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  <front>
    <journal-meta id="journal-meta-1">
      <journal-id journal-id-type="nlm-ta">Biomedical Research and Therapy</journal-id>
      <journal-id journal-id-type="publisher-id">Biomedical Research and Therapy</journal-id>
      <journal-id journal-id-type="journal_submission_guidelines">http://www.bmrat.org/</journal-id>
      <journal-title-group>
        <journal-title>Biomedical Research and Therapy</journal-title>
      </journal-title-group>
      <issn publication-format="print"/>
    </journal-meta>
    <article-meta id="article-meta-1">
      <article-id pub-id-type="doi">10.15419/bmrat.v10i8.821</article-id>
      <title-group>
        <article-title id="at-944998239381">The Engineering Biology Problems Book: Bridging the gap between biomedicine and engineering</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author" corresp="yes">
          <contrib-id contrib-id-type="orcid">0000-0002-2888-7999 </contrib-id>
          <name id="n-315f7bac8a9c">
            <surname>Klabukov</surname>
            <given-names>Ilya. D.</given-names>
          </name>
          <email>ilya.klabukov@gmail.com </email>
          <xref id="x-f5ecb972f3b2" rid="a-ccf67321824b" ref-type="aff">1</xref>
          <xref id="x-e5596a9ba54c" rid="a-2944e8409031" ref-type="aff">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-6154-9959 </contrib-id>
          <name id="n-d873eab56c0d">
            <surname>Baranovskii</surname>
            <given-names>Denis S.</given-names>
          </name>
          <xref id="x-f35188ec9011" rid="a-ccf67321824b" ref-type="aff">1</xref>
        </contrib>
        <aff id="a-ccf67321824b">
          <institution>National Medical Research Radiological Center; Koroleva st. 4, 249036 Obninsk, Russia</institution>
        </aff>
        <aff id="a-2944e8409031">
          <institution>Obninsk Institute for Nuclear Power Engineering, National Research Nuclear University MEPhI; Studgorodok 1, 249039 Obninsk, Russia</institution>
        </aff>
      </contrib-group>
      <volume>10</volume>
      <issue>8</issue>
      <fpage>5801</fpage>
      <lpage>5803</lpage>
      <permissions/>
      <abstract id="abstract-a158654cc7f3">
        <title id="abstract-title-73f9f1cfc664">Abstract</title>
        <p id="paragraph-7aeb53424a95">Progress in the biological sciences requires advanced approaches to biological education. The current well-established paradigm rarely uses engineering design to solve biological problems. Engineering biology is a novel science field and academic discipline that focuses on the engineering of living objects using biological techniques. We believe that the integration of engineering components into biological education together with a wide application of engineering methods can provide considerable benefits to the education system. We developed the “<bold id="s-b3dd35b4fced">Engineering Biology Problems Book</bold>” to bridge the gap between biology, medicine, and engineering. </p>
      </abstract>
      <kwd-group id="kwd-group-1">
        <title>Keywords</title>
        <kwd>biological education</kwd>
        <kwd>biomedicine</kwd>
        <kwd>design</kwd>
        <kwd>engineering biology</kwd>
        <kwd>problems book</kwd>
        <kwd>synthetic biology</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec>
      <title id="t-5ef29b6405e1">Introduction</title>
      <p id="p-c3d4c5148d78">Progress in the biological sciences requires the integration of advanced educational approaches. Although traditional biology teaching methods provide sufficient knowledge of fundamental concepts to meet the requirements of biotechnological companies and research institutes, the current limited paradigm of biological methodology does not stimulate creative thinking, which is necessary for the development of innovative scientific ideas.</p>
      <p id="p-1e607ecde773">Engineering biology is a promising new field that focuses on the engineering of living objects using various biological techniques. As an applied science, engineering biology can achieve biological progress through innovative approaches, while as an academic discipline, it surpasses traditional biological education and stimulates scientific creativity. We suggest that bridging the gap between biological and engineering education is vital for revolutionizing the field of biological sciences. In 2015, the “Biology is Technology” initiative was initiated by officials of the Defense Advanced Research Projects Agency (DARPA) as a strategy to redesign the approach to biological engineering<bold id="s-c2f0d6b14967"><xref rid="R204834528821387" ref-type="bibr">1</xref>, <xref rid="R204834528821388" ref-type="bibr">2</xref></bold>. DARPA's program managers are responsible for the development of new biological programs that are based primarily on engineering concepts<bold id="s-af20b691032d"><xref id="x-77c5717ec17b" rid="R204834528821387" ref-type="bibr">1</xref></bold>.</p>
      <p id="p-3f40115411a1">Despite the proliferation of classic teaching books (<italic id="e-6c3cbb72755a">i.e</italic>., John Wilson and Tim Hunt’s “Molecular Biology of the Cell: Problems Book”<bold id="s-8407f53fcf11"><xref id="x-210f305d3438" rid="R204834528821389" ref-type="bibr">3</xref></bold> and Joseph Feher's “Quantitative Human Physiology”<bold id="s-1c6df30775db"><xref id="x-70744c210e9d" rid="R204834528821390" ref-type="bibr">4</xref></bold>), there are minimal references to essential engineering methods and approaches<bold id="s-3d4959536f56"><xref id="x-56380ec19aea" rid="R204834528821391" ref-type="bibr">5</xref></bold>.</p>
      <p id="p-b6d15ebbccd5">What is the difference between biological and engineering education? To understand this gap, we developed a simple comparison chart (<bold id="s-f7deff4272bc"><xref id="x-3772ae259dc6" rid="tw-f95953c6b351" ref-type="table">Table 1</xref></bold>).</p>
      <p id="p-8a713287ba70"/>
      <table-wrap id="tw-f95953c6b351" orientation="portrait">
        <label>Table 1</label>
        <caption id="c-910a70342c46">
          <title id="t-9ed30171d715">
            <bold id="s-a4deaf1ceb05">Fundamental Differences Between Biological and Engineering Education</bold>
          </title>
        </caption>
        <table id="table-1" rules="rows">
          <colgroup>
            <col width="21.18"/>
            <col width="19.64"/>
            <col width="22.52"/>
            <col width="36.66"/>
          </colgroup>
          <thead id="table-section-header-7fbaf7d80dec">
            <tr id="tr-6a0f22de71f1">
              <th id="tc-b4617afd5fbd" align="left">
                <p id="p-4c259db1cc05"/>
              </th>
              <th id="tc-bf9e81ff3730" align="left">
                <p id="p-ae4cd55a05f5">Biology </p>
              </th>
              <th id="tc-8f576b674ba7" align="left">
                <p id="p-0dff80dd0cfb">Medicine</p>
              </th>
              <th id="tc-0df4b633f5f7" align="left">
                <p id="p-fe9239e927b3">Engineering</p>
              </th>
            </tr>
          </thead>
          <tbody id="table-section-1">
            <tr id="table-row-2">
              <td id="table-cell-5" align="left">
                <p id="p-e431bdef41ec">Calculations</p>
              </td>
              <td id="table-cell-6" align="left">
                <p id="p-1d60faeb0d3d">Bioinformatics only</p>
              </td>
              <td id="table-cell-7" align="left">
                <p id="p-f0a06f48d508">Pharmacokinetics and models for applied software</p>
              </td>
              <td id="table-cell-8" align="left">
                <p id="p-d2a0d2385f0a">In all fields</p>
              </td>
            </tr>
            <tr id="table-row-3">
              <td id="table-cell-9" align="left">
                <p id="p-fe28423adab8">Logic</p>
              </td>
              <td id="table-cell-10" colspan="2" align="left">
                <p id="p-058b221a9287">Limited</p>
              </td>
              <td id="table-cell-11" align="left">
                <p id="p-cc94b36f1549">Full, exception of only a few sections of algebra </p>
              </td>
            </tr>
            <tr id="table-row-4">
              <td id="table-cell-12" align="left">
                <p id="p-558c4edf470f">Engineering design</p>
              </td>
              <td id="table-cell-13" colspan="2" align="left">
                <p id="paragraph-12">For specific domains only </p>
                <p id="p-e776d11f39da">(for example, for drugs and devices)</p>
              </td>
              <td id="table-cell-14" align="left">
                <p id="paragraph-14">Overall</p>
              </td>
            </tr>
            <tr id="table-row-5">
              <td id="table-cell-15" align="left">
                <p id="paragraph-15">Answer options in classic teaching books</p>
              </td>
              <td id="table-cell-16" colspan="2" align="left">
                <p id="p-e5a7b0eca4dd">Mono- and multi-variance with the limited versions of correct answer.</p>
              </td>
              <td id="table-cell-17" align="left">
                <p id="paragraph-17">Multi-variances. The correct answer depends on the approach to solving the problem.</p>
              </td>
            </tr>
            <tr id="table-row-6">
              <td id="table-cell-18" align="left">
                <p id="paragraph-18">Scope of problems</p>
              </td>
              <td id="table-cell-19" colspan="2" align="left">
                <p id="p-d8a25b20856d">Specific problems of the biological/medical field</p>
              </td>
              <td id="table-cell-20" align="left">
                <p id="paragraph-20">Engineering is applied to solve problems in different fields of science and technology: from homework tasks to global issues</p>
              </td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
      <p id="p-27a2337b8872"/>
      <p id="p-e4c82cc70435">The majority of attempts at engineering biology programs have had limited success. The NASA initiative of 2009 that aimed to establish a Singularity University to promote scientific creativity was never fully implemented<bold id="s-4c074b8533a7"><xref id="x-180f040edffe" rid="R204834528821392" ref-type="bibr">6</xref></bold>. Similarly, the latest initiative of 2015–2019 by Representative Eddie Bernice Johnson to amend an educational landscape with engineering biology principles was never implemented in practice<bold id="s-74f85fe077cc"><xref id="x-42aedaa84070" rid="R204834528821393" ref-type="bibr">7</xref></bold>. The Living Foundries program has the potential to provide the next step of a multilevel hierarchical approach for biological machines<bold id="s-cd768409ee13"><xref id="x-4116495d4f55" rid="R204834528821394" ref-type="bibr">8</xref></bold>. However, no significant advancements have been identified from either the Massachusetts Institute of Technology or Boston University. The bottom-up approach for engineering methods in biology has proved unsuccessful; therefore, we decided to contribute to the development of engineering biology.</p>
      <p id="p-43f0a59ebc51">We prepared the “Engineering Biology Problems Book” to bridge the gap between biology and engineering. This book was first published in the Russian language; however, a draft English version was created by a collaborative international effort during the International Genetically Engineered Machine (iGEM) Competition in 2021<bold id="s-54f7fda595b6"><xref id="x-6ad0067ea768" rid="R204834528821395" ref-type="bibr">9</xref></bold>.</p>
      <p id="p-e0c2a8230ed2">“The Engineering Biology Problems Book” was inspired by the book series “The Feynman Lectures on Physics” by the Nobel laureate and physicist Professor Richard Feynman, who provided simple and creative formulations for physics problems. Professor Feynman stated that “There is plenty of room at the bottom” and invited his followers into the new nanoworld<bold id="s-dc2f86475fa5"><xref id="x-1f5beef285dd" rid="R204834528821396" ref-type="bibr">10</xref></bold>. As authors of “The Engineering Biology Problems Book”, we believe that engineering biology represents a new kind of physics for the 21<sup id="superscript-1">st</sup> century.</p>
      <p id="p-226aef7586ec">“The Engineering Biology Problems Book” (hereafter, “Problems book”)<italic id="emphasis-3"> </italic>contains seven chapters and more than 300 problems relating to engineering biology. This book helps to develop scientific creativity by allowing readers to create engineering solutions for problems in fields such as the <italic id="emphasis-4">Design of living machines</italic>, <italic id="emphasis-5">Engineering of human body</italic>, <italic id="emphasis-6">Enhancements of the human performance</italic>, and <italic id="emphasis-7">Design of the living objects that do not yet exist. </italic> The Problems book does not presume that only one correct answer exists for each problem but instead provides multiple possible solutions. The essence of the Problems book is to give the reader a space for creative engineering with the aim of capturing new ideas.</p>
      <p id="p-11b6e666e8ed">Certain engineering solutions used in technical devices naturally exist in living organisms. The bioengineering approach allows creative interventions in the molecular basis of life, which can pave the way for new biotechnological inventions based on “living machines” and the formation of novel biological parts for the human body. Bioengineering approaches have wide clinical outlooks for preventive medicine. The following example of a multivariance problem included in the Problems book<italic id="emphasis-8"> </italic>is presented to illustrate this approach.</p>
      <p id="p-49ff6b069b5e"/>
      <disp-quote id="bq-cdf32dae1143" content-type="block-quote">
        <p>
          <italic id="e-9d331048786f">
            <bold id="s-3b3a35adebb0">Born as an Electrician</bold>
          </italic>
          <italic id="e-97f6a1f6eae6">. The human body is a complex electric conductor surrounded by an imperfect dielectric - the human skin layer. Breakdown of the stratum corneum of the skin is possible if the intensity of the electric field that occurs in it exceeds its breakdown voltage, equal, as experiments show, to 500-2000 V/mm. The European Union’s standard voltage of approximately 200 V always causes a breakdown of the outer layer of the skin. Every year, approximately 30 thousand people in the world die because of electrical injuries. Which gene overexpression in epithelial cells could significantly reduce this number, increasing human resistance to electric shocks?</italic>
        </p>
        <attrib>The Engineering Biology Problems Book</attrib>
      </disp-quote>
      <p id="p-ef4f8e8fda20">The unity of biology and engineering can enhance both of these fields through advancements such as the prediction of intermolecular interactions, exploration of deep space, and treatment of global environmental problems. Given that even the basic principles of living object design have not yet been fully established, the Problems book has been formatted to include stimulating tasks to help readers develop a variety of original solutions using engineering approaches that bridge the gap between the fields of biology and engineering.</p>
      <p id="p-87a720bc4a38">We believe that many scientific and educational challenges can be solved through international collaborations. The prominent collaboration in the field of engineering biology is that of the iGEM community. The annual iGEM Сompetition is an excellent exposition for framing and solving engineering problems in biology. “The Engineering Biology Problems Book” was created to evoke discussions of compelling problems in this field and unite scientists from all parts of the world.</p>
    </sec>
    <sec>
      <title id="t-bc6eb90868fe">Abbreviations</title>
      <p id="p-d275583b099c"> None.</p>
    </sec>
    <sec>
      <title id="t-63ce7d520840">Acknowledgments </title>
      <p id="p-808a6cc2a454"> None.</p>
    </sec>
    <sec>
      <title id="t-fc594e6aa354">Author’s contributions</title>
      <p id="p-9ce0b8b99da6">Writing—original draft preparation, I.D. and D.B.; investigation, I.K.; writing—review and editing, I.D. and D.B. All authors read and approved the final manuscript. </p>
    </sec>
    <sec>
      <title id="t-ea0b081e0df8">Funding</title>
      <p id="p-f0731aae01ec">None.</p>
    </sec>
    <sec>
      <title id="t-594d54bad844">Availability of data and materials</title>
      <p id="paragraph-13">Not applicable. </p>
    </sec>
    <sec>
      <title id="t-daa324a1130d">Ethics approval and consent to participate</title>
      <p id="paragraph-16">Not applicable. </p>
    </sec>
    <sec>
      <title id="t-fe90d0989c0a">Consent for publication</title>
      <p id="paragraph-19">Not applicable. </p>
    </sec>
    <sec>
      <title id="t-8b02174f1892">Competing interests</title>
      <p id="paragraph-22">The authors declare that they have no competing interests.</p>
    </sec>
  </body>
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