Dismiss Notice
Join Physics Forums Today!
The friendliest, high quality science and math community on the planet! Everyone who loves science is here!

Medical Synthetic Human Genomes

  1. May 13, 2016 #1

    1oldman2

    User Avatar
    Gold Member

    Last edited by a moderator: Jun 6, 2016
  2. jcsd
  3. May 14, 2016 #2

    Ygggdrasil

    User Avatar
    Science Advisor

    We are very far away from this goal. First, the technologies for DNA synthesis and assembly are not ready to synthesize the 3 billion base pairs of the human genome. Scientists have synthesized a bacterial genome (0.0005 billion base pairs) and a yeast chromosome (0.0002 billion base pairs). The technology might be ready in a decade, but it is possible that other methods of genome engineering and editing (such as CRISPR) would enable similar experiments within a decade as well. A better starting point would be to finish creating the synthetic yeast genome, which would provide a nice platform for doing many of the studies one might want to do on a synthetic human genome. However, there are things one could learn from studying synthetic human genomes, that one could not learn from studying synthetic yeast genomes (though synthetic yeast genomes would definitely have more potential for applications in biotechnology).

    Second, on the biology side, we also lack the knowledge to rationally design genomes. Earlier this year, researchers published a paper on synthesizing a bacterial genome in which they tried to design the bacterium to have as few genes as possible. Attempts to rationally design such a bacterium failed, and the team had to resort to very tedious trial-and-error approach. So, even if we were to have the capability to fully synthesize a human genome, we would not be able to engineer super soldiers as the NY Times article suggests. Similarly, genetics are not destiny and environmental factors play a huge role in an individual's development. Synthesizing Einstein's genome would likely not produce another genius.

    Scientifically, there are some interesting things that we could learn from such a technology, but whether the synthesis of human genomes enables any practical applications is very unclear.
     
  4. May 14, 2016 #3
    Typically the function of a gene is to act as instructions for building a protein.
    The protein then is used to build some aspect of the physical organism.
    The detailed structure of the proteins differ between individuals (which is why individual examples of the same species are not identical)
    Sometimes a variation of a protein doesn't work very well and the organism may not be able to survive, or will suffer from a disability.
    At the present time we don't know a lot about the function of some proteins, so therefore attempts to make new variations do not lead to a predictable result.
    There has been some success though with replacing genes which are known to be dysfunctional with another sequence which is known to be OK.
     
  5. May 14, 2016 #4

    Ygggdrasil

    User Avatar
    Science Advisor

    IMHO, the benefit synthetic human (or mammalian) genomes for research purposes is not in studying protein function, but in studying non-coding DNA.

    >98% of the human genome does not code for protein, and we don't know the function of many of these sequences. Some of these sequences have been called "junk DNA," but scientists debate about how much of the human genome is junk DNA. To what extent can some of these junk sequences be removed while still maintaining the ability to encode a fully functioning organism? Attempts to synthesize "minimal" mammalian genomes could help answer this question and clarify the function of "junk DNA."

    Some of the non-coding sequences control which protein-coding genes are turned on and off, but many of these regulatory sequences are far away from the genes they regulate. A big area of research is in figuring out the three-dimensional architecture of DNA within the nucleus and whether the physical organization of DNA plays a role in controlling gene expression (for example, by folding the DNA such that the regulatory sequences touch the genes they regulate but not genes that should be maintained off). The ability to synthesize new chromosomes could allow scientists to directly test ideas about how non-coding sequences influence genome architecture and gene expression.

    Enabling experiments to address the above questions (as well as many others) would be the main scientific benefit of such research. I still am skeptical of any practical application for synthesizing human genomes other than helping to advance technologies that might help in other synthetic biology efforts (e.g. in engineering bacteria or yeast for applications in the biotechnology industry).
     
    Last edited: May 14, 2016
  6. May 14, 2016 #5

    1oldman2

    User Avatar
    Gold Member

    Thanks for the replies/opinions, From the layman's point of view its very difficult to get an idea of where this technology is based on a news article such as I have cited here. The concepts the article mentions are very interesting but I felt bringing it up in a thread here would be a good reality check. This is the best possible place I can seek an opinion that is reliable. Did I mention I love this site? Thanks again.
     
  7. Jun 2, 2016 #6

    Ygggdrasil

    User Avatar
    Science Advisor

    Today, the HGP-write team published an article online in the journal Science discussing some of their plans: http://science.sciencemag.org/content/early/2016/06/01/science.aaf6850.full

    Boeke, Church, Hessel, Kelley et al. 2016. The Genome Project–Write. Science. Published online 02 Jun 2016. doi:10.1126/science.aaf6850

    They've also launched a webpage for their project: http://engineeringbiologycenter.org/
     
  8. Jun 2, 2016 #7

    1oldman2

    User Avatar
    Gold Member

  9. Jun 3, 2016 #8

    1oldman2

    User Avatar
    Gold Member

    http://www.genengnews.com/gen-news-...ize-the-human-genome-says-hgp-write/81252790/
    This seems to be getting a lot of attention (as well it should) in the Biomed community. I expect a lot of "doomsaying" in certain circles but I think this will be a great step in the right direction for the cure and even elimination of many diseases and conditions currently prevalent. Once again I need to point out my thoughts here are based on a "laymans" point of view, I'm sure that there are many aspects of the technology I will be hearing about soon, Thanks.

    This one I'll be considering for a while but thought I'd post the link now.
    http://www.scientificamerican.com/article/plan-to-synthesize-human-genome-triggers-a-mixed-response/
     
  10. Jun 3, 2016 #9

    Ygggdrasil

    User Avatar
    Science Advisor

    In my opinion, the rationale for synthesizing a human genome is similar to the rationale for going to the moon. The goal itself is big and flashy, and sure to draw a lot of attention and publicity, but the scientific payoff is not in the goal itself, but in the technologies we develop in the process of achieving the goal. I do not expect synthesizing human genomes to cure or eliminate any diseases in the next few decades. However, some of the spin off technologies and the results of the scientific research it enables will aid in our understanding of the fundamentals of biology and may bring us closer to learning how to cure or eliminate some diseases.
     
  11. Jun 3, 2016 #10

    1oldman2

    User Avatar
    Gold Member

    This is a much more accurate than my statement, thanks for the perspective.
     
  12. Jun 3, 2016 #11

    mfb

    User Avatar
    2016 Award

    Staff: Mentor

    Where do you see the main challenges in that project? Is it just scaling up by a factor of 10000, or are there completely new challenges putting longer and longer gene sequences together?
     
  13. Jun 3, 2016 #12

    1oldman2

    User Avatar
    Gold Member

    I have considerable reading ahead of me to give an answer worth posting.
     
  14. Jun 3, 2016 #13

    Chronos

    User Avatar
    Science Advisor
    Gold Member

    Some big questions remain to be solved. We do not yet grasp the synergy between genes. Apparently unrelated genes may team up to produce subtle but vital biological functions. Also, even some 'bad' genes behave unpredictably. The difference between sickle cell anemia and malaria resistance is one copy of the same gene. One faulty copy of the CFTR gene is harmless and possibly even beneficial, two copies produce cystic fibrosis. Then there is the matter of timing. Certain genes turn on and off at different developmental stages of an organism - from inception through adulthood. Turning the wrong gene on or off at the wrong time can have dire consequences. Until we better understand the interplay and intraplay between genes, their manipulation is a perilous exercise.
     
  15. Jun 3, 2016 #14

    mfb

    User Avatar
    2016 Award

    Staff: Mentor

    My question was mainly directed at @Ygggdrasil. Your post was not there yet when I opened the thread.

    Their manipulation is one way to advance our understanding.
     
  16. Jun 3, 2016 #15

    Ygggdrasil

    User Avatar
    Science Advisor

    Scaling up the capacity to synthesize and work with DNA is certainly a major challenge, but it is not the only challenge. If the goal is simply to copy an existing human genome, we will have to find ways to introduce the newly synthesized chromosomes into an enucleated cell and get them "booted up" correctly. This is not a trivial task given that eukaryotic gene expression is regulated not just by DNA sequence but by the protein and small RNA factors that allow the DNA to be read correctly. There are some fundamental questions, for example, as to the importance of DNA methylation, chromatin structure, and histone modifications, that need to be answered in getting the synthetic genome to function. There is reason to think a small number of factors could enable the genome to boot up (e.g. as in the case of the Yamanaka cell reprogramming experiment), but the situation would be very different starting from a completely synthetic, unmodified and unpackaged genome.

    If the goal is to begin designing new human genomes with new functions, this goal is much more than a decade away. For example, it took Venter six years to go from bacterial genome synthesis to a "minimal" bacterial genome, and even then they couldn't rationally design the minimal bacterial genome. In the end, Venter's efforts were hampered by—and revealed in a very stark way—the fact that we don't understand all of the protein-coding sequences required for life. In eukaryotes, the problem is even more complicated. Not only do we have more genes, but there are many more regulatory non-coding elements in the human genome, and identifying and decoding their function is much more difficult than in the case of protein-coding sequences. Hopefully, the HGP-write effort will spur on progress in this field by developing new tools to understand the function of non-coding genetic elements, but I don't see these efforts translating to practical applications of human genome synthesis anytime soon.
     
  17. Jun 3, 2016 #16

    1oldman2

    User Avatar
    Gold Member

    After reading post #11 I assumed you were likely addressing Y, however I wasn't positive if that was the case or were you asking me a sort of "test question" to see if I was doing my reading. I choose to "error on the side of caution" and post some sort of response rather than appear to be dodging a valid question.
    I just wanted to explain my post.
    At this point the subject is way above me, I'll resort to following posts and see where this goes. Thanks much. :smile:
     
  18. Jun 4, 2016 #17

    TheBlackAdder

    User Avatar
    Gold Member

    I thought we were much closer to positive eugenetics than described here. Nice read.

    If anyone is interested, my friend is doing a PhD on ribosome profiling data. The excerpt below comes from his website: http://sorfs.org/

     
  19. Jun 6, 2016 #18
    Well, using the moon analogy, just like the Apollo missions were preceded by Mercury and Gemini - with smaller goals of putting a man in orbit before we put one on the moon, I'm sure the Synthetic Human Genome project would start with a smaller step first. Perhaps synthesizing a prokaryote genome, or a simpler eukaryote (yeast) genome.

    I fully support this idea. If the LHC was worth sinking billions of dollars into, then this certainly is worth pursuing.
     
  20. Jun 6, 2016 #19

    Ygggdrasil

    User Avatar
    Science Advisor

    A full prokaryotic genome has already been synthesized six years ago: https://www.physicsforums.com/threads/bacterial-cell-with-a-chemically-synthesized-genome.404603/

    Scientists reported the synthesis of a yeast chromosome two years ago: http://www.nature.com/news/first-synthetic-yeast-chromosome-revealed-1.14941

    The synthetic yeast genome will likely be done in a year or two: http://syntheticyeast.org/sc2-0/

    While some of the sub-goals of the synthetic human genome project are definitely worth funding (I am particularly fond of their Aim I: synthesizing “full” gene loci with accompanying noncoding DNA to help explain still-enigmatic roles of noncoding DNA variants in regulating gene expression, and leading to more comprehensive models for the role of noncoding genetic variation in common human diseases and traits), I am not sure a "big science" approach is the correct approach to take. Science would probably move forward better by giving out many smaller grants to individual investigators rather than trying to bring everyone into one centralized endeavor. Big science works well when the means of going forward are clear. There are still many fundamental challenges that need to be solved, so it's better to have many labs exploring a bunch of different ideas on how to go forward than centralizing everything.

    For example, one can look at the example of the human genome project. The NIH centralized the whole effort and was making very slow progress for many years. It wasn't until Craig Venter with Celera Genomics jumped in as outsiders with new ideas that things began progressing faster.
     
  21. Jun 8, 2016 #20
    I'm no biology guru. Is it possible that there is "junk" DNA which serves no purpose in creating a functional individual, but has a purpose in a larger evolutionary sense? For instance if modern cows started hanging out in water for millions of years until evolving into whale like aquatic creatures, is it possible that dormant junk DNA could be activated, to give them some benefits for aquatic life evolved in the distant past?
     
Know someone interested in this topic? Share this thread via Reddit, Google+, Twitter, or Facebook

Have something to add?
Draft saved Draft deleted



Similar Discussions: Synthetic Human Genomes
  1. Human Genome help (Replies: 1)

  2. Human genome project (Replies: 3)

  3. Human Genome Project . (Replies: 3)

Loading...