Human Germ-line Modification Hiatus Proposed (too late?)

Nobel laureates David Baltimore and Paul Berg have recommended pausing active modification of the human germ-line cells until experts can convene a conference to consider the implications of this activity.  (WSJ 4/9/2015 “Let’s Hit Pause Before Altering Humankind”)   They point out that this parallel’s a similar action in 1975 when the emergence of recombinant DNA technology triggered a conference on that topic.

This is a bit afield from IEEE’s domain of affairs, but quite relevant to the Society on Social Implications of Technology dialogs. Let me outline key concepts they put forward to help build a common vocabulary, and then focus on parallel’s in IEEE’s areas of work.

They point out the advent of a bio-tech (CRISPER/Cas9) that simplifies the modification of germ-line DNA alterations that are “quite precise with no undesired changes in the genome.” They point out that modifications can be within an individual without inheritability (somatic cell alteration.) They can be applied to germ-cells, affecting all future generations from that line either to eliminate a defect (therapeutic germ-line alteration.) Although they point out that similar benefits for the next generation may be attainable via embryo-selection methodology.  Finally there is the potential for “voluntary germ-line alteration”, to increase traits parents currently consider desirable. They point out that “we often do not know well enough the total range of consequences of a given gene alteration, potentially creating unexpected physiological alterations that would extend down through generations to come.” (A.k.a. the law of unintended consequences.)  Ergo they recommend a moratorium and conference to address the implications involved.

This is an excellent example parallel to IEEE’s Code of Ethics which includes “to improve the understanding of technology; its appropriate application, and potential consequences.” Actually, it goes one step further in taking action to manage potential consequences before they are fully realized.

If we look at the fields where IEEE’s technologists are engaged (with computing, robotics and bio-medical systems included, there are few areas we don’t touch), there are some interesting examples.  There is some discussion (although no suggested moratoriums) in areas like self-driving or remotely controllable cars, some of these fields are outgrowths of simple ‘improvements’, such as automatic breaking systems or parallel parking.  Others are unintended consequences of remote monitoring services.

Observation #1: we (technologists, our employers, and indirectly stockholders and customers) may not be applying sufficient diligence in considering potential consequences.  In part we may not be providing the time and incentives for quality engineering of quality products. A quality product should not be subject to hacking that can affect public safety and health for example.

Observation #2: The bio-genetics world is miles ahead of our technology in their limited understanding of what may result from their work.  For example, the concept of emerging artificial intelligence and it’s impact is getting coverage in science fiction, and even some awareness in research and industry, but we have very little insight on the potential consequences of passing over some nebulous lines in paths that lead towards intelligent and./or conscious systems.

What other areas do you see that might warrant some serious consideration before we proceed?

[April 24th, Chinese researchers indicate they have completed a trial of this concept, with some ‘off target’ effects.]

Your DNA into Your Picture

A recent Wall St Journal interview with J. Craig Venter indicates his company is currently working on translating DNA data into a ‘photo of you’, or the sound of your voice. The logic of course is that genetics (including epigenetic elements) include the parts list, assembly instructions and many of the finishing details for building an individual.  So it may not come as a surprise that a DNA sample can identify you as an individual (even distinct from your identical twin — considering mutations and epigenetic variations) — or perhaps even to create a clone.  But having a sample of your DNA translated into a picture of your face (presumably at different ages) or an imitation of your voice is not something that had been in my  genomic awareness.

The DNA sample from the crime scene may do more than identify the Perp, it may be the basis for generating a ‘police sketch’ of her face.

The movie Gattaca projected a society where genetic evaluation was a make/break factor in selecting a mate, getting a job, and other social decisions.  But it did not venture into the possibility of not just the evaluation of genetic desirability of a mate, but perhaps projecting their picture some years into the future.  “Will you still need me .. when I’m sixty four?

The interview also considers some of the ethical issues surrounding insurance, medical treatment and extended life spans … What other non-obvious applications can you see from analyzing the genomes and data of a few million persons?

Genomics, Big Data and Google

Google is offering cloud storage and genomic specific services for genome data bases.  It is unclear (to this blogger) what levels of anonymity can be assured with such data.  Presumably a full sequencing (perhaps 100 GB of data) is unique to a given person (or set of identical twins since this does not, yet, include epigenetic data) providing a specific personal identifier — even if it lacks name or social security number. Researchers can share data sets with team members, colleagues or the public.  The National Cancer Institute has moved thousands of patient datasets to both Google and Amazon cloud storage.

So here are some difficult questions:

If the police have a DNA sample from a “perp”, and search the public genome records, and find a match, or parent, or … how does this relate to U.S. (or other jurisdiction) legal rights?  Can Google (or the researcher) be forced to identify the related individual?

Who “owns” your DNA dataset? The lab that analyses it,  the researcher, you?  And what can these various interests do with that data?  In the U.S. there are laws that prohibit discrimination for health insurance based on this data, but not long term care insurance, life insurance or employment decisions.

Presumably for a cost of $1000 or so I can have any DNA sample sequenced.  Off of a glass from a restaurant, or some other source that was “left behind”.  Now what rights, limits, etc. are implicit in this collection and the resulting dataset?  Did you leave a coffee cup at that last staff meeting?

The technology is running well ahead of our understanding of the implications here — it will be interesting.

Prenatal Genomics

A genomics researcher, Razib Khan, sequenced his child’s genes prior to birth, a first for the U.S. with a “normal” child.  This is described, with some of the legal and other issues in an article in MIT’s Technology Review. Khan comments on the issue of “who owns a genome” in this article and part of a regular Blog he posts. Just to be clear, this is the 6 billion base pair analysis, not the half billion 23andMe form, so he now has most of the story.  I don’t think full Genome analysis addresses epigenetic information such as methyl groups and histone variations. These can affect gene expression, and also reflect a path for passing information from generation to generation without mutation and as a result of the activities of the parent.  So, yes, it appears your smoking, drinking, etc. can affect your children and grandchildren — actually one of the evident connections is between famine and longevity of grandchildren.

The FDA is currently blocking 23andMe from providing health analysis related to their genomic testing, but for clients, the results are available in raw form, and online sites allow cross checking. Of course in the world of the Internet, most attempts to control information are futile.  A software package Promethease provides analysis via a literature search “for free”.  Of course one might worry about what the creators of that package do with the information besides telling you about the genome you submit (presumably your own).  It seems that the FDA, while trying to protect consumers from “medical advice not provided by a professional”, have pushed the  liability and challenges associated with this from a contractually obligated partner to the open internet.

Looking forward, we can anticipate that genome sequencing will be available to the public, at least in “free” countries, and that analysis will be possible with varying degrees of quality control in such environments.  It would seem the medical, policy, and ethical community might be better served by focusing on articulating the issues and educating the public rather than trying to get the genie back in the bottle (or should I say the Genome back in the bottle.)

What’s New in DNA – What Does It Mean?

Ok, this one took me by surprise.  “Man-made DNA“, the headlines don’t seem that shocking.  But then I looked a bit inside.  The folks here are not just doing genetic engineering, but actually adding new base pairs to the DNA alphabet.

It’s not your grandmother’s DNA! … she had four base pairs with the ability to create twenty amino acids — all of which is a shared organic chemistry with every other living thing on earth (and I’d assumed, until today, other “goldilocks” planets.)  I recently competed the free Udacity course, sponsored by 23-and-Me, on how the … what do we call them now … “legacy” DNA pairs… work.  Researchers at Scripts Institute in San Diego have managed to find two additional molecules for a new base pair set, that “works” in DNA. They can insert them into bacteria, the bacteria reproduce, and these pairs get copied just like the legacy pairs.  This expands the range of amino acids that can be produced to one hundred and seventy two — that’s one hundred and fifty two more building blocks to play with in building organisms.  Depending on how “likely” these two additional bases are in a given planetary chemistry set, this means we might find DNA based life-forms that simply don’t use the same base pairs that we use.

So what? That’s the big question in my mind.  Our ability to understand the translation of base pairs into proteins into amino acids into cellular components into cells into life forms is somewhat limited at this point.  Give a genetics wizard a new mutation and ask what impact it will have and she won’t have a clue.  Needless to say, give our wizards one hundred and fifty two new building blocks and they will be clueless.  If some of these do good things, we can expect some of them to do bad things — although it is likely that most will do nothing at all.

It took four and one half billion years of playing with the chemistry set on Earth to come up with the thousands of species we have, and thousands of extinct species — presumably guided by the “invisible hand” of evolution.  No doubt we can incorporporate these additions to our “kit” in a tenth of that time (i.e. five hundred million years.) — (are we there yet?) … with a bit more carefully managed range of speciation and extinction.  It’s just the first million years I worry about.

Humans have not demonstrated a great deal of global responsibility in dealing with today’s challenges — governments, corporations, institutions and individuals tend to operate with short-term, self-serving agenda’s — even when they are presented with fairly solid evidence that their courses of action are harmful.  The new Cosmos series on TV does an excellent job of demonstrating that in a recent sequence on the dating of the universe (the transition of uranium into lead) and the closely related battle to stop poisoning the planet with lead in gasoline.  When we move forward into an arena where we have limited or no visibility we need to tread very carefully, at least.

How do you see this next opportunity in evolution?


New Genomics Monkey Business

MIT’s Technical Review announced that scientists in China have created viable monkey twins with explicit genetic modifications using the CRISPR genetic engineering methodology.

The Good news — this will allow the creation of primate models for testing diseases and treatments that are not common outside of humans.  Well, good news if you don’t have any concerns about using primates in such testing.

The Bad news — this approach confirms something we have anticipated, which is the ability to perform specific genetic engineering on primates and have viable offspring.  The range of possible improvements is significant.  Clearly parents will want to eliminate defects that would affect the health of their child.  Some areas of potential “improvement”, such as intelligence, are not well understood — so will require a longer period of time before this becomes possible. — Well, good news if you don’t have concerns about GMO humans.


Is the Singularity Silly?

In the SSIT LinkedIn discussion a pointer was posted to a provocative article “The Closing of the Scientific Mind” from Commentary Magazine. It raises many issues, including skepticism about the “Singularity” and the Cult of Kurzweil (a delightfully evocative concept as well).  One comment posted in that thread suggested that the Singularity was ‘silly’ … which is not a particularly useful observation in terms of scholarly analysis.  That author sought to dismiss the concept as not deserving real consideration, a concept that deserves real consideration (IMHO).

First, let me provide a reference to the singularity as I envision it. The term originated with Vernor Vinge’s paper for a 1993 NASA Conference. It identifies a few paths (including Kurzweil’s favorite: machine intelligence) towards a ‘next generation’ entity that will take control of it’s own evolution such that our generation of intelligence can no longer “see” where it is going. Like a dog in a car, we would be along for the ride, but not have any idea of where we are really going.  Vinge includes biological approaches as well as machine (and perhaps underestimates bio-tech approaches) which establishes the concept beyond the “software/hardware” discussion in Commentary Magazine.

Why might we be able to dismiss (ignore) this concept?

  1. Because God will not allow man to create a  more powerful being. This has precedence in the tower of Babel. Interestingly in that situation God’s fear is that if man is not stopped he will become capable of anything.  (Mileage with your deities may vary.)
    I have not received any tablets or messages specific to the singularity from God, so I will not presume to state what She may or may-not allow. Presumably this will become evident in time and the interpretations of some are unlikely to dissuade others from their research and progress.
  2. It is impossible — Here we need to consider what “It” is. Clearly the creation of a conscious/intelligent being is possible (the current U.S. Congress not withstanding) because we appear to have at least one instance of this.  And since engineering of the current species into Homo Nextus is one of Vinge’s paths, we have the advantage of starting from that given.  So for the bio-tech path(s), presumably the “Impossible” is the significant differentiation needed to move beyond Homo Sapian understanding. Personally I suspect a species of folks who understand quantum mechanics might qualify. There are indications that this has happened before.  Once upon a time there were three or more humanoid species on earth (Neanderthal, Erectus and Sapians)  and indications they interacted (and interbred.)  One suspects that the Neanderthal’s were left scratching their heads as the Sapians started doing many strange things — which ones are the topic of diverse fiction stories.
    The AI/Machine Intelligence path certainly requires a larger leap of faith to either assert it as a certainty, or its impossibility. Note that “faith” is covered under point 1.
  3. It is too complex — This certainly has merits in both the bio and AI approaches.  It would seem axiomatic that a being at stage two cannot design and build a being at stage three.  However, Evolution is the counter point to this (Creationists please see point one) … wherein more complex and in some cases more intelligent beings have emerged from ‘lower’ forms.  Interestingly it is via “Genetic Algorithms”  that John Koza has created patentable devices that are outside of his expertise to create, and in some cases with capabilities he (and others) cannot explain.  An apparent pre-cursor to the singularity, since one would expect similar observations to occur when (if) that arises.
    Often this argument devolves to “since I (often expressed as ‘we’) cannot imagine how to do it, then neither can you”.
    Technology advances both surprise and dismay me — we should have had flying cars already, and where did 3-D printing come from? Vinge anticipates machine intelligence in 2023 and Kurzweil 2018-43; and of course, like the Turing Test, we won’t necessarily agree when it “happened”.

I can envision one bio-tech path towards a new species, it is outlined in Greg Stock’s TED talk on upgrading to humanity 2.0: We add a couple of chromosomes for our kids. I’m thinking two — one has “patches”, for the flaws in our current genome (you know, pesky things like susceptibility to diabetes, breast cancer and Alzheimers), the second has the mods and apps that define “The Best that We Can Be” at least for that month of conception.  Both of these will warrant upgrades over time, but by inserting the double hit of both into the the genome (going from 46 chromosomes to 50)  the “Haves” will be able to reproduce without intervention if they wish (of course not as successfully with have-nots due to a mis-match in the chromosome counts.)  Will such a Homo Nextus species actually yield a singularity?  Perhaps.  Is this a good idea?  — Well that is debatable — your comments welcomed.

Who owns your genome, redux

This week (WSJ Nov 26, 2013) the US  FDA warned 23andMe to stop marketing their genome analysis services.  It is worth taking a look at the issues raised since they vary from lab procedures to the nasty question of who owns your genome (in the U.S.)

An issue identified by the WSJ article is “scrutiny of their laboratory processes.”  This is then reiterated in part by the phrases “false negative” and “false positive”.  It certainly seems reasonable that a service in this business should have as high of assurance that you get results based on the materials you submit, and that the genes identified are actually in your genome. However it appears that this concern is not the real FDA target.

The false positive concern, expressed by the FDA as ”  For instance, if the BRCA-related risk assessment for breast or ovarian cancer reports a false positive, it could lead a patient to undergo prophylactic surgery…”  Which seems to presume that a Doctor would undertake such surgery without obtaining confirming lab results, a path towards malpractice. The false negative concern has more merit … folks convinced by the results that they are not at risk for a disease and ignore the symptoms.

23andMe has a detailed, readable  (!) and informative Terms of Service statement.  It covers the types of disclaimers that one would expect, and also some interesting warnings such as “knowledge is irrevocable” — you may not like what you find out.  “You may learn information about yourself that you do not anticipate” ancestry, parentage, etc. may not be what you think.  Genetic Information you share with others could be used against your interests”— such as health care providers, insurance companies, employers etc. Including the fact that you can not claim that you have not been genetically tested to an insurance company, or answer some questions like “do you have any reason to believe…” on health questionnaires. While, in the U.S., there are laws limiting abuse of genetic information (see, and in theory it cannot be used in Health Insurance, it can be used in life insurance or long term care insurance descisions.

The philosophic crux of the situation is captured in this phrase: “the risk that a direct-to-consumer test result may be used by a patient to self-manage, serious concerns are raised if test results are not adequately understood by patients…” This is where the question of data ownership surfaces.  Do you have a right to know all or part of your genome?  This phrase suggests you do not.  “Direct to consumer” bypasses an important (political funding) constituency known as the medial professionals. And while I am sure there are persons who are not competent to handle genomic information about themselves, it is unclear that regulatory restrictions should prohibit all of us from such information. Ultimately knowledge is power, and when such analysis is done, we have to ask who holds the power aka knowledge?  IEEE Spectrum ran an article about the full genome analysis in March 2013.  I was surprised that the writer was not allowed access to her results, but only though a medical interpretation of a community of doctors. In essence the companies running the tests and the genetic counselors interpreting them do not recognize the right of an individual to know themselves at the genomic level.

23andMe only evaluates genes of interest, not a full genome report. This reduces the possibility that next week’s research will disclose a new genome associated risk that is evident as a result of your already competed tests.  What will you do if a “dumb” gene is discovered, and you have it? (ok, you wouldn’t be reading this blog is my guess.)

Action? — A petition exists at to ask the President  to override the FDA warning. However, this only touches on the essential question of genomic ownership and rights. Some of these questions were raised in this blog in March, and need serious consideration.  This area is moving forward on all fronts.  The supreme court has ruled that genetic content cannot be patented, public figures have undergone preventive surgery, and patents have been issued for designer babies.

So who should have the rights to your geome, and why?

One Small Step for Clone-kind

A Wall Street Journal article May 16, 2013 reports (including informative an video) on work lead by the Oregon Health and Science University in which human embryonic stem cells have been created from skin cells — which means matching a specific individual DNA.  It is a technology targeted at facilitating organ repair/replacement, but is also one step closer to  human cloning.  Interested parties are quick to point out that there are still major steps to be taken before even primate cloning is viable, that human cloning is illegal in some jurisdictions and unethical in some communities or just plain wrong.

Will we see human clones in the next few decades? My answer is “sure”. First there are cultures and jurisdictions where this would not be unethical or illegal. There are significant kudos to be gained by the successful team (even if they are denied the Nobel prize.) There are ‘fat cats’ (wealthy egotistical folks) who would delight in the possibility of a “mini-me”, or in a compatible organ donor. (Societies with different values are likely to accept some variances along these lines). Some of the ‘fat cats’ will be folks with significant, or total political power sufficient to overcome whatever objections you are sure might exist to the implied above uses-abuses.  Give me, say a dozen clones, some for parts, some to :”raise right” as a successor, and maybe a few to see if brain transplants can work, or other form of memory/personality transfer.

Sounds like bad science fiction? Sure, but these plots did not emerge from alien planets and unlikely science. These are IMHO a logical extrapolation of human nature as revealed over the last few hundred years of science, totalitarianism and ego-mania.   Pretending that we are now that much different than those running the world in 1940, or a few other recent periods of time is a type of denial.

So, I’m taking bets … when will we see the first viable human clone? And a second prize for identifying the correct country in which that breakthrough will occur? I’m betting on “before 2030” and “the country will have a logogram appearing written language”.  What’s your best guess?

Know Thy Self — and Thy Genome?

The March Issue of IEEE Spectrum has an article on the technology and experience of having your genome analysed.  This is technology with significant social implications.

There are places where you  can get a partial genome evaluation such as 23andMe. These are fairly cheap ($99 ball park) and target a modest number (500,000 or so) of the 3 Billion base pairs, and some evaluation of mitochondrial DNA as well. The evaluation identifies 200+ health traits, and also your family tree as presented in Y Chromosomes and the mitochondrial DNA. But this is the tip of the proverbial iceberg.

The evaluation done for Eliza Strickland (Spectrum Associate Editor) was testing one of the new technologies which will eventually provide an analysis of your full genome, with a target price tag of $1000. Or as the article more accurately states, $1000 for the test, $100,000 for the analysis.  Eliza’s test results were focused strictly on the exome (30 million base pairs), aka the gene sections.  Significant control and epigenetic considerations were not included. For example, the control over blue eyes is not in your genes but in the “Junk DNA” that represents the vast bulk of your genome. She was not given “raw” data, but a carefully analysed and reviewed report on a subset.   All of which reflects a division of “opinion” on how DNA evaluation results should be presented.  So here are some of the nasty questions … and I encourage readers to provide additional questions, and also insight on how different countries, cultures, etc. are responding to the rapidly emerging field.

  • Who owns/controls the results?  The individual or the medical  consultants or ???
  • And who has access?  — often insurance funded (or even related) results are shared (with your ‘standing’ permission) with your insurance company.
    (In the US, the GINA law provides some protection against insurance companies and employers discriminating based on DNA information– but not life insurance, long term care insurance)  Often in applying for insurance you are asked to disclose medical conditions — does this include information from your DNA analysis?
  • Who can run these tests?  Can I take a sample off the cup you left behind at a restaurant, have it analyzed and use the results? This was done by the LA Police seeking a serial killer (via close relative DNA analysis.)
  • You can pursue some personal research on your results via the National Institute of Health.— but what if you surface a (currently) incurable disease?  And of course it will be a probability — say 60% or 20%?
  • It’s not all about you! — you share genes with parents, children and siblings. What you find out about yourself will have some relation to these relations.
  • There are significant potential benefits — 
    • Preventative action — Diet, treatment — is possible
    • Personalized treatment — Doctors can use this information to avoid medications that won’t help in your situation, or might cause other problems
    • Data mining can take your information and condition, associate it with thousands of others, and identify new genetic factors.

Long term it is hard to imagine that we won’t be carrying (embedded?) a memory chip with our Genome information that provides unique identity, information for all medical care situations, and so forth. In reality, we already carry this in every cell in our body and every cell we leave behind.

What concerns/opportunities does this raise in your mind?
What is your country/culture saying about this?