely hope for him) or a darwin award (thanks to the ignorance of such red flags).
> What is at stakes here can lead either to a nobel price (I sincerely hope for him) or a darwin award (thanks to the ignorance of such red flags).
We need something like this https://iotdarwinaward.com/ but for genetic engineering :-)
We need something like this https://iotdarwinaward.com/ but for genetic engineering :-)
7 Billion People on Planet Earth
3 Billionish Genetic Base Pairs
15,000 disease modalities-ish(and many that are obfuscated or clustered as one disease)
60,000 genetic marker tests on the market.
8-10 new ones each day.
Knowing what they actually do? --- Costs Billions.
3 Billionish Genetic Base Pairs
15,000 disease modalities-ish(and many that are obfuscated or clustered as one disease)
60,000 genetic marker tests on the market.
8-10 new ones each day.
Knowing what they actually do? --- Costs Billions.
add in phenotype, microbiota, mitochrondrial DNA, behaviour , environmental and societal factors, we have some way to go....
>Hanley says he did not secure the approval of the FDA before carrying out his experiment either. The agency requires companies to seek an authorization called an investigational new drug application, or IND, before administering any novel drug or gene therapy to people. “They said ‘You need an IND’ and I said, ‘No, I don’t,’” recalls Hanley, who traded e-mails with officials at the federal agency. He argued that self-experiments should be exempt, in part because they don’t pose any risk to the public.
Until you start modifying the germ line, of course.
Until you start modifying the germ line, of course.
Posing a risk to your potential immediate descendants hardly counts as "the public", and you probably don't want to start down the road of enforcing that people don't have the right to do things to themselves which have the risk of possibly being teratogenic as if it's a public health threat.
I read the whole article and Hanley's comments in the comment section (boy, did he hate the author of the article). I think he's being incredibly naive and overly optimistic. I say that as somebody who's wanted to see gene therapy be successful for a long time (and who learned that solving this problem is far harder than electroporating your cells.
This is a bold step on the path towards comic book super-villains existing in the real world.
Reminds me a lot of the TDCS people.
Human life is not precious anymore. If somebody wants to risk their life for scientific progress, I feel that we should support them instead of discouraging them.
Just as we did when life was more precious.