The Rights and Wrongs of the Human Genome Project—Write

The highly prestigious journal Science carried an unusual article on June 2.  Most scientific papers are about new discoveries—we figured out this theory or we measured thus-and-so in that experiment.  Well, this paper was neither of those things.  In "The Human Genome Project—Write," the twenty-five co-authors announced their intention to synthesize a human genome from scratch.  In layman's terms, they are saying that they are going to design a human being. 

The way they plan to do this is through an organization calling itself the Center of Excellence for Engineering Biology.  They plan to raise $100 million this year pretty much any way they can:  donations, private sources, government funding, you name it.  So far, one of the biggest contributors reportedly is Autodesk, maker of Autocad, the computer-aided design software familiar to mechanical engineers, architects, and lots of other people who make things.  Autodesk has chipped in a quarter million, and so the researchers are at least 0.25% closer to their goal.

I am dwelling on the mechanics of the plan because there is a question here of whether we are looking at science pure and simple, or a scheme that would look more at home in the hands of venture capitalists.  Now there's nothing wrong with doing science (pure or impure), and there's nothing wrong with making money, either.  But one can at least question whether a proposal that looks more like a business plan in some respects deserves to appear in the pages of a journal that usually carries things like Nobel-Prize-winning research that's already been done. 

What exactly are the authors proposing to do?  Well, you may remember the original Human Genome Project.  Its goal was to read a human genome, all 3-some-billion DNA base pairs of the chromosomes of a human being.  In computer-science terms, every base pair encodes one bit of information, and so your chromosomal description can in principle be contained in three billion bits or so, which can easily fit on a flash drive these days.  The Human Genome Project was finished around 2003 at a cost of about $3 billion, according to Wikipedia—about a dollar a base pair, it turns out. 

Reading the genome is one thing, but writing it and trying to use it is quite another.  If you go and synthesize this human genome, how will you know if it works unless you try to make a baby?  And that gets us into really deep ethical waters.

To their credit, the authors of the Science paper address this problem early on, referring to it as "ethical, legal, and social implications (ELSI)."  They call for a lot of discussion of ELSI, and maybe devoting a fixed fraction of their funds to looking at the issues, but they don't say how they would test their creation.  Short of implanting the DNA in a human egg cell and seeing if it will develop normally into a baby, I'm not sure how they would test it. 

They mention stem-cell research as a model of how such tests would be done.  Stem-cell research has also been highly controversial ethically, because it can potentially lead to human cloning.  I am not a biologist, but the question seems to be that once you have a fertilized egg cell, how far do you let it develop?  If you just let it divide a few times and then stop it (=kill it, according to some views), you've shown that it can go that far, but you haven't learned much about its normality or whether all the details you put into the genome will show up in the final product, so to speak.  If you go all the way and try implanting it into a womb, you will learn a lot more about how your product performs, but at the risk of causing the woman to give birth to a baby with no parents—just a computer program.  At the same time, the risk of deformities or other abnormalities in the baby thus created will be very great.  So we have many of the moral issues associated with stem-cell research coming up with this project as well, only more so.

I intentionally used the word "product" to refer to the human who would be created through this process, because that is what he or she would be:  a completely engineered product from the start.  We have already gone pretty far down the unsavory road of regarding children as products, with prenatal genetic testing and selective abortions being used in case of a wide variety of problems ranging from Down's syndrome down to the simple issue of the wrong sex.  There are still countries where a fetus can be, and often is, aborted if the parents wanted a boy and it turns out to be a girl.  A lot of people think this is wrong, but it happens.

I salute the authors of the Human Genome Project—Write paper for recognizing that their proposal carries extremely serious ethical implications.  But I think they are trying to have their scientific cake and eat the profits too.  Although some reports about the organization formed to carry out the project say it is a non-profit, that term appears nowhere in the original paper, although the phrase "patent pools" does.  Patent pools are useful when a small number of powerful companies wish to engineer a functional near-monopoly in a new field.  It's not clear whether early investors in this project will be able to stake a claim on the intellectual property it generates, but my guess is they will.  That doesn't look like non-profit to me.

If this project leads to non-controversial things like being able to grow a replacement kidney for someone whose original kidneys have failed, that would be great.  I have a relative right now who has been needing a kidney transplant for several years, and he wishes he could go down to the kidney store and order a custom-made replacement model for his old kidneys.  If this project makes that possible without doing some reverse-Frankenstein-like thing such as first growing a human clone and then killing it for its kidneys, I hope it succeeds.  But the temptation to use new technical abilities for unethical things is always there, and if the ends require unethical means, I say: don't even go there.

Sources:  The New York Times carried a thorough report on the Human Genome Project—Write on June 2 at http://www.nytimes.com/2016/06/03/science/human-genome-project-write-synthetic-dna.html.  The paper itself, published in Science the same day, can be accessed at http://science.sciencemag.org/content/early/2016/06/03/science.aaf6850.  I also referred to a NYULangone press release at http://nyulangone.org/press-releases/genome-project-write-to-launch-in-2016 and the Wikipedia articles on non-coding DNA and the Human Genome Project (the original "read" project).

Obama’s Brain Project: A Hall of Mirrors?

One of the famous line drawings of the artist M. C. Escher portrays a realistically drawn hand holding a pencil.  The line drawn by the pen turns out to be the cuff of a shirt sleeve, from which emerges a second hand. . . which grows out of the paper somehow and holds a pencil, whose line is the cuff of a shirt sleeve, from which emerges the first hand.  Escher’s “Drawing Hands” came to mind when I read of a planned initiative by the Obama administration to promote a decade-long project to map the human brain.

Officially, the project is still under wraps until the President announces his budget priorities later this month.  But according to a New York Times report by John Markoff, plans include increased federal funding for neurological research directed at mapping increasingly complex brains, ranging from those of a fruit fly up to the world’s smallest mammal, a type of shrew.  But the ultimate goal is to learn how essentially every neuron in the human brain is connected, and how the whole thing works:  a wiring diagram of the brain, if you will.  Hopes are that such knowledge could lead to new therapies for presently incurable brain disorders such as Alzheimer’s disease and other forms of dementia.

Inevitably, this project has been compared to the Human Genome Project, which was completed about a decade ago at a cost of under $4 billion.  Some estimates say that the information gained from that project has returned up to $140 for every dollar spent.  Aside from the purely economic results, the mapping of the human genome was a landmark scientific achievement in its own right, which has led to further questions and discoveries in an already burgeoning field.

Does the human-brain mapping project hold the same amount of promise, either economically or scientifically?  The first question that should be asked is, “Can it work?”  And some scientists are already voicing doubts.

Markoff quotes neuroscientist Donald G. Stein as saying, “I believe the scientific paradigm underlying this mapping project is, at best, out of date and at worst, simply wrong.”  Apparently, the old analogies of the brain as a massive kind of telephone switchboard, or even a “wet computer,” fail to capture essential aspects of an organism which can develop new neurons in response to external stimuli, and has recently proved to be much more plastic than earlier theories supposed.  To the extent that the project imposes an outdated brain model on researchers, it will not succeed.  But every researcher knows that what you say you are going to do in order to get research money, is not necessarily the thing you actually end up doing, so this concern is probably not as great as you might think.

What is of greater concern now is the question of basic feasibility.  When Dr. Rafael Yuste of Columbia University was asked at a September 2011 conference about what he would really like to be able to do with the brain, he replied, “I want to be able to record from every neuron in the brain at the same time.”  Simply storing the data that would result from such an instrument is a brain-boggling proposition.  One estimate is that you would need the data-storage equivalent of about 600 million hard drives the size of the one on my personal computer (500 gigabytes) to store all the neurological activity that goes on in only one brain for a year.  The next time you say “nothing’s on your mind,” think about that.

Of course, data storage has been getting more efficient for decades, and it will probably continue to do so for a while.  But storing the data is nowhere near as hard as obtaining it in the first place.  Right now, the only way to monitor individual brain neurons is to connect wires to them, which requires opening the skull.  There are various means to monitor the brain non-invasively, but at present they have a fairly poor resolution, on the order of a millimeter at best.  And there are thousands of neurons in each cubic millimeter of brain.  Futuristic plans to send molecule-size data recorders into the brain and record the results on DNA are still purely drawing-board notions, and it is not clear they will ever work.

When the Human Genome Project began, we knew that DNA sequencing was possible—it was just very slow and tedious.  Rapid advances in technology enabled the project to finish ahead of schedule.  It is by no means clear that massive monitoring of individual brain neurons is even theoretically possible.  And unmentioned so far is the question brought up by the Escher drawing:  can the brain really understand itself?  In particular, what would happen if Dr. Yuste gets his wish and one day he sits down at a computer monitor that shows him the output of his own brain in some meaningful way.  If you’ve ever pointed a TV camera at a monitor showing the camera’s own field of view, you have seen some weird patterns show up.  It’s not pleasant to contemplate what it might mean for your own brain to watch itself in action.

As with any great leap in scientific knowledge these days, the rationale for it is that it may lead to practical benefits such as cures for diseases like Alzheimer’s and autism.  While we can’t discount these possibilities, neither can we discount the notion that once it’s possible to exhaustively monitor the activity of the human brain, it may be possible to read thoughts in a way that would amount to the ultimate invasion of privacy.  At the very least, this possibility raises concerns that should be taken seriously.  So far, everyone whose brain has been monitored has given consent to the process, we hope.  But the molecule-size brain monitors could be delivered without the patient’s knowledge or consent. 

So far, this kind of thing is in the realm of science fiction rather than fact.  But before it becomes fact, let’s hope that we have a full public discussion of the potential downsides as well as the benefits of a map of the human brain, assuming such a thing is even possible.

Sources:  John Markoff’s article “Obama Seeking to Boost Study of Human Brain,” appeared in the online edition of the New York Times on Feb. 17, 2013, at http://www.nytimes.com/2013/02/18/science/project-seeks-to-build-map-of-human-brain.html.  He followed it with an analysis piece on the same subject on Feb. 24 at http://www.nytimes.com/2013/02/26/science/proposed-brain-mapping-project-faces-significant-hurdles.html.  I relied on both of these pieces for this article.  The M. C. Escher work “Drawing Hands” can be viewed at http://kafee.files.wordpress.com/2009/10/drawing_hands.jpg